Pesticide Toxicology

Course Information

Bettina FrancisEntomology Department

bfrancis@uiuc.edu333-5136

677 Morrill Hall

Barry R. PittendrighEntomology Department

pittendr@illinois.edu 244-0567

518 Morrill Hall

Course Topics

• Classes of Pesticides– Insecticides– Herbicides– Fungicides– Repellants and Miscellaneous Pesticides

• Aspects (of each class and/or selected compounds in each class)– Synthesis– Mechanism of action– Disposition

• Major effect on nontarget organisms– Mammalian toxicity– Ecotoxicity– Genetic toxicology– Reproductive and developmental endpoints

Pesticide Nomenclature

• Structural formula• Generic name• Brand name• CAS number

DDT = dichlorodiphenyltrichloroethane

Verbal Equivalent of Chemical Structure: p,p’-DDT

• 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane• 1,1’-(2,2,2-trichloroethylidene) bis (4-chlorobenzene);• 1,1,1-trichloro-2,2bis(p-chlorophenyl) ethane;• 1,1,1-trichloro-2,2di (4-chlorophenyl) ethane;• 1,1,1-trichloro-2,2di(p-chlorophenyl) ethane;• 1,1-bis(4chlorophenyl)2,2,2-trichlorethane;• 1,1-bis(p-chlorophenyl)2,2,2-trichlorethane;• 2,2,2-trichloro1,1bis (4-chlorophenyl) ethane;• 2,2-bis(p-chlorophenyl)1,1,1-trichloroethane.

CAS # 50-29-3

Parathion-ethyl

O,O-diethyl O-p-nitrophenylphosphorothionateCAS # 56-38-2

Some Brand Names for Parathion-ethyl

• Alkron, Alleron, Corothion, Folidol, Folidol E-65, Genthion, Geofos, Lethalaire, Niran, Orthophos, Paradusto, Paraspra, Penncap-E, Thiophos (USSR), Vapophos, Aphemite, Bladan, Bladan F, Corthione, Danthion, DNTP, DPP, E 605, Ecatox, Ekatox, Etilon, Fosferno, Fosfex, Fosfive, Fosova, Fostern, Genthion, Kolphos, Kypthion, Lirothion, Murfos, Niran, Nitrostigmine, Nourithion, Oleofos 20, Oleoparathion, parathene, Parawet, Pestox plus, Phoskil, Phosphemol, Phosphenol, Phosphostigmine, Rhodiatox, SNP, Soprathion, Stathion, Strathion, Sulphos, Tiofos, Thiophos, Tox 47, Vapophos

1. Insecticides

• Major classes– Organochlorines– Organophosphates– Pyrethroids

• Minor classes– Plant-derived– Growth regulators– Metal-containing

Organochlorine Insecticides

This nomenclature is ambiguous!– More historical than chemical– All contain carbon & chlorine– Other elements present are hydrogen, oxygen – No sulfur, nitrogen, or halogens other than chlorine

• Primarily insecticides– 3 subcategories

• DDT and its analogs• Cyclodienes

– E.g.: dieldrin, chlordane, mirex• Other

– E.g.: hexachlorobenzene, lindane

DDT• 1st of the modern insecticides• Category: organochlorine• History

– Synthesized by Zeidler, 1874– Insecticidal activity recognized by P Muller, 1939– Critical discovery for Allies in WW II– Production: 300,000 lbs/month by late 1943 – DDT and typhus

• 50% mortality before modern antibiotics• In WW I, 25% of Serbian soldiers died of typhus• Naples typhus epidemic began 12/43

– 305 cases in week of 1/11/44– 1,300,000 civilians dusted with DDT at 2 delousing stations– 155 cases week of 1/18– Estimated 30,000 lives saved

– Production: 1,700,000 lbs/month by summer 1944

DDT as icon

• 1950s: – Use and abuse

• 1960s:– Rachel Carson’s Silent Spring

• 1970s– Banning DDT: laws vs science

• 1980s - present– Second-guessing the past

p,p’-DDT

Synthesis of DDT

• Bayer condensation– 2 molecules of chlorobenzene + 1 molecule of chloral hydrate– Stir vigorously– Add excess of concentrated sulfuric acid– Reaction is exothermic– Must be cooled to prevent excess formation of 4-

chlorobenzenesulfonic acid• N.B.: 1-step chemical syntheses are cheap & efficient

Synthesis of DDT from chlorobenzene and chloral hydrate:

Physical Characteristics of DDT

• Technical product– Mixture of isomers

• up to 30% is o,p’-isomer– Waxy solid of indefinite melting point

• p,p’-DDT – White, crystalline solid– Melting point 108.5oC– Vapor pressure 1.9 x 10-7 mm Hg at 20oC– Solubility:

• Readily soluble in most aromatic and chlorinated solvents• In acetone: 580 mg/ml (= 580,000 ppm)• In benzene: 780 mg/ml• In water 0.0012 ppm (= 1.2 ppb)

DDT analogs: DDD

• Originally developed by IG Farben• Marketed by Rohm & Haas, 1945• Rapidly metabolized by vertebrates to DDMU• Major product of the anaerobic degradation of DDT

– DDT ---> DDD takes ca 12 weeks– After 6 months, <1% of DDT has been converted to CO2

• Bioaccumulative: used at Clear Lake, CA

DDT Analogs: DDE

• Metabolite of DDT• Not a commercial product• Human dietary exposure:

– 1981 US consumption estimated at 0.001 ppm/day• Air, water levels very low. • May be released from hazrdous waste sites. • Bioaccumulative.• Major cause of avian eggshell thinning

DDT Analogs: Dicofol

• Acaricide (miticide)• Still in use• Minor degradative byproduct of DDT• May contain DDT as impurity

DDT Analogs: Methoxychlor

• Less persistent than DDT• Narrower range of insecticidal activity• Greater estrogenic activity• Still in commercial use but production is decreasing

– Banned in US in 2003– Banned in EU in 2002

• Considerably more estrogenic than DDT– Considered a serious endocrine disruptor

DDMU