Complementary and Alternative Medicines for Human and ...sciencesearch.defra.gov.uk/Document.aspx?Document=SD0312... · Web viewThis report concerns one group of non-synthetic chemicals,

APPENDIX 1 CAM DATA.................................................................................................................112

APPENDIX 1.1 SEARCH SUMMARY INFORMATION..............................................................................112APPENDIX 1.2 - AVAILABLE DATASET FOR ALL HERBAL MEDICINES AND ESSENTIAL OILS CONSIDERED AND THEIR ACTIVE CONSTITUENTS...............................................................................115BILOBALIDE........................................................................................................................................117GINKGOLIDE A...................................................................................................................................119GINKGOLIDE B...................................................................................................................................121GINKGOLIDE C...................................................................................................................................123QUERCETIN.........................................................................................................................................125ST JOHN’S WORT (HYPERICUM EXTRACT).........................................................................................127HYPERICIN..........................................................................................................................................129GINSENG.............................................................................................................................................131GINSENOSIDE RB1..............................................................................................................................133GINSENOSIDE RB2..............................................................................................................................135GINSENOSIDE RG1..............................................................................................................................137GINSENOSIDE RH2..............................................................................................................................139GARLIC OIL.........................................................................................................................................141ALLICIN..............................................................................................................................................143ECHINACEA........................................................................................................................................145ECHINACEIN.......................................................................................................................................147VALERIAN ROOT.................................................................................................................................149VALTRATE..........................................................................................................................................151BLACK COHOSH EXTRACT..................................................................................................................153ACTEIN...............................................................................................................................................155FORMONONETIN.................................................................................................................................15727-DEOXYACTEIN...............................................................................................................................159MA-HUANG/EPHEDRA........................................................................................................................161EPHEDRINE.........................................................................................................................................163PSEUDOPHEDRINE...............................................................................................................................166FEVERFEW..........................................................................................................................................168PARTHENOLIDE...................................................................................................................................170EVENING PRIMROSE OIL.....................................................................................................................172LINOLEIC ACID...................................................................................................................................174Γ-LINOLEIC ACID................................................................................................................................177TYLOPHORA INDICA...........................................................................................................................179TYLOPHORINE.....................................................................................................................................181GLUCOSAMINE....................................................................................................................................183GLUCOSAMINE SULPHATE AND HYDROCHLORIDE..............................................................................185LAVENDER ESSENTIAL OIL.................................................................................................................188LINALYL ACETATE..............................................................................................................................190PINENE................................................................................................................................................192TEA TREE OIL....................................................................................................................................195CINEOLE.............................................................................................................................................197TERPINEN-4-OL...................................................................................................................................199ORANGE ESSENTIAL OIL.....................................................................................................................201D-LIMONENE.......................................................................................................................................203L-LIMONENE.......................................................................................................................................206CITRAL...............................................................................................................................................210LINALOOL...........................................................................................................................................212PEPPERMINT OIL.................................................................................................................................214MENTHOL...........................................................................................................................................216MENTHONE.........................................................................................................................................218MENTHYL ACETATE............................................................................................................................220THYME ESSENTIAL OIL.......................................................................................................................223THYMOL.............................................................................................................................................225CARVACROL.......................................................................................................................................228BORNEOL............................................................................................................................................230CAMPHOR...........................................................................................................................................232WORMWOOD......................................................................................................................................234

109

ABSINTHIN..........................................................................................................................................236Α-SANTONIN.......................................................................................................................................238Α-THUJONE.........................................................................................................................................240Β-THUJONE..........................................................................................................................................242APPENDIX 1.3 SUMMARY OF FINDINGS FOR INDIVIDUAL HERBAL REMEDIES.................................244

1. Black Cohosh.............................................................................................................................2442. Camphor....................................................................................................................................2443. Echinacea...................................................................................................................................2454. Evening Primrose Oil................................................................................................................2455. Feverfew.....................................................................................................................................2466. Garlic.........................................................................................................................................2467. Ginkgo biloba extract................................................................................................................2478. Ginseng......................................................................................................................................2499. Glucosamine..............................................................................................................................25010. Ma huang.................................................................................................................................25111. St John’s Wort..........................................................................................................................25312. Valerian...................................................................................................................................255

APPENDIX 1.4 – SUMMARY OF FINDINGS FOR INDIVIDUAL ESSENTIAL OILS....................................2571. Lavender Oil..............................................................................................................................2572. Orange Essential Oil.................................................................................................................2593. Peppermint Essential Oil...........................................................................................................2604. Tea Tree oil................................................................................................................................2625. Thyme essential oil.....................................................................................................................2626. Wormwood.................................................................................................................................264

APPENDIX 1.5 GLOSSARY AND LIST OF ABBREVIATIONS...................................................................266

APPENDIX 2 PESTICIDE/BIOCIDES DATA................................................................................267

APPENDIX 2.1: REGULATORY REQUIREMENTS FOR APPROVAL OF PESTICIDES PERMITTED IN EU ORGANIC REGULATIONS IN VARIOUS EU MEMBER STATES..............................................................268APPENDIX 2.2 USAGE, PROPERTIES, ECOTOXICITY AND HAZARD CLASSIFICATION FOR MAJOR SYNTHETIC PESTICIDES.......................................................................................................................270APPENDIX 2.3 UK POLICY CONTEXT – TIMETABLE...........................................................................273APPENDIX 2.4 APPROVED COMMODITY SUBSTANCES.......................................................................274APPENDIX 2.5 EPA BIOPESTICIDE FACT SHEETS...............................................................................275APPENDIX 2.6 AVAILABLE DATASET FOR ALL PESTICIDES/BIOCIDES................................................281

NATURAL ORGANIC PESTICIDES.............................................................................................282ABAMECTIN......................................................................................................................................2824-ALLYL-2-METHOXYPHENOL.......................................................................................................284AMINOETHOXYVINYLGLYCINE......................................................................................................286AZADIRACHTIN................................................................................................................................2886-BENZYLAMINOPURINE.................................................................................................................290BILANAFOS.......................................................................................................................................292BLASTICIDIN-S.................................................................................................................................2943-[N-BUTYL-N-ACETYL]-AMINOPROPRIONIC ACID, ETHYL ESTER...........................................296CANOLA OIL.....................................................................................................................................298CAPSAICIN........................................................................................................................................300CITRONELLA.....................................................................................................................................302CYTOKININS.....................................................................................................................................304DIHYDROAZADIRACHTIN................................................................................................................306DMDP...............................................................................................................................................308EMAMECTIN BENZOATE..................................................................................................................310OLEIC ACID (FATTY ACIDS)...........................................................................................................312GARLIC EXTRACT...............................................................................................................................314GIBBERELLIC ACID.............................................................................................................................316L-GLUTAMIC ACID PLUS GAMMA-AMINOBUTYRIC ACID............................................................318HARPIN PROTEIN..............................................................................................................................320INDOL-3-YLACETIC ACID................................................................................................................322JOJOBA OIL.......................................................................................................................................324

110

KASUGAMYCIN................................................................................................................................326MAPLE LACTONE.............................................................................................................................328P-MENTHANE-3,8-DIOL..................................................................................................................330MILBEMECTIN..................................................................................................................................332MILDIOMYCIN..................................................................................................................................334MILSANA, REYNOUTRIA SACHALINENSIS EXTRACT.......................................................................336NATAMYCIN.....................................................................................................................................338NICOTINE..........................................................................................................................................3401-OCTEN-3-OL..................................................................................................................................342OXYTETRACYCLINE.........................................................................................................................344PELARGONIC ACID...........................................................................................................................346PLANT-DERIVED PORPHYRIN-DERIVATIVES.................................................................................348POLY-D-GLUCOSAIME.....................................................................................................................350POLYNACTINS..................................................................................................................................352POLYOXIN B.....................................................................................................................................354PYRETHRINS.....................................................................................................................................356ROTENONE........................................................................................................................................358RYANIA EXTRACTS..........................................................................................................................360SABADILLA.......................................................................................................................................362SOFT SOAP........................................................................................................................................364SPINOSAD..........................................................................................................................................366STREPTOMYCIN................................................................................................................................368VALIDAMYCIN..................................................................................................................................370

NATURAL INORGANIC PESTICIDES.........................................................................................372BORAX...............................................................................................................................................372BORDEAUX MIXTURE......................................................................................................................374CALCIUM POLYSULPHIDE...............................................................................................................376COPPER HYDROXIDE.......................................................................................................................378COPPER OXYCHLORIDE..................................................................................................................380COPPER OCTANAOTE......................................................................................................................382COPPER SULPHATE..........................................................................................................................384MERCURIC CHLORIDE.....................................................................................................................386MERCURIC OXIDE............................................................................................................................388MERCUROUS CHLORIDE..................................................................................................................390PETROLEUM OILS.............................................................................................................................392SULPHUR...........................................................................................................................................394SULPHURIC ACID..............................................................................................................................396

APPENDIX 3 WORKSHOP INFORMATION................................................................................398

ATTENDEES........................................................................................................................................398AGENDA.............................................................................................................................................399

APPENDIX 4 DATA GENERATED FROM MODELS.................................................................422

APPENDIX 4.1 PREDICTED PROPERTIES AND PERSISTENCE OF IDENTIFIED NON-SYNTHETIC CHEMICALS...........................................................................................................................................................423APPENDIX 4.2 PREDICTED ECOTOXICITY VALUES FOR THE IDENTIFIED CHEMICALS.........................449APPENDIX 4.3 PBT HAZARD CLASSIFICATION CRITERIA...................................................................474Appendix 4.4 Additional CAM data..................................................................................................500

111

Appendix 1 CAM data

Appendix 1.1 Search summary information

Search summary

Search term Operator Search term or subheading

Alternative medicine.ti,ab.Complementary medicine.ti,ab.Herbal medicine.ti,ab.Plants medicinal#Plant preparations#Neutraceutical$1.ti,ab.Aromatherapy.de.

With Subheading – veterinary.de.

And Veterinary drugs#Veterinary medicine#

Toxicity search database summaryDatabase Database producer Coverage

Medline National Library of Medicine 1951-present

ToxFile Dialog Corporation AG1 1965-present

Embase Elsevier B.V. 1974-present

Biosis Biosis 1969-present

Summary of toxicity termsMedline - Set 1 Medline - Set 2

Health adj effect$1.ti,ab,de.Adverse adj effect$1.ti,ab.Toxicology#Toxicity-tests#Toxic$8.ti,ab.Carcinogen$5.ti,de,ab.Teratogen$5.ti,de,ab.Mutagen$5.ti,de,ab.Neurotoxic$8.ti,de,ab.Cytotoxic$8.ti,de,ab.Genotoxic$8.ti,de,ab.Poison$3.ti,de,ab.Toxicokinetics$1.ti,ab.Metabolism#Tolerable adj daily intake$1.ti,de,ab.TDI.ti,ab.ADI.ti,ab.Allowable adj daily adj intake$1.ti,de,ab.Reference adj dose$1.ti,ab.Reference-values#Guidelines#

Toxicity.de.Adverse adj effect$1.de.Metabolism.de.Urine.de.

Embase - Set 1 Embase – Set 2

Health adj effect$1.ti,de,ab. Adverse adj effect$1.ti,de,ab. Toxic$8.ti,de,ab. Toxicity# Toxicity-testing#

Drug adj toxicity.de.Pharmacokinetics.de.

1 using data provided by the National Library of Medicine

112

Carcinogen$5.ti,de,ab. Mutagen$5.ti,de,ab. Teratogen$5.ti,de,ab. Neurotoxic$8.ti,de,ab. Cytotoxic$8.ti,de,ab. Genotoxic$8.ti,de,ab. Poison$3.ti,de,ab. Toxicokinetic$1.ti,de,ab. Tolerable adj daily adj intake.ti,de,ab. TDI.ti,de,ab. Acceptable adj daily adj intake$1.ti,de,ab. ADI.ti,de,ab. Reference adj dose$1.ti,de,ab. Guideline adj value$1.ti,de,ab. Toxicology# Pharmacokinetics#

Biosis

Health adj effect$1.ti,de,ab. Adverse adj effect$1.ti,de,ab. 225#1 toxic$8.ti,de,ab. Carcinogen$5.ti,de,ab. Teratogen$5.ti,de,ab. Mutagen$5.ti,de,ab. Neurotoxic$8.ti,de,ab. Cytotoxic$8.ti,de,ab. Genotoxic$8.ti,de,ab. Poison$3.ti,de,ab. Toxicokinetic$1.ti,de,ab. Tolerable adj daily adj intake.ti,de,ab. TDI.ti,de,ab. Acceptable adj daily adj intake.ti,de,ab. ADI.ti,de,ab. Reference adj dose$1.ti,de,ab. Reference adj value$1.ti,de,ab. Guideline adj value$1.ti,de,ab. Pharmacokinetic$1.ti,de,ab.

1 Concept code for toxicity

113

Fate and behaviour search termsSet 1 Set 2 Operator Set 3

Absorbance Bioaccumulation Bioconcentration Biodegradation Compartmentalisation or compartmentalization Magnification Photodegradation Volatilisation or volatilization Halflife or (half (w) life) Kow Octanol (w) water (w) co (w) efficient Octanol (w) water (w) coefficient Body (w) (load or burden)

Accumulation Behaviour or behavior

Concentration Deposition Distribution Dispersal Exposure Fate Level Load

5N1 Environment? Water Air Food Sediment Soil

1 operator used on the host Dialog to search for terms within 5 words of each other in any order.

114

Appendix 1.2 - Available dataset for all herbal medicines and essential oils considered and their active constituentsParameter Preferred units/format Supporting informationPreparation/chemical name Ginkgo biloba extract

Therapeutic activity Used in traditional medicine for asthma and vascular disease. Nootropic: used in treatment of vascular insufficiency.1

Herbal/dietary supplement.2

An extract of the leaves has been used in cerebrovascular and peripheral vascular disorders. It has also been investigated in Alzheimer’s disease and multi-infarct dementia.3

Chemical structure N/AChemical name N/ACAS no 90045-36-6Molecular formula N/AMolecular weightMajor emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 National Toxicology Program Executive Summary, available [April 2004] at: http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html3 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.

115

Hydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity Mouse (oral) LD50 7.73g kg-1

4Standardised extract corresponding to 2.3 g kg-1 of active ingredients, 1.9 g kg-1 of flavone glycosides, and 464 mg kg-1 of terpene lactones

Mammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

4 http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html viewed April 2004

116

Parameter Preferred units/format Supporting information

Preparation/chemical nameBilobalide

-

Therapeutic activityChemical structure (Beilstein, 2004)

Chemical name 9-tert-butyl-8,9-dihydroxy-dihydro-furo[2,3-b]furo[3’,2’:2,3]cyclopental[1,2-c]furan-2,4,7-trione

(Beilstein, 2004)

CAS no 33570-04-6 -Molecular formula C15H18O8 -Molecular weight 326.3 g mol-1 -Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studies

117

Fate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

118


Preparation/chemical nameGinkgolide A

Therapeutic activityChemical structure

Chemical nameCAS no 15291-75-5Molecular formula C20H24O9

Molecular weight 408.40 g mol-1

Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point Decomposes at ~300°C1

Boiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studies1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.

119


120


Preparation/chemical nameGinkgolide B

-

Therapeutic activityChemical structure (Beilstein, 2004)

Chemical name (1β)-1-Hydroxyginkgolide ACAS no 15291-77-7Molecular formula C20H24O10



Boiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the field

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.

121

Bioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

122

Parameter Preferred units/format Supporting informationPreparation/chemical name

Ginkgolide CTherapeutic activity Used in treatment of severe

sepsis.a

Chemical structure

Chemical name (1α,7β)-1,7-Dihydroxy-ginkgolide

CAS no 15291-76-6Molecular formula C20H24O11



Boiling point N/AOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studies

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.

123


124


Preparation/chemical name Quercetin

-

Therapeutic activityChemical structure -

Chemical name 3,3’,4’,5,7-Pentahydroxyflavone -CAS no 117-39-5 -Molecular formula C15H10O7 -Molecular weight 302.24 g mol-1 -Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 316.5 °C1

Boiling point Sublimes a

Octanol-partition coefficient (Kow, P)

2.042

Solubility in water 0.16 g L-1 3 Determined at 16°CAcid dissociation constant (pKa)

pKa1: 7.03pKa2: 9.15 b

Determined at 25°C using a spectrophotometric method

Vapour pressure 3.74 x 10-12 Pa 4 Estimated at 25°CHenry’s Law Constant 6.68 x 10-16 Pa m3 mol-1 5 Estimated at 25°CSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)1 IARC (1999) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Some Chemicals that Caus Tumours of the Kidney or Urinary Bladder in Rodents and Some Other Substances. Volume 73. Lyon, France, International Agency for Research on Cancer2 Beilstein database (2004)3 Seidell (1941) cited in SRC PhysProp Database4 Neely WB & Blau GE (1985) cited in SRC PhysProp Database5 Meylan WM & Howard PH (1991) cited in SRC Phys Prop Database

125

Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludge

62–105 days b Sludge from municipal wastewater. Anaerobic degradation at 37°C.

Persistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factor ? Test species and

methodBiota-sediment/soil accumulation factor

? Test method and species

Mammalian oral toxicity Mouse (oral) LD50 159 mg kg-1

Rat (oral) LD50 161 mg kg-1 1


1 Material Safety Datasheet at https://fscimage.fishersci.com/msds/56284.htm

126


St John’s Wort (hypericum extract)

Therapeutic activity Antidepressant1

Used, frequently for self-medication, in the treatment of depression. Such preparations are also promoted for the treatment of other nervous disorders such as insomnia and anxiety, particularly if associated with the menopause.2

Chemical structure N/AChemical nameCAS no 68917-49-7Molecular formulaMolecular weightMajor emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sediment

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.

127

Identity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity Rats, mice: NOEL > 5000 mg

kg-1 (Hammerness et al., 2003)


128


Preparation/chemical nameHypericin

Therapeutic activity Antidepressant1

Hypericin oil has been used as an astringent.2

Chemical structure

Chemical name 1,3,4,6,8,13-Hexahydroxy-10,11-dimethyl-phenanthro[1,10,9,8-opqra]perylene-7,14-dione



Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 320 °C 3

Boiling pointOctanol-partition coefficient (Kow, P)

3.43 b

8.78 4 EstimatedSolubility in water 0.04 g L-1 b Determined at 30°CAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition 1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.3 Beilstein, 20044 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database

129

coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

130


GinsengTherapeutic activity Tonic1

Reported to enhance the natural resistance and recuperative power of the body and to reduce fatigue.2

Chemical structure N/AChemical nameCAS no 50647-08-0Molecular formulaMolecular weightMajor emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factor


131

Mammalian oral toxicity Rat (oral) LD50 750 mg kg-1

Mouse (oral) LD50 200 mg kg-1 3

Panax ginseng


3 http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginseng.html

132


Preparation/chemical name Ginsenoside Rb1Therapeutic activityChemical structure

Chemical name 2-O-β-Glucopyranosyl-(3β,12β)-20-((6-O-β-D-glucopyranosyl-β-D-glucopyranosyl)oxy-12-hydroxydammar-24-en-3-yl-β-D-glycopyranoside



Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 205–207°C 1

Boiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation 1 Beilstein database (2004)

133

constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

134


Preparation/chemical name Ginsenoside Rb2Therapeutic activityChemical structure

Chemical name 20-((6-O-α-L-Arabinopyranosl-β-D-glucopyranosyl)oxy)-12β-hydroxydammar-24-en-3β-yl-2-O-β-D-glucopyranosyl-β-D-glucopyranoside



Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 201°C 1

Boiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half life

1 Beilstein database (2004)

135

Persistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

136


Preparation/chemical name Ginsenoside Rg1Therapeutic activityChemical structure

Chemical name (3β,6α,12β)-3,12-Dihydroxydammar-24-ene-6,20-diylbis(β-D-glucopyranoside)



Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 202–205°C 1

Boiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient 1 Beilstein database (2004)

137

(Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

138


Preparation/chemical name Ginsenoside Rh2Therapeutic activityChemical structure

Chemical name (3β,12β)-12,20-dihydroxydammar-24-en-3-yl-(β-D-glucopyranoside)



Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 220–225°C 1 Solvent

methanolBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water

1 Beilstein database (2004)

139

partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

140

Parameter Data Supporting info.Preparation/Chemical name

Garlic oil-

Therapeutic activity Treatment of hypertension and hyperlipidemia1.Expectorant, diaphoretic, disinfectant and diuretic properties2 and recently investigated for antimicrobial, antihypertensive, lipid lowering, fibrinolytic, antiplatelet and cancer protective effects.

Chemical structure - -Chemical name - -CAS no 8000-78-0 -Molecular formula - -Molecular weight - -Major emission routs -0 e.g. to STP; application

to soilApplication/emission rates e.g. kg ha-1; dose (mg kg-1) -Proportion metabolised - Test method and

speciesIdentity of metabolites - Would be nice if all

this info. Could also be obtained for the metabolites

Density 1.04 - 1.09 (25 °C)3 Melting PointBoiling PointOctanol-partition coefficient (Kow, P)

- Test method

Solubility in water - Test methodAcid dissociation constant (pKa)

- Test method

Vapour pressure - Test methodHenry’s Law Constant - Test method;

temperatureSoil/sediment water partition coefficient (Kp)

- Soil/sediment characteristics

Organic carbon normalised soil/sediment water partition coefficient (Koc)


Photolysis half life - Test method

1 Merck Index (2001) [Garlic, entry 4384]2 Martindale (2002) [Garlic, p1614]3 MSDS [Garlic Oil] viewed on-line at http://www.thegoodscentscompany.com; April 2004

141

Hydrolysis half life - Test methodPersistence in air - Test methodPersistence in activated sludge

- Test method; aerobic anaerobic

Persistence in soil - Test method; soil typePersistence in sediment - Test methodIdentity of degradates from above studies

- -

Fate in the field - Test methodBioconcentration factor - Test species and


- Test method and species

Mammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

142


Allicin-

Therapeutic activity Constituent of garlic1,4. Treatment of hypertension and hyperlipidemia (as per garlic oil)1.

Chemical structure -

Chemical name Prop-2-ene-1-sulphinothioic acid S-2-propenyl ester

-

CAS no 539-86-6 -Molecular formula C6H10OS2 -Molecular weight 162.281 -Major emission routs -0 e.g. to STP; application


speciesIdentity of metabolites Amount produced; Chem

draw fileWould be nice if all this info. Could also be obtained for the metabolites

Density (RD) 1.112 Melting PointBoiling Point Decomposes on distilling1;

134ºC2


1.87 (est)3 Test method

Solubility in water 25 g/l1 (pH 6.5) Test methodAcid dissociation constant (pKa)

- Test method




Organic carbon normalised - Soil/sediment 1 Merck Index (2001) [Allicin, entry 257]2 Bielstein Database [Allicin]; accessed April 20043 SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 20044 Martindale (2002) [Garlic, p 1614]

143

soil/sediment water partition coefficient (Koc)

characteristics

Photolysis half life - Test methodHydrolysis half life - Test methodPersistence in air - Test methodPersistence in activated sludge



- -




Mammalian oral toxicityMammalian skin/eye toxicity LD50 in mice: 60 mg/kg (iv);

120 mg/kg (sc)1

Mammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics) LC 50 at 24,48,72 & 96 hrs

6.34, 5.45, 4.48, 3.64 mg L-1 1Toxicity to aquatic invertebrates

Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

1 Beilstein Database, 2004.

144

Parameter Data Supporting info.

Preparation/Chemical name Echinacea

-

Therapeutic activity Treatment of respiratory infections, e.g. colds (immunostimulant)1.Used in herbal preparations for prophylaxis of bacterial and viral infections2.

Chemical structure - -Chemical name - -CAS no Echinacea angustifolia, ext. (84696-11-7)

Echinacea purpurea, ext. (90028-20-9)Echinacea pallida, ext. (97281-15-7)Echinacea angustifolia tincture (129677-89-0)

-

Molecular formula - -Molecular weight - -Major emission routs - e.g. to STP;

application to soil

Application/emission rates

e.g. kg ha-1; dose (mg kg-1) -

Proportion metabolised


Identity of metabolites

Amount produced; Chem draw file Would be nice if all this info. Could also be obtained for the metabolites

Density -Melting Point -Boiling Point -Octanol-partition coefficient (Kow, P)

- Test method


- Test method

Vapour pressure - Test methodHenry’s Law Constant

- Test method; temperature

Soil/sediment water partition coefficient (Kp)


Organic carbon - Soil/sediment

1 Merck Index (2001)2 Martindale (2002) [Echinacea, p 1606]

145

normalised soil/sediment water partition coefficient (Koc)

characteristics



Persistence in soil - Test method; soil type

Persistence in sediment

- Test method

Identity of degradates from above studies

- -

Fate in the field - Test methodBioconcentration factor

- Test species and method

Biota-sediment/soil accumulation factor


Mammalian oral toxicity

Rat (oral) LD50 >15000 mg kg-1 Mouse (oral) LD50 >30000 mg kg-1 1


1 http://ntp-server.niehs.nih.gov./htdocs/Chem_Background/ExecSumm/Echinacea.html viewed, April 2004

146


Preparation/Chemical name Echinacein

-

Therapeutic activity Constituent of Echinacea2

Chemical structure Echinacein -

Chemical name Dodeca-2,6,8,10-tetraenoic acid isobutyl amide

-

CAS no Echinacein (504-97-2, 10076-00-3, 13430-38-1, 119719-30-1)1

-

Molecular formula C16H25NO -Molecular weight 247.381 -Major emission routs -0 e.g. to STP;

application to soil





Identity of metabolites Amount produced; Chem draw file Would be nice if all this info. Could also be obtained for the metabolites

Density -Melting Point 69-70ºC1

Boiling PointOctanol-partition coefficient (Kow, P)

- Test method


- Test method




Organic carbon normalised soil/sediment water partition coefficient


1 Beilstein Database 2004 [Echinacein]; accessed April 20042 [Echinacea] viewed on-line at http://www.naturalproducts.org April 2004

147

(Koc)Photolysis half life - Test methodHydrolysis half life - Test methodPersistence in air - Test methodPersistence in activated sludge




- Test method


- -






148


Valerian root-

Therapeutic activity Sedative1

Valerian has sedative properties and is used to treat anxiety states; it has also been used as a carminative2





Density -Melting PointBoiling PointOctanol-partition coefficient (Kow, P)

Unitless Test method


- Test method








Persistence in soil - Test method; soil typePersistence in sediment - Test methodIdentity of degradates from - -1 Merck Index (2001) [Valerian, entry 9969]2 Martindale (2002) [Valerian, p 1678]

149

above studiesFate in the field - Test methodBioconcentration factor - Test species and



Mammalian oral toxicityMammalian skin/eye toxicityMammalian ADI Daily dose not to exceed

1800mg 1Short-term use only

Mammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

1 http://tangcenter.uchicago.edu/herbal_resources/valerian.shtml

150


Preparation/Chemical name Valtrate

-

Therapeutic activity Constituent of valerian1,2


Chemical name Valtrate -CAS no 18296-44-1 (22173-55-3) -Molecular formula C22H30O8 -Molecular weight 422.471 -Major emission routs -0 e.g. to STP;

application to soil





Identity of metabolites Amount produced; Chem draw file Would be nice if all this info. Could also be obtained for the metabolites


- Test method


- Test method


temperature

1 Beilstein Database [Valtrate]; accessed April 20042 The valepotriates valtrate/isovaltrate and dihydrovaltrate are considered to be the main tranquilizing constituents of drugs derived from the roots of several Valerianaceae (von der Hude et al, 1986)

151









- Test method


- -






152


Black cohosh extract-

Therapeutic activity Treatment of symptoms associated with premenstrual syndrome (PMS), dysmenorrhea, and menopause1.

Chemical structure - -Chemical name - -CAS no 84776-26-1 -Molecular formula - -Molecular weight - -Major emission routs - e.g. to STP; application





- Test method


- Test method








Persistence in soil - Test method; soil typePersistence in sediment - Test method

1 NTP summary [Black Cohosh] viewed on-line at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 2004

153


- -





154

Parameter DataPreparation/Chemical name ActeinTherapeutic activity Constituent of Black Cohosh1.Chemical structure

Chemical name ActeinCAS no 18642-44-9 Molecular formula C37H56O11 Molecular weight 676.842

Major emission routs -0Application/emission rates

e.g. kg ha-1; dose (mg kg-1)


-


Amount produced; Chem draw file


-

Solubility in water -Acid dissociation constant (pKa)

-

Vapour pressure -Henry’s Law Constant

-


-


-

1 NTP summary [Black Cohosh] viewed on-line at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 20042 Beinstein Database [Actein]; accessed April 2004

155

Photolysis half life -Hydrolysis half life -Persistence in air -Persistence in activated sludge

-

Persistence in soil -Persistence in sediment

-


-

Fate in the field -Bioconcentration factor

-


-


156


Formononetin-

Therapeutic activity Treatment of menopausal symptoms. Constituent of Black Cohosh1 and major oestrogenic factor in clover species2


Chemical name 7-hydroxy-3-(4-methoxy-phenyl)-4-benzopyrone

-

CAS no 485-72-3 -Molecular formula C16H12O4 -Molecular weight 268.273 -Major emission routs -0 e.g. to STP; application




Density -Melting Point 256.5ºC4; 258ºC2

Boiling PointOctanol-partition coefficient (Kow, P)

3.11 (est)4 Test method

Solubility in water - Test methodAcid dissociation constant - Test method1 NTP summary [Balck Cohosh] viewed on-line at at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 20042 Merck Index (2001) [Formononetin, entry 4268]3 Beilstein Database [Formononetin]; accessed April 20044 SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 2004

157

(pKa)Vapour pressure - Test methodHenry’s Law Constant - Test method;







Persistence in soil 37-95% degraded in 1-3 weeks (from 5 mg/l);30-60% degraded in 10-15 d3

Test method; soil type

Persistence in sediment - Test methodIdentity of degradates from above studies

- -





158

Parameter DataPreparation/Chemical name 27-deoxyacteinTherapeutic activity Constituent of Black Cohosh1.Chemical structure

Chemical name 27-deoxyacetylacetol-O-D-xylopyranosideCAS no -Molecular formula -Molecular weight 660.84Major emission routs -0Application/emission rates

e.g. kg ha-1; dose (mg kg-1)


-


Amount produced; Chem draw file


-

Solubility in water -Acid dissociation constant (pKa)

-

Vapour pressure -Henry’s Law Constant

-


-


-

1 NTP summary [Black Cohosh] viewed on-line at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/blackcohosh.html April 2004

159

Photolysis half life -Hydrolysis half life -Persistence in air -Persistence in activated sludge

-

Persistence in soil -Persistence in sediment

-


-

Fate in the field -Bioconcentration factor

-


-


160


Ma-huang/Ephedra-

Therapeutic activity Herbal cold relief. Action of ephedra is due to the presence of ephedrine and pseudoephedrine1.Used in traditional Chinese medicine as a diaphoretic, stimulant and antiasthmatic2.Has also been used to aid weight loss3.

Chemical structure - -Chemical name - -CAS no - -Molecular formula - -Molecular weight -Major emission routs -0 e.g. to STP; application





- Test method


- Test method







1 Martindale (2002) [Ephedra, p 1090]2 Merck Index (2001) [Ephedra, entry 3638]3 Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. Viewed on-line at http://www.ahrq.gov/clinic/epcsums/ephedsum.htm April 2004

161




- -




Mammalian oral toxicity Rat (oral) 600mg kg-1 Probable oral lethal dose (human) 5-50mg kg-11


1 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

162


Ephedrine-

Therapeutic activity Major active constituent of Ephedra; also prepared synthetically – used as an expectorant and nasal decongestant4.Bronchodilator. Also used for veterinary purposes as a bronchodilator and to treat urinary incontinence1.


Chemical name (1R,2S)-2-methylamino-1-phenyl-propan-1-ol

-

CAS no 299-42-3 -Molecular formula C10H15NO -Molecular weight 165.231 -Major emission routs -0 e.g. to STP; application




Density g cm-3

Melting Point 34 ºC1,2

37-39 ºC3

36 ºC (anhydrous form, hemihydrate melts at 42 ºC)5

Boiling Point 255 ºC2

260 ºC (745 mmHg)1


1.132

0.934Test method

1 Merck Index (2001) [Ephedrine, entry 3639]2 SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 20043 Chemfinder viewed on-line at http://chemfinder.cambridgesoft.com 4 Martindale (2002) [Ephedra, Ephedrine p 1090]

163

Solubility in water 63.6 g/l (30 ºC)2 Test methodAcid dissociation constant (pKa)

10.3 (0 ºC)2

9.61Test method

Vapour pressure 0.11 Pa (est)2 Test methodHenry’s Law Constant 9 x 10-6 Pa m3 mol-1 (est)2 Test method;








- -




Mammalian oral toxicity Rat (oral) LD50 600mg kg-1 2 LDLO (human) 9mg kg-1 (route unreported)3

Mammalian skin/eye toxicityMammalian ADI 90-180 mg 4 Treatment of diabetic

neuropathic oedemaMammalian inhalation toxicityEcotoxicity (Bird) LD50 (oral) 562 mg kg-1 5

Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

4

1[Ephedrine, PIM 209] viewed on-line via Inchem at http://www.inchem.org/documents/pims/pharm/pim209.htm April 20042 http://ptcl.chem.ox.ac.uk/MSDS/EP/(-)-ephedrine_anhydrous.html viewed April 20043 Material Safety Datasheet at http://physchem.ox.ac.uk/MSDS/ viewed April 20044 Martindale (2002) [Ephedrine, p 1090]5 Material Safety Datasheet viewed at http://www.sigmaaldrich.com Product number: 134910, viewed April 2004

164

165


Pseudophedrine-

Therapeutic activity Active constituent of Ephedra/Ma huang; similar action to ephedrine – used for relief of cough and cold symptoms5.Nasal decongestant1


Chemical name (1S,2S)-2-methylamino-1-phenyl-propan-1-ol

-

CAS no 90-82-4 -Molecular formula C10H15NO -Molecular weight 165.231 -Major emission routs -0 e.g. to STP; application




Density 1.12 g cm-3 2

Melting Point 118-119 ºC 1,3

117 ºC 4

Boiling Point -Octanol-partition coefficient (Kow, P)

0.893 Test method

Solubility in water 106 g/l (est at 25 ºC)3

Sparingly soluble in water1Test method

Acid dissociation constant (pKa)

10.3 (0 ºC)2 Test method

1 Merck Index (2001) [Pseudoephedrine, entry 8007]2 Beilstein Database (2004)3 SRC PhysProp Database viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 20044 Chemfinder viewed on-line at http://esc.syrres.com/interkow/physdemo.htm; April 20045 Martindale (2002) [Pseudoephedrine, p 1099]

166

Vapour pressure 0.11 Pa (est)2 Test methodHenry’s Law Constant 9 x 10-6 Pa m3 mol-1 (est)2 Test method;








- -




Mammalian oral toxicity Rat (oral) LD50 660mg kg-1 Mouse (oral) LD50 500mg kg-1 1

Mammalian skin/eye toxicity Irritating to skin and eyes 2

Mammalian ADIMammalian inhalation toxicity

Harmful by inhalation 3

Ecotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

1 Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PS/(+)-pseudoephedrine.html viewed April 20042Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PS/(+)-pseudoephedrine.html viewed April 20043Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PS/(+)-pseudoephedrine.html viewed April 2004

167


FeverfewFeatherfew, featherful, midsummer daisy, Tanacetum parthenium

Therapeutic activity Herbal remedy used in the prophylactic treatment of migraine and arthritis.1

Chemical structureChemical nameCAS noMolecular formulaMolecular weightMajor emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicity

1 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.

168

Mammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

169


Parthenolide


Chemical name IUPAC formatCAS no 20554-84-1Molecular formula C15H20O3


Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 115–116°C1

Boiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the field1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.

170

Bioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

171


Evening primrose oil

Therapeutic activity In treatment of atopic eczema and mastalgia; dietary supplement1

Used for symptomatic relief of atopic eczema and mastalgia. Also investigated in a variety of other disorders including multiple sclerosis, rheumatoid arthritis and the premenstrual syndrome.2

Chemical structureChemical nameCAS no 90028-66-3Molecular formulaMolecular weightMajor emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensity 0.9283 g cm-3

Melting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sediment


172

Identity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

173


Preparation/chemical name Linoleic acidTherapeutic activity Nutrient (essential fatty acid)1

Chemical structure

Chemical name Octadeca-9,12-dienoic acidCAS no 60-33-3Molecular formula C18H32O2


Major emission routesApplication/emission rates

Estimated European per captia intake (eaters only): 133 µg/day2

Proportion metabolisedIdentity of metabolitesDensity 0.9022 g cm-3 3 Determined

at 20°CMelting point -5°C4

Boiling point 230°C a Determined at 16 mm Hg


7.055

Solubility in water 0.000139 g L-1 6 Estimated at 25°C


4.777 Determined at 25°C

Vapour pressure 1.16 x 10-4 Pa 8 Extrapolated from data at 25°C

Henry’s Law Constant

0.51 Pa m3 mol-1 9 Estimated at 25°C

Soil/sediment water 1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 IPCS (1999) Satefy Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Genva, Switzerland, World Health Organisation3 Lide DR (1997) cited in Hazardous Substances Database (HSBD), available [April 2004] at http://toxnet.nlm.nih.gov/4 Beilstien Database (2004)5 Sangster (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/6 Meylan WM et al. (1996) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/7 Serjeant EP & Dempsey B (1979) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com8 Daubert TE & Danner RP (1991) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com9 Meylan WM & Howard PH (1991) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com

174

partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)

1.6 x 10+5 1 Estimated from measured log Kow.

Photolysis half lifeHydrolysis half life Not expected

to under hydrolysis due to lack of hydrolyzable functional groups2

Persistence in air 0.05–0.125 days3 Based on estimated half-lives for reaction with hydroxyl radicals and ozone, respectively.

Persistence in activated sludge

1.25 days at 20°C4 Unacclimated activated sludge inoculum (an/aerobic not specified)

Persistence in soilPersistence in sedimentIdentity of degradates from above studies

Degradation products identified from anaerobic digester sludge study included:

acetic acid

hexadecanoic acid

1 Hazardous Substances Database (HSBD), available [April 2004] at http://toxnet.nlm.nih.gov/2 Hazardous Substances Database (HSBD), available [April 2004] at: http://toxnet.nlm.nih.gov/3 Hazardous Substances Database (HSBD), available [April 2004] at: http://toxnet.nlm.nih.gov/4 Novak JT & Jruas DL (1973) cited in Hazardous Substances Database (HSBD), available [April 2004] at: http://toxnet.nlm.nih.gov/

175

tetradecanoic acidFate in the fieldBioconcentration factor

1.3 x 10+51 Estimated for aquatic organisms based on measured log Kow

Biota-sediment/soil accumulation factorMammalian oral toxicity

Mouse (oral) LD50 >50 g kg-1 2


1 Hazardous Substances Database (HSBD), available [April 2004] at http://toxnet.nlm.nih.gov/2 Material Safety Datasheet at https://fscimage.fishersci.com/msds/70654.htm viewed April, 2004

176


Preparation/chemical name γ-Linoleic acidTherapeutic activity In treatment of atopic eczema1

Chemical structure

Chemical name Octadeca-6,9,12-trienoic acidCAS no 506-26-3Molecular formula C18H30O2


Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soil1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.

177

Persistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)

Reduced mean survival time at conc 9 – 24 mg l-1 1

Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

1 Beilstein database [-linoleic acid 1712253] accessed April 2004.

178


Tylophora indica(aka Tylophora astmatica)

Therapeutic activity Inconclusive evidence for treatment of asthma.1

Chemical structureChemical nameCAS noMolecular formulaMolecular weightMajor emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADI

1 Huntley A & Ernst E (2000) Herbal medicines for asthma: a systematic review. Thorax, 55, 925–929

179


180


Preparation/chemical nameTylophorine


Chemical name 2,3,6,7-Tetramethoxy-9,10,11,12,12a,13-hexahydro-9a-azacylcopenta[b]triphenylene

CAS no 482-20-2Molecular formula C24H27NO4


Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 282–284°C 1 DecomposesBoiling pointOctanol-partition coefficient (Kow, P)

4.40 2 Estimated

Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in air1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/

181

Persistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

182


Glucosamine-

Therapeutic activity Antiarthritic1.Used for treatment of rheumatic disorders including osteoarthritis. It is isolated from chitin or prepared synthetically4.


Chemical name 2-Amino-2-deoxy-D-glucose -CAS no 3416-24-8 (28905-11-5 for α

form & 28905-10-4 for β)-

Molecular formula C6H13NO51 -

Molecular weight 179.171 -Major emission routs -0 e.g. to STP; application




Density -Melting Point 88˚C (α form)1; β decomposes

at 110˚CBoiling Point -Octanol-partition coefficient (Kow, P)

-4.23 (est)2 Test method

Solubility in water β form very soluble in water1 Test methodAcid dissociation constant (pKa)

6.47 at 20˚C (potentiometric)3 Test method

1 Merck Index (2001) [Glucosamine, entry 4471]2 SRC PhysProp Database [Glucosamine 3416-24-8] Viewed online at http://esc.syrres.com/interkow/physdemo.htm April 20043 Beilstein Database 2004 [Glucosamine 3416-24-8] accessed April 20044 Martindale (2002) [Glucosamine, p 1616]

183








Persistence in soil ‘Turnover time’ of 303.4 h-1 1 Test method; soil typePersistence in sediment - Test methodIdentity of degradates from above studies

- -





1 Swindoll et al (1988) Aerobic biodegradation of natural and xenobiotic organic compounds by subsurface microbial communities. Environmental Toxicology and Chemistry, Vol 7: 291-299

184


Glucosamine sulphate and hydrochloride

-

Therapeutic activity Antiarthritic1.Glucosamine salts are given in the treatment of rheumatic disorders, including osteoarthritis6.

Chemical structure

Glucosamine sulphate

Glucosamine hydrochloride

-

Chemical name 2-Amino-2-deoxy-D-glucose; sulphate &2-Amino-2-deoxy-D-glucose; hydrochloride

-

CAS no 29031-19-4 (sulphate)66-84-2 (hydrochloride)

-

Molecular formula 2C6H13NO5.H2O4S (sulphate)2

C6H13NO5.ClH (hydrochloride)3-

Molecular weight 179.17 + 98.07 (sulphate)2

179.17 + 36.46 (hydrochloride)3-

Major emission routs -0 e.g. to STP; application to soil

Application/emission rates e.g. kg ha-1; dose (mg kg-1) -

1 Merck Index (2001)2 Beilstein Database 2004 [Glucosamine sulphate 29031-19-4] April 20043 Beilstein Database 2004 [Glucosamine hydrochloride 66-84-2] April 2004

185

Proportion metabolised - Test method and species

Identity of metabolites Amount produced; Chem draw file

Would be nice if all this info. Could also be obtained for the metabolites

Density -Melting Point Hydrochloride 190-194˚C

(decomposes)1;300˚C2

Boiling Point -Octanol-partition coefficient (Kow, P)

- Test method

Solubility in water 100 g/l (hydrochloride)5 Test methodAcid dissociation constant (pKa)

- Test method










- -




Mammalian oral toxicity: Hydrochloride Mouse (oral) 15 g kg-1 3

Mammalian oral toxicity: Sulphate Mouse (oral) > 5 g kg-1

4

1 Material Safety Datasheet viewed on-line at http://physchem.ox.ac.uk/MSDS/ April 20042 NTP Glucosamine Data Summary, viewed on-line at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExSumPdf/glucosamine.pdf6 Martindale (2002) [Glucosamine, p 1616]3 http://www.sigmaaldrich.com Glucosamine Hydrochloride, product code G2206, viewed April 20044NTP Glucosamine Data Summary, viewed on-line at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExSumPdf/glucosamine.pdf

186


187


Lavender essential oil-

Therapeutic activity Sleep aid and carminative1

Insecticide2

Used in herbal head lice shampoo, in conjunction with Tea Tree Oil.





Density 0.93 (at 20˚C)3

0.875-0.888 (sg at 25˚C)4

Melting PointBoiling PointOctanol-partition coefficient (Kow, P)

- Test method

Solubility in water ‘Insoluble in water’3 Test methodAcid dissociation constant (pKa)

- Test method






Photolysis half life - Test methodHydrolysis half life - Test methodPersistence in air - Test methodPersistence in activated - Test method; aerobic

1 Martindale (2002) 2 PAN Pesticides Database, viewed on-line at http://www.pesticideinfo.org/Index.html April 20043 Chemfinder [Oil of lavender], viewed on-line at http://chemfinder.cambridgesoft.com/ April 20044 Essential oil information viewed on-line at http://www.perfumersworld.com/essoil/oilotm.htm April 2004

188

sludge anaerobicPersistence in soil - Test method; soil typePersistence in sediment - Test methodIdentity of degradates from above studies

- -




Mammalian oral toxicity -Mammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird) -Ecotoxicity (Fish) -Ecotoxicity (Daphnia) -Ecotoxicity (Algae) -Ecotoxicity (Other aquatics) -Ecotoxicity (Bees) -Ecotoxicity (Worms) -Environmental fate Fate (Animals)Fate (Plants)

189


Linalyl acetate-

Therapeutic activity Constituent of lavender oil1


Chemical name 3,7-Dimethyl-1,6-octadien-3-ol

-

CAS no 115-95-7 -Molecular formula C12H20O2 -Molecular weight 196.281 -Major emission routs -0 e.g. to STP; application




Density 0.895 (at 20 ˚C)1

0.9012

Melting Point <25 ˚C3

Boiling Point 220 ˚C1,2,3


3.933 Test method

Solubility in water 8.2 mg/l (est)3 Test methodAcid dissociation constant (pKa)

- Test method

Vapour pressure 14.8 Pa at 25 ˚C (ext)3 Test methodHenry’s Law Constant 176 Pa m3 mol-1 (est at 25 ˚C)3 Test method;


L kg-1 Soil/sediment characteristics


5800 (est from log Kow)4 Soil/sediment characteristics

Photolysis half life Half life (d) Test methodHydrolysis half life 170 d to 4.8 yr (est at pH 7

and 8, respectively)4Test method

Persistence in air 0.14 dd Test method1 Merck Index (2001) [Linalyl acetate, entry 5518]2 Chemfinder [Linalyl acetate] viewed on-line at http://chemfinder.cambridgesoft.com/ April 20043 SRC PhysProp Database [Linalyl acetate] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 20044 HSDB [Linalyl acetate] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004

190


Thought to be readily degradable4

Test method; aerobic anaerobic

Persistence in soil see above Test method; soil typePersistence in sediment see above Test methodIdentity of degradates from above studies

- -

Fate in the field - Test methodBioconcentration factor 1300 (est)4 Test species and



Mammalian oral toxicity LD50 rat oral 14.55 g/kg (13.35 g/kg mouse)4

Mammalian skin/eye toxicity Rabbit: severe irritant Guinea pig: moderate irritant1

100mg for 24hrs 100mg for 24hrs

Mammalian ADI 0-0.5 mg/kg bw2


1 Material Safety Datasheet at http://sigmaalrich.com Product number L2807 viewed April 20042 JECFA (1998) Linalyl acetate, viewed on-line at http://www.inchem.org/documents/jecfa/jeceval/jec_931.htm April 2004

191


Pinene-

Therapeutic activity Constituent of many volatile oils obtained from plants, including lavender oil

Chemical structure

α pinene (dl-racemate)

β pinene (dl-racemate)

-

Chemical name 2,6,6-Trimethylbicyclo[3.1.1]hept-2-ene (α pinene)6,6-Dimethy-2-methylenebicyclo[3.1.1]heptane (β pinene)

-

CAS no 80-56-8 (α pinene)127-91-3 (β pinene)

-

Molecular formula C10H16 -Molecular weight 136.231 -Major emission routs -0 e.g. to STP;

application to soilApplication/emission rates e.g. kg ha-1; dose (mg kg-1) -Proportion metabolised - Test method and

speciesIdentity of metabolites Amount produced; Chem draw

fileWould be nice if all this info. Could also be obtained for the metabolites

Density 0.8591, 0.8572 (α pinene)0.877, 0.866 (β pinene)

Melting Point -64 ˚C3, -62.5 ˚C4 (α pinene)-61.5 ˚C5 (β pinene)

1 Merck Index (2001) [α-pinene entry 7527, β-pinene entry 7528]2 Chemfinder [alpha Pinene] viewed on-line at http://chemfinder.cambridgesoft.com/ April 20043 SRC PhysProp Database [Alpha-Pinene] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 20044 HSDB Profiles [Alpha-Pinene], [Beta-Pinene] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 20045 SRC PhysProp Database [Beta-Pinene] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004

192

Boiling Point 155-156 ˚C (α pinene)1,3

162-166˚C (β pinene)5,1


4.83 (α pinene at 25 ˚C) 3

4.16 (β pinene)5Test method

Solubility in water 2.49 mg/l2 (α pinene)4.89 mg/l5 (est, β pinene)

Test method


- Test method

Vapour pressure 633 Pa (α pinene at 25 ˚C)3

391 Pa (β pinene at 25 ˚C)5Test method

Henry’s Law Constant 3x104 Pa m3 mol-1 (α pinene, est: VP/sol)3 1.6x104 Pa m3 mol-1 (β pinene, est)5

Test method; temperature


2451L kg-1 (calculated for α pinene based on estimated Kom)2

Soil/sediment characteristics


1200 (est from log Kow, α, β pinene)4

Soil/sediment characteristics

Photolysis half life - Test methodHydrolysis half life - Test methodPersistence in air 0.17 d (est α pinene)4

0.2 d (est β pinene)4Test method


Half life (d); ready/non-ready Test method; aerobic anaerobic

Persistence in soil Rapid biodegradation: ‘removal’ in ~250 hr’ (α pinene )4

α pinene ‘readily degraded’: observed biodegradation rate of 1.1-2.1 ug g-1 h-1 in soil slurrya

Biodegradation also ‘anticipated’ for β pinene4

Test method; soil type

Persistence in sediment Half life (d) Test methodIdentity of degradates from above studies

Amount produced; ChemDraw structure

-

Fate in the field Dissipation half life (d); Measured concs (mg kg-1; mg l-

1)

Test method

Bioconcentration factor 2800 (est, α pinene)4

440 (est, β pinene)4Test species and method



Mammalian oral toxicity LD50 rat oral 3.7 g/kg (α pinene)43

1 Merck Index (2001) [β Pinene]7 Chemfinder [beta-Pinene] viewed on-line at http://chemfinder.cambridgesoft.com/ April 20042 Misra & Pavlostathis (1997) Biodegradation kinetics of monoterpenes in liquid and soil-slurry systems. Appl Microbiol Biotechnol, 47: 572-5773 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

193

Mammalian skin/eye toxicity

Irritating to the skin, eyes and respiratory system1

Mammalian ADIMammalian inhalation toxicity

LCLO rat inhalation 625g m-3

( pinene)LCLO guinea pig 527g m-3

( pinene)LCLO mouse 364g m-3 ( pinene)2

Ecotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

1 Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/PI/alpha-pinene.html viewed April 20042 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

194


Tea Tree Oil-

Therapeutic activity Antiseptic1.Considered to have anti-viral, anti-bacterial and anti-fungal properties. It is used for the treatment of candida and other infections, ringworm and athlete’s foot2.Used in shampoo for treatment of headlice.





Density 0.895-0.905 at 15 ˚C1

0.893

Melting Point -Boiling Point -Octanol-partition coefficient (Kow, P)

- Test method


- Test method







1 Merck Index (2001) [Tea Tree Oil 68647-73-4]2 Worwood VA (1991) The Fragrant Pharmacy: a complete guide to aromatherapy and essential oils3 Chemfinder [Tea-tree oils] viewed on-line at http://chemfinder.cambridgesoft.com/ April 2004

195




- -




Mammalian oral toxicity Rat (oral) LD50 1900 mg kg-

11

Mammalian skin/eye toxicity Rabbit (skin) LD50 5000 mg kg-1 2


1 Material Safety Datasheet at http://www.sigmaaldrich.com/ Product number W3902082 Material Safety Datasheet at http://www.sigmaaldrich.com/ Product number W39020

196


Cineole-

Therapeutic activity Constituent of Tea Tree Oil1 (and numerous other plants)


Chemical name 1,3,3-trimethyl-2-oxa-bicyclo[2.2.2]octane

-

CAS no 470-82-6 -Molecular formula C10H18O -Molecular weight 154.251 -Major emission routs -0 e.g. to STP; application




Density 0.9222

0.9267 g/cm3 (20 ˚C)4

Melting Point 1.5 ˚C3

Boiling Point 176.4 ˚C3,4

174-176.4 ˚C1


2.743,4 Test method

Solubility in water 3.5 g/l3, 3.24 g/l1 Test methodAcid dissociation constant (pKa)

- Test method

Vapour pressure 253 Pa (25 ˚C)3,4 Test methodHenry’s Law Constant 11 Pa m3 mol-1 (est at 25 ˚C)3 Test method;





Photolysis half life - Test method1 Beilstein Database [cineole] accessed April 20042 Chemfinder [1,8-Cineole] viewed on-line at http://chemfinder.cambridgesoft.com/ April 20043 SRC PhysProp Database [1,8-Cineole] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 20044 HSDB [Cineole] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004

197




- -





1

Mammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics) LD50 Artemia salina

737ppm2Brine shrimp


1 Material Safety Datasheet viewed at http://www.sigmaaldrich.com/ Product number C8144 viewed April 20042 Beilstein Database, May 2004

198


Preparation/Chemical nameTerpinen-4-ol

-

Therapeutic activity Constituent of Tea Tree Oil1


Chemical name 4-methyl-1-(1-methylethyl)-3-cyclohexen-1-ol

-





Density 0.9333

Melting Point -Boiling Point 209 ˚C4

210-214 ˚C (at 760 mmHg)2


3.264 Test method

Solubility in water g L-1 Test methodAcid dissociation constant (pKa)

- Test method

Vapour pressure Pa Test methodHenry’s Law Constant Pa m3 mol-1 Test method;




L Kg-1 Soil/sediment characteristics

1 Merck Index (2001) [Tea Tree Oil 68647-73-4]2 Beilstein Database [562-74-3]3 Chemfinder [terpinen-4-ol] viewed on-line at http://chemfinder.cambridgesoft.com/ April 20044 SRC PhysProp Database [562-74-3] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 2004

199

Photolysis half life Half life (d) Test methodHydrolysis half life Half life (d) Test methodPersistence in air Half life (d) Test methodPersistence in activated sludge

Half life (d); ready/non-ready Test method; aerobic anaerobic

Persistence in soil Half life (d) Test method; soil typePersistence in sediment Half life (d) Test methodIdentity of degradates from above studies


-

Fate in the field Dissipation half life (d); Measured concs (mg kg-1; mg l-1)

Test method

Bioconcentration factor - Test species and method




1

Mammalian skin/eye toxicity Rabbit (skin) >2500 mg kg-1 Rabbit skin: moderate irritant 2

Draize test, 500mg / 24 hr


1 Material Safety Datasheet at http://www.fisher.co.uk/ Catalogue number 27043-10002 Material Safety Datasheet at http://www.fisher.co.uk/ Catalogue number 12515-0000

200


Orange essential oil

Therapeutic activity Expectorant1

Used as a flavour and in perfumery.2

Used as a flavour and perfume.

Chemical structureChemical nameCAS no 8008-57-9Molecular formulaMolecular weightMajor emission routesApplication/emission rates 2600 µg/day 3 Estimated European

per captia intakeProportion metabolisedIdentity of metabolitesDensity 0.844–0.847 g cm-3 At 20/20°CMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in water Slightly soluble in water a

Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factor

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.3 IPCS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Aliphatic, Acyclic and Alicyclic Terpenoid Tertiary Alcohols and Structuraaly Related Substances. Geneva, Switzerland, World Health Organization

201

Biota-sediment/soil accumulation factorMammalian oral toxicity Rat (oral) LD50 >5g kg-1 1

Mammalian skin/eye toxicity Rabbit (skin) LD50 >5g kg-1 2


1 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/2 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

202


d-Limonene


Chemical name 4-Isopropenyl-1-methyl-cyclohexene

CAS no 5989-27-5Molecular formula C10H16


Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensity 0.8482 g cm-3 1 Determined at 4/20°CMelting point -73.97°C 2

Boiling point 175.5–176°C 3 Determined at 101725 Pa


4.574

Solubility in water 0.0204 g L-1 5 Determined at 25°CAcid dissociation constant (pKa)Vapour pressure 213 Pa6 Determined at 25°CHenry’s Law Constant 2604 Pa m3 mol-1 7 Estimated at 25°CSoil/sediment water partition coefficient (Kp)

1501L kg-1 (calculated, based on estimated Kom)8


1030–47809 Estimated soil adsorption coefficients

Photolysis half life 0.096–0.10810 Based on experimental rates constants for the gas-phase reaction

1 Beilstein database (2004)2 Beilstein database (2004)3 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.4 Li J & Purdue EM (1995) cited in SRC PhysProp Database, avaialble [April 2004) at: http://esc.syrres.com/5 Beilstein database (2004)6 Beilstein database (2004)7 VP/WSOL cited in SRC PhysProp Database, avaialble [April 2004] at: http://esc.syrres.com/8 Misra & Pavlostathis (1997) Biodegradation kinetics of monoterpenes in liquid and soil-slurry systems. Appl Microbiol Biotechnol, 47: 572-5779Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/10 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

203

with photochemically produced hydroxyl radicals

Hydrolysis half lifePersistence in air 0.008–0.033 days1 Estimated atmospheric

lifetime depending on hydroxyl and ozone conc

Persistence in activated sludgePersistence in soil ‘Readily degraded’: observed

biodegradation rate of 0.9-1.9 ug g-1 h-1 in soil slurryh

Persistence in sedimentIdentity of degradates from above studies

Photolysis of d-limonene in the presence of nitrogen oxides produces:2

formaldehyde

formic acid

carbon monoxide

carbon dioxide

acetaldehyde

peroxyacetyl nitrate

-

1 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/2 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

204

acetone

Degradation products of hydrolysis of limonene include:

formaldehyde

acetic acid

formic acidFate in the field eBioconcentration factor 246–2621 Estimated for aquatic

organisms based on water solubility and estimated log Kow

Biota-sediment/soil accumulation factorMammalian oral toxicity Rat (oral) LD50 4.4g kg-1

Mouse (oral) LD50 5.6g kg-1 2

Mammalian skin/eye toxicity Rabbit (skin) LD50 >5g kg-1 3

Mammalian ADI 0.1 mg kg-1 bw day-1 4

Mammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia) EC50 0.4mg l-1 5

Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms) Earthworm Eisenia fetida

(Savigny) LD50 6.0ppm 6Cutaneous exposure

Environmental fate Fate (Animals)Fate (Plants)

1 Hazardous Substances Data Bank (HSDB) available, [April 2004] at: http://toxnet.nlm.nih.gov/2 http://ptcl.chem.ox.ac.uk/MSDS/LI/(R)-(+)-limonene.html viewed April 20043 http://ptcl.chem.ox.ac.uk/MSDS/LI/(R)-(+)-limonene.html viewed April 20044 Concise International Chemical Assessment Document, viewed April 2004 at http://www.inchem.org/documents/cicads/cicads/cicad05.htm 5CICAD entry http://www.inchem.org/documents/cicads/cicads/cicad05.htm#PartNumber:9 viewed May 20046 Hazardous Substances Data Bank (HSDB) available, [April 2004] at: http://toxnet.nlm.nih.gov/

205


L-LimoneneTherapeutic activityChemical structure

Chemical name 4-Isopropenyl-1-methyl-cyclohexene

CAS no 5989-54-8Molecular formula C10H16


Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensity 0.8407 g cm-3 1 Determined at 4/21°CMelting point -73.95°C 2

Boiling point 175.5–176.5°C 3 Determined at 101725 Pa


4.384

Solubility in water 0.00315 g L-1 5 Estimated at 25°CAcid dissociation constant (pKa6)Vapour pressure 191.98 Pa Determined at 25°CHenry’s Law Constant 38503.5 Pa m3 mol-1 7 Estimated at 25°CSoil/sediment water partition coefficient (Kp)

1501L kg-1 (calculated, based on estimated Kom)8

Organic carbon normalised 1030–47809 Estimated soil

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 Beilstein database (2004)3 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.4 Griffin S et al. (1999) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/5 Meylan WM et al. (1996) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/6 Nadais MH & Bernardo-Gil MG (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/7 Meylan WM & Howard PH (1991) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/8 Misra & Pavlostathis (1997) Biodegradation kinetics of monoterpenes in liquid and soil-slurry systems. Appl Microbiol Biotechnol, 47: 572-5779Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

206

soil/sediment water partition coefficient (Koc)

adsorption coefficients

Photolysis half life 0.108 days1 Half-life based on experimental rate constant for the gas-phase reaction of limonene with photochemically produced hydroxyl radicals.

Hydrolysis half lifePersistence in air 0.008–0.033 days2 Estimated atmospheric

lifetime depending on hydroxyl and ozone conc

Persistence in activated sludgePersistence in soil ‘Readily degraded’: observed

biodegradation rate of 0.9-1.9 ug g-1 h-1 in soil slurryh

Persistence in sedimentIdentity of degradates from above studies

Photolysis of d-limonene in the presence of nitrogen oxides produces:3

formaldehyde

formic acid

carbon monoxide

carbon dioxide

acetaldehyde

1 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/2 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/3 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/

207

peroxyacetyl nitrate

acetone

Degradation products of hydrolysis of limonene include:

formaldehyde

acetic acid

formic acidFate in the fieldBioconcentration factor 246–2621 Estimated for aquatic

organisms based on water solubility and estimated log Kow

Biota-sediment/soil accumulation factorMammalian oral toxicity Rat (oral) LD50 5000 mg kg-1

2

Mammalian skin/eye toxicity Rabbit (skin) LD50 >5000 mg kg-1 3

Mammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)

1 Hazardous Substances Data Bank (HSDB) available, [April 2004] at: http://toxnet.nlm.nih.gov/2 Material Safety Datasheet at http://www.sigmaalrich.com Product number 2183673 Material Safety Datasheet at http://www.sigmaalrich.com Product number 218367

208

Ecotoxicity (Algae) Green alga, LCIC >100mol/lBlue-green alga, LCIC > 100mol/l4

Lowest complete inhibition concentration, rapid microplate assay

Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

4 Beilstein Database, viewed April 2004, Beilstein Registry number 2323991

209


CitralTherapeutic activityChemical structure

Chemical name 3,7-Dimethyl-2,6-octadienalCAS no 5392-40-5Molecular formula C10H16OMolecular weight 152.23 g mol-1

Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensity 0.885–0.891 g cm-3 1 Determined at 25/25°CMelting point <-10°C2

Boiling point 226–228°C 3


3.454 Estimated

Solubility in water 0.5785 g L-1 5 Determined at 25°CAcid dissociation constant (pKa)Vapour pressure 12.17 Pa6 Estimated at 25°CHenry’s Law Constant 4.41 Pa m3 mol-1 7 Estimated at 25°C

using a fragment constant method




150 c Estimated based on molecular connectivity indexes.

Photolysis half lifeHydrolysis half lifePersistence in air 0.03–0.12 days c Based on rate constant

for vapour-phase reaction with ozone and hydroxyl radicals, respectively

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/3 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/4 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/5 Beilstein database (2004)6 Neely WB & Blau GE (1985) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/7 Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/

210

Persistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studies

-

Fate in the fieldBioconcentration factor 2501 Estimated for aquatic

organisms from an estimated log Kow.

Biota-sediment/soil accumulation factorMammalian oral toxicity Rat (oral) LD50 4.96 g kg-1

Mouse (oral) LD50 6 g kg-1 2

Mammalian skin/eye toxicity Irritating to skin and eyes 3

Mammalian ADI Human 500 g kg-1 4


1 Hazardous Substances Data Bank, available [April 2004] at: http://toxnet.nlm.nih.gov/2 Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/CI/citral.html viewed April 20043 Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/CI/citral.html viewed April 20044 Hazardous Substances Data Bank, available [April 2004] at: http://toxnet.nlm.nih.gov/

211


LinaloolTherapeutic activityChemical structure

Chemical name 3,7-Dimethyl-octa-1,6-dien-3-ol

CAS no 78-70-6Molecular formula C10H18OMolecular weight 154.25 g mol-1

Major emission routesApplication/emission rates e.g. kg ha-1; dose (mg kg-1) -Proportion metabolisedIdentity of metabolitesDensity 0.8685 g cm-3 1 Determined at 4/20°CMelting point <25°C 2

Boiling point 198°C3 Determined at 101 325 Pa


2.974

Solubility in water 1.56 g L-1 5 Determined at 25°CAcid dissociation constant (pKa)Vapour pressure 21.33 Pa 6 Determined at 25°CHenry’s Law Constant 2.18 Pa m3 mol-1 7 Test method;

temperatureSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)

758 Determined from an experimental water solubility and a recommended regression-derived equation

Photolysis half life 0.033–0.067 days9 Photooxidation at 21.9°C in 135L. 2m long reaction chamber

1 Beilstein database (2004)2 SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/3 Beilstein database (2004)4 Li J & Perdue EM (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/5 Beilstein database (2004)6 Li J & Perdue EM (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/7 Altschuh J et al. (1999) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/8 Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/9 Beilstein database (2004)

212

Hydrolysis half lifePersistence in air 0.03–0.13 days 1 Based on estimated

vapour phase reaction rate constants in air with ozone and hydroxyl radicals, respectively.

Persistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factor 106 2 Estimated for aquatic

organisms from an experimental log Kow

Biota-sediment/soil accumulation factorMammalian oral toxicity Mouse (oral) LD50 3g kg-1

(oily solution)Mouse (oral) LD50 1.7g kg-1 (10% aqueous arabic gum solution)Rat (oral) LD50 2.79g kg-1 3

Mammalian skin/eye toxicity Rabbit (skin) 5.61g kg-1

Rat (skin) 5.61g kg-1 Rabbit (eye) moderate irritant at 100% 4

Mammalian ADI 0-0.5 mg kg-1 bw 5


1 Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/2 Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/3 Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/4 Material Safety Datasheet at http://www.fisher.co.uk/ Catalogue number 12515-00005 JECFA (1998) http://www.inchem.org/documents/jecfa/jecmono/v042je17.htm viewed April 2004

213


Peppermint oil-

Therapeutic activity Carminative1

Aromatic carminative which relaxes gastrointestinal smooth muscle and relieves flatulence and colic. Enteric-coated capsules containing peppermint oil are used for the relief of symptoms of the irritable bowel syndrome or gastrointestinal spasm secondary to other disorders. Also used as a flavour and with other volatile agents in preparations for respiratory-tract disorders.2

Chemical structureChemical nameCAS no 8006-90-4Molecular formulaMolecular weightMajor emission routesApplication/emission rates e.g. kg ha-1; dose (mg kg-1) -Proportion metabolisedIdentity of metabolitesDensity 0.896–0.908 g cm-3 3 Determined at 25/25°CMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in water Very slightly soluble in water4

Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press.3 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.4 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.

214

Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity Rat (oral) LD50 2.4g kg-1



1 Hazardous Substances Data Bank (HSDB), avaialble [April 2004] at: http://toxnet.nlm.nih.gov/

215


MentholTherapeutic activity Antipruritic (topical)Chemical structure

Chemical name 2-Isopropyl-5-methyl-cyclohexanol


Major emission routesApplication/emission rates 18 000 µg/day1 Estimated European

per capita intakeProportion metabolised - Test method and



Density 0.9 g cm-3 2 Determined at 4/20°CMelting point 41–43°C 3

Boiling point 212–212.5°C 4 Determined at 101325 Pa


3.405

Solubility in water 0.456 g L-1 6 Determined at 25°CAcid dissociation constant (pKa)Vapour pressure 14.67 Pa 7 Extrapolated from data

at 25°CHenry’s Law Constant 1.54 Pa m3 mol-1 8 Estimated at 25°C1 ICPS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Substances Structurally Related to Menthol. Geneva, Switzerland, World Health Organization2 Beilstein database (2004)3 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.4 Beilstein database (2004)5 Griffin S et al. (1999) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/6 Yalkowsky SH & Dannenfelser RM (1992) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/7 Jordan TE (1954) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/8 Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/

216

Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity Rat (oral) LD50 3180 mg kg-1

1

Mammalian skin/eye toxicityMammalian ADI 0 – 4 mg kg-1 bw 2


1 Hazardous substances Database viewed at http://toxnet.nlm.nih.gov/ April 20042 JECFA, 1998 viewed http://www.inchem.org/documents/jecfa/jecmono/v042je04.htm April 2004

217


MenthoneTherapeutic activity Used in perfume and flavour

compositions1

Chemical structure

Chemical name 2-Isopropyl-5-methyl-cyclohexanone


Major emission routesApplication/emission rates 1000 µg/day 2 Estimated European

per capita intakeProportion metabolisedIdentity of metabolitesDensity 0.8924 g cm-3 3 Determined at 4/20°CMelting point -6°C4

Boiling point 202°C 5 Determined at 101325 Pa

Octanol-partition coefficient (Kow, P)Solubility in water 0.7 g L-1 6 Determined at 20°CAcid dissociation constant (pKa)Vapour pressure 13332.2–101325 Pa 7 Determined at 138–

209°CHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 ICPS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Substances Structurally Related to Menthol. Geneva, Switzerland, World Health Organization3 Beilstein database (2004)4 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.5 Beilstein database (2004)6 Beilstein database (2004)7 Beilstein database (2004)

218

Hydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

219


Menthyl acetateTherapeutic activity Used in perfumery1

Chemical structure

Chemical name 5-Methyl-2-(1-methylehtyl)cyclohexanol acetate



Major emission routesApplication/emission rates 420 µg/day 2 Estimated European

per capita intakeProportion metabolised - Test method and



Density 0.9185 g cm-3 3 Determined at 4/20°CMelting point 27°C 4

Boiling point 227–228°C 5 Determined at 101325 Pa


4.396 Estimated

Solubility in water Slightly soluble in water7

Acid dissociation constant (pKa)Vapour pressure 13.33 Pa 8 At 25°C

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 ICPS (1999) Safety Evaluation of Certain Food Additives. WHO Food Additives Series: 42. Substances Structurally Related to Menthol. Geneva, Switzerland, World Health Organization3 Beilstein database (2004)4 Beilstein database (2004)5 Beilstein database (2004)6 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [April 2004] at: http://esc.syrres.com/7 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.8 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/

220

Henry’s Law Constant 84.10 Pa m3 mol-1 1 Estimated using a fragment constant estimation method

Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)

58002 Determined from an estimated log Kow and a regression equation

Photolysis half life 0.875 days 3

Hydrolysis half life 270–2666.33 days 4 Based on an estimated base-catalyzed second-order hydrolysis rate constant, using a structure estimation method. Half-lives correspond to pH 8 and 7, respectively.

Persistence in air 0.875 days 5 Based on estimated half-life for photochemically produced hydroxyl radicals

Persistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factor 13006 Estimated for aquatic

organisms from an estimated log Kow

Biota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)1 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/2 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/3 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/4 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/5 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/6 Hazardous Substances Data Bank (HSDB), available [April 2004] at: http://toxnet.nlm.nih.gov/

221

222


Thyme essential oil-

Therapeutic activity Similarly to thyme, thyme oil has carminative, antiseptic, antitussive, and expectorant properties and is used chiefly in preparations for respiratory-tract disorders.1





Density 0.915-0.935 (sg at 25 ˚C)2

Melting PointBoiling PointOctanol-partition coefficient (Kow, P)

- Test method


- Test method








1 Martindale (2002) [Thyme, Thyme Oil]2 The Good Scent Company [Thyme Oil Red, White] viewed on-line at http://www.thegoodscentscompany.com April 2004

223


- -





1

Mammalian skin/eye toxicity Rabbit (skin) LD50 >5000 mg kg-1 2

Mammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish) LC50 20.5 mg l-1 (coho

salmon)LC50 16.1 mg l-1 (rainbow trout) (Stroh et al., 1998)

96hrs, static acute toxicity in moderately hard fresh water

Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

1 Material Safety Datasheet http://ptcl.chem.ox.ac.uk/MSDS/TH/thyme_oil.html 2 Material Safety Datasheet http://ptcl.chem.ox.ac.uk/MSDS/TH/thyme_oil.html

224


Thymol-

Therapeutic activity Topical application as an antiseptic and as an antihelmintic.Veterinary use as an antihelmintic, and as an antiseptic, external and internal.1

Antifungal and reduces gingivitis2


Chemical name 5-Methyl-2-(1methylethyl)-phenol

-





Density 0.9699 (at 25 ˚C)1

Melting Point 51.5 ˚C1,3

52 ˚C2

Boiling Point ~233 ˚C1,4

232.53


3.302,3

3.89 (at 25 ˚C)5Test method

Solubility in water ~1 g/l1

900 mg/l (at 25 ˚C)3Test method


10.6 (at 20 ˚C)3

10.622Test method

1 Merck Index (2001) [Thymol, entry 89-93-8]2 HSDB [Thymol] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 20043 SRC PhysProp Database [Thymol] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 20044 Chemfinder [Thymol] viewed on-line at http://chemfinder.cambridgesoft.com/ April 20045 Beilstein Database [89-83-8] accessed April 2004

225

9.9 (spectrophotometric at 24.9 ˚C ) & 10.49 (at 25 ˚C)5

Vapour pressure 0.29 Pa (at 25 ˚C)2,3 Test methodHenry’s Law Constant 0.05 Pa m3 mol-1 (est at 25

˚C)3Test method; temperature








- -




Mammalian oral toxicity Rat (oral) LD50 980mg kg-1 1


Guinea pig (oral) LD50 880mg kg-13

? Query mouse oral tox LD50 on sigma msds 640mg kg-1

Mammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish) LC50 3.2 – 4.2 mg l-1 4 96 hr

Pimephales promelasEcotoxicity (Daphnia) EC50 1.7 – 3.2 mg l-1 5 96 hrEcotoxicity (Algae)Ecotoxicity (Other aquatics) LC50 10.71 mg l-1 6

Toxic to aquatic organismsMay cause long-term adverse effects in the aquatic environment 7

Acute toxicity to Lymnaea acuminata (snail) measured at 96 hrs

1 Material Safety Datasheet at http://physchem.ox.ac.uk/MSDS/ viewed April 2004 2 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/3 Hazardous Substances Data Bank (HSDB) available [April 2004] at: http://toxnet.nlm.nih.gov/4 Material Safety Datasheet at http://www.sigmaaldrich.com/ Product code 112097 viewed April 20045 Material Safety Datasheet at http://www.sigmaaldrich.com/ Product code 112097 viewed April 20046 Beilstein Database, viewed April 2004

226


7 Material Safety Datasheet at http://physchem.ox.ac.uk/MSDS/ viewed April 2004

227


Carvacrol-

Therapeutic activity Constituent of Thyme oil.Used as an anti-infective and as antihelminthic1.


Chemical name IUPAC format -CAS no 499-75-2 -Molecular formula C10H14O -Molecular weight 150.221 -Major emission routs -0 e.g. to STP; application




Density 0.976 (at 20 ˚C)1,3

Melting Point ~0 ˚C1

1 ˚C2,3

Boiling Point 237-238 ˚C1

237.7 ˚C2


3.492 Test method

Solubility in water 1.25 g/l (at 25 ˚C)2 Test methodAcid dissociation constant (pKa)

10.35 (at 25 ˚C)4 Test method




Organic carbon normalised soil/sediment water partition


1 Merck Index (2001) [Carvacrol, entry 1887]2 SRC PhysProp Database [499-75-2] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 20043 HSDB [Carvacrol] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 20044 Beilsten Database [499-75-2] accessed April 2004

228

Parameter Data Supporting info.coefficient (Koc)Photolysis half life - Test methodHydrolysis half life - Test methodPersistence in air - Test methodPersistence in activated sludge




-




Mammalian oral toxicity Rat (oral) LD50 810mg kg-11

Mammalian skin/eye toxicity Rabbit (skin) severe irritant 2 500mg 24 hrMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

1 Material Safety Datasheet at http://ptcl.chem.ox.ac.uk/MSDS/ME/2-methyl-5-(1-methylethyl)phenol.html viewed April 20042 Material Safety Datasheet http://www.sigmaaldrich.com/ Product code 282197 viewed April 2004

229


Borneol-

Therapeutic activity Constituent of thyme and valerian.Free or esterified borneol identified in 250 distillates from plants, herbs, leaves etc.4

Chemical structure

(dl enantiomers. Natural borneol can be d or l but v.seldom racemic)4

-

Chemical name endo-1,7,7-Trimethylbicyclo-[2.2.1]heptan-2-ol

-

CAS no 507-70-0 -Molecular formula C10H18O -Molecular weight 154.251 -Major emission routs -0 e.g. to STP;

application to soilApplication/emission rates e.g. kg ha-1; dose (mg kg-1) -Proportion metabolised - Test method and

speciesIdentity of metabolites Amount produced; Chem draw

fileWould be nice if all this info. Could also be obtained for the metabolites

Density 1.011 (d-form)1

Melting Point 206-207 ˚C (dl form)1a

Boiling Point 212 ˚C (d-form)1

210 ˚C2


2.693 Test method

Solubility in water 738 mg/l (at 25 ˚C)3 Test methodAcid dissociation constant (pKa)

- Test method

Vapour pressure 4.7 Pa (est at 25 ˚C)3 Test methodHenry’s Law Constant 0.7 Pa m3 mol-1(est at 25 ˚C)3 Test method;

temperatureSoil/sediment water partition L kg-1 Soil/sediment

1 Merck Index (2001) [Borneol, entry 1328]. 1a Mpt: 208 ˚C for d-form and 204 ˚C for l-form.2 Chemfinder [borneol] viewed on-line at http://chemfinder.cambridgesoft.com/ April 20043 SRC PhysProp Database [507-70-0] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 20044 HSDB [Borneol] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 2004

230

Parameter Data Supporting info.coefficient (Kp) characteristicsOrganic carbon normalised soil/sediment water partition coefficient (Koc)






- -





231


Camphor-

Therapeutic activity Topical analgesic and antipruritic. Veterinary use internally as carminative, externally as an antipruritic, counterirritant and antiseptic1.Also used as a steam inhalant – popular in respiratory diseases of horse and poultry3.

Chemical structure

(d/l enantiomers:natural form is d-camphor, synthetic form is racemic)

-

Chemical name IUPAC format -CAS no 76-22-2 -Molecular formula C10H16O -Molecular weight 152.231 -Major emission routs -0 e.g. to STP; application




Density 0.992 g/cm3 (at 25 ˚C)1

Melting Point 179 ˚C1

180 ˚C2

Boiling Point d-Camphor sublimes at 204 ˚C1


2.382 Test method

Solubility in water 1.25 g/l (at 25 ˚C)1

1.6 g/l (at 25 ˚C)2

2.04 g/l (at 25 ˚C)3

Test method


- Test method

1 Merck Index (2001) [Camphor, entry 1739]2 SRC PhysProp Database [76-22-2] viewed on-line at http://esc.syrres.com/interkow/physdemo.htm April 20043 Beilstein Database [Camphor]

232

Vapour pressure 87 Pa (at 25 ˚C)2,1 Test methodHenry’s Law Constant 8.2 Pa m3 mol-1 (est at 25 ˚C,

VP/WSOL)2Test method; temperature








- -




Mammalian oral toxicity Rabbit LDLO 2g kg-1

Mouse LD50 1.31g kg-12

Human lethal dose 50-500 mg kg-1 (Gibson et al., 2004)

Mammalian skin/eye toxicity Mild skin, eye or respiratory irritantTypical TLV/TWA 2ppmTypical STEL 3ppm3


1 HSDB [Camphor] viewed on-line via TOXNET at http://toxnet.nlm.nih.gov/ April 20042 Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/CA/camphor.html April 20043 Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/CA/camphor.html April 2004

233


WormwoodAbsinthium

Therapeutic activity Antihelminthic1

As flavouring in alcoholic beverages (e.g. vermouth)2

Used as a bitter. Has been used in homeopathic medicine3

Chemical structureChemical nameCAS noMolecular formulaMolecular weightMajor emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting pointBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factor

1 Personal communication2 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.3 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press

234

Biota-sediment/soil accumulation factorMammalian oral toxicity Rat oral LD50 960mg kg-1 1

Mammalian skin/eye toxicity Rabbit dermal LD50 > 5g kg-1

2Not irritant in 48 hour patch test in humans


1WHO Food Additives Series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm , May 20042 WHO Food Additives Series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm, May 2004

235

http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm


Preparation/chemical name Absinthin

-

Therapeutic activityChemical structure -

Chemical name [3S-(3α,3a α,6β,6aα,6bβ,7α,7aβ,8 α,10aβ,11β,13a α,13b α,13cβ,14bβ)]-3,3a,4,5,6a,6b,7,7a,8,9,10,10a,13a,13c,14b-Hexadecahydro-6,8-dihydroxy-3,6,8,11,14,15-hexamethyl-2H-7,13b-ethenopentaleno[1”,2”:6,7;5”,4”:6’,7’]dicyclohepta[1,2-b:1’,2’-b’]difuran-2,12(11H)-dione

-



Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensityMelting point 179–180°C DecomposesBoiling pointOctanol-partition coefficient (Kow, P)Solubility in waterAcid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised

236

soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian inhalation toxicityEcotoxicity (Bird)Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environmental fate Fate (Animals)Fate (Plants)

237


α-SantoninTherapeutic activity Anthelminthic (Nematodes)1

Formerly used as an anthelminthic in the treatment of roundworm infection, but has been superseded by other less toxic anthelminthics. Used as a flavour in food.2

Chemical structure

Chemical name 3,5a,9-Trimethyl-3a,5,5a,9b-tetrahydro-3H,4H-naphthol[1,2-b]furan-2,8-dione



Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensity 1.187 g cm-3 3

Melting point 175°C 4

Boiling pointOctanol-partition coefficient (Kow, P)

1.78 5 Estimated

Solubility in water 0.2 g L-1 6 Experimental determination

Acid dissociation constant (pKa)Vapour pressure 0.000371 Pa 7 Estimated at 25°CHenry’s Law Constant 0.0053 Pa m3 mol-1 8 Estimated at 25°C

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 Sweetman SC (2002) Martindale. The Complete Drug Reference. Thirty-third edition. London, UK, Pharmaceutical Press3 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.4 SRC PhysProp Database available [May 2004] at: http://esc.syrres.com/5 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/6 Yalkowsky SH & Dannenfelser RM (1992) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/7 Neely WB & Blau GE (1985) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/8 Meylan WM & Howard PH (1991) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/

238

Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity Mouse oral LD50 900mg kg-1

1


1 Material Safety Datasheet viewed online at http://www.sigmaaldrich.com Product number 223085, May 2004

239


Preparation/chemical nameα-Thujone


Chemical name 1-isopropyl-4-methylbicyclo(3.1.0)hexan-3-one


Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensity 0.9101 g cm-3 1 Determined at 4/25°CMelting point <25°C 2

Boiling point 203°C 3 Pressure at which determination made not specified


2.654 Estimated

Solubility in water 0.408 g L-1 5 Estimated at 25°CAcid dissociation constant (pKa)Vapour pressure 54.93 Pa 6 Extrapolated to 25°CHenry’s Law Constant 0.0093 Pa m3 mol-1 7 Estimated at 25°CSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half life

1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/3 SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/4 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/5 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/6 Perry RH & Green D (1984) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/7 Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/

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Persistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity Mouse oral LD50 250mg kg-1

Guinea pig oral LD50 396 mg kg-1 1

Rat oral LD50 500 mg kg-1 2

isomer not specified

Mammalian skin/eye toxicityMammalian ADI Not possible to establish on

the data availablea


1 WHO Food Additives Series viewed at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm May 20042 Material Safety Datasheet viewed at http://www.sigmaaldrich.com Product number 89231, May 2004

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β-thujoneTherapeutic activityChemical structure

Chemical name 1-isopropyl-4-methylbicyclo(3.1.0)hexan-3-one


Major emission routesApplication/emission ratesProportion metabolisedIdentity of metabolitesDensity 0.9135 g cm-3 1 Determined at 4/25°CMelting point <25°C 2 Melting point for

thujoneBoiling point 203°C 3 Boiling point for α-

thujoneOctanol-partition coefficient (Kow, P)

2.654 Estimated for α-thujone

Solubility in water 0.408 g L-1 5 Estimated at 25°C for α-thujone

Acid dissociation constant (pKa)Vapour pressure 54.93 Pa 6 Extrapolated to 25°C

for α-thujoneHenry’s Law Constant 0.0093 Pa m3 mol-1 7 Estimated at 25°C for

α-thujoneSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life1 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.2 SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/3 SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/4 Meylan MW & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/5 Meylan WM & Howard PH (1995) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/6 Perry RH & Green D (1984) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/7 Meylan WM & Howard PH (1993) cited in SRC PhysProp Database, available [May 2004] at: http://esc.syrres.com/

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Hydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity Dog oral LD50 250mg kg-1 1

Mammalian skin/eye toxicityMammalian ADI Not possible to establish on

the data available1


1 WHO Food Additives Series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm , May 2004

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Appendix 1.3 Summary of Findings for Individual Herbal Remedies

1. Black CohoshDried preparations of the root of the Black cohosh plant, Cimicifugia racemosa, are used primarily for the treatment of symptoms of the menopause (Sweetman, 1999). In addition, the herb has been included in some cough preparations. The maximum daily dose recommended for Black cohosh preparations available in the UK ranges between 50 and 500 mg/day. In conventional medicine, the symptoms of menopause are managed by synthetic hormone replacement therapy (BMA, 2004).The mechanism of action (if any) of Black cohosh for improvement of menopausal symptoms is unclear (Huntley & Ernst, 2003). Only limited data are available with regard to the tolerability of Black cohosh, but in general it would appear to be safe, with a small risk of minor adverse effects such as rash and gastrointestinal disturbance.Black cohosh has little oestrogen receptor binding activity or oestrogenic activity in vitro (Zava et al., 1998). Difficulties occur in extrapolating in vitro data to the in vivo situation because of variations in absorption, activation/inactivation, metabolic disposition and bioavailability to target tissues.A number of active constituents have been identified in Black cohosh preparations, but no pharmacological or toxicological data were identified by our search strategies.

2. CamphorCamphor is used as a rubefacient and mild analgesic for conditions such as neuralgia. It is also contained in nasal decongestant preparations for inhalation (Sweetman, 1999). Due to potentially serious toxicity, Camphor concentration should not exceed 11% in preparations for external use. Treatments for neuralgia and muscle pain in conventional medicine include topical non-steroidal anti-inflammatory preparations (BMA, 2004).ToxicokineticsThe toxicokinetic data presented here are summarised from the Hazardous Substances Databank entry for Camphor.1 Absorption of Camphor from the skin, gastrointestinal and respiratory systems readily and occurs rapidly, and toxic levels can be reached within minutes of ingestion. Camphor is removed from the bloodstream by the liver. On metabolism, Camphor is partially oxidised and partially conjugated to glucuronic acid. In addition, Camphor is hydroxylated by rat and rabbit liver microsomes in vitro. The majority is eliminated as oxidised camphorol in the urine, with less excreted in breath, sweat and faeces.Toxicity ProfileAcute toxicityNotable adverse effects include nausea, vomiting, colic, headache, dizziness, delirium, muscle twitching, epileptiform convulsions, CNS depression and coma (Sweetman, 1999). Infant collapse following local application of Camphor to the nostrils has also been reported.Camphor (as used as a rubefacient) has been shown to cause abnormal liver function and encephalopathy (Stedman, 2002). Topical use of Camphor has caused erythematous and papulous oedematous skin reactions (Ernst, 2000).

1 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/ April 2004

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Camphor when ingested is extremely toxic, with a rapid onset of action (between 5 and 90 minutes) (Gibson et al., 2004). As little as 1g as been fatal in a 19 month old child. Camphor accumulates in fatty tissues and there is no antidote.Acute toxicity data are summarised on a Material Safety Datasheet.1 In mice the oral LD50 for Camphor was 1310mg kg-1. The lowest published lethal concentration (LDLO) is 2000mg kg-1 in rabbits. Intraperitoneal injection of Camphor in mice gave a LD50 of 3000mg kg-1. Typical threshold limit values/time weighted average (TLV/TWA) are 2ppm, with the short term exposure limit (STEL) set at 3ppm. Repeat dose toxicityChronic ingestion may cause granulomatous hepatitis or fatty metamorphosis.Carcinogenicity and MutagenicityCamphor is non-classifiable as a human carcinogen.2

Reproductive and Developmental Toxicity Evidence compiled in DART/ETIC (Developmental and Reproductive Toxicology)Error: Reference source not found database suggests from studies in animals that Camphor does not affect fetal growth, viability or morphological development at doses causing minor maternal toxicity.

3. EchinaceaDried aerial parts of the Echinacea purpera plant is used to boost the immune system3, and for the prevention of viral upper respiratory tract infections (Sweetman, 1999). The maximum recommended daily dose for preparations available in the UK ranges between 500 and 2500 mg/day. No conventional medicines are licensed for prophylaxis of viral infections. Toxicity ProfileAcute toxicityContact sensitisation has been reported for Echinacea purpera (Paulsen, 2002), with the pollen identified as the responsible component.Acute oral toxicity LD50 values are >15000 and >30000 mg kg-1 for rats and mice respectively.4

Carcinogenicity and MutagencityA commercial preparation of Echinacea purpera has been tested for mutagenicity in Salmonella typhimurium, with and without metabolic activation, and has been shown to be negative in the majority of tests.2 In addition, Echinacea extract produced no significant induction of chromosomal aberrations in human lymphocytes, nor did it increase the number of micronucleated polychromatic erythrocytes in mouse bone marrow. Some tumour inhibition has been shown for Echinacea in vitro.

4. Evening Primrose Oil The major uses for Evening Primrose Oil are in the treatment of premenstrual syndrome and mastalgia, menopausal symptoms and eczema (Sweetman, 1999). Other conditions for which it is used include multiple sclerosis and rheumatoid arthritis. Maximum recommended daily does for preparations available in the UK range between 1000 and 3000 mg/day. In conventional medicine, bromocriptine is licensed for use in moderate to severe cyclical breast pain (BMA, 2004).

1 Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/CA/camphor.html 2 Hazardous Substances Databank entry viewed at http://toxnet.nlm.nih.gov/ April 20043 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/100980.shtml, May 2004 4 http://ntp-server.niehs.nih.gov./htdocs/Chem_Background/ExecSumm/Echinacea.html viewed, April 2004

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4.1 Active constituentsThe constituents of Evening Primrose Oil thought to be responsible for its biological effects are linoleic acid and -linoleic acid. Toxicological data are available for linoleic acid and are detailed below.Linoleic acidToxicokineticsLinoleic acid is a long chain carboxylic acid and is absorbed as micelle aggregates, esterified with glycerol in chylomicrons and very low density lipoproteins, and transported via the lymphatic system1 It is readily metabolised in the oxidation fatty acid metabolism pathway, and consumption presents no safety concern.

Toxicity ProfileAcute toxicityLinoleic acid is classed as practically non-toxic, with a probable oral lethal does of > 15 g kg-1 in humans.2 Carcinogenicity and MutagenicityStudies of oleic acid, a chemically related compound, are considered relevant for linoleic acid. Oleic acid was found to be negative in a large number of tests for mutagenicity. 3 Linoleic acid is not listed by ACGIH, IARC, NIOSH, NTP or OSHA.

5. FeverfewFeverfew, Tanacetum parthenium, is a herbal remedy used in prophylactic treatment of migraine (Sweetman, 1999). The maximum recommended daily dose for Feverfew preparations available in the UK lies between 380 and 760 mg/day. Conventional medications used for migraine prophylaxis include pizotifin, beta-blockers and tri-cyclic anti-depressants (BMA, 2004).5.1 Active constituent The constituent thought to be responsible for the biological activity of Feverfew is parthenolide, for which limited toxicological data are available.ParthenolideToxicokineticsPharmacological effects ascribed to parthenolide include decreased prostaglandin synthesis and decreased platelet aggregation and serotonin secretion (Robles et al., 1995). These effects serve to relieve inflammatory conditions such as arthritis, and to act as anti-migraine therapy.Toxicity ProfileAcute toxicityContact sensitisation has been reported for Feverfew (Paulsen, 2002), with parthenolide identified as the component responsible.Carcinogenicity and MutagenicityIn vitro tests using mammalian cells have shown mutagenic activity for parthenolide.4

1 WHO Food additives series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v042je16.htm April 20042 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/ April 20043 WHO Food additives series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v042je16.htm April 20044 Material Safety Datasheet viewed at http://www.sigmaaldrich.com Apr 04, product number 384283

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6. GarlicGarlic is reported to be of value in lowering blood pressure and blood cholesterol levels.1 In addition, expectorant, diaphoretic, diuretic and disinfectant properties have been attributed to Garlic (Sweetman, 1999). The maximum recommended dose for Garlic preparations available in the UK is between 170 and 670 mg/day for Garlic extract and 2 and 10 mg/day for Garlic oil. Hypertension and hypercholesterolemia are treated in conventional medicine with anti-hypertensives and statins respectively (BMA, 2004). Garlic and Garlic oil are licensed for veterinary use (NOAH, 2004). These preparations are intended for use in dogs and cats for the symptomatic relief of respiratory and digestive complaints, as well as skin infections. The maximum recommended daily dose range between 390 mg/day Garlic extract (equivalent 1.1 mg/day Garlic oil), and 1555 mg/day Garlic extract (equivalent to 4.5 mg/day Garlic oil).Garlic is considered to be a type I and type IV allergen (Jappe et al., 1999). A number of herb-drug interactions have been reported for Garlic (Izzo & Ernst, 2001). Two case reports show an interaction between Garlic and warfarin leading to an increase in INR (international normalised ratio), and clinical trial data suggest that Garlic can change some of the pharmacokinetic properties of paracetamol via an unknown mechanism. Use of Garlic can increase the risk of post-operative bleeding and can have hypoglycaemic effects.Adverse effects reported include nausea and gastrointestinal problems (Ernst, 2003a). Dermatological effects following oral administration of Garlic have been reported to include urticaria and angioedema (Ernst, 2000). Systematic review of Garlic-induced adverse effects showed that causality is well established for allergic reactions, and that the most serious reported adverse effects are those affecting platelet adhesiveness, prothrombin time and partial thromboplastin time (Morbidoni et al., 2001).

7. Ginkgo biloba extractGinkgo biloba extract is used to improve circulation to the brain and muscles, and also for tinnitus.2 This herbal remedy is also reputed to be of use in Alzheimer’s disease and multi-infarct dementia (Sweetman, 1999). The maximum recommended dose for Ginkgo biloba preparations available in the UK range between 60 and 120 mg/day and up to 1000 mg/day. Betahistidine is a drug licensed in the UK for the treatment of tinnitus (BMA, 2004).Toxicokinetics3

Ginkgo biloba extract (standard extract eGb761) is composed of numerous active constituents, among which are quercetin, Ginkgolides A & B, and bilobalide. Information available for any of these are of pertinence to the whole extract. Following oral administration of eGb761 (80mg), the bioavailabilities of Ginkgolides A & B with plasma half lives of 4 and 6 hours respectively, are approximately 80%. Bioavailability of Ginkgolide C is very low. The bioavailability of bilobalide is 70% with a plasma half life of 3 hours following oral administration of 120mg 3Gb761. Excretion is via the urine, accounting for 70%, 50% and 30% for Ginkgolides A & B and bilobalide respectively.

1 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101190.shtml, May 2004 2 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101240.shtml, May 2004 3 The data presented herein is summarised from information obtained from the National Toxicology Program of the US, viewed online at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html

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Adverse effects of Ginkgo biloba extract include dizziness, palpitations, gastrointestinal disturbances, bleeding disorders and skin hypersensitivity reactions (Sweetman, 1999).Toxicity Profile2

Acute toxicityStandardised extract eGb761 administered orally to rats shows an LD50 of 7.73 g kg-

1.Repeat dose toxicityIn a 27 week study in rats and mice, no evidence of renal or hepatic damage was observed following oral administration of doses ranging from 100 to 1600 mg kg-1.Carcinogenicity and MutagenicityNo carcinogenicity studies have been performed using standardised Ginkgo biloba extract, but studies performed on quercetin are relevant.1 Reproductive and Developmental ToxicityIn general, no teratogenic effects for Ginkgo biloba have been reported (Jurgens, 2003). This article does, however, cite one report of decreased chick viability in a study using a high dose.Herb-Drug InteractionsGinkgolides and bilobalides have anti-platelet activity through their action as PAF antagonists (Izzo & Ernst, 2001). Two case reports exist of severe spontaneous bleeding in patients taking warfarin or aspirin following self-medication with Ginkgo biloba at recommended doses. Spontaneous bilateral subdural haematomas have been reported in cases of long-term Ginkgo biloba use. Although Ginkgo biloba is a peripheral vasodilator, it has led to a further increase in blood pressure in a patient prescribed a thiazide diuretic for hypertension. Combination of trazodone and Ginkgo biloba in a patient with Alzheimer’s disease led to coma, due to Ginkgo biloba -induced increase in production of an active metabolite of trazodone (MCPP) causing release of the inhibitory neurotransmitter GABA. Adverse effects following use of Ginkgo biloba include four reported cases of subdural and parietal haematoma and subarachnoid haemorrhage (Ernst, 2003b).7.1 Active constituentsGinkgo biloba extract contains a number of active constituents, including ginkgolides, bilobalide and quercetin. Of these, the toxicology of quercetin in best characterised.QuercetinToxicokineticsFollowing oral administration in rats, quercetin is rapidly excreted into bile and urine within 48 hours as the glucuronide and sulphate conjugates, 3’-O-monomethyl quercetin and 4-monomethyl quercetin.2 As a glycoside, quercetin is hydrolysed to the corresponding aglycone, which is then metabolised by scission of the heterocyclic ring at the 1,2 and 3,4 bonds to yield homoprotocatechuic acid, which is further metabolised by -oxidation of the acyl-side chain, O-methylation and demethylation and aromatic dehydroxylation.Pharmacokinetic studies in man suggest that quercetin is quickly eliminated with a half life of less than 2 hours (Graefe et al., 1999). Distribution in a typical 70kg man has been estimated at 0.003-0.012 molkg-1 from daily oral administration of 25-50 mg.3 Oral administration in man of a Ginkgo biloba extract dose containing 6.8 mg quercetin, has a mean value of 2.17 hours for half life for elimination and 1.51 hours

1 See below section 7.12 Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 043 http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginkgo.html - chemid

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for half life for absorption, demonstrating that the absorption and elimination are rapid (Wang et al., 2003). Bioavailability was low, with cumulative urinary excretion was 0.17%, where quercetin was detected as the sulphate and glucuronic acid conjugates. The low bioavailability was thought to be due to the lack of enzymes capable of cleaving glycosidic bonds in the gut. However, reports from randomised clinical trial in ileostomy patients, subsequently confirmed in healthy subjects, suggested that the presence of the glycoside residue facilitated the intestinal absorption (Ross & Kasum, 2002).The volume of distribution varies among studies, but has important implications for interpreting the pharmacodynamic effects. Due to current technical limitations, there are insufficient data available to determine beyond doubt the mechanism underlying the observed link between consumption of high dietary flavonoids such as quercetin, and decreased risk of coronary heart disease. Toxicity ProfileAcute toxicityAcute oral toxicity LD50 value for mice and rats is 160gmg kg-1 1.Carcinogenicity and MutagenicityFull details of mutagenicity testing are available on the Chemical Carcinogenesis Research Information System2. Briefly, quercetin has produced positive results in the majority of designs of Salmonella typhimurium tests for mutagenicity. However, quercetin has been extensively tested for carcinogenicity and although it has shown positive results in some studies, it was negative in the majority.2 The efficient metabolism and excretion of this compound may explain the lack of carcinogenicity in vivo.

8. GinsengGinseng (Panax ginseng) is reported to enhance resistance to infection, aid recuperation and to reduce fatigue (Sweetman, 1999). It is used to promote general well-being. Maximum recommended daily dose for Ginseng preparations available in the UK range between 1500 and 3000 mg/day. There is no analogous class of conventional medicines.Toxicokinetics3

The chemical constituents responsible for the pharmacological activities of Ginseng extract are the triterpene saponins, termed ginsenosides. These ginsenosides fall into two classes based on the structure of the cognate aglycone, namely protopanaxadiol and protopanaxatriol. The fate of administered ginsenosides is dependant on their class. Ginsenoside Rg1 (protopanaxatriol) has a half life of 27 minutes following intravenous administration to minipigs. In contrast, the protopanaxadiol ginsenoside Rb1 has a half life of 16 hours in the phase, due to high plasma protein binding.Information on absorption and metabolism is available for ginsenoside Rg1, showing that this constituent is rapidly absorbed and metabolised after oral administration, with very low concentrations of the intact molecule detected in urine or faeces. Ginsenoside Rg1 is distributed to the blood, liver, bile, subcutis and epithelia of

1 Material Safety Datasheet at https://fscimage.fishersci.com/msds/56284.htm2 Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr 043 Details of the toxicokinetics of Ginseng are included in a document entitled “Getting to the root of ginseng” viewed online at the ACS Publications division http://pubs.acs.org/hotartcl/chemtech/98/apr/get.html

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oesophagus and the oral and nasal cavities. The concentrations detected in muscle, endocrine organs and brain are low.Adverse effects, termed “Ginseng abuse syndrome”, include morning diarrhoea, skin eruptions, sleeplessness, nervousness, hypertension, euphoria and oedema (Sweetman, 1999).Toxicity ProfileAcute toxicity1

Oral administration of Ginseng to mice and rats show LD50 of 750 and 200 mg kg-1 respectively.Repeat dose toxicityInformation from subacute/subchronic toxicity studies is available for rats and dogs; no evidence for Ginseng toxicity has been observed in either species.2 Carcinogenicity and MutagenicityGinseng has tested negative for mutagenicity in the mouse lymphoma model with and without S9 and aroclor 1254 metabolic activation. 2

Herb-Drug InteractionsIncidences of interaction of Ginseng with prescription drugs are summarised by Izzo and Ernst (2001). Ginseng is reported to interact with the monoamine oxidase inhibitor (MAOI), phenylzine (Ernst, 2003b) and warfarin. Ginsenosides inhibit cAMP phosphodiesterase leading to an increase in cAMP, which may explain in part the psychoactive central effect of Ginseng both alone and in combination with MAOIs. Use of Ginseng reduces blood alcohol concentration, with induction of the essential components of the microsomal alcohol oxidising system suggested as the underlying mechanism.Adverse effects following Ginseng ingestion include nausea, vomiting, arteritis, deterioration of schizophrenia and mania (Ernst, 2003b).

9. Glucosamine Glucosamine supplements have been reported to be of use in the treatment of osteoarthritis.3 Maximum recommended dose for Glucosamine preparations available in the UK range between 1000 and 2000 mg/day. In conventional medicine, non-steroidal anti-inflammatory drugs (NSAIDs) are routinely prescribed for osteoarthritis (BMA, 2004). 9.1 Active constituentsGlucosamine preparations contain the active ingredients Glucosamine hydrochloride and Glucosamine sulphate. The toxicokinetics of Glucosamine sulphate in man are well described (see below).Glucosamine sulphate ToxicokineticsThe toxicokinetics of Glucosamine sulphate in man has been reported recently (Setnikar & Rovati, 2001). Following oral administration, free Glucosamine sulphate in blood was below the limit of quantification. After 1.5 hours, Glucosamine sulphate appeared incorporated in plasma globulins, with a peak at 9 hours, and was eliminated

1 Summarised from information obtained from the National Toxicology Program of the US, viewed online athttp://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExecSumm/Ginseng.html 2 Chemical Carcinogenesis Research Information System (CCRIS) viewed online at http://toxnet.nlm.nih.gov/, April 20043 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101260.shtml, May 2004

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with a half life of 58 hours. Gastrointestinal absorption is approximately 90%, but oral bioavailability is only 44% due to the hepatic first pass metabolism effect.Incorporation into plasma proteins occurs with all routes of administration, with the liver being the site of incorporation. Glucosamine sulphate is covalently bound to plasma globulins (predominantly -globulins) and is transported to peripheral tissues where it is enzymatically released and made available for local use. Urinary excretion following oral administration is 8% of the administered dose, with faecal excretion 11.4%. Respiratory excretion accounts for the majority (60%), highlighting the effect of hepatic first pass metabolism.Following oral administration, Glucosamine sulphate is largely distributed to the stomach walls and contents. Concentrations of Glucosamine sulphate in the liver peak at 2 hours and decrease slowly thereafter. There is also rapid uptake in articular cartilage.In a study of dogs administered Glucosamine sulphate in a mixture of purified chondroitin sulphate and manganese ascorbate, minor but not clinically important changes in haematological and haemostatic variables were observed (McNamara et al., 1996). These changes included a decrease in median haematocrit and a decreased neutrophil count.Toxicity profileAcute ToxicityBoth Glucosamine sulphate and Glucosamine hydrochloride are in the slightly toxic range, with acute oral toxicity in mice > 5 g kg-1 1 and 15 g kg-1 2 respectively.

10. Ma huangIn traditional Chinese Medicine, Ma Huang is used in mild respiratory disorders including asthma. 3,4 Maximum recommended daily dose for the treatment of bronchial asthma range between 45 and 90 mg (Bielory & Lupoli, 1999). In addition, it has been reported to be used as a stimulant and to boost athletic performance and weight loss.5 The maximum daily dose recommended for Ma huang contained in a training supplement available in the UK is 1000 mg/day (80 mg/day ephedrine).6 Asthma is treated conventionally using inhaled corticosteroids and selective beta2 agonists. 7

Three incidences of hepatotoxic events associated with the use of Ma Huang have been reported (Pittler & Ernst, 2003). The adverse effects noted included nausea, vomiting, abdominal discomfort, jaundice, fatigue, cough, chest pain and haemoptysis. Where liver biopsies were performed, diffuse hepatic necrosis, polymorphonuclear neutrophil (PMN) infiltrates and fibrosis were observed. However, the evidence for hepatotoxicity related to use of Ma huang was said to be anecdotal, therefore it is difficult to define precise incidence figures.

1 http://www.sigmaaldrich.com Glucosamine Hydrochloride, product code G2206, viewed April 20042NTP Glucosamine Data Summary, viewed on-line at http://ntp-server.niehs.nih.gov/htdocs/Chem_Background/ExSumPdf/glucosamine.pdf3 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101040.shtml, May 2004 4 Merck Index (2001) [Ephedra, entry 3638]5 Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. Viewed on-line at http://www.ahrq.gov/clinic/epcsums/ephedsum.htm April 20046 Product information for “Thermogen XS” available, May 2004, at http://www.creatinestore.co.uk/products/Thermogen_XS.asp?details=1 7 BNF (2004) British National Formulary 47, viewed online at http://www.bnf.org/ May 2004

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One active component of Ma huang, ephedrine, is absorbed more slowly from powdered herbal preparation than from either ephedrine tablet or oral solution forms (White et al., 1997). However, despite this, onset of effect and absorption are the same. Ephedrine content varies between Ephedra species.Additional adverse effects of Ma huang use include hallucination, stroke, acute dysphoric disorder, and seizures (Ernst, 2003b). Ma huang may interact with other CNS stimulants, -blockers, monoamine oxidase inhibitors, phenothiazines and theophylline (Ernst, 2003a). Reports exist of acute autoimmune hepatitis, with massive necrosis (disproportionate severity for clinical picture) observed on biopsy (Stedman, 2002).10.1 Active ConstituentsThe alkaloids L-ephedrine and pseudoephedrine are the constituents of Ma huang that have been identified to have pharmacological activity.10.1.1 L-EphedrineToxicokineticsIn rats, L-ephedrine is converted to L-norephedrine and 4-hydroxy-L-ephedrine. In rabbits, L-norephedrine is also produced on metabolism of ephedrine, as well as phenylgycol. L-ephedrine is rapidly absorbed after oral, intramuscular and sub-cutaneous administration (species not specified), with a plasma half life of 6 hours. Elimination of L-ephedrine is via the urine, where it is detected largely as the unchanged drug. 1

The fraction of ephedrine eliminated by N-demethylation to norephedrine is 8-20% following oral administration. Norephedrine is excreted in urine, largely unchanged, with approximately 4% biotransformation to 4-hydroxynorephedrine and hippuric acid (Haller et al., 2002). Among the most serious adverse effects reported are tachycardia, anxiety, restlessness and insomnia, increased blood pressure and cardiac arrhythmia (Sweetman, 1999). L-ephedrine interacts with a number of other drugs including halothane and other general anaesthetics, theophylline and monoamine oxidase inhibitors. L-ephedrine can antagonise anti-hypertensive therapy.Ephedrine acts as 1-, 1- and 2- adrenergic agonist and promotes release noradrenaline and dopamine. Ephedrine is a more potent vasopressor and cerebral stimulant than pseudoephedrine (Berlin et al., 2001).Toxicity ProfileAcute toxicityL-ephedrine is classed as extremely toxic, with a probable oral lethal dose between 5 and 50 mg kg-1 in humans.2 Acute oral toxicity has been measured with an LD50 of 600 mg kg-1 and 689 mg kg-1 for rats3 and mice4 respectively. Toxicity is dependant on the route of administration, with LD50 values decreasing with route in the following order: intraperitoneal, parenteral and intravenous.Carcinogenicity and MutagenicityWhen tested using four standard strains of Salmonella typhimurium, with or without metabolic activation, no evidence of L-ephedrine mutagenicity was observed. In addition, no evidence of chromosomal aberrations or sister chromatid exchange was

1 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.2 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.3 Material Safety Datasheet viewed at http://physchem.ox.ac.uk/MSDS/EP/(-)-ephedrine_anhydrous.html, April 20044 Material Safety Datasheet viewed at http://www.sigmaaldrich.com, April 2004

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detected. In a two year carcinogenicity study, no evidence of carcinogenicity was observed in either F344 rats of B6C3F1 mice. Reproductive and Developmental Toxicity No animal reproduction studies have been performed,1 and it is not known whether L-ephedrine can have adverse effects on the fetus when administered to pregnant humans.10.1.2 PseudoephedrineToxicokinetics1

Following oral administration of pseudoephedrine hydrochloride, the pharmacological effect (nasal decongestion) is observed within 30 minutes, and lasts for 4-6 hours. Although sufficient evidence is lacking, pseudoephedrine is presumed to cross the placenta and into the CSF. Pseudoephedrine has a short half life, and elimination of the drug is renal, with 55-75% excreted unchanged. In rabbits, D-pseudoephedrine yields D-norpseudoephedrine and L-pseudoephedrine yields L-norpseudoephedrine. Norpseudoephedrine is classified as a schedule IV controlled substance (Haller et al., 2002).Pseudoephedrine is less potent than ephedrine with respect to pressor, cardiac, mydriatic and CNS stimulant actions.Adverse effects include tachycardia, anxiety, restlessness, insomnia, skin rashes, urinary retention, and rarely hallucinations especially in children (Sweetman, 1999).

11. St John’s WortSt John’s Wort is used as a herbal remedy for the treatment of anxiety and mild to moderate depression (Sweetman, 1999). Other reported minor uses include treatment of skin inflammation, wounds and burns.2 The maximum daily dose recommended for preparations available in the UK (standardised to hypericin content) range between 900 and 2700 g/day hypericin (450-900 mg/day dried St John’s Wort extract).3,4 In conventional medicine, tricyclic and SSRI (selective serotonin reuptake inhibitor) antidepressants are used in the treatment of depression, while anxiety is treated with anxiolytics such as benzodiazepines.5

ToxicokineticsThe pharmacodynamics and kinetics of St John’s Wort have been described recently (Hammerness et al., 2003). The absorption of hypericin and pseudohypericin is 14 and 21% respectively following oral administration. The time to peak is between 2 and 6 hours, with a dose-dependant half-life of 24 to 36 hours. Steady state is achieved within 4 days. St John’s Wort exerts multiple effects on the cytochrome P450 enzyme complex and activates P-glycoprotein.Numerous pharmacological effects have been described for St John’s Wort that may underlie its anti-depressant action (Hammerness et al., 2003). These include inhibition of MAO (monoamine oxidase inhibitor) A &B and COMT (catechol-O-methyl transferase) enzymes, decrease in serotonin, dopamine, and noradrenaline reuptake, and increases in serotonin receptor density. Actions at benzodiazepine, adenosine, inositol trisphosphate, glutamate (NMDA) and cholinergic receptors may contribute to the psychotropic effects.

1 Summarised from information contained in the Hazardous Substances Databank entry for pseudoephedrine viewed at http://toxnet.nlm.nih.gov/ Apr 042 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/102670.shtml, May 2004 3 Holland and Barrett product information leaflet, available at http://www.hollandandbarrett.co.uk/ 4 Lichtwer Pharma UK product information leaflet, available at http://www.lichtwer.co.uk/ May 20045 BNF (2004) British National Formulary 47, viewed online at http://www.bnf.org/ May 2004

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Although St John’s Wort is generally well tolerated, adverse effects have been documented. These include gastrointestinal symptoms, skin reactions, fatigue and sedation, restlessness and anxiety, dizziness, headache and dry mouth. Phototoxicity has also been reported for St John’s Wort (Mantle et al., 2001). A report on a European drug monitoring study (3250 individuals) showed a 2.4% rate of adverse drug reaction, that were generally mild, transient and similar to placebo (Greeson et al., 2001).Toxicity ProfileAcute toxicityAn acute NOEL value of >5000 mg kg-1 in mice and rats has been published (Hammerness et al., 2003).Repeat dose toxicityA study of long-term effects of St John’s Wort was conducted in dogs, and only non-specific symptoms were reported (Hammerness et al., 2003).Carcinogenicity and MutagenicityNo significant mutagenic properties have been ascribed to St John’s Wort; one study of genotoxicity in Salmonella typhimurium found that the mutagenicity observed was quercetin-mediated (Hammerness et al., 2003).Reproductive and Developmental ToxicityNo adverse reproductive effects have been ascribed to use of St John’s Wort (Jurgens, 2003).Herb-Drug InteractionsSt John’s Wort extract interacts with drugs metabolised by cytochrome P450 monoxygenase enzyme system and with selective serotonin reuptake inhibitors (SSRIs) (Izzo & Ernst, 2001). Four clinical studies showed an increase or a tendency to increase the metabolic capacity of CYP450 enzymes. In addition, St John’s Wort can increase the activity of P-glycoprotein. Due to a combination of these mechanisms, use of St John’s Wort can lead to reduced plasma concentrations of warfarin, phenprocoumon, oral contraceptives, cyclosporin, amitriptyline, theophylline and indinavir. The concentration of digoxin is also likely to be decreased. Concomitant use of St John’s Wort and SSRIs can lead to symptoms of serotonin excess, “serotonin syndrome” (Ernst, 2003b).An important herb-drug interaction occurs between St John’s Wort and cyclosporin, where concomitant use leads to reduced plasma levels of the anti-rejection drug due to St John’s Wort-mediated induction of CYP3A/3A4. This has led to severe acute transplant rejection documented in a patient following liver transplantation (Hammerness et al., 2003).St John’s Wort has effects on numerous components of the cytochrome P450 complex, including CYP1A2, CYP2C9, CYP2D6.11.1 Active ConstituentsThe pharmacologically active constituents of St John’s Wort have been identified as quercetin,1 hypericin, and hyperforin. Limited pharmacological and toxicological information is available for these compounds, described below.11.1.1 HypericinToxicokineticsHypericin is thought to be the constituent of Hypericum extract (St John’s Wort) responsible for the photosensitivity reactions observed in some individuals (Sweetman, 1999).

1 see Annex 1, section 7.1: Ginkgo biloba extract, active constituent

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Investigations of the pharmacodynamics and pharmacokinetics of hypericin, with a view to exploitation of its potential chemotherapeutic effects, have shown a two compartment model for its pharmacokinetics in primates, with a terminal elimination half life of 26 hours (Fox et al., 2001). 2 mg kg-1 was sufficient to maintain an effective cytotoxic plasma concentration for up to 12 hours post-administration.Metabolism of hypericin is poorly defined, with no free hypericin detected in urine, with or without glucuronidase or sulphatase. However, based on its chemical structure and molecular size, metabolism is predicted to be via glucuronic acid conjugation and biliary excretion (Fox et al., 2001).Toxicity ProfileAcute toxicityIn non-human primates, dose-limiting toxicity was skin reactions at 5 mg kg-1, and so-called “hypericinism,” symptoms of which include anorexia, increased liver transaminases and evolution of a skin rash in light-exposed areas (Fox et al., 2001). Carcinogenicity and MutagenicityHypericin has been found to be negative in mutagenicity tests using two standard strains of Salmonella typhimurium, with and without metabolic activation. 1

11.1.2 HyperforinToxicokineticsThe pharmacodynamics and pharmacokinetics of hyperforin have been reported (Biber et al., 1998). Hyperforin, administered as hypericum extract and therefore in the presence of other active constituents, is orally bioavailable and is not quickly metabolised or decomposed in the gut. Elimination half lives and plasma retention times are long, but it does not accumulate in plasma following once daily administration in human volunteers. After administration of a therapeutic dose, plasma levels increased only after a 1 hour lag, and reached the maximum at 3 hours. Mean Cmax and area under the time concentration curve did not increase with highest doses, but elimination half life was unchanged, implying that loss of bioavailability was due to high lipophilicity of the agent or some other interaction in the gastrointestinal tract. No serious adverse effects were noted, even at the maximum dose administered (5mg hyperforin).

12. ValerianValerian has sedative properties and is used for treatment of stress and anxiety (Sweetman, 1999) and insomnia.2 The maximum recommended dose for preparations available in the UK ranges between 300 and 900 mg/day. In conventional medicine, stress and anxiety are treated with anxiolytics such as benzodiazepines (BMA, 2004).Valerian is licensed for veterinary use (NOAH, 2004), in a preparation combining other active ingredients for the treatment of nervous disorders, shyness or over-excitement in dogs and cats. The maximum recommended daily dose ranges between 194 mg/day and 1555 mg/day, dependent on animal size.Toxicity ProfileReproductive and Developmental Toxicity No fetotoxicity or external malformations have been observed in rats (Jurgens, 2003). However, an increase in the number of fetuses with retarded ossification was reported.12.1 Active constituent

1 Chemical Carcinogenesis Research Information System viewed online at http://toxnet.nlm.nih.gov/ April 2004.2 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/102830.shtml May 2004

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A number of active constituents have been identified in extracts of Valerian root. Of these, toxicological data are available for borneol.BorneolToxicokineticsAbsorption, distribution, metabolism and excretion are as described for Camphor1.Toxicity ProfileAcute toxicityAcute toxicity of borneol is indistinguishable from Camphor. Laboratory animals are much less susceptible to borneol toxicity than man (as is the case for Camphor). Borneol is classified as Very Toxic, with a probable oral lethal dose in man of between 50 and 500 mg kg-1.2

Carcinogenicity and MutagenicityBorneol has been shown to be non-mutagenic in the Ames test, using three strains of Salmonella typhimurium, with and without metabolic activation. 3

1 see Annex 2, section 2: Camphor2 Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov April 20043 Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov April 2004

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Appendix 1.4 – Summary of Findings for Individual Essential Oils

1. Lavender OilLavender oil is used as a carminative and as a flavouring ingredient. In addition, it is occasionally topically applied as an insect repellant (Sweetman, 1999). Additional suggested uses include aromatherapy for appetite loss, insomnia and nervousness.1 Recommended quantities range from 1-4 drops of essential oil in a carrier1, to topical application of neat oil.2

Topical administration of Lavender oil has been reported to cause allergic contact dermatitis (Ernst, 2000). Traces of linalool and linalyl acetate are detected in the blood within 5 minutes of dermal application of Lavender oil (Bickers et al., 2003), with the maximum concentration reached at 19 minutes. 1.1 Active ConstituentsActive constituents identified in Lavender essential oil include -pinene and linalool and its ester linalyl acetate.1.1.1-PineneToxicokineticsThe toxicokinetics of -pinene have been studied in man and are summarised in the Hazardous Substances Databank.3 Exposure was by inhalation, and uptake was 59% of the exposure concentration. The concentration of -pinene in the blood rose sharply, then tapered off, and was linearly related to the exposure concentration. Elimination from blood was shown to be triphasic, with half lives of 4.8, 39 and 695 minutes for each phase.-pinene is absorbed from skin, lungs and intestines, and is readily metabolised with elimination of unchanged -pinene very low. Urinary excretion of verbenols after -pinene inhalation is complete 20 hours following a 2 hour exposure. In primary cultures of chick embryo liver cells, -pinene was shown to be porphyrogenic.Toxicity ProfileAcute toxicityThe fatal dose in man is approximately 180g as turpentine (58-65% -pinene). Acute oral toxicity LD50 value is 3700 mg kg-1 in rats. By inhalation, LCLO (lowest published lethal concentration) values for rats, mice and guinea pigs are 625, 364 and 572 gm-3 respectively. 4

Carcinogenicity and Mutagenicity-pinene is not listed by IARC, but there is a documented increased risk of developing respiratory cancer if duration of occupational exposure to turpentine is greater than five years.1

No evidence of mutagenicity was observed using four standard strains of Salmonella typhimurium, with or without metabolic activation.5

1.1.2 Linalool and Linalyl acetateToxicokinetics

1 http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/101680.shtml, May 2004 2 http://hcd2.bupa.co.uk/fact_sheets/html/aromatherapy.html May 20043 Viewed at http://toxnet.nlm.nih.gov/ Apr 044 Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 045 Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr 04

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Linalool is representative of a number of tertiary alcohols and their related esters used as flavouring agents, and therefore its metabolism in mammals is well characterised.1 In rats, following a single oral dose of radioactively labelled linalool, 55% of the radioactivity was excreted in the urine as the glucuronic acid conjugate and 23% as expired CO2. Of the remainder, 15% was excreted within 72 hours in the faeces, with minor amounts (0.5, 0.6, 0.8 and 1.2%) in the liver, gut, skin and skeletal muscle respectively. Linalyl acetate, an ester of linalool, is metabolised by hydrolysis to yield linalool and the corresponding aliphatic carboxylic acid (acetic acid).2 Metabolism proceeds as for linalool.The biological half-life for both linalool and linalyl acetate is 14 minutes (Bickers et al., 2003).Toxicity ProfileAcute toxicityAcute oral toxicity LD50 values for linalool are 3000 mg kg-1 for mice and 2790 mg kg-1 for rats.3 LD50 value following application to skin in rabbits and rats is 5610 mg kg-1 in both species.Acute oral toxicity LD50 values are 14.55 g kg-1 and 13.36 g kg-1 for rats and mice respectively.4 Repeat dose toxicityA 20 day study1 in rats showed that cytochrome P450 (CYP450)-induced allylic oxidation becomes important on repeated dosing, yielding urinary metabolites such as 8-hydroxylinalool and 8-carboxylinalool. A transient rise in liver microsome CYP450 activity was observed.A 29 day study of dermal application of linalool has been conducted in rats (Bickers et al., 2003). Lethargy, ataxia and moderate to severe erythema were observed at all doses. The toxic signs and dermal irritation were dose-related. At necropsy, abnormalities were detected in the treated skin area, as well as gross liver, kidney and intestinal abnormalities. Histopathology revealed very slight to slight changes in liver and kidneys, but these were not related to treatment. In a 90 day study, linalool treatment led to a decrease in body weight and increased in liver and kidney weight. Haematology, clinical chemistry and urinalysis were normal.Carcinogenicity and MutagenicityLinalool has been tested for mutagenicity in a series of standard tests,5,6 and was not found be mutagenic in the majority. However, weak positive results were detected one design of the mouse lymphoma and Bacillus subtilis H17 (rec+) and M45 (rec-) tests.Linalyl acetate was negative for mutagenicity in five strains of Salmonella typhimurium, with and without metabolic activation. Neither linalool nor linalyl acetate caused chromosomal aberrations or unscheduled DNA synthesis (Bickers et al., 2003). Reproductive and Developmental Toxicity

1 WHO Food Additives series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v042je17.htm, April 20042 Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 043 Material Safety Datasheet viewed online at http://www.fisher.co.uk/ Product number 12515-10004 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.5 WHO Food Additives series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v042je17.htm, April 20046Chemical Carcinogenesis Research Information System viewed online at http://toxnet.nlm.nih.gov/, April 2004

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Studies of coriander oil in rats in mice have concluded that linalool does not affect reproductive performance or subsequent growth and survival of offspring except where there is maternal toxicity (Bickers et al., 2003). No developmental toxicity data were available.

2. Orange Essential OilOrange essential oil is used as a flavour and in perfumery (Sweetman, 1999). 2.1 Active constituentsThe natural oil contains a number of active constituents, including linalool and its ester linalyl acetate1, citral, and d-limonene.2.1.1 CitralToxicokineticsDetailed information on the absorption, distribution, metabolism and excretion are contained in the Hazardous Substances Databank entry for citral.2 Citral is a naturally occurring aliphatic aldehyde, and undergoes detoxification in a manner expected for aldehydes. Two routes for aldehyde detoxification exist, firstly oxidation to yield readily metabolised acids (fatty acid oxidation pathways and the Krebs cycle), and secondly, inactivation by reaction with sulphydryl groups e.g., glutathione. In experimental animals, citral is converted in part to the “Hildebrandt acid”, where a double omega oxidation reaction has taken place. In rats and mice, absorption from the gastrointestinal tract is rapid, and excretion is via the urine, with no evidence for long-term storage. Metabolism is rapid; urinary metabolites include several acids and a biliary glucuronide.Toxicity ProfileAcute toxicityAcute toxicity data are summarised in a Material Safety Datasheet3. Acute oral toxicity studies in rats showed an LD50 value of 4960 mg kg-1, while the value in mice was 6000 mg kg-1. Citral was more toxic when administered via intraperitoneally in rats, with an LD50 460 mg kg-1 for this route. No human toxic dose has been established. 4

Citral is an irritant, causing contact or allergic dermatitis and irritation of the membranes of the nose and throat.Repeat dose toxicityA repeated dose toxicity test in mice showed that on percutaneous absorption, citral caused an increase in lymph node weight compared to untreated controls 5

Carcinogenicity and MutagenicityCitral showed no evidence of mutagenicity when tested using 4 strains of Salmonella typhymurium, with and without S9 metabolic inactivation.6

Reproductive and Developmental Toxicity Citral has been shown to be teratogenic in animals but not in humans,7 causing craniofacial abnormalities in chick embryos. In rats, citral caused a decrease in both the number of follicles per section and in implantation number and litter size. In

1 see section 1.1.2 linalool and linalyl acetate2 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 20043Material Safety Datasheet viewed http://physchem.ox.ac.uk/MSDS/CI/citral.html April 20044 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 20045 Beilstein database, viewed May 20046 Chemical Carcinogenesis Research Information System viewed online at http://toxnet.nlm.nih.gov/7 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.

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addition, an increase in post-implantation fetal death was observed. The no observed adverse effect level (NOAEL) for embryofetotoxicity was < 60 mg kg-1 by oral administration in rats. However, no developmental toxicity was observed in rats following inhalation of citral up to the maternally toxic dose. 2.1.2 D-limoneneToxicokineticsData for absorption and metabolism of D-limonene is available for humans.3 In humans following oral administration, 75-95% was excreted in urine and <10% excreted in faeces within 2-3 days. A relative pulmonary uptake for D-limonene was determined to be 70% of the amount supplied. D-limonene is readily metabolised and accumulates in adipose tissue (long half life in blood in the slow elimination phase). The major metabolite in urine following oral administration is perillic acid 8,-9 diol in rats and rabbits, perillyl--D-glucopyranosiduronic acid in hamster, P-menth-1-ene-8,-9 diol in dogs, and 8-hydroxy-P-menth-1-en-9-yl--D-glucopyranosiduronic acid in guinea pigs and man.Toxicity ProfileAcute toxicityOrally administered D-limonene has an LD50 of 4400 mg kg-1 in rats and 5600 mg kg-

1 in mice.1 Intravenous administration in rats results in a much lower LD50 value of 110 mg kg-1.Carcinogenicity and MutagenicityThe IARC classification2 of D-limonene is Group 3 (not classifiable as to its carcinogenicity to humans). National Toxicology Program studies3 in rats and mice showed no evidence for carcinogenicity of D-limonene. D-limonene has been tested in a number of short-term tests and has been shown to be non-genotoxic.The nephropathy and renal tumour-induction observed in male rats is due to 2-microglobulin, a male rat specific protein, and is not relevant to human carcinogenesis. When combined, the lack of evidence for a genotoxic mechanism and the demonstration of a plausible epigenetic mechanism (accumulation of 2-microglobulin) implies a species-specific mechanism for d-limonene carcinogenesis (Whysner & Williams, 1996).Reproductive and Developmental Toxicity No evidence for embryotoxicity or teratogenicity has been observed in the absence of maternal toxicity.4

3. Peppermint Essential OilPeppermint essential oil is used as a carminative and relaxes gastric smooth muscle, and is used in the management of irritable bowel syndrome (IBS) (Sweetman, 1999). Recommended dose for Peppermint essential oil is 0.6-1.2 ml/day for up to 3 months (Sweetman, 1999). Conventional treatments for IBS symptoms include anti-spasmodics, anti-motility drugs and laxatives. However, Peppermint oil is also prescribed for IBS in conventional medicine.Peppermint oil is licensed for veterinary use (NOAH, 2004), for the treatment of digestive disorders and motion sickness in cats and dogs. The maximum

1 Material Safety Datasheet viewed online at http://ptcl.chem.ox.ac.uk/MSDS/LI/(R)-(+)-limonene.html, April 20042 IARC classification viewed online at http://www.inchem.org/documents/iarc/vol73/73-11.html, April 20043 http://ntp-server.niehs.nih.gov/htdocs/Results_Status/Resstatl/10071-T.Html 4Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/ April 2004.

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recommended daily dose ranges between 0.001 ml/day and 0.004 ml/day, dependent on animal size.3.1 Active constituentsMenthol and the related compound menthyl acetate are the active constituents of Peppermint essential oil.Menthol & Menthyl acetateToxicokineticsAdverse effects include hypersensitivity, abdominal pain, nausea, vomiting, vertigo, ataxia, drowsiness and coma (Sweetman, 1999). Application of decongestants containing menthol to the nostrils of infants and children may lead to acute respiratory distress with cyanosis and respiratory arrest. In humans, menthol is readily absorbed (100%) and metabolised, with approximately 80% of an oral dose eliminated as the glucuronic acid conjugate in the urine within 6 hours.1 Menthol ingestion in animals has been shown to have a number of enzyme effects. Elevation of glucuronidase activity was observed in mice. Menthol caused elevation of hepatic microsomal cytochrome c and NADPH-cytochrome P450 reductase in rats while two other CYP450 complexes were unchanged. As an ester of menthol, menthyl acetate is presumed to be hydrolysed in the gastrointestinal tract to yield menthol and acetic acid, and metabolism is assumed to proceed as for menthol.Toxicity ProfileAcute toxicityMenthol is classed as very toxic, with a probable oral lethal dose of between 50 and 500 mg kg-1 in humans.2 However, the published oral toxicity LD50 values are of the order 3000 mg kg-1 for rats and mice.2 Repeat dose toxicityMenthol produced no toxicity in either mice or rats in a 103 week study.2

Carcinogenicity and MutagenicityLong-term studies of menthol in mice and rats produced no evidence for carcinogenicity.2,3 Neither menthol nor its metabolites have been shown to be genotoxic in vitro or in vivo.Reproductive and Developmental Toxicity No developmental toxicity or teratogenicity have been noted for menthol.2

1WHO Food Additives series, viewed at http://www.inchem.org/documents/jecfa/jecmono/v042je04.htm Apr 042Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ Apr 043Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr 04

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4. Tea Tree oilTea Tree oil is used as an antiseptic and disinfectant. 1 It can be applied neat to the skin.2

4.1 Active constituentCineole has been identified as an active constituent of Tea Tree oil, and for which toxicological data are available.CineoleToxicokineticsOral administration of cineole (also known as Eucalyptol) to bushtailed possums led to the detection of 19 metabolites in urine and faeces,3 among which were p-cresol, 9-hydroxycineole and cineol-9-oic acid.Following oral administration in Swiss albino mice, cineole was found to reduce significantly the hepatic necrosis caused by GalN/LPS. In vitro tests have shown cineole to act as an inhibitor of cyclooxygenase 2, and to reduce lipid peroxidation. Investigation of the effects of cineole on cytochrome P450 enzymes, measured in rat liver microsomes, showed no effect on total CYP450 content, with elevation of the levels of 2B1 and 3A2 isoforms.Toxicity ProfileAcute toxicityCineole is listed as Very Toxic, that is, the probable lethal dose in humans is between 50 and 500 mg kg-1. 4 Adverse effects such as nausea, vomiting, vertigo, ataxia, muscle weakness, stupor, pallor and sometimes cyanosis have been reported. Acute toxicity data are summarised in a Material Safety Datasheet.5 Acute oral toxicity measured in rats gave LD50 of 2480 mg kg-1. Behavioural effects observed were somnolence and coma. LD50 values measured in mice were 1000 mg kg-1 for the intramuscular route and 1070 mg kg-1 for subcutaneous administration.Repeat dose toxicitySubcutaneous cineole (2450mg kg-1, cumulative in 10 days) showed no evidence of effects on liver regeneration.Carcinogenicity and MutagenicityCineole (12 g kg-1 for 8 weeks) was not positive for tumour induction in a mouse primary lung tumour model.6 In mutagenicity tests, cineole gave negative results in tests using four standard strains of Salmonella typhimurium, with and without S9 metabolic activation.1

5. Thyme essential oilThyme essential oil has carminative, antiseptic, antitussive and expectorant properties and is used chiefly in preparations for respiratory-tract disorders (Sweetman, 1999). Thyme EO is recommended for use at no more than 2% in a suitable carrier.7

5.1 Active constituents

1http://www.pdrhealth.com/drug_info/nmdrugprofiles/herbaldrugs/102757.shtml, May 2004 2http://hcd2.bupa.co.uk/fact_sheets/html/aromatherapy.html May 20043 Beilstein Database [cineole] accessed May 20044 Hazardous Substances Databank record viewed at http://toxnet.nlm.nih.gov/ April 20045 Material Safety Datasheet viewed at http://www.sigmaaldrich.com product number C8144, April 20046 Beilstein Database [cineole] accessed May 20047 http://www.naturedirect2u.com/Essential%20oils/thyme.htm May 2004

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Thyme EO has been shown to contain a number of compounds for which biological activity has been shown. Of these, toxicological data are available for borneol,1 carvacrol and thymol.5.1.1 CarvacrolToxicokineticsCarvacrol2 is slowly absorbed from the gastrointestinal tract in rabbits, with 30% of the administered dose remaining in the intestine 22 hours post administration. It is metabolised by conjugation to glucuronic acid and sulphate. No absorption of carvacrol applied to intact mouse skin was observed after 2 hours.Toxicity ProfileAcute toxicityCarvacrol is listed as very toxic, with probable oral lethal dose between 50 and 500 mg kg-1 in humans.4 When applied to intact or abraded rabbit skin, neat carvacrol was shown to be a severe irritant. Acute toxicity values are summarised in a Material Safety Datasheet.3 The oral LD50 was shown to be 810 mg kg-1 in rats, and a number of behavioural effects were also observed; these included somnolence and convulsions or effect on seizure threshold. Additional acute toxicity data are available for mice, where intraperitoneal injection of carvacrol resulted in LD50 of 73.3 mg kg-

1, intravenous administration gave an LD50 value of 80 mg kg-1, and subcutaneous administration gave an LD50 of 680 mg kg-1. The behavioural effects observed in mice were similar to those observed in rats.Carcinogenicity and MutagenicityCarvacrol was negative in Ames tests for mutagenicity.4

5.1.2 ThymolApplied topically, thymol is used as an antiseptic and as an antihelmintic. Veterinary uses as an antihelmintic, and as an external and internal antiseptic, have also been described .5

ToxicokineticsSubstituted monophenols such as thymol are conjugated with glucuronic acid and sulphate.6

The systematic availability following oral administration of thymol in humans has been studied (Kohlert et al., 2002). The sulphate conjugate of thymol but not free thymol was detected in plasma. The glucuronic acid and sulphate conjugates of thymol but not free thymol were detected in urine. Thymol was quickly absorbed, with significant plasma levels observed at 20 minutes and Cmax achieved at 2 hours. The bioavailability was 16%.Toxicity ProfileAcute toxicityThymol is a mild local irritant and its toxicity is classified as borderline between moderately and very toxic. Ingestion can cause gastric pain, nausea, vomiting, central hyperactivity, occasional convulsions, and cardiac and respiratory collapse. Acute oral

1 See Annex 2, section 12.1: Valerian, active constituent Borneol 2Hazardous Substances Databank viewed at http://toxnet.nlm.nih.gov/ April 2004.3Material Safety Datasheet downloaded from https://www.sigmaaldrich.com Product number 282197, Apr 044Chemical Carcinogenesis Research Information System (CCRIS) database viewed at http://toxnet.nlm.nih.gov/ Apr 04.5O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc. [Thymol, entry 89-93-8]6 Hazardous Substances Databank viewed online at http://toxnet.nlm.nih.gov/, April 2004.

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toxicity LD50 values for mice, rats and guinea pigs are 1800, 980 and 880 mg kg-1 respectively. Carcinogenicity and MutagenicityThe IARC classification1 for thymol is Group 3, that is, not classifiable as to its carcinogenicity to humans. Thymol gave negative results in Salmonella typhimurium tests for mutagenicity2, and was also negative for the induction of chromosome aberration.3

6. WormwoodThe essential oil of Artemisia absinthium, Wormwood EO, has been used as flavouring in alcoholic beverages (e.g. vermouth)2, as a bitter and in homoeopathic medicine (Sweetman, 1999). Acute toxicity data for Wormwood EO shows an LD50 value of 960 mg kg-1 by oral administration in rats.4 Details on the use of Wormwood (among other plants) as de-worming preparations in Nordic countries are available (Waller et al., 2001). However, this information is historical and/or anecdotal in nature, and serves to detail the plants used, the target organism and the livestock species.6.1 Active constituentsWormwood EO contains a number of active constituents, including absinthin, -santonin, and - and - thujone. Significant toxicological data is available only for - and - thujone.6.1.1 -santoninAcute toxicity testing of -santonin shows LD50 value of 900 mg kg-1 following oral administration in mice.5 In addition, anti-helminthic activity has been ascribed to -santonin.6 6.1.2 -/- thujoneToxicokineticsData on metabolism of or - thujone is lacking, as is information on long-term and/or reproductive effects.7

Thujone administration can lead to convulsions that are epileptiform in nature and are preceded by vasodilation, fall in blood pressure and slowing of cardiac rhythm.Toxicity ProfileAcute toxicityAcute oral toxicity for thujone isomers is complicated by the use of mixtures of isomers, or the isomer is not specified in some acute tests. However, it is clear that the acute oral LD50 value of -thujone in rats and mice is 250 and 5008 mg kg-1 respectively. -thujone has LD50 for oral toxicity of 250 mg kg-1 in dogs.

Repeat dose toxicity1 http://www.inchem.org/documents/iarc/vol71/027-phenol.html 2 Chemical Carcinogenesis Research Information System viewed at http://toxnet.nlm.nih.gov/ Apr 043 Genetox database viewed at http://toxnet.nlm.nih.gov/ Apr 044WHO Food Additives Series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm , May 20045 Material Safety Datasheet viewed online at http://www.sigmaaldrich.com Product number 223085, May 20046 O’Neil MJ, Smith A, Heckelman PE et al. (2001) The Merck Index. An Encyclopedia of Chemicals, Drugs, and Biologicals. Thirteenth Edition. New Jersey, USA, Merck & Co., Inc.7WHO food additives series viewed online at http://www.inchem.org/documents/jecfa/jecmono/v16je25.htm, May 2004.8 Material Safety Datasheet viewed online at http://www.sigmaaldrich.com Product number 89231, May 2004

264

A 14 week study in rats demonstrated no significant differences in weight gain, haematology, or heart, liver, kidney, spleen or adrenal gland weights following thujone treatment (isomer not specified). NOEL values for female and male rats were calculated to be 5 mg kg-1 per day and 10 mg kg-1 per day respectively.Carcinogenicity and Mutagenicity-thujone was found to be negative for mutagenicity using five standard strains of Salmonella typhimurium.1

1Chemical Carcinogenesis Research Information System viewed online at http://toxnet.nlm.nih.gov/, May 2004

265

Appendix 1.5 Glossary and list of abbreviationsGlossary1

Antitussivea drug that suppresses coughingCarminativea drug that relieves flatulence, used to treat gastric discomfort and colicDiaphoretica drug that causes an increase in sweating which stimulates the sweat glands directlyDysphoria (dysphoric)a feeling of uneasiness, discomfort, anxiety, or anguishin vitrotaking place in a living organismin vivotaking place in a test tube, culture dish, or elsewhere outside a living organismRubefacient an agent that causes reddening and warming of the skin. Rubefacients are often used as counterirritants for the relief of muscular painStatinany one of a class of drugs that inhibit the action of hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase), an enzyme that is involved in the liver's production of cholesterol.AbbreviationsACGIH: American Conference of Governmental Industrial HygienistsCAM: Complementary and Alternative MedicineCCRIS: Chemical Carcinogenesis Research Information SystemCOMT: Catechol-O-methyl transferaseCYP450: Cytochrome P450EO: Essential OilHRT: Hormone Replacement TherapyHSDB: Hazardous Substances DatabankIARC: International Agency for Research on CancerLCLO: Lowest published Lethal ConcentrationLD50: Dose estimated to kill 50% of the animals dosedMAOI: Monoamine Oxidase InhibitorMSDS: Material Safety DatasheetNIOSH: National Institute for Occupational Safety and HealthNOEL/NOAEL: No Obseved (Adverse) Effect LevelNSAID: Non-Steroidal Anti-Inflammatory DrugNTP: National Toxicology ProgramOSHA: Occupational Safety and Health AdministrationPAF: Platelet Activating FactorQSAR: Quantitative Structure-Activity Relationships QSDR: Quantitative Structure-Degradability RelationshipsQSPR: Quantitative Structure-Property RelationshipsSSRI: Selective Serotonin Re-Uptake InhibitorTCM: Traditional Chinese Medicine

1 definitions obtained from The Oxford Concise Medical Dictionary, available at Oxford Reference Online

266

Appendix 2 Pesticide/biocides data

267

Appendix 2.1: Regulatory requirements for approval of pesticides permitted in EU Organic Regulations in various EU Member States.

Regulatory factor UK Netherlands

Germany Sweden Ireland Greece

Organic permitted substances commercially available

Yes Yes Yes Yes Yes Yes

Evaluation by regulator

Yes Yes Yes Yes No Yes

Human safety data & evaluation

Same as for all pesticide Same as for all pesticides

Same as for all pesticides Same as for all pesticides

Basic tox data, including acute, short and chronic

Environment safety data & evaluation

Same as for all pesticide Same as for all pesticides

Same as for all pesticides Same as for all pesticides

Few data on eco-tox required (e.g. acute toxicity to bees)

Use of ‘reasoned argument’ acceptable

Reasoned arguments can be accepted in place of data, where appropriate.

In accordance with Directive 91/414/EEC

Yes for many, with justification accepted by National Chemical Inspectorate. Thus in practice full data & evaluation not required

Same as for all pesticides.

Yes, in some cases if well substantiated

Efficacy requirements for organic pesticides

No distinction is made. All products are required to be regulated under UK pesticide legislation are evaluated in the same way. The key criteria for

In accordance with Directive 91/414/EEC

Efficacy requirements the same for all pesticides

Same as for all pesticides

Standard efficacy data required. In some cases efficacy data from other countries accepted

268

efficacy evaluation is how the efficacy claimed relates to the label claims

Annex II(b) substances not sold as plant protection products

None known Some. A chemical may be used as a pesticide provided use does not cause danger to humans or environment

Not known

Not known

Regional regulation No No No No No NoPesticide Directive (91/414) appropriate to organic or non-conventional active substances?

Yes Yes (in absence of agreed directives/ guidelines)

Yes Yes Yes, but there is a need for amendments to give flexibility in data requirements for authorization of products falling into the category of “low risk”

269

Appendix 2.2 Usage, properties, ecotoxicity and hazard classification for major synthetic pesticidesArea treated in 2000 (ha) Fish Daphnia Algae Kow DT50 (soil) P B T

min maxFungicide on top fruitBupirimate 16300 1 7.3 - 3.9 35 90 P N TCaptan 58910 0.034 7 - 2.8 1 - I N VCarbendazim 8366 0.83 0.13 1.3 1.5 8 32 P N VCopper oxychloride 4961 0.78 3.5 - - - - - - -Dinocap 1437 0.015 0.05 32 4.5 4.5 6.1 I B VDithianon 38537 0.1 2.4 12 2.84 P - P N VDodine 15318 0.53 - - -0.88 20 - I N VFenarimol 602 1.8 0.0068 1.5 3.7 60 130 P N VFenbuconazole 3349 1.5 1 0.66 3.2 28 84 P N VFlusilazole 2931 1.2 3.4 7.3 3.7 420 - P N TKresoxim-methyl 17794 0.19 0.19 0.063 3.4 0.5 0.9 I N VMancozeb 4804 2.2 0.58 1100 0.62 6 15 I N VMyclobutanil 40203 4.2 11 2.7 2.9 66 - P N TPenconazole 27262 1.7 7 0.83 3.7 133 343 P N VPyrifenfox 17594 7.1 3.6 0.095 3.7 50 120 P N VPyrmethanil 10513 11 2.9 1.2 2.8 7 54 P N TTriademefon 4902 17 11 1.7 3.1 6 18 I N TVinclozolin 899 22 4 4 3 20 I N T

270

InsecticidesDiflubenzuron 1234 140 0.0071 0.045 3.9 6 7 I N VCarbaryl 2275 1.3 0.006 0.03 1.6 7 28 I N V

271

Area treated in 2000 (ha) Fish Daphnia Algae Kow DT50 (soil) P B T

min maxPirimicarb 7329 29 0.017 140 1.7 7 234 P N VAmitraz 1173 0.74 0.035 >12 5.5 1 - I B VFenoxycarb 8814 1.6 0.4 1.1 4.1 few 31 P B VGamma-HCH 521 0.022 1.6 0.78 3.5 28 209 P N VChlorpyrifos 32364 0.003 0.0017 0.23 4.7 60 120 P B VFenitrothion 902 1.7 0.011 4.8 3.5 12 28 I N VPirimiphos-methyl 1874 0.64 0.00008 1 5 30 - P B VFenproximate 952 0.079 0.2 - 5 27 50 P B VTebufenpyrad 764 0.018 0.04 0.54 4.6 20 30 P B VCypermethrin 2719 0.00069 0.00015 3.2 6.6 112 - P B VLambda-cyhalothrin 548 0.00024 0.00036 1 7 28 84 P B VClofentazin 580 >0.15 >.0014 0.32 4.1 28 85 P B V

PotatoesCymoxanil (+mancozeb) 348867 61 27 5.2 0.67 0.9 9 I N TFluzinam 284889 0.11 0.22 >5.7 3.6 33 62 P N VMancozeb 127966 2.2 0.58 1100 0.62 6 15 I N VDimethomorph (+ mancozeb) 122038 >14 49 >29 2.6 80 90 I N HFentin hydroxide 121312 0.022 0.016 0.002 3.4 20 40 P N V

272

Appendix 2.3 UK Policy context – Timetable

Policy initiative (see section 3.4) Timetable

3.4.1 EU Pesticides Directive 91/414 Review – particularly 4th stage

All decisions on Annex I of active substances in the fourth list are due to be taken by December 2008

EU Thematic Strategy and the EU 6th Environmental Action Plan

The European Commission is due to publish its position on the Thematic Strategy on the Sustainable Use of Pesticides in September 2004

3.4.3 UK National Pesticides Strategy (Defra, Pesticide Safety Directorate)

A draft Strategy may be available for consultation in May 2004

3.4.4 PSD Small Business Champion Ongoing3.4.5 PSD pilot project on registration of biological products

Ongoing, due for review mid 2004

PSD research on regulation of pheromone products

Research should be completed in 2004

Advisory Committee on Pesticides sub-group report: Alternative approaches to chemical pesticides

The Committee has published a draft final report in November 2003. Revisions to be expected in 2004

3.4.8 FSA residue minimisation policy The FSA Board will discuss the policy at its May 2004 meeting

3.4.9 Cabinet Office Better Regulation biopesticide engagement

The final report was published in January 2004. No further work is planned at present

3.4.10 European Action Plan for Organic Food and Farming

In early 2004, the Commission will prepare the final Action Plan in the form of a Communication to the Council and the European Parliament.

3.4.11 UK Organic Action Plan Published in 2002 and implementation is ongoing

273

Appendix 2.4 Approved Commodity substancesThe commodity substances that can be used as a pesticide in the UK are listed below. For some substances separate approval is given for different fields of use. The approval detailing the conditions which a user must follow when the commodity substance is used as a pesticide can be viewed via the webpage(www.pesticides.gov.uk).

4-chloro-m-cresol CamphorCarbon dioxide (Only as an insecticide, acaricide and rodenticide in food storage practice, Only as a rodenticide, Only in vertebrate control )Disodium Octoborate Tetrahydrate EthanolEthyl acetate Ethylene Formaldehyde (Only as an agricultural/horticultural fungicide and sterilant, Only as an insecticide/preservative)Isopropanol Methyl bromide Liquid nitrogenParaffin oilPeroxyacetic acidPotassium Hydrogen Carbonate (Bicarbonate)Sodium chlorideSodium hypochloriteStrychnine hydrochlorideSulphuric acidTetrachloroethylene ThymolUreaWhite spirit

274

Appendix 2.5 EPA Biopesticide fact sheetsThe EPA web pages contains a list of the Biopesticide active ingredients regulated by the Office of Pesticide Programs. The program is in the process of preparing a series of documents about each of the active ingredients. Chemical name (common name) (EPA ID number) [currently few common names are included](1R-Z)-1-methyl-2-(1-methylethenyl) cyclobutane ethanol (112401) (E)-(3,3-Dimethylcyclohexylidene)acetaldehyde (112403) (E)-11-Tetradecen-1-ol (129020)(E)-11-Tetradecen-1-yl acetate (129019)(E)-4-Tridecen-1-yl acetate (121902)(E)-5-Decenol (078038)(E)-5-Decenol acetate (117703)(E)-8-Dodecen-1-yl acetate (128907)(E)-9-Dodecen-1-yl acetate (119004)(E)-9-Tricosene (103202) (E,E)-8,10-Dodecadien-1-ol (129028)(E,Z)-3,13-Octadecadien-1-ol acetate (117202)(R,Z)-5-(1-Decenyl) dihydro-2(3H)-furanone (nuranone) (116501)(Z)-(3,3-Dimethylcyclohexylidene) acetaldehyde (112404)(Z)-2-(3,3-Dimethylcyclohexylidene)ethanol (112402)(Z)-4-Tridecen-1-yl acetate (121901) (Z)-8-Dodecen-1-ol (128908)(Z)-8-Dodecen-1-yl acetate (128906)(Z)-9-Dodecenyl acetate (129004)(Z)-9-Tetradecen-1-ol (119409) (Z)-9-Tricosene (103201) (Z)-11-Hexadecenal(virelure) (120001) (Z)-11-Hexadecenyl acetate (129101)(Z)-11-Tetradecenyl acetate (128980) (Z,E)-7,11-Hexadecadien-1-yl acetate (114101)(Z,E)-9,12-Tetradecadienyl acetate (117203)(Z,Z)-3,13-Octadecadien-1-yl acetate (117201)(Z,Z)-7,11-Hexadecadien-1-yl acetate (114102) (Z,Z)-11,13-Hexadecadienal (000711) 1-Butanethiol (125001) 1-Methylcyclopropene (MCP) (224459) 1-Octen-3-ol (069037) 1,2,4-Trimethoxyhbenzene (040515) 1,4 Dimethylnaphthalene (055802) 1,7-dioxaspiro-(5,5)-undecane (Olive Fly Pheromone) (124851) 2,6-bis(1-methylethyl)-Napthalene (2,6-DIPN) (055803)2-Hydroxy-3-methyl 2-cyclopenten-1-one (maple lactone) (004049)2-Phenylethyl propionate 2-Propynyl (S-(E,E))-3,7,11-trimethyl-2,4-dodecadienate (107502)3-(N-Butyl-N-acetyl)-aminopropionic acid, ethyl ester (IR3535) (113509)3-Methyl-2-cyclohexene-1-one (MCH) (219700)3,7,11-Trimethyl-2,6,10-dodecatriene-3-ol (farnesol) (128911) 3,7,11-Trimethyl-1,6,10-dodecatriene-3-ol (nerolidol) (128910)

275

4-Allyl Anisole (062150)4-(or 5-)Chloro-2methylcyclohexane-carboxylic acid, 1,1-dimethyl ester (trimedlure)(112603) 7,11-Hexadecadien-1-ol acetate (114103) Acetic Acid (044001) Agrobacterium radiobacter K84 (114201) Agrobacterium radiobacter K1026 (006474) Allium sativum (Garlic) (128827) Allyl isothiocyanate (Mustard, oil of) (004901) Aminoethoxyvinylglycine hydrochloride (AVG) (129104)Ammonium bicarbonateAmpelomyces quisqualis M10 (021007) Anagrapha falcifera Nucleopolyhedrosis Virus (NPV) (127885)Anise oil (004301) Anthraquinone (122701) Aspergillus flavus strain AF36 (006456)Aspergillus flavus strain NRRL 21882 (006500)Azadirachtin (121701)Bacillus cereus Strain BP01 (119802)Bacillus licheniformis Strain SB3086 (006492) Bacillus popilliae (054502) Bacillus pumilus strain GB 34 (006493)Bacillus sphaericus Serotype H5a5b strain 2362 (128128) Bacillus subtilis GBO3 (129068)Bacillus subtilis MBI 600 (129082) Bacillus subtilis QST713 (006479) Bacillus subtilis var. amyloliquefaciens strain FZB24 (006480) Bacillus thuringiensis Berliner (006400)Bacillus thuringiensis Cry1A(c) & Cry I(c) delta-endotoxin in killed Pseudomonas fluorescens (006457)Bacillus thuringiensis Cry1A(b) delta-endotoxin and the genetic material necessary for its production in corn (006430) Bacillus thuringiensis Cry3Bb1 Protein and the Genetic Material Necessary for its Production (Vector ZMIR13L) in Event MON 863 Corn & Bacillus thuringiensis Cry1Ab Delta-Endotoxin and the Genetic Material Necessary for its Production in Corn (STACKED PIP) (006430 & 006484)Bacillus thuringiensis Cry1A(b) delta-endotoxin and the genetic material necessary for its production (pZ01502) in field corn, sweet corn, and popcorn (006461) Bacillus thuringiensis Cry1A(b) in corn from PV CIB4431 (006458)Bacillus thuringiensis Cry1A(c) delta-endotoxin and the genetic material necessary for its production in cotton (006445) Bacillus thuringiensis Cry1F protein and the genetic material necessary for its production (plasmid insert PHI8999) in corn plants (006481) Bacillus thuringiensis Cry2Ab2 protein and the Genetic Material Necessary for Its Production in Cotton (006487)Bacillus thuringiensis Cry3A delta-endotoxin and the genetic material necessary for its production in potato (006432)Bacillus thuringiensis Cry3Bb1 Protein and the Genetic Material Necessary for its Production (Vector ZMIR13L) in Event MON863 Corn (006484)Bacillus thuringiensis K Cry1A(b) delta-endotoxin and the genetic material necessary

276

for its production in corn produced by HD-1 gene from PV pZ01502 (006444) Bacillus thuringiensis K Cry1A(c) delta-endotoxin and the genetic material necessary for its production in corn (006463) Bacillus thuringiensis subsp. aizawai delta-endotoxin in killed Pseudomonas fluorescens (006462)Bacillus thuringiensis subsp. aizawai (006403)Bacillus thuringiensis subsp. aizawai GC-91 (006426)Bacillus thuringiensis subsp. israelensis (006401)Bacillus thuringiensis subsp. israelensis EG2215 (006476)Bacillus thuringiensis subsp. kurstaki (006402)Bacillus thuringiensis subsp. kurstaki BMP123 (006407)Bacillus thuringiensis subsp. kurstaki delta-endotoxin in killed Pseudomonas fluorescens (006409)Bacillus thuringiensis subsp. kurstaki EG2348 (006424)Bacillus thuringiensis subsp. kurstaki EG2371 (006423)Bacillus thuringiensis subsp. kurstaki EG2424 (006422)Bacillus thuringiensis subsp. kurstaki EG7673 Coleoptera Toxin (006447)Bacillus thuringiensis subsp. kurstaki EG7673 Lepidoptera Toxin (006448)Bacillus thuringiensis subsp. kurstaki EG7826 (006459)Bacillus thuringiensis subsp. kurstaki EG7841 (006453) Bacillus thuringiensis subsp. kurstaki M200 (006452) Bacillus thuringiensis subsp. San Diego delta-endotoxin in killed Pseudomonas fluorescens (006410) Bacillus thuringiensis subsp. tenebrionis (006405)Beauveria bassiana ATCC 74040 (128818) Beauveria bassiana GHA (128924) Beauveria bassiana strain 447 (128815) Bergamot oil -- Black Pepper oilBurkkholderia cepacia Candida oleophila isolate I-182 (021008) Canola oil (011332)Capsaicin (070701) Castor oil (031608) Cedarwood oil (040505) Chitin (128991) Chitosan (128930) Cinnamaldehyde (040506) cis-7,8-Epoxy-2-methyloctadecane (114301) Citronella oil (021901) Citronellol (167004)Colletotrichum gloeosporioides f.sp.aeschynomene ATCC 20358 (226300) Coniothyrium minitans strain CON/M/91-08 (028836) Corn gluten meal (100137) Cydia pomonella granulosis virus (GV) (129090) Cyclohexanecarboxylic acid (112603) Cytokinin (116801) Decanoic acid, monoester with 1,2-propanediolDecanoic acid, monoester with 1,2,3-propanetriol Diallyl sulfides (DADs) (129087)

277

Dodecanoic acid, monoester with 1,2-propanediol Dodecanoic acid, monoester with 1,2,3-propanetriol Dipotassium phosphate (176407) Douglas fir tussock moth NPV (107302) Dried blood (000611) Dyer's Woad Rust (Puccinia thlaspeos strain woad) (006489) Ethyl (2E,4E,7S)-trimethyl-2,4-dodecadienoate (128966)Ethylene (041901) Eucalyptus oil (040503) Eugenol (102701)Fish oil (122401) Formic acid (214900) Gamma aminobutyric acid (GABA) (030802) Geraniol (597501) German Cockroach Pheromone (029028) Gibberellic acid (043801) Gibberellic acid, monopotassium salt (043802) Gibberellin A4 mixed with Gibberellin A7 (116902) Gliocladium catenulatum Strain J1446 (021009) Gliocladium virens G-21 (129000)Glycerol monocaprateGlycerol monocaprylateGlycerol monolaurateGround Sesame Stalks (128970) Gypsy moth NPV (107303) Harpin Protein (006477) Helicoverpa zea NPV (previously Heliothis zea NPV) (107300) Hydrogen peroxide (000595)Indian meal moth Granulovirus (Plodia interpunctella GV) (108896) Indole (025000) Indole-3-butryric Acid (046701) Iron phosphate (Ferric phosphate) (034903) Isopropyl (2E,4E)-11methoxy-3,7,11-trimethyl-2-4 dodecadienoate (methoprene) (105401) Isopropyl (2E,4E,7S)-11methoxy-3,7,11-trimethyl-2-4 dodecadienoate (105402) Jojoba oil (067200) Kaolin (100104) Kinetin (N-(2-furanylmethyl)-1-H-Purin-6-amine) (116802) L-Glutamic acid (374350) Lagenidium giganteum (129084) Lauryl alcohol (001509) Lavandin oil (040500) Lemon Grass oil (040502)Linalool (128838)Lysophosphatidylethanolamine (LPE)(105120)Mamestra configurata NPV (107308) Maple Lactone (004049) Meat Meal (100628) Metarhizium anisopliae ESC1 (129056)

278

Metarhizium anisopliae strain F52 (029056)Methoprene (105401)Methyl anthranilate (128725) Methylcyclopropene (MCP) (224459) Methyl salicylate (076601) Mint Oil (128800) Mono & dipotassium salts of phosphorus acid (076416) Mustard oil (004901) Myristyl alcohol (001510) Myrothecium verrucaria, Dried fermentation solids & solubles of (119204) Neem oil (025006)Neem oil, clarified hydrophobic (025007) Nitrogen, Liquid (128962) Nosema locustae (117001) N6-Benzyladenine (116901)Octenol (069037) Orange oil (040517)Oxypurinol (447509) p-Menthane-3,8-diol (011550) Paecilomyces fumosoroseus Apopka strain 97 (115002) Pelargonic acid (217500) Phosphorous acid and it's ammonium, sodium, and potassium salts (076002) Phytophthora palmivora MWV (111301)Piperine Plant Extract 620 (169007) Polyoxin D zinc salt (230000) Potassium bicarbonate (073508) Potassium dihydrogen phosphate (076413) Potato Leafroll Virus (PLRV) replicase protein as produced in potato plants (006469)Propylene glycol monocapratePropylene glycol monocaprylatePropylene glycol monolaurate Pseudomonas chlororaphis strain 63-28 (006478)Pseudomonas aureofaciens strain Tx-1 (006473) Pseudomonas fluorescens A506 (006438) Pseudomonas syringae 742RS (006411) Pseudomonas syringae ESC 10 (006441) Pseudomonas syringae ESC 11 (006451) Pseudozyma flocculosa strain PF-A22 UL (119196) Puccinia thlaspeos strain woad (dyer’s woad rust) (006489) Putrescent whole egg solids (105101)Red pepper (070703) Reynoutria sachalinensis (055809) Rhamnolipid biosurfactant (110029)S-hydroprene (128966) S-kinoprene (107502) S-methoprene (105402) Sesame stalks (128970) Silver nitrate (072503) Sodium 5-nitroguaiacolate (129075)

279

Sodium bicarbonate (073505) Sodium carbonate peroxyhydrate (128860) Sodium lauryl sulfate (079011)Sodium o-nitrophenolate (129076)Sodium p-nitrophenolate (129077) Soybean oil (031605) Sucrose octanoate esters (035300) Spodoptera exigua NPV (129078)Streptomyces griseoviridis K61 (129069)Streptomyces lydicus WYEC 108 (006327)Thyme (herb) (128894) Trichoderma harzianum ATCC 20476 (128903) Trichoderma harzianum Rifai strain T-22 (119202) Trichoderma harzianum strain T-39 (119200) Trichoderma polysporum ATCC 20475 (128902)Trypsin Modulating Oostatic Factor (105403) Verbenone (128986) Yeast Extract HydrolysateXanthine (116900)

280

Appendix 2.6 Available dataset for all pesticides/biocides

Parameter Preferred units/formatChemical structure ChemDraw fileChemical name IUPAC formatCommon name -CAS no -Molecular formula -Molecular weight g mol-1

Major emission routs -0Application/emission rates e.g. kg ha-1; dose (mg kg-1)Proportion metabolised -Identity of metabolites Amount produced; Chem draw

fileOctanol-partition coefficient (Kow, P)

Unitless

Solubility in water g L-1


-

Vapour pressure PaHenry’s Law Constant Pa m3 mol-1


L kg-1


L Kg-1

Photolysis half life Half life (d)Hydrolysis half life Half life (d)Persistence in air Half life (d)Persistence in activated sludge Half life (d); ready/non-ready Persistence in soil Half life (d)Persistence in sediment Half life (d)Identity of degradates from above studies


Fate in the field Dissipation half life (d); Measured concs (mg kg-1; mg l-

1)Bioconcentration factor -Biota-sediment/soil accumulation factor

-

281

NATURAL ORGANIC PESTICIDES

Parameter Pesticide DataPesticide Name

Abamectin Pesticide Activity Insecticide, acaricideChemical structure

(i) R = -CH 2CH3 (avermectin B 1a)

(ii) R = -CH 3 (avermectin B 1b)

O

CH3CH3

CH3

O

OO

OH

CH3

OH

O

OH

H

H

OCH3

OCH3

O

OCH3OH

OCH3

CH3

HH R

Common name abamectinCAS no [71751-41-2] (abamectin)Molecular formula C48H72O14 (avermectin B1a); C47H70O14 (avermectin B1b)Molecular weight 873.1 (avermectin B1a); 860.1 (avermectin B1b) Major emission routsApplication/emission rates

Application rates are 5.6 to 28 g/ha for mite control, 11 to 22 g/ha for control of leaf miners.

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)

4.4±0.3 (pH 7.2, room temperature)

Solubility in water 7-10 g/l (20 ºC)Acid dissociation constant (pKa)Vapour pressure <3.7 x 10-3 mPa (25 °C)Henry’s Law Constant 2.7 x 10-3 Pa m3 mol-1 (25 °C)Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life U.V. irradiation causes conversion first to the 8,9-Z- isomer, then

to unidentified decomposition products.Hydrolysis half life Stable to hydrolysis in aqueous solutions at pH 5, 7, and 9 (25 ºC)

282

Parameter Pesticide DataPersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats 10, mice 13.6 mg/kg (in sesame oil)


Acute percutaneous LD50 for rabbits >2000 mg/kg. Mild eye irritant; non-irritating to skin (rabbits).

Mammalian ADI (JMPR) 0.002 mg/kg b.w.Mammalian InhalationToxicity Class (EPA) (formulation) IV

Ecotoxicity (Bird) Acute oral LD50 for mallard ducks 84.6, bobwhite quail >2000 mg/kg.

Ecotoxicity (Fish) LC50 (96 h) for rainbow trout 3.2, bluegill sunfish 9.6 μg/l.Ecotoxicity (Daphnia) EC50 (48 h) 0.34 ppb, LC50 0.00034 mg/ml. Ecotoxicity (Algae) EC50 >100 mg/l.Ecotoxicity (Other aquatics)

LC50 (96 h) for pink shrimp (Panaeus duorarum) 1.6, blue crab (Callinectes sapidus) 153 ppb

Ecotoxicity (Bees) Toxic to bees. LD50 (contact) 0.0090 ug/lEcotoxicity (Worms) LC50 (28 d) for earthworms 28 mg/kg soil.

Environ fate (Animals) Rapidly eliminated (80-100% in 96 h), mainly via faeces; urinary excretion was 0.5-1.4%

Environ fate (Plants) Degradation/metabolism in each of three different plants is similar and occurs predominantly by photolysis on the plant surfaces. The definition of the residues is thus expressed as the combined residues of avermectin B1 and its 8,9-Z-avermectin B1 photoisomer

Environ fate (Soil/Environment)

Binds tightly to soil, with rapid degradation by soil micro-organisms. No bioaccumulation. DT50 in soil 28 days

283


4-Allyl-2-methoxyphenol Pesticide Activity Plant-derived insecticide/deterrentChemical structureCommon name EugenolCAS no [97-53-0]Molecular formula C10H12)2Molecular weight 164Major emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)

2.27 (Exp.)

Solubility in water 2460mg/l (25)Acid dissociation constant (pKa)

10.2 (25)

Vapour pressureHenry’s Law Constant 4.81E-008 atm-m3/mole (25)Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicity

Irritant

Mammalian ADIMammalian Inhalation

284

Parameter Pesticide DataToxicity ClasssEcotoxicity (Bird) Naturally occurring plant phenolic not expected to be hazardous.Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

285


Aminoethoxyvinylglycine Pesticide Activity Plant growth regulatorChemical structure O

NH2

CO2HH2N

Common name Aviglycine (aviglycine hydrochloride)CAS no [49669-74-1], formerly [73360-07-3] Molecular formula C6H12N2O3

Molecular weight 160.2 Major emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)

-4.36

Solubility in water 42.18 g/100 ml (room temperature). Acid dissociation constant (pKa)

2.84, 8.81, 9.95

Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats >5000 mg/kg.


Acute dermal LD50 for rabbits >2000 mg/kg.

Mammalian ADI RfD 0.002 mg/kg b.w. [1997

286

Parameter Pesticide DataMammalian Inhalation LC50 (4 h) for rats 1.13 mg/l. Toxicity Class EPA (formulation) III; (formulation and tech. a.i.) IV Ecotoxicity (Bird) Acute oral LD50 for northern bobwhite quail 121 mg/kg. Dietary

LC50 (5 d) for northern bobwhite quail 230 ppm.Ecotoxicity (Fish) LC50 (96 h) for trout >139 mg/l. NOEL (96 h) for trout 139 mg/l. Ecotoxicity (Daphnia) EC50 (48 h) >135 mg/l. NOEL 135 mg/lEcotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) LD50 (48 h, oral) for honey bees >100 µg/bee. Ecotoxicity (Worms) LC50 for earthworms >1000 ppm. Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

287


AzadirachtinPesticide Activity InsecticideChemical structure

OOH

CO2CH3

O

OCH3OC

O

O OHCCH3

CH3

O

CH3O

OO

HOCH3

H

O

CH3C

Common name azadCAS no [11141-17-6] Molecular formula C35H44O16 Molecular weight 720.7 Major emission routsApplication/emission rates

100 to 500g a.i. per hectare (frequent applications)

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 0.26 g/l.Acid dissociation constant (pKa)Vapour pressure 3.6 x 10-6 mPa (azadirachtin) Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life Stable in the darkHydrolysis half life . DT50 50 d (pH 5, room temperature); rapidly decoposed at higher

temperatures, in alkaline, and strongly acidic mediaPersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil

288

Parameter Pesticide Dataaccumulation factorMammalian oral toxicity



Acute percutaneous LD50 for rabbits >2000 mg/kg. No skin irritation; slight eye irritation (rabbits). Slight skin sensitisation (guinea pigs).

Mammalian ADIMammalian Inhalation LC50 for rats 0.72 mg/l. Toxicity Class EPA (formulation) IV Ecotoxicity (Bird) Mallard duck (Margosan O) 1-16mg/kg (14 days) no negative

effectsEcotoxicity (Fish) LC50 trout (96h) with Margosan O 8.8ml/l for tilapia fingerlings

(24h) with neem oil – 1124.6ppm for carp (24h) with neem oil 302.7ppm.

Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants) On foliage, DT50 c. 17 h Environ fate (Soil/Environment)

In soil DT50 c. 25 d. Commercial formulations contain stabilisers to retard hydrolytic and photodegradation.

289


6-BenzylaminopurinePesticide Activity Plant growth regulatorChemical structure

N

N

N

NH

HNCH2

Common name 6-benzylaminopurineCAS no [1214-39-7Molecular formula C12H11N5Molecular weight 225.3 Major emission routsApplication/emission rates

30 g/a for apple trees


logP = 2.13 (unstated pH)

Solubility in water 60 mg/l (20 °C)Acid dissociation constant (pKa)Vapour pressure 2.373 x 10-6 mPa (20 °CHenry’s Law Constant 8.91 x 10-9 Pa m3 mol-1 (calc.) Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life Stable to light and heat (8 h, 120 °C).

Hydrolysis half life Stable in acidic, alkaline and neutral aqueous solution.Persistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factor

290

Parameter Pesticide DataMammalian oral toxicity

Acute oral LD50 for male rats 2125, female rats 2130, mice 1300 mg/kg.


Acute percutaneous LD50 for rats >5000 mg/kg. Not a skin or eye irritant (rabbits); not a skin sensitiser.

Mammalian ADI 0.05 mg/kgMammalian InhalationToxicity Class WHO (a.i.) U (company classification); EPA (formulation) III Ecotoxicity (Bird) Practically non-toxicEcotoxicity (Fish) LC50 (48 h) for carp >40 mg/l. Ecotoxicity (Daphnia) LC50 (24 h) for D. carinata >40 mg/l.Ecotoxicity (Algae) EC50 (96 h) 363.1 mg/l ('Paturyl' 10 SL formulation). Ecotoxicity (Other aquatics)Ecotoxicity (Bees) LD50 (oral) 400 μg/bee, (contact) 57.8 l/ha (both 'Paturyl' 10 SL

formulation).

Ecotoxicity (Worms)Environ fate (Animals) Almost all of administered 14C was excreted in urine and faeces.

Three metabolites were identifiedEnviron fate (Plants) More than 9 metabolites were identified from metabolism studies

in soya beans, grapes, maize and cocklebur. Urea is an end product. Environ fate (Soil/Environment)

16 Days after application to soil at 22 °C, 6-benzylaminopurine had degraded to 5.3% (sandy loam) and 7.85% (clay loam soil) of applied dose. Other studies indicate DT50 7-9 w.

291


Bilanafos Pesticide Activity HerbicideChemical structure O

PCH3

OHCH2

H2N

HCCH3

HC CO2HCH3

HCCH2 C

NH

OC

NH

O

Common name Bilanfos, Bilanafos sodiumCAS no [35597-43-4] , [71048-99-2] Molecular formula C11H22N3O6P, C11H21N3NaO6PMolecular weight 323.3, 345.3 Major emission routsApplication/emission rates

0.5-1.0 kg a.i. / ha

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 1 kg/l, >1000 g/l.Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life Stable to lightHydrolysis half life Unstable in strong acids and strong alkalis. Persistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for male rats 268, female rats 404 mg/kg.


Acute percutaneous LD50 for rats >3000 mg/kg. Non-irritating to skin and eyes (rabbits).

292

Parameter Pesticide DataMammalian ADIMammalian Inhalation LC50 for male rats 2.57, female rats 2.97 mg/l. Toxicity Class WHO (a.i.) II Ecotoxicity (Bird) Acute oral LD50 for chickens >5000 mg/kg. Ecotoxicity (Fish) LC50 (48 h) for carp >1000 mg/l. Ecotoxicity (Daphnia) LC50 (3 h) >5000 mg/l. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms) Not toxic to earthwormsEnviron fate (Animals) In mice, the main metabolite in the faeces following oral

administration was glufosinate (q.v.)Environ fate (Plants)Environ fate (Soil/Environment)

Rapidly degraded in soil and water.

293


Blasticidin-SPesticide Activity FungicideChemical structure

N

N

NH2

OO

HO2C

NHNH2

CCH2CH2 CH2CO

H

CH3

NH2NCNH

blasticidin S

SO3H

NHCH2

benzylaminobenzenesulfonic acidCommon name blasticidin-S, benzylaminobenzenesulfonate (BABS) saltCAS no [2079-00-7] formerly [11002-92-9], [12767-55-4] and [51775-28-

1] Molecular formula C17H26N8O5, C30H39N9O8SMolecular weight 422.4, 685.6 Major emission routsApplication/emission rates

Control of rice blast (Pyricularia oryzae) by foliar application at 100-300 g/ha. Benzylaminobenzenesulfonate (BABS) salt - Control of rice blast (Pyricularia oryzae) by foliar application at 10-40 g/ha.

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water >30 g/l (20 ºC)Acid dissociation constant (pKa)

pKa1 2.4 (carboxyl), pKa2 4.6, pKa3 8.0, pKa4 >12.5 (three bases)

Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life Stable to lightHydrolysis half life Stable at pH 5-7; unstable at pH <4 and in alkali.Persistence in air

294

Parameter Pesticide DataPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

‘Rather toxic to mammals.’.Acute oral LD50 for male rats 56.8, female rats 55.9, male mice 51.9, female mice 60.1 mg/kg.


Acute percutaneous LD50 for rats >500 mg/kg. Severe eye irritant.

Mammalian ADIMammalian InhalationToxicity Class WHO (a.i.) Ib; EPA (formulation) II Ecotoxicity (Bird)Ecotoxicity (Fish) blasticidin-S - LC50 (48 h) for carp >40 mg/l Ecotoxicity (Daphnia) blasticidin-S LC50 (3 h) for D. pulex >40 mg/l.

Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals) Almost all of 3H-blasticidin-S administered to mice was excreted

in the urine and faeces within 24 h. Environ fate (Plants) In rice plants, cytomycin and deaminohydroxy blasticidin-S were

identified as the main metabolites. Environ fate (Soil/Environment)

In soil, DT50 <2 d (two soil types, o.c. 2.53%, 9.6%; moisture 42.6%, 87%, respectively; pH 6.0, 25 °C).

295


3-[N-butyl-N-acetyl]-aminoproprionic acid, ethyl ester Pesticide Activity Insect repellentChemical structureCommon name [52304-36-6]CAS noMolecular formulaMolecular weightMajor emission routs Apply to skinApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Has been used as an insect repellents for thirty years with no adverse effects. Toxicity testes show it is not harmful when ingested, inhaled or used on skin. Eye irritant

Mammalian skin/eye toxicityMammalian ADIMammalian Inhalation

296

Parameter Pesticide DataToxicity ClassEcotoxicity (Bird)Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals) Because the a.i. is used only in products applied to human skin, no

risks to environ are expected.Environ fate (Plants)Environ fate (Soil/Environment)

297


Canola oil Pesticide Activity InsecticideChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Products applied either by spray of irrigation systems.

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

No harmful health effects are expected (similar to those of other vegetable oils used as food.)

Mammalian skin/eye toxicityMammalian ADIMammalian InhalationToxicity Class

298

Parameter Pesticide DataEcotoxicity (Bird) Adverse effects to the environment or to organisms other than

insects not anticipated because of low toxicity.Ecotoxicity (Fish) Ecotoxicity (Daphnia) Not allowed to be directly applied to water bodies therefore

exposure of aquatics extremely limited.Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Rapid decomposition

299


CapsaicinPesticide Activity Insect repellentChemical structureCommon name Hot pepper extractCAS no 57-06-7Molecular formulaMolecular weightMajor emission routsApplication/emission rates

Foliar and soil


Not considered to be toxic to mammals (GRAS)


Severe irritant

Mammalian ADIMammalian InhalationToxicity Class

300

Parameter Pesticide DataEcotoxicity (Bird)Ecotoxicity (Fish) Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) ToxicEcotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Rapidly degraded

301


Citronella Pesticide Activity Insect repellentChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Skin and clothing


Natural, and has not shown any allergic or other adverse effects on mammals


302

Parameter Pesticide DataEcotoxicity (Bird) Is a naturally occurring compound and it is note expected that it

will have any adverse effects on non-target organisms or the environment. It has a non-cidal effect on target insects repelling rather than killing them.

Ecotoxicity (Fish)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

303


CytokininsPesticide Activity Plant growth regulator and nematicideChemical structure

N

N

N

NH

NHR

CH2

CH CCH2OH

CH3

kinetin R =OCH2

6-isopentenylaminopurine R =

zeatin R =

CH2

CH CCH3

CH3

Common name Cytokinins, 6-isopentenylaminopurine, kinetin, zeatinCAS no cytokinins [308064-23-5], 6-isopentenylaminopurine [2365-40-4],

formerly [13255-47-5] and [5122-37-2] , kinetin [525-79-1], formerly [525-80-4] and [33446-70-7] zeatin [1637-39-4], formerly [10052-59-2] and [129900-07-8]

Molecular formula 6-isopentenylaminopurine C10H13N5, kinetin C10H9N5O, zeatinC10H13N5O

Molecular weight 6-isopentenylaminopurine 203.2, kinetin 215.2, zeatin 219.2

Major emission routsApplication/emission rates

Soil and foliar

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)

Kinetin pKa1 2.7; pKa2 9.9

Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in

304

Parameter Pesticide Dataactivated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats >5 g/kg.


Acute percutaneous LD50 for rabbits >2 g/kg. Slight skin and eye irritant (rabbits).

Mammalian ADIMammalian InhalationToxicity ClassEcotoxicity (Bird) Natural and not expected to have any adverse effects on non-targets or

environment.Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Zeatin not toxic to beesEcotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Rapidly degraded in soil

305


DihydroazadirachtinPesticide Activity InsecticideChemical structureCommon name DAZACAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Foliar application at 50g/ha


‘DAZA’ Acute oral LD50 for rats >5 g/kg

Mammalian skin/eye toxicityMammalian ADIMammalian Inhalation ‘DAZA’ Rats LC50 > 2.9mg/lToxicity Class

306

Parameter Pesticide DataEcotoxicity (Bird) Acute oral LD50 for DAZA bobwhite quail > 816mg/kgEcotoxicity (Fish) DAZA LC50 rainbow trout 17.65 mg/l and LC50 blue gill sunfish –

17.65mg/l. Ecotoxicity (Daphnia) LC50 11.62mg/kgEcotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Non-toxic (96 hour acute dust exposure)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Short-lived (matter of days).

307


DMDPPesticide Activity NematicideChemical structureCommon name (2R,5R)-dihydroxymethyl-(3R,4R)-dihydroxypyrrolidineCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Foliar


Preliminary tests indicate DMDP is of low toxicity to mammals (further test needed to meet registration requirements)


308

Parameter Pesticide DataToxicity ClassEcotoxicity (Bird) Environmental impact expected to be low. Data awaited.Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

309


Emamectin benzoate Pesticide Activity InsecticideChemical structure

NH2CH3

O

O

OCH3

CH3

O

OO

OH

CH3

HO

O

H

H

OCH3

R

CH3HOCH3

CH3

OCH3

CH3O

CO2

B1a R = CH3CH2-

B1b R = CH3-Common name Emamectin benzoateCAS no emamectin benzoate - [155569-91-8]; formerly [137512-74-4] and

[179607-18-2]. emamectin [119791-41-2]; formerly [123997-28-4] and [137335-79-6]

Molecular formula emamectin benzoate C56H81NO15 (B1a); C55H79NO15 (B1b) ; emamectin C49H75NO13 (B1a); C48H73NO13 (B1b)

Molecular weight emamectin benzoate 1008.3 (B1a); 994.2 (B1b)’ emamectin 886.1 (B1a); 872.1 (B1b)


Spray at 5 and 25g a.i./ha


emamectin benzoate logP = 5.0 (pH 7)

Solubility in water emamectin benzoate 0.024 g/l (pH 7, 25°C). Acid dissociation constant (pKa)Vapour pressure emamectin benzoate 4 x 10-3 mPa (21 °C) Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in

310


Acute oral LD50 for rats 76-89 mg/kg.


Acute dermal LD50 for rabbits >2000 mg/kg. It is not irritant to skin, and has no sensitising potential.

Mammalian ADI 0.0025 mg/kg. Mammalian Inhalation LC50 (4 h) for rats 2.12-4.44 mg/m3. Toxicity Class WHO (a.i.) II (company classification) Ecotoxicity (Bird) Acute oral LD50 for mallard ducks 46, bobwhite quail 264 mg/kg.

Dietary LC50 (8 d) for mallard ducks 570, bobwhite quail 1318 ppm.

Ecotoxicity (Fish) LC50 (96 h) for rainbow trout 174, sheepshead minnow 1430 g/l. Toxic to fish not used on water courses .

Ecotoxicity (Daphnia) LC50 0.99 ug/l. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Toxic to bees. Ecotoxicity (Worms) LC50 >1000 mg/kg dry soil.Environ fate (Animals) Emamectin benzoate is partially metabolised but rapidly cleared

(DT50 following oral dosing 34-51 h), indicating that it has no potential for bioaccumulation.

Environ fate (Plants) Metabolism has been investigated in lettuce, cabbage and sweet corn. It is non-systemic, and rapidly degrades in sunlight to various complex residues in which undegraded parent is the only significant residue. The residues were very low.


Rapidly degraded. Binds tightly to soil. No bioaccumulation

311


Oleic acid (Fatty acids)Pesticide Activity Herbicide, fungicide, insecticideChemical structure CH3(CH2)7CH CH(CH2)7CO2M

M = H, Na or KCommon nameCAS no [112-80-1] (Z)- isomer; [112-79-8] (E)- isomer; [2027-47-6]

unspecified stereochemistry; [143-18-0] (Z)- isomer, potassium salt;[84776-33-0] ammonium salt

Molecular formula C18H34O2Molecular weight 282.5 Major emission routsApplication/emission rates

Foliar spray


Acute oral rats and mice LD50 > 5g/kg

Mammalian skin/eye Acute dermal LD50 rate >2g/kg

312

Parameter Pesticide DatatoxicityMammalian ADIMammalian Inhalation LC50 rats >2g/kgToxicity Class EPA formulations IIEcotoxicity (Bird) Non-toxic to non-target organisms or the environment. Dietary

LC50 mallard duck >5,620 ppmEcotoxicity (Fish) LC50 (48h) for carp 59.2 ppmEcotoxicity (Daphnia) LC50 (3h) >100 ppmEcotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) LD50 (contact) >25ug/beeEcotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Fully biodegradable. Rapidly degraded in soil.

313


Garlic extractPesticide Activity Insect repellentChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Foliar, repeat applications every 10 days


Garlic is used as food supplement, not considered to be hazardous.


314

Parameter Pesticide DataEcotoxicity (Bird) Repellent to many animals including bees and wasps but not toxicEcotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals) Not persistentEnviron fate (Plants)Environ fate (Soil/Environment)

315


Gibberellic acid Pesticide Activity Plant growth regulatorChemical structure

HOCH3

CO2H

O

OC

OH

CH2

H

H

Common nameCAS no [77-06-5]

Molecular formula C19H22O6

Molecular weight 346.4 Major emission routsApplication/emission rates

Application rates up to 80 g/a.i. per application


-2.0

Solubility in water 5 g/l (room temperature).Acid dissociation constant (pKa)

4.0

Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half life Slowly undergoes hydrolysis in aqueous or aqueous-alcoholic

solutions, DT50 (20 ºC) c. 14 d (pH 3-4), 14 d (pH 7Persistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral Acute oral LD50 for rats and mice >15 000 mg/kg.

316

Parameter Pesticide DatatoxicityMammalian skin/eye toxicity

Acute percutaneous LD50 for rats >2000 mg/kg. Non-irritating to skin and eyes

Mammalian ADIMammalian Inhalation No ill-effect on rats subjected to 400 mg/l for 2 h/d for 21 d.Toxicity Class WHO (a.i.) U; EPA (formulation) III Ecotoxicity (Bird) Acute oral LD50 for bobwhite quail >2250 mg/kg. Acute oral LC50

>4640 mg/kg. Ecotoxicity (Fish) LC50 (96 h) for rainbow trout >150 ppm. Ecotoxicity (Daphnia) Acute LC50 143 mg/lEcotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxicEcotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)


317


L-glutamic acid plus gamma-aminobutyric acidPesticide Activity Plant growth regulator/fungicide/plant metabolic primerChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Spraying or soil drenching


Toxicity test in animals and humans show no adverse effect from GABA or L-glutamic acid.


318

Parameter Pesticide DataToxicity ClassEcotoxicity (Bird) No risks to the environment are expected because they occur in

nature and do not persistEcotoxicity (Fish) Products not approved for application directly to water. AuxiGro

WP practically non-toxic to fish (>100mg/l)Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)

AuxiGro WP practically non-toxic to freshwater invertebrates (>100mg/l)

Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

319


Harpin protein Pesticide Activity Elicitor (micro-organisms derived) for systemic acquired resistanceChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Pre-planting or foliar spray, 5-25g/ a.i. ha at 14 day intervals


Acute oral LD50 rats > 5g/kg


Acute dermal LD50 rats >6g/kg, not irritating

Mammalian ADIMammalian Inhalation Acute LC50 >2mg/lToxicity Class EPA IV

320

Parameter Pesticide DataEcotoxicity (Bird) LC50 dietary bobwhite quail 100,000ppm, LC50 acute oral

>4000mg/kgEcotoxicity (Fish) LC50 Rainbow trout > 3,720mg/lEcotoxicity (Daphnia) EC50 1,173mg/lEcotoxicity (Algae) EC50 >182mg/lEcotoxicity (Other aquatics)Ecotoxicity (Bees) LD50 >1258ug/beeEcotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Harpin protein is non-persistent (degraded by light and micro-organisms) and rapidly broken down in soil

321


Indol-3-ylacetic acid Pesticide Activity Plant growth regulatorChemical structure

N

CH2CO2H

H

Common nameCAS no [87-51-4] Molecular formula C10H9NO2Molecular weight 175.2 Major emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 1.5 g/l (20 ºC).Acid dissociation constant (pKa)

4.75

Vapour pressure <0.02 mPa (60 ºC) Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half life Unstable to lightHydrolysis half life Very stable in neutral and alkaline mediaPersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute LD50 for mice 1,000mg/l

322

Parameter Pesticide DataMammalian skin/eye toxicity

Acute percutaneous LD50 for mice 1000 mg/kg.

Mammalian ADIMammalian InhalationToxicity ClassEcotoxicity (Bird)Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxic to bees.

Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Rapidly degraded in soil.

323


Jojoba oil Pesticide Activity Fungicide/insecticideChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Foliar spray


No harmful effects are expected from the use of jojoba oil in crop protection


324

Parameter Pesticide DataEcotoxicity (Bird) Adverse effects to the environment and non-target organisms are

not anticipated because of the low toxicity of jojoba oil and its rapid decomposition in the environment

Ecotoxicity (Fish) Not allowed to be applied to direct to water bodies; therefore exposure of aquatic should be extremely limited

Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

325


Kasugamycin Pesticide Activity Fungicide, bactericideChemical structure

O

O

NH2CH3

NH

HO2CNH

HOHO OH

OHOH

Common name Kasugamycin, kasugamycin hydrochloride hydrate

CAS no kasugamycin [6980-18-3] , kasugamycin hydrochloride hydrate [19408-46-9]

Molecular formula Kasugamycin C14H25N3O9 , kasugamycin hydrochloride hydrateC14H28ClN3O10

Molecular weight Kasugamycin 379.4, kasugamycin hydrochloride hydrate433.8


Foliar spray 20-10g/ha or seed treatment 20g/l


kasugamycin hydrochloride hydrate <1

Solubility in water kasugamycin hydrochloride hydrate 228 g/l (pH 7, 25 ºC).Acid dissociation constant (pKa)

Kasugamycin pKa1 3.23, pKa2 7.73, pKa3 11.0,

Vapour pressure kasugamycin hydrochloride hydrate <1.3 x 10-2 mPa (25 ºC) Henry’s Law Constant kasugamycin hydrochloride hydrate <2.9 x 10-8 Pa m3 mol-1

(calc.) Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half life kasugamycin hydrochloride hydrate DT50 (50 ºC) 47 d (pH 5), 14

d (pH 9). Persistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studies

326

Parameter Pesticide DataFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

kasugamycin hydrochloride hydrate - Acute oral LD50 for male rats >5000 mg/kg.


kasugamycin hydrochloride hydrate - Acute percutaneous LD50 for rabbits >2000 mg/kg. Non-irritating to eyes and skin (rabbits).

Mammalian ADIMammalian Inhalation kasugamycin hydrochloride hydrate - LC50 (4 h) for rats >2.4

mg/l.Toxicity Class kasugamycin hydrochloride hydrate - WHO (a.i.) U; EPA

(formulation) IV Ecotoxicity (Bird) kasugamycin hydrochloride hydrate - Acute oral LD50 for male

Japanese quail >4000 mg/kg. Ecotoxicity (Fish) kasugamycin hydrochloride hydrate - LC50 (48 h) for carp and

goldfish >40 mg/l.Ecotoxicity (Daphnia) kasugamycin hydrochloride hydrate - LC50 (6 h) >40 mg/l. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) kasugamycin hydrochloride hydrate LD50 (contact) >40 ug/bee. Ecotoxicity (Worms)Environ fate (Animals) Kasugamycin hydrochloride hydrate orally administered to rabbits

was mostly excreted in the urine within 24 h. When injected intravenously to dogs, it was mostly excreted within 8 h. After oral administration to rats at 200 mg/kg, no residues were detected in eleven organs or blood; 96% of administered dose remained in the digestive tract 1 h after administration

Environ fate (Plants) Degraded to kasugamycinic acid and kasuganobiosamine; finally degraded to ammonia, oxalic acid, CO2 and water.


Degradation proceeds as in plants.

327


Maple lactone Pesticide Activity Insect attractantChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Tablet/traps (3-5 traps/m2)


Not likely to produce adverse health effects in humans. Essentially non-toxic


328

Parameter Pesticide DataEcotoxicity (Bird) No harmful environmental effects are expected – no exposure to

any species but cockroaches. Not shown to be toxic to any organisms against which it has been tested.

Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

329


p-Menthane-3,8-diol Pesticide Activity Insect repellentChemical structureCommon nameCAS no [42822-86-6]Molecular formulaMolecular weightMajor emission routsApplication/emission rates

Sprayed on skin and clothing


No adverse effects


Eye irritant

Mammalian ADIMammalian InhalationToxicity Class

330

Parameter Pesticide DataEcotoxicity (Bird) Minimal or no risk to wildlife – low toxicity and limited usesEcotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

331


Milbemectin Pesticide Activity Acaricide, insecticideChemical structure

CH3

CH3O

O

CH3

R

OO

O CH3OH

OH

H

H

H

H

Milbemycin A3: R = -CH3

Milbemycin A4: R = -CH2CH3

Common nameCAS no [51596-10-2] A3; [51596-11-3] A4 Molecular formula A3: C31H44O7; A4: C32H46O7 Molecular weight A3: 528.7; A4: 542.7 Major emission routsApplication/emission rates

Applied at 5.6-28 g/ha.


A3: logP = 5.3; A4: logP = 5.9

Solubility in water A3: In water 0.88 ppm (20 °C). A4: In water 7.2 ppm (20 °C). Acid dissociation constant (pKa)Vapour pressure A3: <1.3 10-5; A4: <1.3 10-5 (both in mPa, 20 °C)Henry’s Law Constant <9.93 10-4 Pa m3 mol-1 (calc.)Soil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration

332

Parameter Pesticide DatafactorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for male mice 324, female mice 313, male rats 762, female rats 456 mg/kg.


Acute percutaneous LD50 for male and female rats >5000 mg/kg. Not a skin irritant.

Mammalian ADI 0.03 mg/kgMammalian Inhalation LC50 (4 h) for male rats 1.90, female rats 2.80 mg/kg. Toxicity ClassEcotoxicity (Bird) LD50 for male chickens 660, female chickens 650, male Japanese

quail 1005, female Japanese quail 968 mg/kg. Ecotoxicity (Fish) LC50 (96 h) for rainbow trout 4.5, carp 17 ug/l. Ecotoxicity (Daphnia) LC50 (3 h) for D. pulex >100 ppm. Ecotoxicity (Algae) NOEL (72 h) 7.3 mg/l. Ecotoxicity (Other aquatics)Ecotoxicity (Bees) LD50 (oral) 0.46 ug/bee; (contact) 0.025 ug/bee. Ecotoxicity (Worms) LC50 (14 d) for Eisenia foetida 61 ppm. Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Soil DT50 16-33 d.

333


MildiomycinPesticide Activity FungicideChemical structure

O

NHCO

HO

CO2HNHC

NH NH2

OHN

N

O

CH2OHNH2

HH2NCH2OH

Common nameCAS no [67527-71-3] formerly [57497-78-6], [67983-11-3]Molecular formula C19H30N8O9Molecular weight 514.50 Major emission routsApplication/emission rates

Spray, 5-10 g/hl.

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)

2.8, 4.3, 7.2, >12

Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil

334

Parameter Pesticide Dataaccumulation factorMammalian oral toxicity

Acute oral LD50 for male rats 4300, female rats 4120, male mice 5060, female mice 5250 mg/kg.


Acute percutaneous LD50 for rats and mice >5000 mg/kg. Non-irritating to skin and eyes (rabbits).

Mammalian ADIMammalian InhalationToxicity ClassEcotoxicity (Bird)Ecotoxicity (Fish) LC50 (96 h) for carp >100 mg/l; (168 h) for killifish >40 mg/l. Ecotoxicity (Daphnia) EC50 (48 h) for D. pulex 6.12 mg/l. Ecotoxicity (Algae) EbC50 (72 h) for Selenastrum 8.05 mg/l. Ecotoxicity (Other aquatics)Ecotoxicity (Bees) LD50 (48 h, oral and contact) >100 ug/bee. Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

335


Milsana, Reynoutria sachalinensis extractPesticide Activity Fungicide, Plant activatorChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

The extract is applied at 0.5% v/v in 500-1000 l/ha.


Acute oral LD50 (of concentrate) >5000 mg/kg.


Acute percutaneous LD50 (of concentrate) >2000 mg/kg. Moderately irritating to eyes, not irritating to skin (rabbits). Not a skin sensitiser (guinea pigs).

Mammalian ADIMammalian Inhalation LC50 (of concentrate) >2.6 mg/l.

336

Parameter Pesticide DataToxicity ClassEcotoxicity (Bird) No known toxicity. There is no evidence of allergic or other

negative reactions form researchers, manufactures, formulators or other users. EPA has waived data requirements since this is a natural plant extract and already exists in the environment.

Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Locally systemic; the increased phenolics dissipate over a period of time.

337


Natamycin Pesticide Activity FungicideChemical structureCommon nameCAS no [7681-93-8]Molecular formula C33H47NO13Molecular weight 665.7 (anhydrous)Major emission routsApplication/emission rates

Bulbs are dipped in a solution of the product

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 4.1 g/l (20-22 ºC).Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral rats 2730-4670 mg/kg


No acute toxicity. Not a skin sensitiser. Not a skin or eye irritant (rabbits)

Mammalian ADIMammalian InhalationToxicity Class WHO (a.i.) III

338

Parameter Pesticide DataEcotoxicity (Bird) No adverse effect have been observed on non-target organisms or

environmentEcotoxicity (Fish) Not toxic to fishEcotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Readily biodegradable

339


Nicotine Pesticide Activity InsecticideChemical structure

N

CH3N

HCommon nameCAS no [54-11-5] (S)- isomer; [22083-74-5] (RS)- isomers; [75202-10-7]

unstated stereochemistry; [65-30-5] (S)- isomer, sulfate Molecular formula C10H14N2 Molecular weight 162.2 Major emission routsApplication/emission rates

Foliar application


0.93 (25 °C, unionized)

Solubility in water Miscible with water below 60 ºC, forming a hydrate, and above 210 ºC. 24,000mg/l


pKa1 3.1, pKa2 8.2

Vapour pressure 5.65 Pa (25 ºC) Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity


340

Parameter Pesticide DataMammalian skin/eye toxicity

Acute percutaneous LD50 for rabbits 50 mg/kg. Toxic to man by skin contact.

Mammalian ADIMammalian Inhalation Toxic to man by inhalationToxicity Class WHO (a.i.) Ib; EPA (formulation) I Ecotoxicity (Bird) Toxic to birds. Ecotoxicity (Fish) LC50 for larval rainbow trout 4 mg/l. Fish chronic NOEC for trout

2.9mg/lEcotoxicity (Daphnia) LC50 for D. pulex 0.24 mg/l.Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Toxic to bees, but has a repellent effect. Ecotoxicity (Worms)Environ fate (Animals) Readily absorbed through the skin. Environ fate (Plants)Environ fate (Soil/Environment)

Nicotine decomposes relatively quickly under the influence of light and air. DT50 in soil 2.0 days

341


1-Octen-3-olPesticide Activity Insect attractantChemical structureCommon nameCAS no [3391-86-4]Molecular formulaMolecular weightMajor emission routsApplication/emission rates

Insect traps


Acute oral LD50 rats 340mg/kg


Acute dermal rats 3300mg/kg

Mammalian ADIMammalian Inhalation Acute inhalation LC50 rats 3.72 mg/lToxicity Class

342

Parameter Pesticide DataEcotoxicity (Bird) Minimal risk due to low exposure from the productsEcotoxicity (Fish) Exposure to fish, insects and plants is expected to be minimal

because it is attached to electric insect traps. Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

343


OxytetracyclinePesticide Activity BactericideChemical structure

O

N(CH3)2

OH

H

OH

OHH

O

OHCH3

OH

OH

CONH2

Common nameCAS no [79-57-2]; [2058-46-0] hydrochloride Molecular formula C22H24N2O9 Molecular weight 460.4 Major emission routsApplication/emission rates

Applied as foliar spray to infected plants


Considered to be non-toxic to mammalian systems

Mammalian skin/eye

344

Parameter Pesticide DatatoxicityMammalian ADIMammalian InhalationToxicity ClassEcotoxicity (Bird) Not expected to show adverse effects on non-target organisms or

on the environment.Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

345


Pelargonic acid Pesticide Activity Herbicide, plant growth regulatorChemical structure CH3(CH2)7CO2H

Common name Nonanoic acidCAS no [112-05-0] Molecular formula C9H18O2Molecular weight 158.2 Major emission routsApplication/emission rates

Application by spray at blossom


3.45

Solubility in water In water 0.032 g/l (30 °C). Acid dissociation constant (pKa)

4.95

Vapour pressure 1 x 105 mPa (20 °C) Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats and mice >5000 mg/kg.


Acute percutaneous LD50 for rats >2000 mg/kg.

Mammalian ADIMammalian Inhalation LC50 (4 h) for rats >5.29 mg/l. Toxicity Class

346

Parameter Pesticide DataEcotoxicity (Bird) Dietary LC50 for mallard ducks >5620 ppm. Ecotoxicity (Fish) LC50 (48 h) for carp 59.2 ppm. Ecotoxicity (Daphnia) LC50 (3 h) for D. similis >100 ppm. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) LD50 (contact) >25 ug/bee. Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)


347


Plant-derived porphyrin-derivatives Pesticide Activity Plant growth regulator/nematicideChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

150g/ha


Acute oral LD50 rats > 5000mg/kg


Acute dermal LD50 > 2.04ml/l. Minimal eye irritation in rabbits

Mammalian ADIMammalian InhalationToxicity Class EPA (formulation)IV

348

Parameter Pesticide DataEcotoxicity (Bird) LC50 bowhite quail >2,500mg/kgEcotoxicity (Fish) LC50 (96h) fathead minnow 879.2ppm (Agrispon)Ecotoxicity (Daphnia) LC50 53.76 ppm (Agrispon)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxicEcotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)


349


Poly-D-glucosaime Pesticide Activity Plant defence boosterChemical structureCommon name ChitosanCAS no [9012-76-4]Molecular formulaMolecular weightMajor emission routsApplication/emission rates

Tank mix ratio (1 Elexa 4:water) up to 900l/ha


Exempt from tolerance product


350

Parameter Pesticide DataEcotoxicity (Bird) Not shown adverse effects on no-target organismsEcotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Does not accumulate in environment

351


PolynactinsPesticide Activity AcaricideChemical structure

O

CH3

O

O

R4

OO

CH3

O

O

R2O

O

CH3

O

R1

O

CH3

O

R3

dinactin: R1, R3 = CH3- ; R2, R4 = C2H5-

tetranactin: R1, R2, R3, R4 = C2H5-trinactin: R1 = CH3- ; R2, R3, R4 = C2H5-

Common nameCAS no [33956-61-5] tetranactin; [7561-71-9] trinactin; [20261-85-2]

dinactin Molecular formula C44H72O12 tetranactin; C43H70O12 trinactin; C42H68O12

dinactinMolecular weight 793.1 (tetranactin); 779.0 (trinactin); 765.0 (dinactin)Major emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 0.02 g/l (25 °C).Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soil

352

Parameter Pesticide DataPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for mice >15 000 mg/kg.


Acute percutaneous LD50 for mice >10 000 mg/kg. Mild skin and eye irritant.

Mammalian ADIMammalian InhalationToxicity Class EPA (formulation) IV Ecotoxicity (Bird)Ecotoxicity (Fish) TLm for carp 0.003 ppm. Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

353


Polyoxin B Pesticide Activity FungicideChemical structure

N

NH

OR

O

HO

O

OH

C

HO2C

C

C

C

C

CH2OCONH2

OH

H2N

HO H

H

H

H

polyoxin B: R = -CH2OH

polyoxorim: R = -CO2H

NHO

Common nameCAS no polyoxins [11113-80-7], polyoxin B [19396-06-6], polyoxorim

[22976-86-9]; [146659-78-1] zinc salt

Molecular formula polyoxin B C17H25N5O13, polyoxorim C17H23N5O14Molecular weight polyoxin B 507.4, polyoxorim 521.4 Major emission routsApplication/emission rates

Polyoxorim at 200 g/ha;


polyoxin B -1.21, polyoxorim -1.45

Solubility in water polyoxin B >1 kg/l (20 ºC). polyoxorim 35.4 g/l (pH 3.5, 30 °C).Acid dissociation constant (pKa)

polyoxin B pKa1 (carboxyl) 2.65, pKa2 (amino) 7.25, pKa3 (uracil) 9.52 polyoxorim pKa1 (carboxyl) 2.66, pKa2 (carboxyl) 3.69, pKa3 (amino) 7.89, pKa4 (uracil) 10.20

Vapour pressure polyoxin B <1.33 x 105 mPa (20, 30 and 40 °C) polyoxorim <1.33 x 105 mPa (20, 30 and 40 °C)

Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half life polyoxin B Hygroscopic, and thus should be stored in tightly

closed containers under dry conditions. Stable between pH 1 and pH 8.

Persistence in airPersistence in activated sludge

354

Parameter Pesticide DataPersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

polyoxin B Acute oral LD50 for male rats 21 000, female rats 21 200, male mice 27 300, female mice 22 500 mg/kg. polyoxorimAcute oral LD50 for male and female rats >9600 mg/kg.


polyoxin B Acute percutaneous LD50 for rats >2000 mg/kg. Non-irritant to mucous membranes and skin (rats). polyoxorimAcute percutaneous LD50 for rats >750 mg/kg

Mammalian ADIMammalian Inhalation polyoxin B LC50 (6 h) for rats 10 mg/l air. Polyoxorim LC50 (4 h)

for male rats 2.44, female rats 2.17 mg/l air.Toxicity Class polyoxin B EPA (formulation) IV Ecotoxicity (Bird) Polyoxorim LD50 for mallard ducks >2150 mg/kg. Ecotoxicity (Fish) polyoxin B LC50 (96 h) for carp >100 mg/l. Japanese killifish

unaffected by 100 mg/l for 72 h. polyoxorim LC50 (96 h) for carp >100 mg/l.

Ecotoxicity (Daphnia) polyoxin B LC50 (3 h) for D. pulex >40 mg/l. polyoxorim LC50 (48 h) for D. pulex >7 mg/l.

Ecotoxicity (Algae) polyoxin B EbC50(72 h) for Selenastrum capricornutum >100 mg/l. polyoxorim EbC50 (72 h) for Selenastrum capricornutum >100 mg/l.

Ecotoxicity (Other aquatics)

polyoxin B LC50 (3 h) for Moina macrocopa >40 mg/l. polyoxorimLC50 (3 h) for Moina macrocopa >40 mg/l.

Ecotoxicity (Bees) polyoxorim LD50 (96 h) for honey bees >28.774 µg/bee. Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

polyoxin B In upland conditions at 25 °C, DT50 <2 d (two soils, o.c. 6.2%, pH 6.3, moisture 23.3% and o.c. 1.1%, pH 6.8, moisture 63.6%, respy.). In water, DT50 15 d (pH 7.0, 20 °C), 4.2 d (pH 9.0, 35 °C). polyoxorim In flooded soil at 25 °C, DT50 <10 d (two soil types, o.c. 2.5%, pH 6.0 and o.c. 9.6%, pH 6.0, respy.). In upland conditions at 25 °C, DT50 <7 d (two soil types, o.c. 0.6%, pH 6.4, moisture 10.7% and o.c. 6.2%, pH 6.3, moisture 61.9%, respy.). In water, DT50 15.4 d (pH7, 25 °C), 4.2 d (pH 9.0, 30 °C).

355


Pyrethrins Pesticide Activity Insecticide, acaricideChemical structure

R = -CH3 (chrysanthemates) or -CO2CH3 (pyrethrates)R1 = -CH=CH2 (pyrethrin) or -CH3 (cinerin) or -CH2CH3 (jasmolin)

H

CH3 CH3

C

CH HO

O HCH3

O

CH2 CC

R1

H

H

CCH3

R

Common nameCAS no pyrethrins (pyrethrum) [8003-34-7] , pyrethrins (chrysanthemates)

[121-21-1] pyrethrin I; [25402-06-6] cinerin I; [4466-14-2] jasmolin I pyrethrins (pyrethrates) - [121-29-9] pyrethrin II; [121-20-0] cinerin II; [1172-63-0] jasmolin II

Molecular formula pyrethrins (chrysanthemates) pyrethrin I: C21H28O3; cinerin I: C20H28O3; jasmolin I: C21H30O3

Molecular weight pyrethrins (chrysanthemates) pyrethrin I: 328.4; cinerin I: 316.4; jasmolin I: 330. pyrethrins (pyrethrates) pyrethrin II: 372.4; cinerin II: 360.4; jasmolin II: 374.5


Foliar spray


pyrethrins (chrysanthemates) 5.9 (pyrethrin I) pyrethrins (pyrethrates) 4.3 (pyrethrin II)

Solubility in water pyrethrins (chrysanthemates) 0.2 ppm (pyrethrin I) pyrethrins (pyrethrates) 9.0 ppm (pyrethrin II).

Acid dissociation constant (pKa)Vapour pressure pyrethrins (chrysanthemates) 2.7 mPa (pyrethrin I) pyrethrins

(pyrethrates) 5.3 x 10-2 mPa (pyrethrin II) Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in

356


pyrethrins (pyrethrum) Acute oral LD50 for male rats 2370, female rats 1030, mice 273-796 mg/kg.


pyrethrins (pyrethrum)Acute percutaneous LD50 for rats >1500, rabbits 5000 mg/kg. Slightly irritating to skin and eyes. Constituents of the flowers may cause dermatitis to sensitised individuals, but are removed during the preparation of refined extracts

Mammalian ADI pyrethrins (pyrethrum) (JMPR) 0.04 mg/kg b.w. [1999]. Mammalian Inhalation pyrethrins (pyrethrum)LC50 (4 h) for rats 3.4 mg/l. Toxicity Class pyrethrins (pyrethrum)WHO (a.i.) II; EPA (formulation) IIIEcotoxicity (Bird) pyrethrins (pyrethrum) Acute oral LD50 for mallard ducks >10 000

mg/kg.

Ecotoxicity (Fish) pyrethrins (pyrethrum) Highly toxic to fish. LC50 (96 h) (static tests) for coho salmon 39, channel catfish 114 mg/l. LC50 for bluegill sunfish 10, rainbow trout 5.2 ug/l.

Ecotoxicity (Daphnia) pyrethrins (pyrethrum) LC50 12 ug/l. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) pyrethrins (pyrethrum) Toxic to bees, but exhibits a repellent

effect. LD50 (oral) 22 ng/bee; (contact) 130-290 ng/bee.

Ecotoxicity (Worms)Environ fate (Animals) In mammals, rapidly degraded by oxidationEnviron fate (Plants)Environ fate (Soil/Environment)

In the environment, degradation, promoted by sunlight and u.v. light, begins at the alcohol group and involves the formation of numerous unknown cleavage products. DT50 in soil 12 days

357


Rotenone Pesticide Activity Insecticide/acaricideChemical structure

CH3OOCH3

OO O

C

CH3

CH2

OH

H

Common nameCAS no [83-79-4] Molecular formula C23H22O6Molecular weight 394.4 Major emission routsApplication/emission rates

Foliar and to control fish populations in fish management; applied at 0.005-0.250 ppm or


4.16

Solubility in water 0.142 ug/ml (20 °C). Acid dissociation constant (pKa)Vapour pressure <1 mPa (20 ºC) Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factor

358

Parameter Pesticide DataBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for white rats 132-1500, white mice 350 mg/kg.


Acute percutaneous LD50 for rabbits >5.0 g/kg.

Mammalian ADIMammalian Inhalation LC50 for male rats 0.0235, female rats 0.0194 mg/l. Toxicity Class WHO (a.i.) II; EPA (formulation) III, I (EC)Ecotoxicity (Bird)Ecotoxicity (Fish) LC50 (96 h) for rainbow trout 1.9, bluegill sunfish 4.9 ug/l. . Ecotoxicity (Daphnia) Acute LC50 0.0012 mg/lEcotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxic alone to bees, but very toxic in combination with

pyrethrum.

Ecotoxicity (Worms)Environ fate (Animals) In rat liver and in insects, the furan ring is enzymically opened and

cleaved, leaving behind a methoxy group. The principal metabolite is rotenonone. An alcohol has been found as a further metabolite, this being formed via oxidation of a methyl group of the isopropenyl residue

Environ fate (Plants)Environ fate (Soil/Environment)

DT50 in soil 3.0 days

359


Ryania extractsPesticide Activity InsecticideChemical structureCommon name RyanodineCAS no [15662-33-6] (formerly [1361-01-9] , [1580-06-9] , [25800-57-

1] , [15800-60-9] ) ryanodine; [94513-55-0] 9,21-dehydroryanodine;[8047-13-0] formerly ryania, now a deleted number for ryanodine

Molecular formula C25H35NO9Molecular weight 493.6Major emission routsApplication/emission rates

Applied at 10-72 kg ryania/ha (20-145 g alkaloid/ha).

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Soluble in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 rats 1200mg/kg


360

Parameter Pesticide DataMammalian ADIMammalian InhalationToxicity Class EPA (formulation) IIIEcotoxicity (Bird)Ecotoxicity (Fish) Ryania extracts are toxic to fish Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

361


SabadillaPesticide Activity InsecticideChemical structure

N

CH3

CH3

OH

OH

OHOH

OHCH3

O

OOH

H H

H

H

H

C CCH3 C

CH3

O

H

CO

CH3O

CH3O

cevadine (i) R =

veratridine (ii) R =R

Common nameCAS no [8051-02-3] (sabadilla or veratrine); [62-59-9] (i); [71-62-5] (ii) Molecular formula C32H49NO9 (i); C36H51NO11 (ii) Molecular weight 591.7 (i); 673.8 (ii) Major emission routsApplication/emission rates

Used for control of thrips in citrus and avocado, at 20-100 g total alkaloid/ha.

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 555 mg/l (veratrine); 12.5 g/l (pH 8.07)Acid dissociation constant (pKa)

9.54 (ii)

Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studies

362

Parameter Pesticide DataFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats 4000 mg/kg.


Irritant to mucous membranes, with a sternutatory action.

Toxicity Class WHO (a.i.) O Ecotoxicity (Bird)Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxic to beneficial insectsEcotoxicity (Worms)Environ fate (Animals)

Readily absorbed through the skin.

Environ fate (Plants)Environ fate (Soil/Environment)

Breaks down rapidly in air and sunlight, with little residual activity 7 dat.

363


Soft soap Pesticide Activity InsecticideChemical structureCommon nameCAS noMolecular formulaMolecular weightMajor emission routsApplication/emission rates

Foliage application 20g/l


The active components are considered as ‘Generally regarded as Safe’


364

Parameter Pesticide DataEcotoxicity (Bird)Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

It is rapidly degraded in the environment and is not expected to cause any long-term adverse effects

365


Spinosad Pesticide Activity InsecticideChemical structure

O

O

OCH3

(CH3)2NCH3

CH3CH2 HH

H H

RH

OOO

OOCH3

OCH3CH3

OCH3

spinosyn A, R = H-

spinosyn D, R = CH3-Common nameCAS no [168316-95-8]; [131929-60-7] spinosyn A; [131929-63-0]

spinosyn D Molecular formula C41H65NO10 (spinosyn A); C42H67NO10 (spinosyn D)Molecular weight 732.0 (spinosyn A); 746.0 (spinosyn DMajor emission routsApplication/emission rates

Foliar 12-150g/ha


2.8 (pH 5), 4.0 (pH 7), 5.2 (pH 9) (spinosyn A); 3.2 (pH 5), 4.5 (pH 7), 5.2 (pH 9) (spinosyn D)

Solubility in water Spinosyn A: In water 89 ppm (distilled water), 235 ppm (pH 7) (both 20 °C). Spinosyn D: In water 0.5 ppm (distilled water), 0.33 ppm (pH 7) (both 20 °C).


8.1 (spinosyn A); 7.87 (spinosyn D)

Vapour pressure 3.0 x 10-5 mPa (25 °C) (spinosyn A); 2.0 x 10-5 mPa (25 °C) (spinosyn D)

Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half life Stable to hydrolysis at pH 5 and 7; DT50 (pH 9) 200 d (spinosyn

A), 259 d (spinosyn D). Aquatic photodegradation DT50 (pH 7) 0.93 d (spinosyn A), 0.82 d (spinosyn D).

Persistence in airPersistence in activated sludge

366

Parameter Pesticide DataPersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for male rats 3783, female rats >5000 mg/kg.


Acute percutaneous LD50 for rabbits >2000 mg/kg. Non-irritating to skin; slight irritation to eyes (rabbits). Not a skin sensitiser (guinea pigs).

Mammalian ADI (JMPR) 0.02 mg/kg b.w. [2001]; (US) 0.027 mg/kg b.w.; (Japan, Australia) 0.024 mg/kg b.w.

Mammalian Inhalation LC50 (4 h) for rats >5.18 mg/l. Toxicity Class WHO (a.i.) U; EPA (formulation) IV (tech.), IV ('Tracer') Ecotoxicity (Bird) Acute oral LD50 for bobwhite quail and mallard ducks >2000

mg/kg. Acute dietary LC50 for bobwhite quail and mallard ducks >5156 ppm

Ecotoxicity (Fish) LC50 (96 h) for rainbow trout 30, bluegill sunfish 5.9, common carp 5, Japanese carp 3.5, sheepshead minnow 7.9 mg/l.

Ecotoxicity (Daphnia) EC50 (48 h) 14 ppm. Ecotoxicity (Algae) EC50 for Selenastrum capricornutum >105.5, Skeletonema

costatum 0.2, Navicula pelliculosa 0.09, Anabaena flos-aquae 8.9 ppm

Ecotoxicity (Other aquatics)

EC50 (96 h) for Eastern oyster 0.3, grass shrimp >9.76 ppm. EC50 for Lemna gibba 10.6 ppm.

Ecotoxicity (Bees) Highly toxic to honeybees when sprayed directly; topical LD50 (48 h) 0.0029 ug/bee; residues have little effect once dry.

Ecotoxicity (Worms) LC50 (14 d) for Eisenia foetida >1000 mg/kg soil.Environ fate (Animals) Spinosad is rapidly absorbed, extensively metabolised, and

eliminated mainly via urine and faeces. Metabolites include glutathione conjugates and N- and O- demethylated macrolides. No residues of spinosad were found in meat, milk or eggs

Environ fate (Plants) On plant surfaces, DT50 1.6-16 d; degradation is mainly by photolysis. No residues of spinosad or metabolites were found in cotton seed.


Rapidly degraded by u.v. light and soil microbes to naturally-occurring substances. Soil DT50 for aerobic metabolism 9.4-17.3 d (spinosyn A), 14.5 d (spinosyn D); the major metabolite from spinosyn A is spinosyn B (N-demethylation product); spinosyn D is metabolised similarly. DT50 for photodegradation on soil 8.7 d (spinosyn A), 9.4 d (spinosyn D). DT50 for anaerobic aquatic metabolism 161 d (spinosyn A), 250 d (spinosyn D). Adsorption Freundlich K for spinosyn A 5.4-323; not determined for spinosyn D (expected to be less mobile); for A metabolite (spinosyn B) 4.3-179. DT50 for field dissipation is 0.5 d, with no detectable radiolabel below 24 inches.

367


Streptomycin Pesticide Activity BactericideChemical structure

NHNH

H2NCNHOH OH

OCH2OH

HO

OH

O

OO

CHO

OH

HO

NHCNH2

CH3

CH3NH

Common nameCAS no Streptomycin [57-92-1] , streptomycin sesquisulfate [3810-74-0]

Molecular formula Streptomycin C21H39N7O12 streptomycin sesquisulfate C42H84N14O36S3

Molecular weight Streptomycin 581.6; streptomycin sesquisulfate 1457.3 Major emission routsApplication/emission rates

Foliar spray 200g a.i. per hectolitre

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water streptomycin sesquisulfate >20 g/l (pH 7, 28 ºC).Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in

368


Streptomycin Acute oral LD50 for mice >10 000 mg/kg. streptomycin sesquisulfate Acute oral LD50 for rats 9000, mice 9000, hamsters 400 mg/kg.


Streptomycin Acute percutaneous LD50 for male mice 400, female mice 325 mg/kg. May cause allergic skin reaction.

Mammalian ADIMammalian InhalationToxicity Class EPA (formulation) IVEcotoxicity (Bird) Not considered to be hazardous to non-target organisms or the

environment.Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

369


ValidamycinPesticide Activity FungicideChemical structure

NHO

OCH2OH

OHOH

OH

OH

CH2OH OH

OHHOH2C

OHOH

Common nameCAS no [37248-47-8]; [38665-10-0] validoxylamine A (metabolite)

Molecular formula C20H35NO13Molecular weight 497.5 Major emission routsApplication/emission rates

Foliar spray; 30g per hectoliter to give good control


-4.21 (calc.)

Solubility in water >610 x 103 mg/l (20 °C).Acid dissociation constant (pKa)

6.14 (20 °C)

Vapour pressure <2.6 x 10-3 mPa (25 °CHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factor

370

Parameter Pesticide DataMammalian oral toxicity

Acute oral LD50 for rats and mice >20 000 mg/kg.


Acute percutaneous LD50 for rats >5000 mg/kg. Non-irritating to skin (rabbits). Not a skin sensitiser (guinea pigs).

Mammalian ADIMammalian Inhalation LC50 (4 h) for rats >5 mg/l air. Toxicity Class WHO (a.i.) U; EPA (formulation) IV

Ecotoxicity (Bird) No effect on chickens or quail at 12.5 g/kg administered orally. Ecotoxicity (Fish) LC50 (72 h) for carp >40 mg/l. Ecotoxicity (Daphnia) LC50 (24 h) for D. pulex >40 mg/l. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals) In rats, following oral administration, cleavage to glucose and

validoxylamine A occurs.Environ fate (Plants) As for animals. Environ fate (Soil/Environment)

Stable in sunlight. Rapid microbial degradation in soil, forming validoxylamine A; DT50 x 5 h.

371

NATURAL INORGANIC PESTICIDESParameter Pesticide DataPesticide Name

Borax Pesticide Activity Herbicide, fungicide and insecticideChemical structure Na2B4O7 H2O.10 Common nameCAS no borax: [1303-96-4] (formerly [1344-90-7]); sodium tetraborate

(anhydrous): [1330-43-4]; sodium octaborate (anhydrous): [12008-41-2]; sodium metaborate: [7775-19-1]

Molecular formula B4H20Na2O17Molecular weight 381.4 Major emission routsApplication/emission rates

Spray application/insect baits

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 47.1 g/l (pH 9.3, 20 ºC). Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity


Mammalian skin/eye Acute percutaneous LD50 for rabbits >10 000 mg/kg. Not an eye

372

Parameter Pesticide Datatoxicity or skin irritant. Mammalian ADIMammalian InhalationToxicity Class WHO (a.i.) U; EPA (formulation) III Ecotoxicity (Bird)Ecotoxicity (Fish) LC50 (24 d) for rainbow trout 1320 mg/l (disodium tetraborate

decahydrate). Ecotoxicity (Daphnia) LC50 (48 h) 1170 mg/l (disodium tetraborate decahydrate). Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not hazardous to bees. Ecotoxicity (Worms)Environ fate (Animals) Not metabolised in animals. Environ fate (Plants)Environ fate (Soil/Environment)

No microbial degradation. Disappearance from soil is by washing out. Persistence in soil is <2 y, depending on rainfall and soil structure.

373


Bordeaux mixture Pesticide Activity FungicideChemical structureCommon nameCAS no [8011-63-0] Bordeaux mixture; [11125-96-5] Burgundy mixture Molecular formulaMolecular weightMajor emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats >4000 mg/kg (WP formulation).


374

Parameter Pesticide DataEcotoxicity (Bird)Ecotoxicity (Fish) Toxic to fish. Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxic to bees. Ecotoxicity (Worms)Environ fate (Animals) Copper is an essential element and is under homeostatic control in

mammals. Environ fate (Plants)Environ fate (Soil/Environment)

375


Calcium polysulphide Pesticide Activity Fungicide, insecticide, acaricideChemical structure CaSx

Common name lime sulphurCAS no [1344-81-6] Molecular formula CaSx

Molecular weightMajor emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Causes eye damage and skin irritation.

Mammalian skin/eye toxicityMammalian ADIMammalian InhalationToxicity Class EPA (formulation) I

376


377


Copper hydroxidePesticide Activity Fungicide, bactericideChemical structure Cu(OH)2Common nameCAS no [20427-59-2] Molecular formula CuH2O2 Molecular weight 97.6 Major emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 2.9 mg/l (pH 7, 25 ºC). Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats 489 mg/kg (tech.).


Acute percutaneous LD50 for rabbits >3160 mg/kg. Severely irritating and corrosive to eyes, mild skin irritant.

Mammalian ADIMammalian Inhalation LC50 > 2 mg/l air. Toxicity Class WHO (a.i.) III; EPA (formulation) III

378

Parameter Pesticide DataEcotoxicity (Bird) High concentrations of this type of copper are toxic to aquatic

organisms and may cause a significant decrease in populations of aquatic invertebrates, plants, and fish. Acute oral LD50 for bobwhite quail 3400, mallard ducks >5000 mg/kg. Dietary LD50 (8 d) for bobwhite quail and mallard ducks >10 000 ppm.

Ecotoxicity (Fish) LC50 (24 h) for rainbow trout 0.08 mg/l; (96 h) for fathead minnow 0.023, bluegill sunfish >180 mg/l.

Ecotoxicity (Daphnia) LC50 6.5 ppb. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Non-toxic to honeybees.

Ecotoxicity (Worms)Environ fate (Animals) Copper is an essential element and is under homeostatic control in

mammals. Environ fate (Plants) Plants resist copper accumulation and translocation to stems, leaves

or seeds. Most plants growing on soils containing up to 1000 ppm copper showed only slight elevation in copper content compared to plants grown in normal soils.


Copper is a basic chemical element and does not dissipate in the soil. Soluble copper ions in the soil water are rapidly complexed by organic matter, precipitated as hydroxides, or insolubilised as precipitates with sulfides, hydroxides, carbonates, or phosphates.

379


Copper Oxychloride Pesticide Activity FungicideChemical structure 3Cu(OH) 2.CuCl2

Common nameCAS noMolecular formula Cl2Cu4H6O6

Molecular weight 427.1Major emission routsApplication/emission rates

Foliar application

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water <10-5 mg/l (pH 7, 20 ºC)Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats 700-800 mg/kg


Acute percutaneous LD50 for rats >2000 mg/kg.

Mammalian ADIMammalian Inhalation LC50 (4 h) >30 mg/l.

380

Parameter Pesticide DataToxicity Class WHO (a.i.) III; EPA (formulation) IIIEcotoxicity (Bird)Ecotoxicity (Fish) LC50 (48 h) for carp 2.2 mg/l. Ecotoxicity (Daphnia) LC50 (24 h) 3.5 mg/lEcotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxic to bees. Ecotoxicity (Worms)Environ fate (Animals) Copper is an essential element and is under homeostatic control in

mammals. Environ fate (Plants) Plants resist copper accumulation and translocation to stems,

leaves or seeds. Most plants growing on soils containing up to 1000 ppm copper showed only slight elevation in copper content compared to plants grown in normal soils.


Strongly adsorbed by soils.

381


Copper OctanaotePesticide Activity Fungicide, bactericide, algicideChemical structure (CH3(CH2)6CO2)2Cu

Common nameCAS no [20543-04-8] Molecular formula C16H30CuO4Molecular weight 350.0 Major emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats >2000 mg NEU1140F formulation/kg.


Acute dermal LD50 for rats >2000 mg NEU1140F formulation/kg. No skin or eye irritation (rabbits). Not a skin sensitiser (guinea pigs).

Mammalian ADI

382

Parameter Pesticide DataMammalian Inhalation EC50 for rats >0.38 mg NEU1140F formulation/l. Toxicity Class EPA (formulation) III

Ecotoxicity (Bird)Ecotoxicity (Fish) Toxic to fishEcotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Not toxic to bees. Ecotoxicity (Worms) Not toxic to earthwormsEnviron fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

Degrades to free copper and octanoic acid; the latter is expected to degrade further microbially.

383


Copper sulphate Pesticide Activity Algicide, fungicideChemical structure CuSO4.5H2O

Common nameCAS no [7758-98-7] anhydrous; [7758-99-8] pentahydrate Molecular formula CuH10O9S (pentahydrate) Molecular weight 249.7 (pentahydrate) Major emission routsApplication/emission rates

Foliar application

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 148 (0 ºC), 230.5 (25 ºC), 335 (50 ºC), 736 (100 ºC) (all in g/kg)Acid dissociation constant (pKa)Vapour pressure Non-volatile Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 difficult to determine, since oral intake leads to nausea.


Causes severe skin irritation.

Mammalian ADIMammalian Inhalation LC50 for rats 1.48 mg/kg.

384

Parameter Pesticide DataToxicity Class WHO (a.i.) II; EPA (formulation) I Ecotoxicity (Bird) Less toxic to birds than to other animals. Lowest lethal dose for

pigeons 1000 mg/kg, for ducks 600 mg/kg. Ecotoxicity (Fish) Very toxic to fish. Ecotoxicity (Daphnia) EC50 (14 d) 2.3 mg/l; NOEC 0.10 mg/l. Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Toxic to bees. Ecotoxicity (Worms)Environ fate (Animals) Copper is an essential element and is under homeostatic control in

mammals. Environ fate (Plants) Plants resist copper accumulation and translocation to stems, leaves

or seeds. Most plants growing on soils containing up to 1000 ppm copper showed only slight elevation in copper content compared to plants grown in normal soils.


Copper is strongly adsorbed to surfaces of minerals and organic matter, hence soil mobility is very low. In water, copper ions have a strong tendency to form complexes or to be adsorbed, followed by sedimentation. In the sediment, copper reacts with organic matter or sulfides; these reactions reduce bioavailability

385


Mercuric Chloride Pesticide Activity FungicideChemical structure HgCl2

Common nameCAS no [7487-94-7] Molecular formula Cl2HgMolecular weight 271.5 Major emission routsApplication/emission rates

Application on turf

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 69 g/l (20 ºC).Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity



386

Parameter Pesticide DataToxicity Class WHO (a.i.) Ia Ecotoxicity (Bird)Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

387


Mercuric oxide Pesticide Activity Fungicide, wound protectantChemical structure HgOCommon nameCAS noMolecular formula HgOMolecular weight 216.6 Major emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 53 mg/l (25 ºC).Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

oral LD50 for rats 18 mg/kg. Extremely poisonous orally to all animals.


388

Parameter Pesticide DataToxicity Class WHO (a.i.) Ib; EPA (formulation) I Ecotoxicity (Bird)Ecotoxicity (Fish) Toxic to fish. Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

389


Mercurous chloride Pesticide Activity Fungicide, insecticideChemical structure Hg2Cl2

Common nameCAS no [10112-91-1] Hg2Cl2; [7546-30-7] HgCl Molecular formula Cl2Hg2Molecular weight 472.1 Major emission routsApplication/emission rates

Soil application

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water 2 mg/l (25 ºC).Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Acute oral LD50 for rats 210 mg/kg.

Mammalian skin/eye toxicityMammalian ADI

390

Parameter Pesticide DataMammalian InhalationToxicity Class WHO (a.i.) II; EPA (formulation) II Ecotoxicity (Bird)Ecotoxicity (Fish) Toxic to fish. Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

391


Petroleum oils Pesticide Activity Acaricide, insecticide, herbicide, adjuvantChemical structureCommon nameCAS no [64742-55-8] Molecular formulaMolecular weightMajor emission routsApplication/emission ratesProportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity

Dermal LD50 for rabbits >5000 mg/kg . Not a skin sensitiser (Buehler guinea pig test).


392

Parameter Pesticide DataToxicity Class EPA (formulation) I Ecotoxicity (Bird)Ecotoxicity (Fish) . Ecotoxicity (Daphnia)Ecotoxicity (Algae)Ecotoxicity (Other aquatics)Ecotoxicity (Bees)Ecotoxicity (Worms)Environ fate (Animals)Environ fate (Plants)Environ fate (Soil/Environment)

No risk of polynuclear aromatic compounds entering the food chain.

393


SulphurPesticide Activity Fungicide, acaricideChemical structureCommon nameCAS no [7704-34-9] Molecular formula Sx Molecular weight 32.1Major emission routsApplication/emission rates

Control of scab on apples, pears, and peaches; powdery mildews on a range of crops, including fruit (at 1.75-6.25 kg/ha), vines (1.75-4 kg/ha), hops (1.75-6.25 kg/ha), beet (1.5 kg/ha), cereals (6 kg/ha), citrus (c. 6 kg/ha), ornamentals, cucumbers, vegetables, and in forestry (1.2 kg/ha); shot-hole of stone fruit; and acarinosis of vines. Also controls mites (particularly eriophyid mites) on a range of crops

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressure 0.527 mPa (30.4 ºC) (rhombic); 8.6 mPa (59.4 ºC)Henry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicity


Mammalian skin/eye Irritating to skin, eyes, and mucous membranes; (not observed with

394

Parameter Pesticide Datatoxicity 'Kumulus DF'). Mammalian ADIMammalian InhalationToxicity Class WHO (a.i.) III (Table 5); EPA (formulation) IV

Ecotoxicity (Bird) Acute oral LC50 (8 d) for bobwhite quail >5000 ppm. Ecotoxicity (Fish) Non-toxic to fish. Ecotoxicity (Daphnia) LC50 (48 h) >1000 mg/l. Ecotoxicity (Algae) EC/LC50 >100 mg/l. Ecotoxicity (Other aquatics)Ecotoxicity (Bees) Non-toxic to bees. Ecotoxicity (Worms) LC50 (14 d) >2000 mg/l. Environ fate (Animals)Environ fate (Plants) Degradation proceeds primarily by microbial reduction in and on

plants. Environ fate (Soil/Environment)

In the environment, slight oxidation to the volatile oxides.

395


Sulphuric acidPesticide Activity Herbicide, desiccantChemical structureCommon nameCAS no [7664-93-9] Molecular formula H2O4SMolecular weight 98.08 Major emission routsApplication/emission rates

Foliar application

Proportion metabolisedIdentity of metabolitesOctanol-partition coefficient (Kow, P)Solubility in water Acid dissociation constant (pKa)Vapour pressureHenry’s Law ConstantSoil/sediment water partition coefficient (Kp)Organic carbon normalised soil/sediment water partition coefficient (Koc)Photolysis half lifeHydrolysis half lifePersistence in airPersistence in activated sludgePersistence in soilPersistence in sedimentIdentity of degradates from above studiesFate in the fieldBioconcentration factorBiota-sediment/soil accumulation factorMammalian oral toxicityMammalian skin/eye toxicityMammalian ADIMammalian InhalationToxicity Class

396


397

Appendix 3 Workshop information

AttendeesName/Affiliation Workgroup EmailJack Kay –VMD Regulatory [email protected] Cole Environment Agency

Regulatory [email protected]

David Buffin Pesticides Action Network-UK

Regulatory [email protected]

Adrian Terry– ADAS Regulatory [email protected] Osborn -CEH Regulatory [email protected] Matthiessen - CEH Regulatory [email protected] Holmes – IEH Regulatory [email protected] Hardy –CSL Regulatory

(facilitator)[email protected]

Helen Thompson - CSL Regulatory (rapporteur)

[email protected]

Gavin Lewis.-JSC Risk Assessment [email protected] Hoy PSD Risk Assessment [email protected] Chadwick – HSE Risk Assessment [email protected] Wright – FoE Risk Assessment [email protected] Lewis -Defra Risk Assessment [email protected] Boxall - Cranfield Risk Assessment [email protected] Stopes – Ecos Consultants Risk Assessment


Richard Watkins – CSL Risk Assessment (rapporteur)

[email protected]

Peter Campbell – Syngenta Scenarios [email protected] Cook - Soil Association Scenarios [email protected] Ashdown Global Herbs UK Scenarios [email protected] Hasler - NFU Scenarios [email protected] Burne – Defra Scenarios [email protected] Sylvester EcoSpray Scenarios [email protected] Paul Harrison - IEH Scenarios


Ed Stutt – IEH Scenarios (rapporteur)

[email protected]

398

AgendaFuture Environmental Effects of Non-Synthetic Chemicals

Workshop Programme25 June 2004CSL, York

09:30 – Arrival

10:00 – Introduction (Chair Tony Hardy, CSL)

Overview Defra Horizon Scanning Programme –Rupert Lewis, Defra

Agricultural Pesticides & Biocides – Helen Thompson, CSL

Human & Veterinary medicines, Phil Holmes, IEH

10:45 – Coffee

11:00 – Workgroups: Introduction- Helen Thompson, CSL

Risk assessment (Facilitator, Chris Stopes, EcoS)

Scenarios (Facilitator, Paul Harrison, IEH)

Regulatory Context (Facilitator, Tony Hardy, CSL)

13:00 – Lunch

14:00 – Report from each Workshop

15:00 – Tea

15:15 - Brain storm on knowledge gaps, future research needs and regulatory needs (Facilitator

Chris Stopes, EcoS)

16:30 – Close

399

400

401

402

403

404

405

406

407

408

409

410

411

412

413

414

415

416

417

418

419

Risk assessment and risk perceptionAre non-synthetics perceived to be as or more effective/safer than synthetics? What is driving those beliefs?

Are there potential environmental problems, direct and indirect, that may arise from increased use of non-synthetics?

Would an increase in the proportion of non-synthetic vs synthetic usage have beneficial or harmful ecological/biodiversity impacts? What is the evidence base?What other factors need to be taken into account in the uses of non-synthetic compounds?

Focusing on complementary and alternative medicines, do the public see non-synthetics as a REPLACEMENT or just a SUPPLEMENT to synthetic products?

ScenariosWhat is the current market penetration of non-synthetic chemicals in relation to agrochemical and human and veterinary medicine in the UK and Europe? What supporting data exist?

Are the UK and European markets for non-synthetics increasing? If so, is this at the expense of synthetics, and what will be the position in 5, 10 and 20 years time? Which industries/sectors are likely to increase?

What is preventing - or encouraging - wider adoption of non-synthetic products?

Will changing demographics impact on usage and acceptance of non-synthetics?

Are there particular sectors of the population for whom non-synthetics are particularly suitable or for which additional care is necessary?

420

RegulatoryShould the same environmental risk assessment process be applied to synthetic and non-synthetic chemicals – if not, what justification is there for this?

Should regulation of non-synthetics be based on comparison with equivalent synthetics?

Should increased use of non-synthetics be encouraged through the regulatory process?

Is it acceptable for less stringent safety/efficacy regulations to be imposed on non-synthetic than on synthetic chemicals? If so why?

What is preventing – what would encourage - wider registration of non-synthetic products?

What might the regulatory position be in 5, 10, 20 years time?

Brainstorming - gap filling--------------------What are the gaps in current understanding, and what research is needed?

What are the priorities for further work in this area?

What are the options for, and implications of, systems level replacement of chemical usage in current farming practice?

421

Appendix 4 Data generated from models

422

Appendix 4.1 Predicted properties and persistence of identified non-synthetic chemicals

Substance Structure MW Log KowSolubility

(mg/l)Biodegradation

(linear)Biodegradation

(non-linear)Biodegradation

(ultimate)Biodegradation

(primary Koc AOP T1/2 (d)Hydrolysis

T1/2 (d)HLC atm-m3/mole

3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester 3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester.cdx 215.3 1.51 1867 F F W D 109 4.4 >1000 5.29E-10

4-allyl-2-methoxyphenol 4-allyl-2-methocyphenol.cdx 164.2 2.73 754 F F W D-W 1120 22.9 NA 4.81E-08

6-benzylaminopurine 6-benzylaminopurine.cdx 225.25 1.23 1472 F DBF W-M D-W 1130 0.601 NA 1.24E-14

OH

O

NH

N

N NH

N

O

O

N O

423








6-isopentenylaminopurine 6-isopentenylaminopurine.cdx 217.23 0.39 16440 F F W-M D-W 90.7 3.72 NA 2.95E-16

absinthin absinthin.cdx 496.65 3.99 0.292 DBF DBF R W 5520 2.83 NA 2.74E-12

allicin allicin.cdx 162.27 1.87 1693 F F W D-W 103.3 11.5 NA NA

SS

O

N

N NH

N

NH

O

O

OO

HH

OH

HH

HHOH

H H

O

H

424








aminoethoxyvinylglycine aminoethoxyvinylglycine.cdx 160.17 -4.46 1000000 F F D-W D 10 4.84 NA 1.87E-14

avermectin B1a avermectin B1a.cdx 873.1 4.39 0.00043 DBF DBF R W-M 1288 0.25 NA 1.37E-27

avermectin B1b avermectin B1b.cdx 857.1 5.65 4.60E-05 DBF DBF R W-M 666 0.25 NA 1.56E-25

COOHN2H

O

NH2

O

O

OH

O

O

O

O

O

O

O

OO

OH

OH

H

H

H

O OO

O

O O

O

O

O

OH O

OH

OH

425








azadirachtin azadirachtin.cdx 646.69 -0.43 183.5 DBF DBF R W 10 2.1 >1000 7.40E-25

bilanofos bilanofos.cdx 323.29 -3.19 233000 F F W D 8190 1.28 NA 6.50E-23

bilobalide bilobalide.cdx 327.3 -2.4 942700 F F M D-W 10 12.98 NA 2.07E-12

O

OO

OO

OHO

OH

OO

O

O

O

N

OOH

NH2

O

O

NH2

P OOH

O

OO

O

O

O

H

OHHOH

426








blasticidin-S blasticidin-S.cdx 422.45 -4.68 1000000 F DBF W-M D 1461 1.36 NA 1.45E-34

borneol borneol.cdx 154.25 2.85 1186 DBF DBF W-M D-W 56.7 11.25 NA 2.94E-06

capsaicin capsaicin.cdx 305.42 4 4.409 F F W-M D-W 42730 1.38 NA 1.04E-13

N2H N NH

NH NH2 OO

NN

NH2

OOH

O

HOH

NH

O

O

OH

427








carvacrol carvacrol.cdx 150.22 3.52 286 F F W D-W 2188 1.29 NA 1.62E-06

carvone carvone.cdx 150.22 3.07 182.1 F F W D-W 123.7 3.2 NA 7.73E-05

cevadine cevadine.cdx 591.75 0.89 320.4 DBF DBF R M 96820 28.1 >1000 8.69E-22

OH

O

N

CH3

H

CH3

OHOH

OHOH

H

HOH

OCH

CH3

OH

HO

OC3H

HCH3

428








cineole cineole.cdx 154.25 3.13 532.4 DBF DBF W-M D-W 107 5.7 NA 1.31E-04

cinerin I cinerin I.cdx 330.5 6.38 0.029 F F W-M D-W 8837 0.365 NA 1.27E-06

cinerin II cinerin II.cdx 374.5 5.43 0.1 F F W-M D-W 2557 0.397 >1000 1.22E-09

O

H

HC3H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

CO2CH3

H

HC3H

O

CH3

H

O

O

CH3C3H

HC3H

429








citral citral.cdx 152.2 3.45 84.7 F F W D 147.7 0.5 NA 3.76E-04

dihydroazadirachtin dihydroazadirachtin.cdx 646.7 -0.43 183.5 DBF DBF R W 10 2.1 >1000 7.40E-25

dinactin dinactin.cdx 765 7.75 0.0000003 DBF DBF M D-W 4280000 1 NA 3.38E-23

O

O

OO

OO

OHO

OH

OO

O

O

O

C2H5

C2H5O

O

C3H

O

CH3

O

O

CH3

O

OO

CH3

O

CH3

O

OC3H

O

430








DMDP DMDP.cdx 191.2 -0.02 518300 F F D-W D 10 0.797 NA 7.18E-14

emamectin emamectin.cdx 901.2 4.09 0.0005 DBF DBF R W-M 2590 0.25 NA 8.60E-37

ephedrine ephedrine.cdx 165.2 0.68 71480 F F W D 82.2 1.29 NA 8.65E-11

OH

NH

NH

OH

OH

OH

OH

OCH3

OCH3

O

O O

O

O

CH3

C3H

OO

O

NH2

C3H C3H OCH3

CH3

CH3

OHH

OH

C3H

431








formaldehyde formaldehyde.cdx 30.03 0.35 57020 F F W D 1 15.8 NA 9.30E-05

gamma-aminobutyric acid gamma-aminobutyric acid.cdx 103.1 -3.6 496400 F F D-W D 3.1 3.72 NA 9.93E-11

giberellic acid giberellic acid.cdx 346.4 0.45 10090 DBF DBF W-M D-W 10 12.1 NA 1.58E-15

O

H H

O

OHN2H

OHH

HO

OH

OH O

O

432








ginkgolide a ginkgolidea.cdx 410.4 -3.62 1000000 DBF DBF M W 10 1.62 NA 3.11E-15

ginkgolide b ginkgolideb.cdx 420.46 -2.96 773800 DBF DBF R W 10 4.84 NA 1.08E-17

ginkgolide c ginkgolidec.cdx 440.4 -2.5 233100 DBF F M D-W 19.5 3.44 NA 1.74E-17

O

O

O

OH

H

OHO

OOH

O

O

O OH

H

O

OHH

OH

O

HO

O

O

O

O

OH

OH

O

HO

OH

O HOH

433








glucosamine glucosamine.cdx 179.2 -2.2 1000000 F F D-W D 10 0.9 NA 2.73E-17

glutamic acid glutamic acid.cdx 147.1 -3.83 941600 F F D-W H-D 14.5 3.13 NA 1.47E-14

hydrogen cyanide hydrogen cyanide.cdx 27.03 -0.69 95400 F F W D 2.7 8400 NA 2.42E-02

O

OH

OH NH2

OH

OH

O

OH

NH2

OH

O

N

434








indol-3-yl acetic acid indol-3-yl acetic acid.cdx 175.1 1.49 9016 F F W D 161 0.699 NA 7.27E-12

jasmolin I jasmolin I.cdx 344.5 6.87 0.009 F F W-M D-W 16300 0.365 NA 1.69E-06

jasmolin II jasmolin II.cdx 388.5 5.92 0.032 F F W-M D-W 4716 0.397 NA 1.62E-09

CH2CO2H

NH

CH2CH3

H

H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

CH2CH3

CO2CH3

H

H

O

CH3

H

O

O

CH3C3H

HC3H

435








kasugamycin kasugamycin.cdx 379.4 -5.75 1000000 F DBF D-W H-D 10 0.549 NA 1.07E-28

kinetin kinetin.cdx 215.22 0.6 11240 DBF DBF W-M D-W 612.6 0.5 NA 1.24E-14

limonene limonene.cdx 136.24 4.83 3.15 F F W D-W 1324 0.5 NA 3.80E-01

ONH2

NH

NHOH

O

O

OH

OH

OH

OH

OH

NH

NO

N NH

N

436








linalool linalool.cdx 154.3 3.38 684 DBF DBF W-M D-W 56.3 0.5 NA 4.23E-05

linalyl acetate linalyl acetate.cdx 196.3 4.39 8.2 F F W-M D-W 518 0.5 >1000 1.74E-03

maple lactone maple lactone.cdx 112.13 1.29 8501 F F W D 1 1.26 NA 3.50E-05

OH

O

O

OH

O

437








milbemectin milbemectin.cdx 528.7 5.21 113.7 DBF DBF M W 113.7 0.25 NA 3.78E-15

mildeomycin mildeomycin.cdx 514.5 -7.29 1000000 F DBF W-M D 45.2 0.25 NA 3.57E-37

natamycin natamycin.cdx 665.7 -3.67 682.9 DBF DBF W-M D 15.1 0.25 NA 2.24E-31

O

O

O

OH

H

OH

OH H

OH

OH

O

O O

OH

NH2

OH

O

O

O O

O

CH3 CH3

H

CH3

CH3

OHH

C3H

OH H

H

CO2H

CH2OH

CH2OHN

NO

OH

OHNH

NH NH2

NH

HN2H

NH2

O

O

438








nicotine nicotine.cdx 162.2 1 1000000 DBF DBF W-M D-W 2376 1.41 NA 3.00E-09

octene-3-ol octene-3-ol.cdx 128.2 2.6 1836 F F D-W D 24.8 3.18 NA 2.31E-05

oleic acid oleic acid.cdx 282.5 7.73 0.011 F F W D 11670 1.38 NA 4.48E-05

N N

OH

OH

O

439








oxytetracycline oxytetracycline.cdx 460.4 -1.39 3646 F DBF M W 97.2 0.5 NA 1.95E-29

pelargonic acid pelargonic acid.cdx 158.2 3.52 207.8 F F D-W H-D 47.3 13.1 NA 3.30E-06

p-menthane-3,8-diol p-Menthane-3,8-diol.cdx 172.3 2.29 671 F DBF W D-W 10 4.3 NA 2.62E-10

OH

OH

H

OH O

N

O

H

OH

OHOH

NH2

O

OH

O

OH

OH

440








polyoxon B polyoxon B.cdx 507.4 -7.39 1000000 F F W H-D 10 0.68 >1000 7.55E-41

polyoxorim polyoxorim.cdx 521.4 -7.75 1000000 F F D-W H 10 0.74 >1000 5.61E-45

pseudoephedrine pseudoephedrine.cdx 165.2 0.68 71480 F F W D 82.2 1.29 NA 8.65E-11

NH

OH

CH2OH

CO2H

CH2OCONH2

N

NH

O

O

O

OH OH

HNHO

HN2H

OHH

HOH

COOH

CO2H

CH2OCONH2

N

NH

O

O

O

OH OH

HNHO

HN2H

OHH

HOH

441








pyrethrin I pyrethrin I.cdx 342.5 6.74 0.012 DBF DBF M D-W 16300 0.5 >1000 1.03E-06

pyrethrin II pyrethrin II.cdx 372.5 5.33 0.13 F F W-M D-W 3027 0.5 >1000 7.39E-10

quercetin quercetin.cdx 302.2 1.48 2472 F F W D 540 0.54 NA 6.60E-21

O

OH

OH

OH

OOH

OH

CH=CH2

H

H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

O

OO

O

O

442








rotenone rotenone.cdx 394.4 4.31 1.045 F F M D-W 346000 0.5 NA 1.12E-13

ryanodine ryanodine.cdx 493.6 1.06 97.5 DBF DBF R W-M 3374 0.71 >1000 5.63E-22

santonin santonin.cdx 246.3 1.78 753 F F W-M D-W 217 1.24 NA 5.27E-08

O

OO

O

O

O

O

O

O

OOH

OHOH

CH3

OHCH3

OHO

ONH

H

OHCH3

C3H

CH3

H

443








spinosyn A spinosyn D.cdx 730 4.04 0.08 DBF DBF R W-M 2420 1 NA 1.26E-21

spinosyn D spinosyn.cdx 744 4.59 0.022 DBF DBF R W-M 4001 0.25 NA 1.97E-21

streptomycin streptomycin.cdx 581.6 -7.53 1000000 DBF DBF W-M D 10 0.25 NA 8.41E-44

NH

OH

NH

NH2NH

OH

OHN2H

NH O

O

OH

O

OO

OHOH

OH

NH

CH2CH3

N(CH3)2

OCH3 OCH3

OCH3

O

O

OO

OO

C3H CH3

H

HH

HH

H

CH3

CH2CH3

N(CH3)2

OCH3 OCH3

OCH3

O

O

OO

OOC3H CH3

H

HH

HCH3

H

CH3

444








strychnine strychnine.cdx 334.4 1.85 172.8 DBF DBF M W 258 0.5 NA 5.96E-14

terpinen-4-ol terpinen-4-ol.cdx 154.3 3.33 335.7 DBF DBF W-M D-W 61.2 0.5 NA 3.15E-06

tetranactin tetranactin.cdx 793.1 8.73 0.00000003 DBF DBF M D-W 15990000 0.97 NA 6.74E-23

N

O

O

HH

NH

OH

C2H5

C2H5

C2H5

C2H5

O

O

C3H

O O

O

CH3

O

OO

CH3

OO

OC3H

O

445








thujone thujone.cdx 152.2 2.65 407.7 DBF DBF W-M D-W 119 25 NA 7.00E-05

thymol thymol.cdx 150.2 3.52 437.4 F F W D-W 2188 1.2 NA 1.20E-06

trinactin trinactin.cdx 779 8.24 0.00000009 DBF DBF M D-W 8277000 0.99 NA 4.58E-19

OH

O

C2H5

C2H5

C2H5

O

O

C3H

O

CH3

O

O

CH3

O

OO

CH3

OO

OC3H

O

446








validamycin validamycin.cdx 497.5 -8.32 1000000 F F D H-D 439 0.3 NA 1.86E-27

veratridine veratridine.cdx 679.9 0.17 348 DBF DBF R M 11340 0.5 >1000 1.67E-25

zeatin zeatin.cdx 219.3 0.16 1237 F DBF W-M D-W 15.9 0.5 NA 1.82E-17

F = BIODEGRADES FAST

DBF = DOES NOT BIODEGRADE FAST

H = HOURS

CH2OH

CH2OH

CH2OH

O

NH

OH

OH

O

OH

OH

OH

OH

OH

OH

OCH3

OCH3

N

CH3

H

CH3

OHOH

OHOH

H

HOH

O

HCH3

OH

HO

O

N

N NH

NH

N

OH

447








D = DAYS

W = WEEKS

M = MONTHS

448

Appendix 4.2 Predicted ecotoxicity values for the identified chemicals

Substance Structure MW

Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h

EC50 Algae ChV Fish ChVDaphnid

ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester 3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester.cdx 215.3 772 59.6 na 477.5 na 4.66 3.57 31.9 na na na na na na Esters

4-allyl-2-methoxyphenol 4-allyl-2-methocyphenol.cdx 164.2 51 8.6 na 4.44 na 18.4 na na na 1.28 na 0.09 0.93 2.81 Phenols

6-benzylaminopurine 6-benzylaminopurine.cdx 225.25 1417 193 na 12.9 na 18.7 na na na na na na na 3.49 Imidazoles

OH

O

NH

N

N NH

N

O

O

N O

449


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

6-isopentenylaminopurine 6-isopentenylaminopurine.cdx 217.23 7366 642 na 38.5 na 41.7 na na na na na na na 6.42 Imidazoles

absinthin absinthin.cdx 496.65 12.3 6.5 na 6.1 na 0.56 0.45 0.65 na na na na na na Esters

allicin allicin.cdx 162.3 283 159 283 169 8.2 105 na na na 20.1 na na na 9.74neutral

organics

SS

O

N

N NH

N

NH

O

O

OO

HH

OH

HH

HHOH

H H

O

H

450


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

aminoethoxyvinylglycine aminoethoxyvinylglycine.cdx 160.17 9.10E+07 6.01E+06 na1.93E5 - 7.15E6 na

3.9E4 - 1.5E7 5.60E+06 na 6.80E+05 na na na na na

aliphatic amines (acids),

vinyl allyl ethers (acids)

avermectin B1a avermectin B1a.cdx 873.1 9.7 2.94-6.96 na 3.59-4.64 na 0.61-2.17 0.49-2.21 0.012-0.53 0.45 na na na na na

esters, vinyl allyl ethers, vinyl allyl alcohols

avermectin B1b avermectin B1b.cdx 857.1 0.76 1.45-2.52 na 0.064-0.325 na 0.132-0.246 0.11-0.29 0.004-0.047 0.064 na na na na na


COOHN2H

O

NH2

O

O

OH

O

O

O

O

O

O

O

OO

OH

OH

H

H

H

O OO

O

O O

O

O

O

OH O

OH

OH

451


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

azadirachtin azadirachtin.cdx 646.7 114000 484-4679 291 1231-83560 na 142-6203 104-3615 3870 556 na na na na na

epoxides, esters,

methacrylates,

vinyl/allyl ethers

bilanofos bilanofos.cdx 323.3 144000001870000-15500000 na 70559 na 22185 1500 na na na na na na 1500

aliphatic amines-

acid, imides-acid

bilobalide bilobalide.cdx 326.3 2980000 11159 na 2620000 na 755 534 83527 na na na na na na esters

O

OO

OO

OHO

OH

OO

O

O

O

N

OOH

NH2

O

O

NH2

P OOH

O

OO

O

O

O

H

OHHOH

452


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

blasticidin-S blasticidin-S.cdx 422.5 373000000 21900000 na684000-2660000 na

128000-58800000 21000000 na 2510000 na na na na 6164

aliphatic amines (acids),

vinyl allyl ethers (acids)

borneol borneol.cdx 154.3 37.7 18.2 37.7 20.6 1.54 13.6 2.22 na na 2.68 na na na 2.22neutral

organics

capsaicin capsaicin.cdx 305.4 7.43 2.63 na 2.5 na 2.58 na na na 0.38 na 0.047 0.29 0.82 Phenols

N2H N NH

NH NH2 OO

NN

NH2

OOH

O

HOH

NH

O

O

OH

453


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

carvacrol carvacrol.cdx 150.2 9.6 2.56 na 1.93 na 3.37 na na na 0.38 na 0.04 0.28 0.81 Phenols

carvone carvone.cdx 150.2 23.6 20.3 na 9.6 na 4.6 2.04 1.09 1.25 na na na na navinyl/allyl ketones

cevadine cevadine.cdx 591.8 7361 487-837 na 53.5 na 68.8 na na na na na na na 11.9

aliphatic amines,

methacrylates

OH

O

N

CH3

H

CH3

OHOH

OHOH

H

HOH

OCH

CH3

OH

HO

OC3H

HCH3

454


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

cineole cineole.cdx 154.3 21.5 9.9 21.5 11.5 0.97 7.66 na na na 1.53 na na na 1.47neutral

organics

cinerin I cinerin I.cdx 330.5 0.068 0.227-0.337 na 0.027-0.055 na 0.021-0.027 0.018-0.035 0.005-0.006 0.01 na na na na na

esters, vinyl/allyl ketones

cinerin II cinerin II.cdx 374.5 0.52 0.83-1.55 na 0.23-0.39 na 0.08-0.17 0.06 0.03 0.06 na na na na na


O

H

HC3H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

CO2CH3

H

HC3H

O

CH3

H

O

O

CH3C3H

HC3H

455


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

citral citral.cdx 152.2 11.2 4.47 na 1.07 na 3.94 0.91 na na na 0.11 na na na aldehydes

dihydroazadirachtin dihydroazadirachtin.cdx 646.7 114000 484-1953 291 1231-5152 na 142-6203 105-3615 3870 556 na na na na na

epoxides, esters,

methacrylates,

vinyl/allyl ethers

dinactin dinactin.cdx 765 0.01 0.1 na 0.004 na 0.01 0.008 0.0008 na na na na na na esters

O

O

OO

OO

OHO

OH

OO

O

O

O

C2H5

C2H5O

O

C3H

O

CH3

O

O

CH3

O

OO

CH3

O

CH3

O

OC3H

O

456


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

DMDP DMDP.cdx 191.2 14756 1034 na 58.8 na 55.2 na na na na na na na 7.75aliphatic amines

emamectin emamectin.cdx 901.2 18.3 3.13-10.39 na 5.94-8.97 na 0.89-3.75 0.72-3.68 0.02-0.98 na na na na na na

esters, vinyl/allyl ethers,

vinyl/allyl alcohols

ephedrine ephedrine.cdx 165.2 3132 318-1493 na 19.8-56.3 na 23.7 na na na na na na na 3.91

aliphatic amines, benzyl

alcohols

OH

NH

NH

OH

OH

OH

OH

OCH3

OCH3

O

O O

O

O

CH3

C3H

OO

O

NH2

C3H C3H OCH3

CH3

CH3

OHH

OH

C3H

457


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

formaldehyde formaldehyde.cdx 30.03 1103 8.3 na 16.1 na 430 16.6 na na na 2.7 na na na aldehydes

gamma-aminobutyric acid gamma-aminobutyric acid.cdx 103.1 10400000 1090000 na 39062 na 10660 na na na na na na na 656aliphatic

amines-acid

giberellic acid giberellic acid.cdx 346.4 10414 17.7-3538 na 70804 na 266 200 1.43-3872 na na na na na na

esters-acid, vinyl/allyl alcohols-

acid

O

H H

O

OHN2H

OHH

HO

OH

OH O

O

458


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

ginkgolide a ginkgolidea.cdx 410.4 43300000 63086 na 42400000 na 4083 2815 1080000 na na na na na na esters

ginkgolide b ginkgolideb.cdx 420.5 11800000 3.08-28663 na178000-

10900000 na1900-

3080001328-

1340003.24-

313000 17701 na na na na na

esters, vinyl/allyl ethers,


ginkgolide c ginkgolidec.cdx 440.4 4910000 17035 na 4350000 na 1149 811 136000 na na na na na na esters

O

O

O

OH

H

OHO

OOH

O

O

O OH

H

O

OHH

OH

O

HO

O

O

O

O

OH

OH

O

HO

OH

O HOH

459


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

glucosamine glucosamine.cdx 179.2 1100000 24059 na 1033 na 457 na na na na na na na 38.8aliphatic amines

glutamic acid glutamic acid.cdx 147.1 23600000 2180000 na 75932 na 19139 1117 na na na na na na naaliphatic

amines-acid

hydrogen cyanide hydrogen cyanide.cdx 27.03 7994 6767 7994 6021 95.2 3224 na na na 565 na na na 68.1neutral

organics

O

OH

OH NH2

OH

OH

O

OH

NH2

OH

O

N

460


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

indol-3-yl acetic acid indol-3-yl acetic acid.cdx 175.2 654 3917 6542 4051 166 2460 na na na 465 na na na 183neutral

organics

jasmolin I jasmolin I.cdx 344.5 0.027 0.129-0.17 na 0.01-0.02 na 0.011-0.012 0.011-0.0150.0019-0.002 0.005 na na na na na


jasmolin II jasmolin II.cdx 388.5 0.2 0.081-0.78 na 0.08-0.16 na 0.043-0.073 0.036-0.071 0.013 0.026 na na na na na

esters, methacrylat

es, vinyl/allyl ketones

CH2CO2H

NH

CH2CH3

H

H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

CH2CH3

CO2CH3

H

H

O

CH3

H

O

O

CH3C3H

HC3H

461


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

kasugamycin kasugamycin.cdx 379.4287000000

0 9530000 na 259000 na 33617 na na na na na na na 1261aliphatic amines

kinetin kinetin.cdx 215.2 4789 467 na 28.7 na 33.5 na na na na na na na 5.41 Imidazoles

limonene limonene.cdx 136.2 0.63 0.22 0.63 0.29 0.05 0.21 na na na 0.05 na na na 0.11neutral

organics

ONH2

NH

NHOH

O

O

OH

OH

OH

OH

OH

NH

NO

N NH

N

462


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

linalool linalool.cdx 154.3 13 0.58 na n na na na 0.005 na na na na na navinyl/allyl alcohols

linalyl acetate linalyl acetate.cdx 196.3 2.18 1.56 na 1.04 na 0.14 0.11 0.12 na na na na na na esters

maple lactone maple lactone.cdx 112 625 0.524-209 na 161 na 82.2 22.4 0.022-23.8 19 na na na na na

vinyl/allyl ketones, vinyl/allyl alcohols

OH

O

O

OH

O

463


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

milbemectin milbemectin.cdx 528.7 1.14 1.53-1.63 na 0.504-0.60 na 0.137-0.323 0.11-0.36 0.004-0.07 na na na na na na


mildeomycin mildeomycin.cdx 514.5 8.53E+1059.7-

1.25E+9 na2.8E+7-1.96E+9 na

2.1E+6-6.3E9 1.66E+09 1631 1.69E+08 na na na na 55878

aliphatic amines-

acid, vinyl/allyl

ethers-acid, vinyl allyl alcohols-

acid

natamycin natamycin.cdx 665.7 7.80E+07 1057-7.8E6 396942.77E+5-8.7E+5 na

39958-1.6E+7 na na na na na na na 4467

acrylates-acid,

aliphatic amines-acide,

epoxides-acid,

vinyl/allyl thers-acid

O

O

O

OH

H

OH

OH H

OH

OH

O

O O

OH

NH2

OH

O

O

O O

O

CH3 CH3

H

CH3

CH3

OHH

C3H

OH H

H

CO2H

CH2OH

CH2OHN

NO

OH

OHNH

NH NH2

NH

HN2H

NH2

O

O

464


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

nicotine nicotine.cdx 162.2 1619 195 na 12.7 na 16.9 na na na na na na na 3aliphatic amines

octene-3-ol octene-3-ol.cdx 128.2 51.7 0.52 na na na na na 0.008 na na na na na navinyl/allyl alcohols

oleic acid oleic acid.cdx 282.5 0.004 na na na na na na na na na na na na naneutral

organics

N N

OH

OH

O

465


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

oxytetracycline oxytetracycline.cdx 460.4 554000 2.86-1.88E5 na 596-71316 na 522-2.3E+5 5260 0.92-15673 7218 1352 na 18.01 878 3224

aliphatic amines, phenols, vinyl/allyl ketones, benzyl

alcohols, vinyl/allyl alcohols

pelargonic acid pelargonic acid.cdx 158.2 10.1 43.7 100.8 52 5.19 35.5 na na na 7.19 na na na 8.5neutral

organics

p-menthane-3,8-diol p-Menthane-3,8-diol.cdx 172.3 129 68.2 129 74.5 4.3 47.4 na na na 9.2 na na na 5.6neutral organics

OH

OH

H

OH O

N

O

H

OH

OHOH

NH2

O

OH

O

OH

OH

466


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

polyoxon B polyoxon B.cdx 507.4 1.00E+11 59.5-3.8E10 na3.13E7-1.4E12 na

2.3E6-4.6E6 2.90E+06

1753-1.8E10 na na na na na 59514

aliphatic amines-

acid, esters-acid,

imides-acid, vinyl/allyl alcohols-

acid

polyoxorim polyoxorim.cdx 521.4 2.20E+111.3E8-7.3E10 na

5.2E7-3.1E12 na

3.4E6-7.2E6 4.60E+06 3.60E+10 na na na na na 80662

aliphatic amines-

acid, esters-acid,

imides-acid

pseudoephedrine pseudoephedrine.cdx 165.2 3132 56.3-318 na 3.62-19.8 na 23.7 na na na na na na na 3.91

aliphatic amines, benzyl

alcohols

NH

OH

CH2OH

CO2H

CH2OCONH2

N

NH

O

O

O

OH OH

HNHO

HN2H

OHH

HOH

COOH

CO2H

CH2OCONH2

N

NH

O

O

O

OH OH

HNHO

HN2H

OHH

HOH

467


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

pyrethrin I pyrethrin I.cdx 342.5 0.034 0.15-0.21 na 0.01-0.03 na 0.014-0.015 0.012-0.018 0.002 0.006 na na na na na


pyrethrin II pyrethrin II.cdx 372.5 0.63 0.21-1.79 na 0.28-0.47 na 0.08-0.2 0.07-0.17 0.04 0.07 na na na na na

esters, methacrylat

es, vinyl/allyl ketones

quercetin quercetin.cdx 302.2 1152 1.38-426 na 26.5-426 na 110-433 45.2-79.8 0.05-44.7 37.1 14.3 na 0.62 9.97 na

phenols, vinyl/allyl ketones, vinyl/allyl ethers,


O

OH

OH

OH

OOH

OH

CH=CH2

H

H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

O

OO

O

O

468


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

rotenone rotenone.cdx 394.4 5.15 na na 1.84 na 1.13 1.13 na 0.23 na na na na navinyl/allyl

ethers

ryanodine ryanodine.cdx 493.6 4366 238 na 2810 na 18.3 13.9 172 na na na na na na esters

santonin santonin.cdx 246.3 514 48.9-223 na 149-310 na 3.86-75.2 2.98-23 20.6-21.8 18.2 na na na na na


O

OO

O

O

O

O

O

O

OOH

OHOH

CH3

OHCH3

OHO

ONH

H

OHCH3

C3H

CH3

H

469


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

spinosyn D spinosyn D.cdx 744 5.5 4.5-10.7 na 0.47-3.33 na 0.41-2.15 0.33-1.02 0.30-0.31 0.48 na na na na 0.87

aliphatic amines, esters,

vinyl/allyl ketones

Spinosyn A spinosyn.cdx 730 16.4 8.95-23.5 na 0.96-8.6 na 0.77-3.93 2.29 0.84 1.18 na na na na 1.3

aliphatic amines, esters,

vinyl/allyl ketones

streptomycin streptomycin.cdx 581.6 1.60E+11 47900-2E+8 na4.4E6-1.9E7 na

3E+5-7.9E10 3.20E+07 na na na 1.20E+07 na na 7597

aldehydes, aliphatic amines

NH

OH

NH

NH2NH

OH

OHN2H

NH O

O

OH

O

OO

OHOH

OH

NH

CH2CH3

N(CH3)2

OCH3 OCH3

OCH3

O

O

OO

OO

C3H CH3

H

HH

HH

H

CH3

CH2CH3

N(CH3)2

OCH3 OCH3

OCH3

O

O

OO

OOC3H CH3

H

HH

HCH3

H

CH3

470


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

strychnine strychnine.cdx 334.4 607 114 na 8.3-74 na 14.9-64.6 48.9 na 8.6 na na na na 3.2

aliphatic amines, vinyl allyl

ethers

terpinen-4-ol terpinen-4-ol.cdx 154.3 14.4 6.4 14.4 7.6 0.69 5.1 na na na 1.03 na na na 1.1neutral

organics

tetranactin tetranactin.cdx 793 0.0015 0.03 na 0.00047 na 0.003 0.003 0.000124 na na na na na na esters

N

O

O

HH

NH

OH

C2H5

C2H5

C2H5

C2H5

O

O

C3H

O O

O

CH3

O

OO

CH3

OO

OC3H

O

471


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

thujone thujone.cdx 152.2 55.5 27.6 55.5 31 2.11 20.1 na na na 3.95 na na na 2.93neutral

organics

thymol thymol.cdx 150.2 9.6 2.6 na 1.9 na 3.37 na na na 0.38 na 0.04 0.28 0.81 phenols

trinactin trinactin.cdx 779 0.004 0.054 na 0.0013 na 0.005 0.005 0.00031 na na na na na na esters

OH

O

C2H5

C2H5

C2H5

O

O

C3H

O

CH3

O

O

CH3

O

OO

CH3

OO

OC3H

O

472


Fish 14 d LC50

(Baseline)Fish 96 h

LC50Fish 14 d

LC50Daphnid 48

h LC50Daphnid 16

d LC50Algae 96 h


ChVFish 30 d

ChVFish 32 d

ChVFish 90 d

ChVDaphnid 21

d ChVAlgae 96 h

ChVECOSAR

class

validamycin validamycin.cdx 497.5 6.50E+11 6.4-5.5E8 na 1.10E+07 na 5.80E+05 na 382 na na na na na 11931

aliphatic amines, vinyl/allyl alcohols

veratridine veratridine.cdx 679.9 35838 981-2777 na 162-24987 na 73-162 54.4 1296 na na na na na 23.8

aliphatic amines, esters

zeatin zeatin.cdx 219.3 11792 1.16-909 na 52.9 na 52.9 na 0.12 na na na na na 7.74

vinyl/allyl alcohols,

imidazoles

CH2OH

CH2OH

CH2OH

O

NH

OH

OH

O

OH

OH

OH

OH

OH

OH

OCH3

OCH3

N

CH3

H

CH3

OHOH

OHOH

H

HOH

O

HCH3

OH

HO

O

N

N NH

NH

N

OH

473

Appendix 4.3 PBT Hazard classification criteria

Experimental

Substance Structure Use Persistence Bioaccumulation Toxicity PBT? Persistence Bioaccumulation Toxicity

3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester 3-[N-butyl-N-acetyl]-aminopropionic acid, ethyl ester.cdx p I N T N U U U

4-allyl-2-methoxyphenol 4-allyl-2-methocyphenol.cdx p I N T N U N U

6-benzylaminopurine 6-benzylaminopurine.cdx p U N H N I N H/PNT

6-isopentenylaminopurine m I N H N U U U

O

O

N O

OH

O

NH

N

N NH

N

N

N NH

N

NH

O

474

Experimental


6-isopentenylaminopurine.cdx

absinthin absinthin.cdx m P B V Y U U U

allicin allicin.cdx m I N PNT N U N T

aminoethoxyvinylglycine aminoethoxyvinylglycine.cdx p I N PNT N U N PNT

O

OO

HH

OH

HH

HHOH

H H

O

H

SS

O

COOHN2H

O

NH2

475

Experimental


avermectin B1a avermectin B1a.cdx p P B V Y I/P B V

avermectin B1b avermectin B1b.cdx p P B V Y I/P B V

azadirachtin azadirachtin.cdx p P N PNT N I N PNT

bilanofos p I N PNT N I N PNT

O

O

OH

O

O

O

O

O

O

O

OO

OH

OH

H

H

H

O OO

O

O O

O

O

O

OH O

OH

OH

O

OO

OO

OHO

OH

OO

O

O

O

N

OOH

NH2

O

O

NH2

P OOH

476

Experimental


bilanofos.cdx

bilobalide bilobalide.cdx m I N PNT N U U U

blasticidin-S blasticidin-S.cdx p U N PNT N I N H/PNT

borneol m U N H N U N U

O

OO

O

O

O

H

OHHOH

N2H N NH

NH NH2 OO

NN

NH2

OOH

O

HOH

477

Experimental


borneol.cdx

capsaicin capsaicin.cdx p I B T N U U U

carvacrol carvacrol.cdx m I N T N U N U

carvone p I N T N U U U

NH

O

O

OH

OH

O

478

Experimental


carvone.cdx

cevadine cevadine.cdx m P N H N U U U

cineole cineole.cdx m U N T N U N <PNT

N

CH3

H

CH3

OHOH

OHOH

H

HOH

OCH

CH3

OH

HO

OC3H

HCH3

O

479

Experimental


cinerin I cinerin I.cdx p I B V N I B U

cinerin II cinerin II.cdx p I B V N I U U

citral citral.cdx m I N T N U N U

dihydroazadirachtin p P N PNT N U U H

H

HC3H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

CO2CH3

H

HC3H

O

CH3

H

O

O

CH3C3H

HC3H

O

O

OO

OO

OHO

OH

OO

O

O

O

480

Experimental


dihydroazadirachtin.cdx

dinactin dinactin.cdx m U B V P U U U

DMDP DMDP.cdx p I N H N U U U

C2H5

C2H5O

O

C3H

O

CH3

O

O

CH3

O

OO

CH3

O

CH3

O

OC3H

O

NH

OH

OH

OH

OH

481

Experimental


emamectin emamectin.cdx p P B V Y I B V

ephedrine ephedrine.cdx m I N H N U N U

formaldehyde formaldehyde.cdx p I N T N U N U

gamma-aminobutyric acid gamma-aminobutyric acid.cdx p I N PNT N U U U

OCH3

OCH3

O

O O

O

O

CH3

C3H

OO

O

NH2

C3H C3H OCH3

CH3

CH3

OHH

OH

C3H

OH

NH

O

H H

O

OHN2H

482

Experimental


giberellic acid giberellic acid.cdx p U N H N I N PNT

ginkgolide a ginkgolidea.cdx m P N PNT N U U U

ginkgolide b ginkgolideb.cdx m P N PNT N U U U

OHH

HO

OH

OH O

O

O

O

O

OH

H

OHO

OOH

O

O

O OH

H

O

OHH

OH

O

HO

483

Experimental


ginkgolide c ginkgolidec.cdx m U N PNT N U U U

glucosamine glucosamine.cdx m I N PNT N U N U

glutamic acid glutamic acid.cdx p I N PNT N U U U

hydrogen cyanide hydrogen cyanide.cdx p I N PNT N U U U

O

O

O

O

OH

OH

O

HO

OH

O HOH

O

OH

OH NH2

OH

OH

O

OH

NH2

OH

O

N

484

Experimental


indol-3-yl acetic acid indol-3-yl acetic acid.cdx p I N PNT N I N U

jasmolin I jasmolin I.cdx m I B V N U U U

jasmolin II jasmolin II.cdx m I B V N U U U

CH2CO2H

NH

CH2CH3

H

H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

CH2CH3

CO2CH3

H

H

O

CH3

H

O

O

CH3C3H

HC3H

485

Experimental


kasugamycin kasugamycin.cdx p U N PNT N U N H/PNT

kinetin kinetin.cdx m P N H N U U U

limonene limonene.cdx m I B V N U U U

ONH2

NH

NHOH

O

O

OH

OH

OH

OH

OH

NH

NO

N NH

N

486

Experimental


linalool linalool.cdx m U N V N U N U

linalyl acetate linalyl acetate.cdx m I B V N U U U

maple lactone maple lactone.cdx p I N V N U U U

milbemectin p P B V Y P B V

OH

O

O

OH

O

O

O

O O

O

CH3 CH3

H

CH3

CH3

OHH

C3H

OH H

H

487

Experimental


milbemectin.cdx

mildeomycin mildeomycin.cdx p U N PNT N U U T

natamycin natamycin.cdx p U N PNT N I U U

CO2H

CH2OH

CH2OHN

NO

OH

OHNH

NH NH2

NH

HN2H

NH2

O

O

O

O

O

OH

H

OH

OH H

OH

OH

O

O O

OH

NH2

OH

488

Experimental


nicotine nicotine.cdx p U N H N I N V

octene-3-ol octene-3-ol.cdx p I N V N U U U

oleic acid oleic acid.cdx p I B V N U U H

oxytetracycline oxytetracycline.cdx p U N PNT N U N U

N N

OH

OH

O

OH

OH

H

OH O

N

O

H

OH

OHOH

NH2

O

489

Experimental


pelargonic acid pelargonic acid.cdx p I N H N I N H

p-menthane-3,8-diol p-Menthane-3,8-diol.cdx p U N H N U U U

polyoxon B polyoxon B.cdx p I N PNT N I N H/PNT

OH

O

OH

OH

CH2OH

CO2H

CH2OCONH2

N

NH

O

O

O

OH OH

HNHO

HN2H

OHH

HOH

490

Experimental


polyoxorim polyoxorim.cdx p I N PNT N U U U

pseudoephedrine pseudoephedrine.cdx m I N T N U N U

pyrethrin I pyrethrin I.cdx p P B V Y I B V

COOH

CO2H

CH2OCONH2

N

NH

O

O

O

OH OH

HNHO

HN2H

OHH

HOH

NH

OH

CH=CH2

H

H

O

CH3

H

O

O

CH3C3H

HC3H

C3H

491

Experimental


pyrethrin II pyrethrin II.cdx p I B V N I U V

quercetin quercetin.cdx m I N T N P N U

rotenone rotenone.cdx p I B T N I B V

O

OO

O

O

O

OH

OH

OH

OOH

OH

O

OO

O

O

O

492

Experimental


ryanodine ryanodine.cdx p P N H N U U U

santonin santonin.cdx m I N T N U N U

spinosyn A spinosyn D.cdx p P B V Y I B T

OOH

OHOH

CH3

OHCH3

OHO

ONH

H

OHCH3

C3H

CH3

H

O

O

O

CH2CH3

N(CH3)2

OCH3 OCH3

OCH3

O

O

OO

OOC3H CH3

H

HH

HCH3

H

CH3

493

Experimental


spinosyn D spinosyn.cdx p P B V Y I B T

streptomycin streptomycin.cdx p U N PNT N U U U

strychnine strychnine.cdx p P N T N U B U

CH2CH3

N(CH3)2

OCH3 OCH3

OCH3

O

O

OO

OO

C3H CH3

H

HH

HH

H

CH3

NH

OH

NH

NH2NH

OH

OHN2H

NH O

O

OH

O

OO

OHOH

OH

NH

N

O

O

HH

NH

494

Experimental


terpinen-4-ol terpinen-4-ol.cdx m U N T N U N U

tetranactin tetranactin.cdx m U B V P U U U

thujone thujone.cdx m U N H N U N U

OH

C2H5

C2H5

C2H5

C2H5

O

O

C3H

O O

O

CH3

O

OO

CH3

OO

OC3H

O

O

495

Experimental


thymol thymol.cdx m I N T N U N T

trinactin trinactin.cdx m U B V P U U U

validamycin validamycin.cdx p I N PNT N U U H/PNT

OH

C2H5

C2H5

C2H5

O

O

C3H

O

CH3

O

O

CH3

O

OO

CH3

OO

OC3H

O

CH2OH

CH2OH

CH2OH

O

NH

OH

OH

O

OH

OH

OH

OH

OH

OH

496

Experimental


veratridine veratridine.cdx m P N H N U U U

zeatin zeatin.cdx m U N T N U U U

Medicines only Linear Non-linear Primary

Persistence Impersistent 48.2759 14 48.27586207F F H, D OR D-W

Persistent 20.6897 6 20.68965517DBF DBF W, W-M or M

Unkown 31.0345 9 31.03448276Any other combination

Bioaccumulation Non-bioaccumulative 72.4138 21 72.4137931

Bioaccumulative 27.5862 8 27.5862069Bioaccumulative Non-bioaccumulative

Toxicity Practically non-toxic 17.2414 5 17.24137931Log Kow > or = 4 Log Kow <4

Harmful 20.6897 6 20.68965517

Toxic 31.0345 9 31.03448276Actute EC/LC50 for fish, daphnids or algae

Very toxic 31.0345 9 31.03448276>100 mg/l

PBT Non-PBT 86.2069 25 86.2068965510-100 mg/l

PPBT 10.3448 3 10.344827591-10 mg/l

OCH3

OCH3

N

CH3

H

CH3

OHOH

OHOH

H

HOH

O

HCH3

OH

HO

O

N

N NH

NH

N

OH

497

Experimental


PBT 3.44828 1 3.448275862<1 mg/l

Pesticides onlyNon-synthetic

Persistence Impersistent 52.2727 23 52.27272727Persistence Impersistent 38 14 50.6667

Persistent 25 11 25 Persistent 18 23 24

Unknown 22.7273 10 22.72727273 Unknown 19 0 25.3333

Bioaccumulation Non-bioaccumulative 70.4545 31 70.45454545Bioaccumlation

Non-bioaccumulative 53 26 70.6667

Bioaccumulative 29.5455 13 29.54545455Bioaccumulative 22 11 29.3333

Toxicity PNT 38.6364 17 38.63636364Toxicity PNT 24 0 32

Harmful 15.9091 7 15.90909091 Harmful 14 1 18.6667

Toxic 15.9091 7 15.90909091 Toxic 15 8 20

Very toxic 29.5455 13 29.54545455 Very toxic 22 28 29.3333

PBT Non PBT 84.0909 37 84.09090909PBT Non PBT 65 29 86.6667

PBT 15.9091 7 15.90909091 Possibe PBT 7 0 9.33333

1 PBT 3 8 4

498

Appendix 4.4 Additional CAM data


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50

Algae 96 h EC50 Algae ChV Fish ChV

Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

1,2-dimercaptocyclopentane 1,2-dimercaptocyclopentane.cdx 134.3 77.6 1.06NA 0.049NA NA NA NA NA NA NA NA NA NAThiols (mercaptans)

2-vinyl-4H-1,3-dithiin 2-vinyl-4H-1,3-dithiin.cdx 144.3 24.06 11.26 24.06 12.96 1.05 8.6NA NA NA 1.72NA NA NA 1.57neutral organics

3-decyne 3-decyne.cdx 138.3 1.14 0.42 1.14 0.54 0.084 0.39NA NA NA 0.081NA NA NA 0.17neutral organics

SH

SH

S

S

499


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

3-octanol 3-octanol.cdx 130.2 40.4 19.9 40.4 22.4 1.58 14.6NA NA NA 2.88NA NA NA 2.23neutral organics

ascaridole ascaridole.cdx 168.2 9.69 0.42NA 1.48NA NA NA NA NA NA NA NA NA NA peroxy acids

a-thujene a-thujene.cdx 136.2 0.98 0.36 0.98 0.46 0.073 0.33NA NA NA 0.07NA NA NA 0.15neutral organics

camphene camphene.cdx 136.2 1.64 0.62 1.64 0.79 0.11 0.56NA NA NA 0.12NA NA NA 0.22neutral organics

OH

OO

500


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

caryophyllene caryophyllene oxide.cdx 220.4 0.44 1.12 1.07 0.25NA NA NA NA NA NA NA NA NA NA epoxides

chrysanthenol chrysanthenol.cdx 121.9 47.3 23.2 47.3 26.2 1.85 17.1NA NA NA 3.37NA NA NA 2.6neutral organics

chrysanthenyl acetate chrysanthenyl acetate.cdx 178.3 24.8 11.5 24.8 13.3 1.12 8.85NA NA NA 1.77NA NA NA 1.7neutral organics

diallyl disulfide 146.3 8.6 3.71 8.6 4.42 0.45 3.02NA NA NA 0.61NA NA NA 0.75neutral organics

OH

H

OH

C

CH3

O

SS

501


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

diallyl disulfide.cdx

diallyl trisulfide diallyl trisulfide.cdx 178.3 10.5 4.52 10.5 5.39 0.55 3.69NA NA NA 0.75NA NA NA 0.91neutral organics

geraniol geraniol.cdx 154.3 10.86 0.57NA NA NA NA NA 0.005NA NA NA NA NA NAvinyl/allyl alcohols

geranyl acetate geranyl acetate.cdx 196.3 1.82 1.4NA 0.86 0.12 0.1 0.1NA NA NA NA NA NA esters

S

S S

OH

O

O

502


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

germacrene d germacrene d.cdx 204.4 0.012 0.003 0.012 0.005 0.002 0.004NA NA NA 0.00089NA NA NA 0.007neutral organics

isobutyl isothiocyanate isobutyl isothiocyanate.cdx 115.2 37.99NA NA NA NA NA NA NA NA NA NA NA NA NA not available

isorhamnetin isorhamnetin.cdx 316.3 660.21.40-516.2 NA 20.9-386 NA 68.8-246 30.1-51.7 0.04-58.1 9.1-48.1 9.7NA 0.47NA 21.6

phenols, vinyl/allyl ketones, vinyl allyl ethers

kaempferol 286.2 416.51.25-353 NA 15.99-246 NA 45.7-154 20.7-35.1 0.03-36.5 6.2-31.5 6.77NA 0.36NA 15.1

phenols, vinyl/allyl ketones, vinyl allyl ethers

N S

O

O

OH

OH

OH

OC3H

OH

OOH

O

OH

OH

OH

503


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

kaempferol.cdx

linalol linalol.cdx 154.3 13 0.58NA NA NA NA NA 0.005NA NA NA NA NA NAvinyl/allyl alcohols

methyl allyl sulfide methyl allyl sulfide.cdx 88.2 191.6 110 192 116 5.35 71.4NA NA NA 13.6NA NA NA 6.2neutral organics

methyl allyl trisulfide methyl allyl trisulfide.cdx 152.3 48.3 23.8 48.3 26.8 1.88 17.4NA NA NA 3.44NA NA NA 2.64neutral organics

OH

S

SS

S

504


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

myrcene myrcene.cdx 136.2 0.57 0.2 0.57 0.26 0.05 0.19NA NA NA 0.04NA NA NA 0.1neutral organics

nerol nerol.cdx 154.3 10.86 0.57NA NA NA NA NA 0.005NA NA NA NA NA NAvinyl/allyl alcohols

neryl acetate neryl acetate.cdx 196.3 1.82 1.4NA 0.86NA 0.12 0.1 0.1NA NA NA NA NA NA esters

ocimene 136.2 0.67 0.24 0.67 0.31 0.05 0.23NA NA NA 0.05NA NA NA 0.11neutral organics

OH

O

O

505


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

ocimene.cdx

p-cymene p-cymene.cdx 134.2 3.27 1.3 3.27 1.6 0.2 1.13NA NA NA 0.23NA NA NA 0.36neutral organics

pinene pinene.cdx 136.2 1.93 0.74 1.93 0.93 0.13 0.66NA NA NA 0.14NA NA NA 0.25neutral organics

propyl allyl disulfide propyl allyl disulfide.cdx 148.3 6.58 2.77 6.58 3.43 0.36 2.31NA NA NA 0.47NA NA NA 0.62neutral organics

H

SS

506


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

sabinene sabinene.cdx 136.2 0.83 0.3 0.83 0.39 0.06 0.28NA NA NA 0.06NA NA NA 0.13neutral organics

terpinolene terpinolene.cdx 136.2 0.57 0.2 0.57 0.26 0.05 0.19NA NA NA 0.04NA NA NA 0.1neutral organics

terpinyl acetate terpinyl acetate.cdx 196.3 2.4 1.66NA 1.15NA 0.14 0.12 0.13NA NA NA NA NA NA esters

OO

507


Fish 14 d LC50

(Baseline)

Fish 96 h LC50

Fish 14 d LC50

Daphnid 48 h LC50

Daphnid 16 d LC50


Daphnid ChV

Fish 30 d ChV

Fish 32 d ChV

Fish 90 d ChV

Daphnid 21 d ChV

Algae 96 h ChV

ECOSAR class

valencene valencene.cdx 204.4 0.05 0.014 0.05 0.02 0.007 0.016NA NA NA 0.004NA NA NA 0.019neutral organics

508

Documents

Complementary and Alternative Medicines for Human and ...sciencesearch.defra.gov.uk/Document.aspx?Document=SD0312... · Web viewThis report concerns one group of non-synthetic chemicals,