SUPPLEMENT Monoalkylglycol Dialkyl Acid Esters …1620 L Street, NW Suite 1200, Washington, DC 20036 (Main) 202-331-0651 (Fax) 202-331-0088 (Email) [email protected] (Website)

SUPPLEMENT

Monoalkylglycol Dialkyl Acid Esters

Plant-Derived Protein and Peptide Ingredients

CIR EXPERT PANEL MEETING DECEMBER 5-6, 2016

__________________________________________________________________________________________ 1620 L Street, NW Suite 1200, Washington, DC 20036

(Main) 202-331-0651 (Fax) 202-331-0088 (Email) [email protected] (Website) www.cir-safety.org

Commitment & Credibility since 1976

MEMORANDUM

To: CIR Expert Panel and Liaisons

From: Lillian C. Becker, M.S. Scientific Analyst and Writer

Date:

November 22, 2016

Subject: Wave 2 Data for the Safety Assessment of Monoalkylglycol Dialkyl Acid Esters as Used in Cosmetics

Additional data were submitted by the Personal Care Products Council. This data includes: Glycol Distearate - summary results [magdae122016Data1]:

• Oral metabolism • Dermal irritation using rabbits (not irritating) • Dermal sensitization in guinea pigs (not sensitizing) • Oral repeated dose toxicity (NOAEL=200 mg/kg/d for 2 years) • Ames test (negative) • Mammalian cell gene mutation assay (negative) • Prenatal developmental toxicity in rats (NOAEL maternal toxicity and teratogenicity >900 mg/kg/d)

Glycol Distearate - summary results of related chemicals/mixtures for read-across [magdae122016Data1]:

• Toxicokinetics • Acute dermal toxicity in rats • Acute eye irritation in rabbits • Repeated dose oral toxicity in rats • Chromosomal aberration test • Three-generation reproduction study in rats

Neopentyl Glycol Dicaprate - summary data [magdae122016Data2]:

• Acute oral toxicity (no deaths at 2000 mg/kg) • HET-CAM ocular irritation assay (no ocular irritation at 50%) • Ames test (negative) • Human patch test (not irritation at 100%, 3 mg)

Distributed for Comment Only -- Do Not Cite or Quote

mailto:[email protected]

http://www.cir-safety.org/



Diethylpentanediol Dineopentanoate - material safety data sheet summary results [magdae122016Data3] • Chemical/physical properties • Oral acute toxicity for rats (>2500 mg/kg) • Skin irritation in rabbits (mild irritant) • Skin irritation in humans (non-irritant) • Eye irritation in rabbits (minimal irritant) • Guinea pig maximization test (non-sensitizer) • Ames test (negative)




Personal Care Products CouncilCommitted to Safety,Quality & Innovation

Memorandum

TO:

FROM:

DATE:

SUBJECT:

Anonymous.

Lillian Gill, D.P.A.Director - COSMETIC INGREDIENT REVIEW (CIR)

Beth A. Jonas, Ph.D.Industry Liaison to the CIR Expert Panel

November 11,2016

Information on Glycol Distearate (SLR release dated: October 6, 2016)

2016. Glycol Distearate: Summary’ of product data with reference to toxicology.

1620 L Street, N.W., Suite 1200 Washington, D.C. 20036 202.331.1770 202.331.1969 (fax) www.personalcarecouncil.org


(RjccI D’sfcq-cjc

Zusammenfassung der Produktdaten zurToxikologie und Okologie* /Summary of Product Data with Reference to Toxicology

Prufung Methode Ergebnis DatumTest Method Result Date

Grundlegende Toxikokinetik OECD TODIbOX Metaboliten identifiziert ) 2010Basic toxicokinetics vi .1 metabolites identified

Akute orale Toxizitat (Ratte) OECD 401 LD5: > 2,000 mg/kg bw 06/1 982Acute oral toxicity (rat)

Akute dermale Toxizitat (Ratte) OECD 402 LDc > 2,000 mg/kg bw 2)

Acute dermal toxicity (rat)

Haucverträglichkeit (Kaninchen) OECD 404 nicht reizend 03/i 976Acute dermal irritation / corrosion (rabbit) not irritant

Schleimhautvertraglichkeit (Kaninchen) OECD 405 nicht reizend 3) 06/1 ggAcute Eye Irritation/Corrosion (rabbit) not irritating

Hautsensibilisierung (Meerschweinchen) OECD 406 nicht sensibilisierend 1984Skin Sensitisation (guinea pig) not sensitising

Toxizität bei wiederholter Verabreichung (Ratte) OECD 452 NOAEL 200 mg/kg bw/day (nominal)2 years repeated dose toxicity (rat) 4)

Gentoxizitat (Ames) OECD 471 Kein Effekt OS/i 991Gene Toxicity (Ames) negative

5ugetierzellen—Mutationsversuch OECD 476 Kein Effekt 08/2010Mammalian cell gene mutation assay negative

Chromosomale Aberration OECD 474 Nicht clastogen 2)

Chromosomal aberration not clastogenic

3—Generationen Reproduktionstoxizitat (Ratte) OECD 416 NOAEL P. Fl and F2 , 1,000 mg/kg3 generation reproduction toxicity study (rat) bw/day’)

Pranatale Entwicklungstoxizitat (Ratte) OECD 4i4 NOAEL maternal toxicity and 05/1997Prenatal Developmental Toxicity Study (rat) teratogenicity > 900 mg/kg bw/day

Absorption/Desorption QSAR Estimated Koc: 8245 L/kg (EthyleneGlycol Monopalmitate)Estimated Koc: 7,583 L/kg (EthyleneGlycol Monostearate)

2010

—- 1/2 Revisionsdatum / Revision Date 07.03.2016

Personal Care Druckdatum / Print Date 06.04.2016


U Potential metabolites were calculated by OECD toolbox 1.1.02. Here, the liver metabolism simulator

provided the products of the beta oxidation of fatty acids as potential metabolites. Ethylene glycol

distearate is cleaved into ethylene glycol monostearate and stearic acid which Is processed by beta

oxidation to acetic acid. The ethylene glycol monostearate is further processed to Octadecanoic acid

carboxymethyl ester which is then also processed to acetic acid by beta oxidation. Additionally, these

substances were partly calculated as potential metabolites in the Cl tract simulator but no substances

were calculated in the skin metabolism simulator or for hydrolysis.

Read—Across from fatty acid, Cl 8 and Cl 8 unsaturated, epoxidized, ester with ethylene glycol

3) Read—Across from ethylene glycol palmitostearate and stearate

4) Read—Across from ethylene glycol

5) Read—Across from 1 ,2—propanedioldiester of Octanoic/Decanoic acid (70:30)

—--.----i

Zusammenfassung der Produktdaten zurToxikologie und Okologie* /Summary of Product Data with Reference to Toxicology and Ecology*

* Full Robust Study Summaries can be checked under the ECHA Registered Substance

website and with the following registration number: 01—2119489414—31

2/2 Revisionsdatum / Revision Date

Druckdatum / Print Date

-

07.03.2016

06.04.2016 H[FE!


Personal Care Products Council

Memorandum

Committed to Safety,Quality & Innovation

TO:

FROM:

DATE:

Lillian Gill. D.P.A.Director - COSMETIC INGREDIENT REVIEW (CIR)


November 11,2016

SUBJECT: Information on Neopentyl Glycol Dicaprate (SLR release dated: October 6, 2016)

Anonymous. 2016. Information concerning Neopentvl Glycol Dicaprate product.

1620 L Street, N.W., Suite 1200 I Washington, D.C. 20036 202.331.1710 I 202.331.1969 (fax) www.personalcarecouncil.org


November 11,2016

Information concerning Neopentyl Giveol Dicaprate product

Impurity (Residue on ignition)The average of residue on ignition of the Neopentyl Glycol Dicaprate product is 0.05%.

Single dose toxicity (Oral)LD5O> 2500 mg/kg (rat, as is, 2004, OECD 423)

Test Animals: 6 Sprague-Dawley CD strain rats (6 females)Test Material: Neopentyl Glycol Dicaprate, as isMethod: A group of 3 fasted females was treated with the test material at a

dose level of 2000 mg/kg bodnveight. This was followed by afurther group of 3 fasted females at the same dose level.The test material was administered orally undiluted as supplied.Clinical signs and bodyweight development were monitored duringthe study. All animals were subjected to gross necropsy.

Mortality: There were no deaths.Clinical Observation: There were no signs of systemic toxicity.Bodvweight: All animals showed expected gains in bodyweight over the study

period.Necropsy: No abnormalities were noted at necropsy.

Ocular Irritation (HET-CAM)Non-irritant (25% active solution in corn oil, 2004)

Test System: Fertile, white Leghorn hen’s eggs incubated for 10 daysTest Concentration: Neopentyl Glycol Dicaprate product was diluted in corn oil to

25%.Dosing Procedure: 0.3 mL of the test sample was administered to the chorio-allantoic

membrane (CAM). 20 seconds later, the test sample was rinsedfrom CAM with 5 mL of physiological saline.

Results: The average of scores was 1.50.Conclusion: Under the conditions of this test, the results indicate that the

Neopentyl Glycol Dicaprate product, at 50%, would have

practically no ocular irritation potential in viva.

Genotoxicitv (Ames test)Non-mutagenic (as is, 2006, OECD 471)

Methods: Salmonella lyphimurium strains 1A1535, TA1537, TA98, TA100 and

Escherichia coli strain WP2uvrK were treated with the test material (Neopentyl Glycol


Dicaprate product, as is) using the Ames plate incorporation method at 5 dose levels, intriplicate, both with and without the addition of a rat liver homogenate metabolizingsystem (10% liver S9 in standard co-factors). The dose range for the rage-finding testwas determined in a preliminary toxicity’ assay and was 50 to 5000 pg/plate. Theexperiment was repeated on a separate day using the same dose range as the rage-finding

test, fresh cultures of the bacterial strains and fresh test material formulations.

Results: The vehicle (acetone) control plates gave counts of revertant colonies within thenormal range. All of the positive control chemicals used in the test induced markedincreases in the frequency of revertant colonies, both with or without metabolic activation.Thus, the sensitivity of the assay and the efficacy of the S9-mix were validated.

The lest material caused no visible reduclion in the growth of the baclerial backgroundlawn at any dose level. The test material was, therefore, tested up to the maximumrecommended dose level of 5000 jig/plate. A precipitate (oily in appearance) wasobsen’ed at and above 1500 jig/plate, this did not prevent the scoring of revertant

colonies.

No significant increases in the frequency of revertant colonies were recorded for any of

the bacterial strains, with any dose of the test material, either with or without metabolic

activation.

Dermal Inilation - HumanNon-irritant (Japanese, 23 subjects, as is. 2003)

The irritation potential of Neopentyl Glycol Dicaprate product was investigated in a 24

hours human patch test (occlusive) of 23 subjects (21 females and 2 males). The backs

of the subjects were treated with the lest sample (Neopentyl Glycol Dicaprate, as is) using

Finn Chambers on Scanpor Tape. AboiLt 3 mg of the test sample was applied. At

30-60 minutes and 24 hours after removal of the patch, any subjects did not have

erythema.


Personal Care Products Council

M cm 01-and urn

Committed to Safety,Quality & Innovation

TO:

FROM:

DATE:

Lillian Gill. D.P.A.Director - COSMETIC INGREDIENT REVIEW (CIR)


November 21, 2016

SUBJECT: Information on Diethylpentanediol Dineopentanoate (SLR release dated: October6, 2016)

Anonymous. 2004. Material safety data sheet: Diethylpentanediol Dineopentanoate.

1620 L Street, N.W., Suite 1200 Washington, D.C. 20036 202.331.1770 202.331.1969 (fax) www.penonalcarecouncil.org


MATERIAL SAFETY DATA SHEET

in accordance with Directive 9311121EC

1. IDENTIFICATION OF THE SUBSTANCE/PREPARATION AND OF THE COMPANY IProductname: DeFh.ttpenI-aflCdcI Oinecprn4qnct-(-e

Company:

2. COMPOSITIONIINFORMATION ON INGREDIENTS IChemical characterizationof the substance:

Name Concentration CAS No Symbol R-Phrases

2,4-Diethyl-1,5-Pentanediol 100% 762268-78-0 none noneDineopentan oate

3. HAZARDS IDENTIFICATION INot classified according to pertinent EC regulation.

FIRST-AID MEASURES ISkin contactWash off with plenty of water and soap.

Eye contact:Wash out with water. Get medical attention if any sensations persist.

Ingestion:Give a plenty of water and call medical care. If fallen unconscious or convulsion,get medicalattention immediately.

Inhalation:Bring person to fresh air after inhalation. Symptomatic treatment. In case of indisposition, seekimmediately medical advice.

General information;There is no antidote known.

PAGE 115DATE Sop.220D4


Product name:

5. FIRE-FIGHTING MEASURES

Suitable extinguishing media:Powder fire extinguisher, C02 foaming fire extinguisherwater extinguishing media appropriate tosurrounding materials.

Special exposure hazards arising from combustion products, resulting gases:Carbonoxides, Nitrogenoxides and other gases.

Special fire fighting procedures:Cool down the containers with water spray. Untrained personel should be removed to a safe place.

Special protective equipment for fire-fighters:Wear full protective clothing and self-contained breathing apparatus.

6. ACCIDENTAL RELEASE MEASURES

Personal precautions:Wear proper protective equipment (suitable gloves and safety goggles).

Environmental precautions:Avoid the release to aquatic systems.

Methods for cleaning up:Transfer product to suitably labelled containers for disposal at an approved sue. Absorb liquid spillageonto inert material(e.g. sand). Residues and small spillages may be washed away with water anddetergent

7. HANDLING AND STORAGE

7.1 Handling

Technical measures:Good local ventilation is recommended.Precautions for handling:The usual precautions for safe handling of chemicals have to be followed. Avoid skin and eye contact.

7.2 Storage

Technical measures I conditions for safe storage:Stored in closed containers in appropriate storage rooms. Avoid substance residues on the conlainers.

Incompatible materials:None known.Other information:For quality reasons, to be stored under cool, dry and dark conditions.

PAGE 215DATE. sep 2,2004


Product name:

EXPOSURE CONTROLSIPERSONAL PROTECTION

Technical measures:Good local ventilation is recommended.

Personal protection:Hand protection:Wear suitable gloves.Eye protection:Safety glassesHygiene measures:Wash hands with soap and water after handling

• PHYSICAL AND CHEMICAL PROPERTIES

method:

Appearance: liquid(20°C)Colour: colorless to very pale yellowOdour: A faint characteristic odorpH-Value: no data availableBoiling point: >200°CRelative density: no data availableVapor pressure: no data availableSolubility in water: InsolublePartition coefficient: no data availableFlammability: Not applicableFlash point: 162°CSelf-ignition temperature: no data availableExplosive properties: Not to be expected

10. STABILITY AND REACTIVITY IStability:Stable at 25°C under storage conditions.

Conditions to avoid:Direct sunbeams

Substances to avoid:Strong oxidizers

Hazardous materials produced upon decomposition:Thermal decomposition will evolve irritant vapors and COx.

PAGE: 3/5DATE. Sep 2, 2O4


Product name:

Iii. TOXICOLOGICAL INFORMATION

Acute toxicity:Oral LD5O, rat: >2500mg/kg (OECD 423)

Skin-irritation:Mild irritant (rabbit, OECD 404)Non irritation (Human closed patch , 24hrs)

Eye-irritation:Minimal irritant (rabbit! OECD 405)

Sensitization:Non—sensitiser (guinea pig, maximization study, OECD 406)

Repeatedllong-term exposure:no data available NOEL = no data available

Mutagen icityicarcinogenicity:Ames test: NegativeCytogenetic test: no data available

12. ECOLOGICAL INFORMATION

Degradability:Ready Biodegradability: no data available

Inhibition of Microbial Activity (3h): lCso: no data availableNDEC: no data available

Ecotoxicity:Acute fish toxicity (Rainbow trout): EC5O (95 h): > no data available

Acute daphnia toxicity (Daphnia magna): EC5O (48 h): > no data available

Acute algal toxicity:- with Scenedesmus subspicatus: EC5O (72 h): > no data available

PAGE 415DATE Sep.2. 20c4


Product name:

113. DISPOSAL CONSIDERATIONS

Product:Incinerate solid waste in a controlled and accepted incinerator (Code EEC 660) and treat waste waterby controlled discharge to a waste water treatment plant (Code EEC 641). Local legislation has to beobserved -

Empty Packaging:Recycling is highly recommended.

114. TRANSPORT INFORMATION INot classified according to pertinent transport regulations

15. REGULATORY INFORMATION I

16. OTHER INFORMATION I

The information of this Material- Safety- Data- Sheet has been established based on the available datawhich are believed to be correct. These information should serve as basis to ensure the safety inhandling, storing, transporting and disposal of this product. No guarantee or warranty of any kindexpressed or implied is made with respect to the information contained herein.

PAGE: 515DATE: Seo 22004




Commitment & Credibility since 1976

Memorandum

To: CIR Expert Panel Members and Liaisons From: Christina L. Burnett, Senior Scientific Writer/Analyst Date: November 22, 2016 Subject: Wave 2 – Plant-Derived Protein and Peptide Ingredients Attached for the Panel’s review are data from the Council on plant-derived proteins and peptides (pltpep122016_w2_data1.pdf and pltpep122016_w2_data2.pdf). The data include average molecular weights, composition, and hydrolysis methods for Hydrolyzed Brazil Nut Protein, Hydrolyzed Cottonseed Protein, Hydrolyzed Pea Protein, and Hydrolyzed Vegetable Protein, as well as in vitro ocular and dermal studies and genotoxicity studies for Hydrolyzed Pea Protein and Hydrolyzed Vegetable Protein. For convenience, the data have been summarized in Table 1 and Table 2 below. Table 1. Average molecular weights, composition, and hydrolysis methods for hydrolyzed plant proteins.

Ingredient Average Molecular Weight (Da)

Hydrolysis Method Composition

Hydrolyzed Brazil Nut Protein (10.0% to 25.0%)

1000 Enzyme >50% water, 0-7% ash (mostly sodium chloride), 0.5% sodium benzoate, and 0.3% potassium sorbate

Hydrolyzed Cottonseed Protein (10.0% to 25.0%)

1700 Enzyme >50% water, 0-6% ash (mostly sodium chloride), 0.2% disodium EDTA, 1% phenoxyethanol, and 0.3% potassium sorbate

Hydrolyzed Pea Protein (10.0% to 25.0%)

1500 Enzyme >50% water, 0-6% ash (mostly sodium chloride), 1% phenoxyethanol, and 0.3% potassium sorbate

Hydrolyzed Vegetable Protein (Source: Potato; 10.0% to 25.0%)

750 Enzyme >50% water, 0-6.5% ash (mostly sodium chloride), 0.2% disodium EDTA, 1% phenoxyethanol, and 0.3% potassium sorbate

Hydrolyzed Vegetable Protein (Source: Potato; 7.5% to 15.0%)

100,000 Alkali >50% water, 0-2.5% ash (mostly sodium chloride), 0.1% ethylhexylglycerin, 0.9% phenoxyethanol, 0.5% sodium benzoate, and 0.3% potassium sorbate






Table 2. In vitro dermal and ocular irritation studies and genotoxicity studies for hydrolyzed plant proteins

Ingredient Concentration Test Method Result Dermal Irritation

Hydrolyzed Pea Protein 10% to 25% in a solution of >50% water

Episkin™ reconstructed human epidermis model

predicted to be non-irritating

Hydrolyzed Vegetable Protein (Source: Potato; molecular weight ~100,000 Da)

10% in a solution of 87% water and 1% sodium chloride



Ocular Irritation Hydrolyzed Pea Protein 19% in a solution of 75% water and

4.5% sodium chloride SkinEthic reconstructed human corneal epithelial model (10 min exposure)



7.5% to 15% in a solution of >50% water



Genotoxicity Hydrolyzed Pea Protein 19% in solution of 75% water and

4.5% sodium chloride; 50-5000 µg/plate

Ames test in Salmonella typhimurium strains TA1535, TA1537, TA98, TA100 and Escherichia coli strain WP2uvrA, with and without S9 metabolic activation

not mutagenic


10.9% in solution of 87% water Ames test in S. typhimurium strains TA1535, TA1537, TA98, TA100 and E. coli strain WP2uvrA, with and without S9 metabolic activation

not mutagenic








































































































































































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SUPPLEMENT Monoalkylglycol Dialkyl Acid Esters …1620 L Street, NW Suite 1200, Washington, DC 20036 (Main) 202-331-0651 (Fax) 202-331-0088 (Email) [email protected] (Website)