wave 2 alkyl phosphates alkyl polysiloxanes … phosphates alkyl polysiloxanes ceramides citrus peel...

WAVE 2 Alkyl Phosphates Alkyl Polysiloxanes Ceramides Citrus Peel Oils Hydroquinone & p-Hydroxyanisole Methylisothiazolinone Styrene and Vinyl-type Styrene Copolymers CIR EXPERT PANEL MEETING JUNE 9-10, 2014

__________________________________________________________________________________________ 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 Members and Liaisons From: Monice M. Fiume MMF Assistant Director/Senior Scientific Analyst Date: May 30, 2014 Subject: Wave 2 – Safety Assessment of Alkyl Phosphates as Used in Cosmetics Enclosed are the Wave 2 data for the Draft Report on the Safety Assessment of Alkyl Phosphates as Used in Cosmetics. An updated data profile is provided. The following were received since the draft final amended report was prepared for the March meeting, and are included with this submission:

1. EViC-CEBA. 1995. Acute dermal irritation/corrosion of substance Mexoryl SY (dimyristyl phosphate). a. The undiluted test material, applied under a semi-occlusive patch for 4 h, was classified as not

irritating to rabbit skin.

2. EViC-CEBA. 1997. Evaluation du potential sensibilisant cutané de al substance Mexoryl SY (dimyristyl phosphate).

a. This document needs to be translated.

3. EViC-CEBA. 1996. Acute eye irritation/corrosion of the substance Mexoryl SY (dimyristyl phosphate). a. The undiluted test maerial was classified as not irritating to rabbit eyes.

4. EViC-CEBA. 1996. Acute oral toxicity in the rat of the substance Mexoryl SY (dimyristyl phosphate).

a. The LD50 in the rat was >2 g/kg, which was the highest dose tested.

Distributed for Comment Only -- Do Not Cite or Quote

CIR Expert Panel Meeting Data Supplement

mailto:[email protected]

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

Alkyl Phosphates* – June 2014, includes Wave 2 – Monice Fiume Re

port

ed U

se

Met

hod

of M

fg

Toxi

coki

neti

cs

Der

mal

Pe

netr

atio

n An

imal

Tox

–

Acut

e, D

erm

al

Anim

al T

ox –

Ac

ute,

Ora

l

Anim

al T

ox,

Acut

e, In

hal.

Anim

al T

ox –

Rp

td D

ose,

D

erm

Anim

al T

ox,

Rptd

Dos

e, O

ral

Anim

al T

ox –

Rp

td D

ose,

Inha

l

Repr

o/D

ev T

ox

Geno

tox

Carc

inio

geni

city

Phot

ocar

d

Der

mal

Irr/

Sens

Phot

otox

icit

y

Ocu

lar

Irri

tati

on

Potassium Cetyl Phosphate X

gene

ral i

nfo

avai

labl

e fo

r alk

yl p

hosp

hate

s

X X X X X Potassium C9-15 Alkyl Phosphate X X X X Potassium C11-15 Alkyl Phosphate Potassium C12-13 Alkyl Phosphate X Potassium C12-14 Alkyl Phosphate Potassium Lauryl Phosphate X X X X X X X C8-10 Alkyl Ethyl Phosphate C9-15 Alkyl Phosphate X C20-22 Alkyl Phosphate X X X X X X X X Castor Oil Phosphate X Cetearyl Phosphate Cetyl Phosphate X X X X Disodium Lauryl Phosphate Disodium Oleyl Phosphate Lauryl Phosphate X X Myristyl Phosphate X Octyldecyl Phosphate Oleyl Ethyl Phosphate Oleyl Phosphate X X X X X X X Sodium Lauryl Phosphate X X Stearyl Phosphate X Dicetyl Phosphate X X X X X Dimyristyl Phosphate X X in

French X

Dioleyl Phosphate X Tricetyl Phosphate Trilauryl Phosphate Trioleyl Phosphate X Tristearyl Phosphate *“X” indicates that data were available in a category for the ingredient



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



Memorandum

To: CIR Expert Panel Members and Liaisons From: Ivan Boyer, Senior Toxicologist Date: May 30, 2014 Subject: Draft Safety Assessment on Ceramides Data received through the Council from a supplier include a tabulated summary of the results for Ceramide 2 of an unpublished (1) acute rabbit dermal irritation study, (2) acute rabbit ocular irritation study, (3) Guinea pig skin sensitization study, and (4) bacterial reverse-mutation assay. The information provided includes a description and list of physicochemical properties of Ceramide 2. Also submitted by the Council is a list of 3 safety assessment study reports on “pseudo-ceramide SLE66” conducted by Morita et al. in 2009. The supplier uses the data from these studies to read across from SLE66 to Ceramide 2. Copies of the 3 papers are available to the Panel. As noted previously, CIR staff considered data on a pseudo-ceramides (such as that found in an approved medical device to serve a skin “barrier repair” function) are not relevant for the assessment of safety for the use of ceramide ingredients in cosmetics. The Panel should determine whether they disagree. An additional submission from the Council presented the reports of several studies on Ceramide 2, including an acute rat oral toxicity test, (2) skin irritation test conducted with human subjects, (3) rabbit eye irritation test, and (4) bacterial mutation assay. The information provided included a UV/VIS absorption spectrum study. Also noteworthy, the INCI nomenclature for ceramides has been described as archaic and flawed,1 and is under review by the INCI Committee:

“The term “ceramide” may only be used in an International Nomenclature of Cosmetic Ingredients (INCI name to designate CERs identified in a 1985 article by Wertz et al.2 Newer more sensitive analytical techniques have identified additional classes of CERs and CER species in human skin that were not identified by Wertz et al. However, because of the archaic INCI nomenclature, these CERs may not be called “ceramides” on ingredient labels. Until the INCI nomenclature is updated to reflect our current understanding of CERs, identifying CERs as ingredients may continue to be challenging.”1

The Panel should consider whether the data submitted is sufficient to complete a safety assessment for this ingredient group and, if not, specify the remaining data needs.

References

1. Meckfessel MH and Brandt S. The structure, function, and importance of ceramides in skin and their use as therapeutic agents in skin-care products. J.Am.Acad.Dermatol. 3-19-2014.





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


2. Wertz PW, Miethke MC, Long SA, Strauss JS, and Downing DT. The composition of the ceramides from human stratum corneum and from comedones. J.Invest Dermatol. 1985;84(5):410-412.





Morita O, Knapp JF, Tamaki Y, Stump DG, Nemec MD, Yoshimura K. Safety studies

of pseudo-ceramide SLE66. Part 3: Effects on embryo/fetal development in rats.

Food Chem Toxicol. 2009 Apr;47(4):681-6. doi: 10.1016/j.fct.2008.11.023. Epub

2008 Nov 25. PubMed PMID: 19059452.

Morita O, Ogura R, Hayashi K, Okuda M, Yoshimura K. Safety studies of

Pseudo-Ceramide SLE66. Part 2: Metabolism, cytotoxicity and genotoxicity. Food

Chem Toxicol. 2009 Jan 28. [Epub ahead of print] PubMed PMID: 19709590.

Morita O, Ogura R, Hayashi K, Okuda M, Yoshimura K. Safety studies of

pseudo-ceramide SLE66: acute and short-term toxicity. Food Chem Toxicol. 2009

Apr;47(4):669-73. doi: 10.1016/j.fct.2008.11.022. Epub 2008 Nov 21. PubMed PMID:

19059301.






Memorandum

To: CIR Expert Panel Members and Liaisons From: Christina L. Burnett, Senior Scientific Writer/Analyst Date: May 30, 2014 Subject: Wave 2 for Citrus Peel Oils A few members of the CIR Science and Support Committee have submitted published papers for the Panel’s consideration regarding the constituents of citrus essential oils. The essential oils in these papers are of various citrus varieties, are not described by INCI name, and are not described as cosmetic grade. It is unclear from these papers if the oils studied are manufactured (extracted) in manners similar to those used in cosmetic products. From previous reviews of botanical ingredients, we have learned that the extraction method and solvents involved in the extraction are important when analyzing constituents in a botanical ingredient and determining overall safety.

Does the Panel find the constituent data in these papers useful in their determination of the safety of citrus peel oils or does the Panel feel that constituent and manufacturing/extraction data specific to cosmetic-grade citrus peel oils needs to be provided before the information can be included in the report? Unfortunately, we do not have copyright permission to distribute most of the papers that the CIR Science and Support Committee members have submitted. However, we will have a copy of these papers for your review at the Panel meeting.

Additionally, we have received information from RIFM on which citrus peel oils are in the RIFM database. Based on comparison with the International Cosmetic Dictionary and Handbook’s descriptions of these ingredients, it appears that Citrus Aurantium Bergamia (Bergamot) Peel Oil and Citrus Paradisi (Grapefruit) Peel Oil function solely as fragrance ingredients and fall under RIFM’s purview, and, thus, should be removed from the CIR safety assessment.





CITRUS PEEL OILS IN THE DATABASE

Name CAS Number

RIFM Number

EINECS Number

Botanical Name

Bergamot oil expressed 8007-75-8 1091-G2.5 289-612-9; 296-429-8 Registered as CAS #’s 89957-91-5;

92704-01-3

Citrus aurantium L. bergamia Risso et Poiteau (Rutaceae)

Bergamot oil, furocoumarin free

68648-33-9 1091-G2.33 289-612-9 Registered as CAS # 89957-91-5

Citrus aurantium L. bergamia (Risso) Wright & Arn.

(Rutaceae) Citron oil 68991-25-3 7067-G2.5 N/A Citrus medica L. (Rutaceae) Grapefruit oil cold pressed 8016-20-4 189-G2.5 289-904-6

Registered as CAS # 90045-43-5 Citrus paradisi Macf.

(Rutaceae) Kaffir lime extract 91771-50-5 5580-G2.5 294-942-1 Citrus hystrix DC (Rutaceae) Lemon oil 8008-56-8 136-G2.5 284-515-8

Registered as CAS # 84929-31-7 Citrus limon (L.) Burm. f.

(Rutaceae) Lime oil, expressed 8008-26-2 171-G2.5 290-010-3; 297-608-3

Registered as CAS #’s 90063-52-8; 93685-55-3

Citrus aurantifolia (Christman) Swingle (Rutaceae)

Mandarin oil 8008-31-9 250-G2.5 284-521-0 Registered as CAS # 84929-38-4

Citrus reticulata Blanco (Rutaceae)

Orange oil, bitter 68916-04-1 233-G2.5 277-143-2 Registered as CAS # 72968-50-4

Citrus aurantium L. spp. Amara Link (Rutaceae)

Orange oil, sweet 8008-57-9 192-G2.5 232-433-8 Registered as CAS # 8028-48-6

Citrus sinensis (L.) Osbeck (Rutaceae)

Tangelo oil 8016-85-1 6607-G2.5 297-672-2 Registered as CAS # 93686-22-7

Citrus reticulata Blanco "Tangelo" Swingle

Tangerine oil 8016-85-1 6607-G2.5 297-672-2 Registered as CAS # 93686-22-7

Citrus reticulata Blanco (Rutaceae)

Yuzu oil 233683-84-6 6514-G2.5 N/A Citrus junos Siebold ex. Tanaka ichangensis × reticulata var. austera) (reticulata var. austera)

(Rutaceae)



Ahmad, MM, Salim-ur-Rehman, Iqbal, Z, Anjum, FM, Sultan, JI. Genetic Variability To Essential Oil Composition In Four Citrus Fruit Species. Pak. J. Bot., 38(2): 319-324, 2006. Dugo P, Mondello L, Dugo L, Stancanelli R, Dugo G. LC-MS for the identification of oxygen heterocyclic compounds in citrus essential oils. J Pharm Biomed Anal. 2000 Dec;24(1):147-54. PubMed PMID: 11108548.

Kamal G. M, Anwar F, Hussain A. I, Sarri N, Ashraf M. Y. Yield and chemical composition of Citrus essential oils as affected by drying pretreatment of peels. International Food Research Journal 01/2011; 18(4):1275-1282.

Lota ML, de Rocca Serra D, Tomi F, Jacquemond C, Casanova J. Volatilecomponents of peel and leaf oils of lemon and lime species. J Agric Food Chem. 2002 Feb 13;50(4):796-805. PubMed PMID: 11829647.

Qiao Y, Xie BJ, Zhang Y, Zhang Y, Fan G, Yao XL, Pan SY. Characterization of aroma active compounds in fruit juice and peel oil of Jinchen sweet orange fruit (Citrus sinensis (L.) Osbeck) by GC-MS and GC-O. Molecules. 2008 Jun 12;13(6):1333-44. PubMed PMID: 18596659.

Sarrou E, Chatzopoulou P, Dimassi-Theriou K, Therios I. Volatile constituents and antioxidant activity of peel, flowers and leaf oils of Citrus aurantium L. growing in Greece. Molecules. 2013 Sep 2;18(9):10639-47. doi:10.3390/molecules180910639. PubMed PMID: 24002139.

Husain Shahnaz Sultana, Mohammed Ali, Bibhu Prasad Panda. Influence of volatile constituents of fruit peels of Citrus reticulata Blanco on clinically isolated pathogenic microorganisms under In–vitro. Asian Pacific Journal of Tropical Biomedicine 2(3):S1299–S1302. DOI:10.1016/S2221-1691(12)60404-3

Neng-guo Tao, Yue-jin Liu, Miao-ling Zhang . Chemical composition and antimicrobial activities of essential oil from the peel of bingtang sweet orange (Citrus sinensis Osbeck). College of Chemical Engineering, Xiangtan University, Xiangtan 411105, China. International Journal of Food Science & Technology (Impact Factor: 1.24). 06/2009; 44(7):1281 - 1285. DOI:10.1111/j.1365-2621.2009.01947.x



http://www.researchgate.net/researcher/2007777973_Kamal_G_M

http://www.researchgate.net/researcher/9993259_Anwar_F

http://www.researchgate.net/researcher/33402384_Hussain_A_I

http://www.researchgate.net/researcher/2007766841_Sarri_N

http://www.researchgate.net/researcher/8823164_Ashraf_M_Y

http://www.researchgate.net/journal/1985-4668_International_Food_Research_Journal

http://www.researchgate.net/researcher/2034379063_Husain_Shahnaz_Sultana

http://www.researchgate.net/researcher/2034415745_Mohammed_Ali

http://www.researchgate.net/researcher/2034404032_Bibhu_Prasad_Panda

http://www.researchgate.net/researcher/22416682_Neng-guo_Tao

http://www.researchgate.net/researcher/2025868421_Yue-jin_Liu

http://www.researchgate.net/researcher/22416681_Miao-ling_Zhang

http://www.researchgate.net/journal/1365-2621_International_Journal_of_Food_Science_Technology

http://www.researchgate.net/journal/1365-2621_International_Journal_of_Food_Science_Technology

__________________________________________________________________________________________ 1101 17th Street, NW Suite 412, Washington, DC 20036



MEMORANDOM

To: CIR Expert Panel and Liaisons

From: Lillian C. Becker, M.S. Scientific Analyst and Writer Ivan J. Boyer, Ph.D. Senior Toxicologist

Date: May 30, 2014

Subject: Additional Data for the Use of UV Light to Cure Nail Gels in the Hydroquinone and p-Hydroxyanisole Safety Assessments

Attached is a letter from the Nail Manufacturers Council on Safety (NMC) of the Professional Beauty Association. NMC suggests that the Panel give extra consideration to the Dowdy and Sayre (2013; attached to the email notification) assessment of safety of UV nail lamps because the authors based their finding on the guidelines of the American National Standards Institute/Illuminating Engineering Society of North America (ANSI/IESNA) and the American Conference of Governmental Industrial Hygienists (ACGIH). Below is a summary, with analysis, of these guidelines and how they were applied in the Dowdy and Sayre (2013) study.

CIR has purchased the ANSI/IESNA report and the current ACGIH report (2010, 1992 is no longer available), and they will be available at the June Panel meeting for examination, as will the ANSI/IESNA RP-27.3 Errata (mentioned below).

NMC’s letter states their opinion that the Dowdy and Sayre (2013) study, which concluded that there is low-to-moderate risk associated with the use of any one of 6 selected UV nail lamps as intended, is the most rigorous of the relevant studies reported, to date. This is because the Dowdy and Sayre (2013) study estimated “permissible daily exposure” durations ranging from about 30 to 300 minutes for the selected lamps using the ANSI/IESNA RP-27.1-05 and ACGIH guidelines for calculating permissible occupational exposures to UV light.

The “three-part ANSI/IESNA standard” referred to in NMC’s letter includes (1) measurement techniques, (2) general requirements, and (3) risk group classification and labeling. The third part of the standard indicates that lamps and lamp systems that emit optical radiation in excess of the exposure limits should contain label(s) that include “an abbreviated statement that specifies the Risk Group (assuming an applicable Risk Group classification exists).” The RP-27.3 Errata, which is available online (https://www.ies.org/PDF/Erratas/RP_27.3_Errata.pdf), indicates that the upper S(λ)-corrected actinic UV emission limit (Es) defining the “exempt” risk group is 0.1 µW/cm2; the limit for risk group 1 (RG-1; low risk) is 0.3 µW/cm2 and the limit for risk group 2 (RG-2; moderate risk) is 3.0 µW/cm2. These limits appear to be the basis





https://www.ies.org/PDF/Erratas/RP_27.3_Errata.pdf



for the categorization of the 6 selected UV nail lamps into risk groups (ES for 1 lamp = 0.2 µW/cm2, ES for the other 5 lamps range from 0.4 to 1.7 µW/cm2) by Darby and Sayre (2013).

Dowdy and Sayre (2013) noted that the cumulative exposure times estimated from the usage-instruction pamphlets supplied with several of the UV nail lamps studied would be substantially lower than the calculated “permissible daily exposure” durations that these authors calculated for the lamps.

As indicated in ANSI/IESNA RP-27.1-05, the UV exposure limits calculated in accordance with the guidelines:

• “represent conditions under which it is believed that nearly all individuals may be repeatedly exposed without adverse effects”

• “do not apply to photosensitive individuals or to individuals concomitantly exposed to photosensitizing drugs or other agents”

• “shall be used as guides in the control of exposures and shall not be regarded as a fine line between safe and dangerous levels”

NMC emphasized that Dowdy and Sayre (2013) analyzed their spectral data from the selected UV nail lamps by the approach that FDA specifies for tanning devices. Dowdy and Sayre (2013) used this approach to show that the maximum FDA-prescribed exposure time for the UV nail lamps, if they were tanning devices, would be about an order of magnitude greater than the “permissible daily exposure” durations calculated for the lamps in accordance with the ANSI/IESNA and ACGIH guidelines. Although not mentioned in NMC’s letter, Dowdy and Sayre (2013) also note that FDA guidelines for tanning devices recommend a 4-week, 3 day/week exposure schedule for un-acclimated tanners, including “first week initial exposure” durations that would be comparable to the “permissible daily exposure” durations calculated for the lamps in accordance with the ANSI/IESNA and ACGIH guidelines.





May 13, 2014

Lillian J. Gill, Ph.D.

The Cosmetic Ingredient Review

1620 L St. N.W., Suite 1200

Washington, D.C. 20036

Dear Dr. Gill:

On behalf of the Nail Manufacturers Council on Safety (NMC), a working group within the Professional Beauty

Association that represents the manufacturers of professional nail products, we are making this submission to address

questions raised by the CIR Expert Panel over the safety of UV nail lamps used for curing of artificial nail coatings.

During the recent CIR review of hydroquinone and p-hydroxyanisole, an issue was raised by the Expert Panel regarding

the safety of UV nail lamps used for curing of artificial nail coatings. On behalf of the Nail Manufacturers Council on

Safety (NMC), we are making this submission to be included as part of the official record.

UV nail lamps have been widely used and have been popular as a nail service in both Europe and the United States for

more than 25 years, with a long history of safe use.

While several studies or papers have recently been published on the subject, the most rigorous one, and the only one to

utilize the relevant three-part ANSI/IESNA standard on photobiological safety,1

sophisticated spectroradiometric

equipment, and ACGIH standards,2, is the study published by Dowdy and Sayre, world-renowned UV experts, which

finds UV nail lamps safe, with UV levels an order of magnitude lower than tanning bed lamps.3

The NMC is firmly of the opinion that the data, when fully considered, strongly supports the safety of UV nail lamps used

to cure UV artificial nail coatings.

Respectfully,

Eric Schwartz

Co-Chairman, Nail Manufacturers Council

on Safety

Professional Beauty Association

Doug Schoon

Co-Chairman, Nail Manufacturers Council

on Safety

Professional Beauty Association

cc: Carol Eisenmann, Ph.D., Personal Care Products Council, 1620 L Street, Suite 1200, NW, Washington, DC 20036

1 ANSI/IESNA RP-27.1-05 Recommended Practices for Photobiological Safety for Lamps and Lamp System- General Requirements;

RP-27.2-00 Recommended Practices for Photobiological Safety for Lamps and Lamp System-Measurement Techniques; RP-27.3-96

Recommended Practices for Photobiological Safety for Lamps and Lamp System-Risk Group Classifications & Labeling. 2 American Conference of Governmental Industrial Hygienists (ACGIH) (1992) Threshold Limit Values for Chemical Substances and

Physical Agents and Biological Exposure Indices. ACGIH, Cincinnati, OH. 3 Dowdy, J., Sayre, R., Photobiological Safety Evaluations of UV Nail Lamps, Photochemistry and Photobiology, 2013, 89:961-967.



Dowdy JC, Sayre RM. Photobiological safety evaluation of UV nail lamps. Photochem Photobiol. 2013; 89(4):961-7.



http://www.ncbi.nlm.nih.gov/pubmed?term=Dowdy%20JC%5BAuthor%5D&cauthor=true&cauthor_uid=23550905

http://www.ncbi.nlm.nih.gov/pubmed?term=Sayre%20RM%5BAuthor%5D&cauthor=true&cauthor_uid=23550905

http://www.ncbi.nlm.nih.gov/pubmed/23550905




Memorandum

To: CIR Expert Panel Members and Liaisons From: Christina L. Burnett, Senior Scientific Writer/Analyst Date: May 30, 2014 Subject: Wave 2 for Methylisothiazolinone (MI) The CIR Science and Support Committee has completed additional calculations based on the quantitative risk assessment (QRA) performed by Cosmetics Europe. These calculations include product categories, like hair spray, that were not included in the QRA performed by Cosmetics Europe.

Additionally, CIR staff received updated information regarding the FDA’s VCRP database that details the break-out of uses of MI as a stand-alone ingredient, as opposed to possibly being in mixture with MCI. The updated use table can be found on page 2 of this memo. Language in the use section of the report will be revised to reflect that stand-alone uses.

The Council’s memo, spreadsheet with the product category QRA calculations, and the updated raw VCRP are attached to this wave 2 package.







Table 1. Historical and current use and concentration of use data for methylisothiazolinone.1,4,5 # of Uses Max Conc of Use (%) Data Year 2007* 2014** 2007 2014 Totals1 1125 745 4 x 10-6-0.01 3.5 x 10-8-0.01 Duration of Use Leave-On 236 478 0.002-0.01 3.5 x 10-8-0.01 Rinse-Off 807 260 4.0 x 10-6-0.01 2.5 x 10-7-0.01 Diluted for (Bath) Use 82 7 NR 0.0002-0.01 Exposure Type

Eye Area 6 22 NR 0.00019-0.01 Incidental Ingestion NR 1 NR 0.0048 Incidental Inhalation-Spray?2,6 144 385 0.005-0.009 0.00018-0.01 Reported Spray3 NR NR NR 0.0002-0.01a

Incidental Inhalation-Powder?4,6 101 270 NR NR Reported Powder5 NR NR NR NR Dermal Contact 469 544 0.0008-0.01 3.5 x 10-8-0.01b,c

Deodorant (underarm)-Spray?2 2 NR NR NR Reported Spray3 NR NR NR NR Reported as Not Spray3 NR NR NR 0.0095 Hair - Non-Coloring 579 190 4.0 x 10-6-0.01 4.0 x 10-6-0.01 Hair-Coloring 76 NR NR 5.6 x 10-5-0.0095 Nail 1 5 NR 0.0002-0.006 Mucous Membrane 241 103 0.0015-0.01 9.0 x 10-7-0.01b

Baby Products 14 6 0.002-0.01d 0.0002-0.0075 * Data provided are not clear as to whether uses are MI alone or include uses of MI/MCI. ** Data provided are for uses of MI alone. NR = Not reported 1. Because each ingredient may be used in cosmetics with multiple exposure types, the sum of all exposure types may not equal the sum of total uses. 2. It is possible these products may be sprays, but it is not specified whether the reported uses are sprays. 3. Use in a spray product has been reported in response to a survey conducted by the Council. 4. It is possible these products may be powders, but it is not specified whether the reported uses are powders. 5. Use in a powder product has been reported in response to a survey conducted by the Council. 6. Not specified whether a powder or a spray, so this information is captured for both categories of incidental inhalation. a. 0.01% in an aerosol hair spray; 0.0002-0.01% in a pump hair spray; 0.006-0.0095% in a pump hair tonic or dressing. b. 0.00023-0.01% in a hand soap; 0.01% in a foot scrub. c. The Council survey requested that wipe products be identified. One product containing MI was identified as being used as a skin cleansing wipe at a concentration of 0.005%. d. 0.01% in baby wipes.








MEMORANDOM

To: CIR Expert Panel and Liaisons

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

Date: May 30, 2014

Subject: Data Submitted for Alkoxy Polysiloxanes as Used in Cosmetics

The Personal Care Products Council (Council) submitted additional data on the sensitization of an eye brow pencil containing cetyl PEG/PPG-10/1 dimethicone. Below are summaries of the data. An eye brow pencil containing cetyl PEG/PPG-10/1 dimethicone (15%) was found to be nonirritating in a human patch test (n = 20). There were no signs of any irritation. The test substance was administered under occlusion for 24 h. An eye brow pencil containing cetyl PEG/PPG-10/1 dimethicone (15%) was found not to be sensitizing in a maximization assay (n = 23 female, 5 male). Irritation was not observed during the induction phase. The test material was administered to the upper outer forearm or the back. Aqueous sodium laurel sulfate (SLS; 0.25%; 0.05 mL) was administered to the test site under occlusion for 24h followed by the test substance, also under occlusion, for 48 or 72 h. This was repeated for a total of 5 applications. If there was irritation observed after the administration of the test material, no SLS was used for the next application. The challenge was administered 10 days after the last induction on a naïve site. SLS was administered for 1 h followed by the test substance for 48 h. The test sites were scored at 15-30 min and at 24 and 48 h.








Memorandum

To: CIR Expert Panel Members and Liaisons From: Wilbur Johnson, Jr. Senior Scientific Analyst Date: May 30, 2014 Subject: Wave 2 Data on Styrene and Vinyl-type Styrene Copolymers Industry data on styrene and vinyl-type styrene copolymers (in data3 and data4 pdf files) that were not available for inclusion with the June 2014 Panel documents are being submitted as attachments to the accompanying summary document on these data. The toxicity information (on trade name materials) submitted includes toxicity data as well as statements relating to toxicity potential, in the absence of data. Additionally, data on similar trade name materials, whereby the composition is either known or unknown, were provided to support the safety of other trade name materials. Brief data summaries are presented below. The negative classification below refers to test results or statements relating to potential toxicity in the absence of data. Toxicity data were provided on either the ingredient trade name material or a similar trade name material; however, only the cosmetic ingredient names (INCI name and trade name) associated with the negative, or other, classification are listed below. Acute Inhalation Toxicity (Negative)

• Polyacrylate-15 (Syntran® PC 5208) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) • Polyacrylate-21 (Syntran® PC 5100CG) • Polystyrene (Syntran® 5900)

Acute Oral Toxicity (Negative)

• Ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) mixture • Polyacrylate-15 (Syntran® PC 5208) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) • Polyacrylate-21 (Syntran® PC 5100CG) • Polystyrene (Syntran® 5900) • Styrene/acrylates copolymer (Syntran® PC 5903) • Polystyrene (Syntran® 5900)

Acute Dermal Toxicity (Negative)

• Polyacrylate-15 (Syntran® PC 5208) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) • Polyacrylate-21 (Syntran® PC 5100CG) • Polystyrene (Syntran® 5900)

Ocular Irritation (Negative)

• Ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) mixture (in vivo) • Polyacrylate-15 (Syntran® PC 5208) (in vitro) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) (in vitro) • Polyacrylate-21 (Syntran® PC 5100CG) (in vitro)

Skin Irritation (Negative/Weak irritant)

• Ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) mixture) (animal) (negative) • Styrene/acrylates copolymer (Syntran® PC 5903) (human) (negative) • Styrene/acrylates copolymer (Syntran® PC 5903) (in vitro) (weak irritant) • Polyacrylate-15 (Syntran® PC 5208) (in vitro) (negative) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) (in vitro) (negative)







• Polyacrylate-21 (Syntran® PC 5100CG) (in vitro) (negative) • Polystyrene (Syntran® 5900) (human) (negative) • Polystyrene (Syntran® 5900) (in vitro) (weak irritant)

Skin Sensitization (Negative)

• Styrene/acrylates copolymer (Syntran® PC 5903) (animal) • Ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) mixture (human) • Polyacrylate-15 (Syntran® PC 5208) (human) • Polyacrylate-15 (Syntran® PC 5208) (in vitro) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) (human) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) (in vitro) • Polyacrylate-21 (Syntran® PC 5100CG) (human) • Polyacrylate-21 (Syntran® PC 5100CG) (in vitro) • Polystyrene (Syntran® 5900) (animal)

Genotoxicity (Negative, Ames test)

• Styrene/acrylates copolymer (Syntran® PC 5903) • Polyacrylate-15 (Syntran® PC 5208) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) • Polyacrylate-21 (Syntran® PC 5100CG) • Polystyrene (Syntran® 5900)

After reviewing the information provided, the Panel should identify the data on trade name materials that should be added to this safety assessment. Please note that composition/impurities data on only the following trade name materials were provided:

• Ethylene/propylene/styrene copolymer and butylene/ethylene/styrene copolymer mixture • Polyacrylate-15 (Syntran® PC 5208) • Polyacrylate-18 and Polyacrylate-19 mixture (Syntran® PC 5117 & Syntran® PC 5107) • Polystyrene (Syntran® 5900)





1

WAVE 2 DATA ON STYRENE AND VINYL-TYPE STYRENE COPOLYMERS

CHEMISTRY

Chemical and Physical Properties Polyacrylate-15 Polyacrylate-15 (Syntran® PC 5208) has a molecular weight reported as m + n > 100.1 Polyacrylate-18 and Polyacrylate-19 Polyacrylate-18 and Polyacrylate-19 (Syntran® PC 5117; trade name corresponds to CAS No. 848236-12-4) has a molecular weight reported as n > 50.2 Polyacrylate-18 and Polyacrylate-19 (Syntran® PC 5107; trade name corresponds to CAS No. 848236-12-4) has a molecular weight reported as n > 50.3 Polyacrylate-21 Polyacrylate-21 (Syntran PC 5100 CG (corresponds to CAS Nos. 68541-61-7 and 26316-50-7) is comprised of acrylate copolymers in an aqueous phase with a typical pH of 8.0.4 It has a dry extract of 25% non-volatiles. Polystyrene Polystyrene (Syntran® 5900) has a molecular weight of ~ 50,000 daltons.5 Styrene/Acrylates Copolymer Syntran® 5903 (corresponds to CAS Nos. 9011-14-7 and 9010-92-8) consists mainly of styrene/acrylates copolymer in an aqueous phase.6 It is a white, milky dispersion (pH 7) consisting of a dry extract of 35% (polymers). [Don’t know if 35% polymers refers to 35% styrene acrylates copolymer, and don’t know the remaining 65% composition.] Styran® 5904 (corresponds to CAS Nos. 9011-14-7 and 9010-92-8) consists mainly of styrene/acrylates copolymer in an aqueous phase.7 It is a white, milky dispersion (pH 2.5) consisting of a dry extract of 40% (polymers). This white, milky dispersion has to be kept away from the frost. [Don’t know if 40% polymers refers to 40% styrene acrylates copolymer, and don’t know the remaining 60% composition.] Styran® 5907 (corresponds to CAS Nos. 9010-92-8 and 9003-63-8) consists of styrene/acrylates copolymer in an aqueous phase, and is described as a white, milky dispersion that has to be kept away from the frost.8 It has a dry extract of 40% (polymers) and a pH of 2.5. [Don’t know if 40% polymers refers to 40% styrene acrylates copolymer, and don’t know the remaining 60% composition.] Styran® 5905 (corresponds to CAS Nos. 9011-14-7 and 9010-92-8) consists mainly of styrene/acrylates copolymer in an aqueous phase.9 It is a white, milky dispersion (pH 2.5) consisting of a dry extract of 40% (polymers). This white, milky dispersion has to be kept away from the frost. [Don’t know if 40% polymers refers to 40% styrene acrylates copolymer, and don’t know the remaining 60% composition.]



2

Method of Production

The ethylene/propylene/styrene copolymer and butylene/ethylene/styrene copolymer used as thickeners are made by anionic polymerization, which results in little or no residual monomer in the polymer.10

Composition/Impurities Ethylene/Propylene/Styrene Copolymer and Butylene/Ethylene/Styrene Copolymer Ethylene/propylene/styrene copolymer and butylene/ethylene/styrene copolymer are used in ingredient mixtures in which the total polymer content is usually in the range of 5 to 20 weight % and the main component may be either of the following:10

• mineral oil • isohexadecane • isododecane • hydrogenated polyisobutene • isopropyl palmitate • isononyl isononanoate • residual monomer (below limit of detection [100 ppb])

Polyacrylate-15

Styran® PC 5208 (corresponds to CAS No. 67892-91-5) has the following composition:1

• olefin-acrylic graft polymer (37%) • ethoxylated secondary alcohol (3%) • 1,3-butanediol (2%) • 0.20% methylparaben; 0.15% propylparaben • residual monomer (< 5 ppm) • water (58%)

Polyacrylate-18 and Polyacrylate-19 (mixture)

Styran® PC 5117 (corresponds to CAS No. 848236-12-4) consists of the following:2

• acrylate copolymer (35%) • 1,3-butanediol (4%) • methylparaben (0.20%) and propylparaben (0.15%) • residual monomer (< 5 ppm) • water (60%)

Styran® PC 5107 (also corresponds to CAS No. 848236-12-4) consists of the following:3 • acrylate copolymer (30%) • 1,3-butanediol (4%) • methylparaben (0.20%) and propylparaben (0.15%) • residual monomer (< 5 ppm) • water (65%)



3

Polystyrene

Styran® 5900 (corresponds to CAS No. 9003-53-6) has the following composition:5

• polystyrene (31% to 33%) • surfactants (2% to 3%) • residual monomer (< 5 ppm) • balance is water

Acute Inhalation Toxicity

Polyacrylate-15 According to an acute toxicity profile on Syntran® PC 5208, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutely hazardous.1 Thus, little or no systemic toxicity would be expected via the inhalation route of exposure. Polyacrylate-18 and Polyacrylate-19 (mixture)

According to an acute toxicity profile on Syntran® PC 5117 (polyacrylate-18 and polyacrylate-19), the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutelyhazardous.2 Thus, little or no systemic toxicity would be expected via the inhalation route of exposure. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3

In the same acute toxicity profile, the airborne particle size of a commercial aerosol (~ 19% concentrate,

91% of which was Syntran® EX 107 [composition not stated], and ~ 81% solvent/propellant) after spraying from a commercial aerosol can was evaluated.2 The mean aerosol particle diameter was 45.1 µm, and approximately 95% of the particles had a diameter of > 10 µm. It was noted that since particles with diameters greater than 10 µm are not respirable in humans, similar aerosol formulations of Syntran® PC 5117 (polyacrylate-18 and polyacrylate-19) do not pose an acute inhalation toxicity hazard.

Polyacrylate-21

According to an acute toxicity profile on Syntran® PC 5100CG, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutely hazardous.4 Thus, little or no systemic toxicity would be expected via the inhalation route of exposure.

In the same acute toxicity profile, the airborne particle size of a closely-related product, Syntran® PC 5100

(composition not stated) was evaluated.4 This was done after spraying from a commercial aerosol can. The aerosol formulation consisted of 65% concentrate, approximately half of which was Syntran® PC 5100, and 35% 152A propellant. The mean aerosol particle diameter was 54.7 µm, and approximately 97% of the particles had a diameter that was greater than 10 µm. It was noted that since particles with diameters greater than 10 µm are not respirable in humans, similar aerosol formulations of Syntran® PC 5100CG (polyacrylate-21) do not pose an acute inhalation hazard.

Polystyrene According to an acute toxicity profile on Syntran® 5900, the large molecular weight limits its bioavailability, none of the components is considered to be acutely hazardous, and little or no systemic toxicity would be expected via the inhalation route of exposure.5



4

Acute Oral Toxicity Ethylene/Propylene/Styrene Copolymer and Butylene/Ethylene/Styrene Copolymer (mixture) A trade name mixture containing ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) was evaluated in an acute oral toxicity study.11 The mixture was fed in large doses to male and female rats (number of animals not stated). Details relating to the test protocol were not included. The estimated acute oral LD50 was > 5,050 mg/kg (nontoxic). It was noted that this finding was expected because the primary ingredient of the trade name mixture is white mineral oil.

Polyacrylate-15

According to an acute toxicity profile on Syntran® PC 5208, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutely hazardous.1 Thus, little or no systemic toxicity would be expected via the oral route of exposure. Polyacrylate-18 and Polyacrylate-19 (mixture)

According to an acute toxicity profile on Syntran® PC 5117, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutelyhazardous.2 Thus, little or no systemic toxicity would be expected via the oral route of exposure. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3

Polyacrylate-21

According to an acute toxicity profile, on Syntran® PC 5100CG, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutely hazardous.4 Thus, little or no systemic toxicity would be expected via the oral route of exposure.

Polystyrene According to an acute toxicity profile on Syntran® 5900, the large molecular weight limits its bioavailability, none of the components is considered to be acutely hazardous, and little or no systemic toxicity would be expected via the oral route of exposure.5 Styrene/Acrylates Copolymer and Polystyrene An oral LD50 of > 2,000 mg/kg body weight (rats) for Syntran® 5903 was reported in a study performed according to OECD guideline n˚423.5,6 There were no effects on body weight change, and no clinical and behavioral signs or mortalities were observed after dosing. In a toxicological assessment certificate on Syntran® 5907 (another styrene acrylates copolymer trade name material), it was noted that the acute oral toxicity data on Syntran® 5903 can be extrapolated to Syntran® 5907.8 It was noted that the formulation of Syntran® 5907 involves no modification able to affect the toxicological profile of Syntran® 5903, the differences being: (1) the suppression of preservative (methylchloroisothiazolinone/methylisothiazolinone), which decreases significantly the pH of the complex ingredient and (2) the addition of a surfactant (disodium laureth sulfosuccinate) at a weak concentration. However, taking into account the intended use of the opacifying agent in the finished complex ingredient at a low concentration, this pH modification can be considered negligible. In a toxicological assessment report on Syntran® 5904 (another styrene acrylates copolymer trade name material), it was determined that the acute oral toxicity study results for Syntran® 5903 are applicable to Syntran® 5904.7 It was noted that the formulation of Syntran® 5904 involves no modification that is able to affect the toxicological profile of Syntran ® 5903, the only difference being the suppression of preservative (chloromethylisothiazolinone/methylisothiazolinone), which decreases significantly the pH of the complex ingredient. However, when considering the intended use of Syntran® 5904 in the finished product at a low concentration, this pH modification can be considered negligible.



5

In a toxicological assessment report on Syntran® 5905 (another styrene acrylates copolymer trade name material), it was determined that the acute oral toxicity study results for Syntran® 5903 are applicable to Syntran® 5905. It was noted that the formulation of Syntran® 5905 involves no modification that is able to affect the toxicological profile of Syntran ® 5903, the only difference being the introduction of a nonionic surfactant (polyethoxylated secondary alcohols) at a very low concentration and the suppression of preservative (chloromethylisothiazolinone), which decreases significantly the pH of the complex ingredient. However, when considering the intended use of Syntran® 5905 in the finished product at a low concentration, this pH modification can be considered negligible.

Acute oral toxicity data on polystyrene (Syntran® 5900) were not provided by industry; however, it was

noted that acute oral toxicity data (summarized in this section) on a closely related product, Syntran® 5903, are available.5

Acute Dermal Toxicity

Polyacrylate-15

According to an acute toxicity profile on Syntran® PC 5208, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutelyhazardous.1 Thus, little or no systemic toxicity would be expected via the dermal route of exposure. Polyacrylate-18 and Polyacrylate-19 (mixture)

According to an acute toxicity profile on Syntran® PC 5117, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutelyhazardous.2 Thus, little or no systemic toxicity would be expected via the dermal route of exposure. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3 Polyacrylate-21

According to an acute toxicity profile, on Syntran® PC 5100CG, the large molecular size of this polymer limits its bioavailability and none of the components is considered to be acutely hazardous.4 Thus, little or no systemic toxicity would be expected via the dermal route of exposure. Polystyrene

According to an acute toxicity profile on Syntran® 5900, the large molecular weight limits its bioavailability, none of the components is considered to be acutely hazardous, and little or no systemic toxicity would be expected via the dermal route of exposure.5

Ocular Irritation Animal Ethylene/Propylene/Styrene Copolymer and Butylene/Ethylene/Styrene Copolymer (mixture)

A trade name mixture containing ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) was evaluated in an ocular irritation study involving albino rabbits (number of animals not stated).12 Details relating to the test protocol were not included. The trade name mixture was not a primary ocular irritant in this study. It was noted that, under EPA Guideline No. 81-4, this trade name mixture was “minimally irritating” in rinsed and unrinsed eyes. Additionally, the minimal irritation observed was reversible and the trade name material was assigned to Category IV, EPA’s lowest toxicity category for ocular irritation.



6

In Vitro Polyacrylate-15 Using the EpiOcularTM human cell construct in a topical application ocular irritation screening assay, the potential toxicity of Syntran® PC 5208 was evaluated at the following exposure times: 2 h, 4 h, 8 h, 16 h, and 24 h.1 The duration of exposure resulting in a 50% decrease in 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) conversion (ET50) in test article-treated EpiOcularTM human cell constructs, relative to control cultures, was determined. An ET50 value of 22.5 h was reported, with 41.9% cell viability at the 24 h exposure period. Based on the results of this study, Syntran® PC 5208 was classified as non-irritating to the eye. Polyacrylate-18 and Polyacrylate-19 (mixture)

The EpiOcularTM ocular irritation screening assay (preceding protocol) was used to evaluate the potential

toxicity of Syntran® PC 5117 (polyacrylate-18 and polyacrylate-19).2 An ET50 of 3.3 h, with 15.2% cell viability at the 24-h exposure period, was reported for Syntran® PC 5117. Based on the results of this study, Syntran® PC 5117 was classified as non-irritating to the eye. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3

The EpiOcularTM ocular irritation screening assay (preceding protocol) was also used to evaluate the

potential toxicity of the wet form of Syntran® PC 5117.2 An ET50 of 6.3 h, with 10.9% cell viability at the 24-h exposure period, was reported. Based on the results of this study, the wet form of Syntran® PC 5117 was classified as non-irritating to the eye. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3 Polyacrylate-21 The EpiOcularTM

ocular irritation screening assay (preceding protocol) was used to evaluate the potential toxicity of a product (100.58BM, composition data not provided) described as closely related to polyacrylate-21 (Syntran® PC 5100CG).4 An ET50 of 16.7 h (with -8.5% cell viability at the 24 h exposure period) was reported for product 100.58BM. Based on these results, Syntran® PC 5100CG was classified as non-irritating to the eye.

Skin Irritation

Animal Ethylene/Propylene/Styrene Copolymer and Butylene/Ethylene/Styrene Copolymer (mixture)

A trade name mixture containing ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) was evaluated in a skin irritation study involving albino rabbits (number of animals not stated).13 Details relating to the test protocol were not included. The trade name material was not a primary skin irritant in this study. It was noted that the descriptive rating (under EPA Guideline No. 81-5) for this trade name mixture was “slightly irritating”, the lowest descriptive rating possible. Additionally, because this slight irritation was reversible, the trade name material was assigned to the EPA’s lowest toxicity category (Categorty IV) for dermal irritation. Human

Styrene/Acrylates Copolymer and Polystyrene Syntran® 5903 (5% in distilled water) was classified as having good skin compatibility in 10 volunteers patch tested (single application patch test). Study details were not provided.5,6 No signs of irritation were recorded, and observations throughout the test interval were within normal limits. Based on these results for Syntran® 5903, Syntran® 5904 (another styrene acrylates copolymer trade name material), Syntran® 5907 (another styrene/acrylates copolymer trade name material), Syntran® 5905 (another styrene/acrylates copolymer trade name



7

material), and Syntran® 5900 (polystyrene trade name material) were classified as non-irritants.5,7,8,9 Syntran® 5904, Syntran® 5907, Syntran® 5905, and Syntran® 5900 were not tested in this skin irritation study. In Vitro Polyacrylate-15

In a cosmetic ingredient safety dossier on Syntran® PC 5208, skin irritation data on this trade name material were not included.1 However, it was noted that the absence of ocular irritation potential in the EpiOcularTM

assay on Syntran® PC 5208 indicates that this trade name material is not likely to produce skin irritation, since skin is less susceptible to irritation than eye tissue. Polyacrylate-18 and Polyacrylate-19 (mixture)

In a cosmetic ingredient safety dossier on polyacrylate-18 and polyacrylate-19 (Syntran® PC 5117), skin irritation data on this trade name material were not included.2 However, it was noted that the absence of ocular irritation potential in the EpiOcularTM

assay on a closely related product (Syntran® 5100, composition not stated) indicates that Syntran® PC 5117 is not likely to produce dermal irritation, since skin is less susceptible to irritation than eye tissue. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3 Polyacrylate-21 In a cosmetic ingredient safety dossier on polyacrylate-21 (Syntran® PC 5100CG), skin irritation data on this trade name material were not included.4 However, it was noted that the absence of ocular irritation potential in the EpiOcularTM

assay on a closely related product (100.58BM, composition data not provided) indicates that Syntran® PC 5100CG is not likely to produce dermal irritation, since skin is less susceptible to irritation than eye tissue. Styrene/Acrylates Copolymer and Polystyrene In the embryonic hen’s egg chorioallantoic membrane (HET-CAM) assay, a 5% dilution of Syntran® 5903 in distilled water was classified as a weak irritant.5,6 In this test system, the hen’s egg chorioallantoic membrane was treated with the test material for 20 seconds and the following endpoints were evaluated: hyperemia, hemorrhage, and coagulation (including opacity and thrombosis). Based on these results for Syntran® 5903, Syntran® 5904 (another styrene/acrylates copolymer trade name material), Syntran® 5907 (another styrene/acrylates copolymer trade name material), Syntran® 5905 (another styrene/acrylates copolymer trade name material), and Syntran® 5900 (polystyrene trade name material) were also classified as weakly irritating to the chorioallantoic membrane.5,7,8,9 Syntran® 5904, Syntran® 5907, Syntran® 5905, and Syntran® 5900 were not tested in this assay.

Based on the results of this HET-CAM assay, it was concluded that Syntran® 5900 is safe for use in cosmetic formulations when formulated to avoid irritation.5

Skin Sensitization

Animal Styrene/Acrylates Copolymer and Polystyrene Syntran® 5903 (undiluted) was classified as a non-sensitizer in a guinea pig sensitization test, performed according to OECD guideline n˚406.5,6 Based on these results for Syntran® 5903, Syntran® 5904 (another styrene/acrylates copolymer trade name material), Syntran® 5907 (another styrene/acrylates copolymer trade name material), Syntran® 5905 (another styrene/acrylates copolymer trade name material), and Syntran® 5900 (polystyrene trade name material) were classified as non-sensitizers.5,7,8,9 Syntran® 5904, Syntran® 5907, Syntran® 5905, and Syntran® 5900 were not tested in this study.



8

Human Ethylene/Propylene/Styrene Copolymer and Butylene/Ethylene/Styrene Copolymer (mixture)

A trade name mixture containing ethylene/propylene/styrene copolymer (4 to 15%) and butylene/ethylene/styrene copolymer (0.1 to 2%) was evaluated in a human repeated insult patch test involving 117 subjects.14 Details relating to the test protocol were not included. The subjects were evaluated for redness, swelling, “flares” and itching. The trade name mixture did not induce allergic contact dermatitis in any of the subjects. It was noted that this conclusion was confirmed by a board-certified dermatologist. Polyacrylate-15

Data on a closely-related product, Syntran® EX 105 (composition data not provided), were used to evaluate the sensitization potential of polyacrylate-15 (Syntran® PC 5208).1 A human repeated insult patch test (HRIPT; protocol not included) on Syntran® EX 105 was performed using 100 male and female volunteers. Observations throughout the test interval were within normal limits. Therefore, based on these data, it was concluded that Syntran® PC 5208 would not produce allergic contact sensitization following repetitive dermal exposure. Polyacrylate-18 and Polyacrylate-19 (mixture)

Data on a closely related product, Syntran® PC 5100 (composition data not provided), were used to evaluate the sensitization potential of Syntran® PC 5117 (polyacrylate-18 and polyacrylate-19).2 A human repeated insult patch test (HRIPT; protocol not included) on Syntran® PC 5100 was performed using 100 male and female volunteers. Observations throughout the test interval were within normal limits. Therefore, based on these data, it was concluded that neither Syntran® PC 5100 nor Syntran® PC 5117 would produce allergic contact sensitization following repetitive dermal exposure. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3

Polyacrylate-21 Data on a closely related product, Syntran® PC 5100 (composition data not provided) were used to evaluate the sensitization potential of polyacrylate-21 (Syntran® PC 5100CG).4 A human repeated insult patch test (HRIPT; protocol not included) on Syntran® PC 5100 was performed using 100 male and female volunteers. Observations throughout the test interval were within normal limits. Therefore, based on these data, it was concluded that Syntran® PC 5100CG would not produce allergic contact sensitization following repetitive dermal exposure. In Vitro Polyacrylate-15

In a cosmetic ingredient safety dossier on Syntran® PC 5208, skin irritation data on this trade name material were not included.1 However, it was noted that the absence of ocular irritation potential in the EpiOcularTM

assay on Syntran® PC 5208 indicates that this trade name material is not likely to produce skin sensitization, since skin is less susceptible to irritation than eye tissue. Polyacrylate-18 and Polyacrylate-19 (mixture)

In a cosmetic ingredient safety dossier on polyacrylate-18 and polyacrylate-19 (Syntran® PC 5117), skin irritation data on this trade name material were not included.2 However, it was noted that the absence of ocular irritation potential in the EpiOcularTM

assay on a closely related product (Syntran® 5100, composition not stated) indicates that Syntran® PC 5117 is not likely to produce dermal sensitization, since skin is less susceptible to irritation than eye tissue. These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3



9

Polyacrylate-21 In a cosmetic ingredient safety dossier on polyacrylate-21 (Syntran® PC 5100CG), skin irritation data on this trade name material were not included.4 However, it was noted that the absence of ocular irritation potential in the EpiOcularTM

assay on a closely related product (100.58BM, composition data not provided) indicates that Syntran® PC 5100CG is not likely to produce dermal sensitization, since skin is less susceptible to irritation than eye tissue.

GENOTOXICITY Styrene/Acrylates Copolymer and Polystyrene In the Ames test (OECD guideline n˚471), Syntran® 5903 (doses up to 5,000 µg/plate) was non-genotoxic with and without metabolic activation in Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and in Escherichia coli strains WP2, pKM101, and uvr A-.5,6 Based on these results for Syntran® 5903, Syntran® 5904 (another styrene/acrylates copolymer trade name material), Syntran® 5907 (another styrene/acrylates copolymer trade name material), Syntran® 5905 (another styrene/acrylates copolymer trade name material), and Syntran® 5900 (polystyrene trade name material) were classified as non-genotoxic.5,7,8,9 Syntran® 5904, Syntran® 5907, Syntran® 5905, and Syntran® 5900 were not tested in this assay. Polyacrylate-15 When Syntran® EX 105 (composition data not provided) was evaluated for genotoxicity in the preceding Ames test (same strains, except strain WP2 uvrA was the only E. coli strain tested; doses up to 5,000 µg/plate), results were negative with and without metabolic activation.1 Genotoxicity data on polyacrylate-15 (Syntran® PC 5208) were not provided, and data on a closely related product (Syntran® EX 105) were used to evaluate the genotoxicity of Syntran® PC 5208. It was noted that negative results would be expected for Syntran® PC 5208. Polyacryate-18 and Polyacrylate-19 (mixture) When Syntran® PC 5117 (polyacrylate-18 and polyacrylate-19) was evaluated for genotoxicity in the preceding Ames test (same strains, except strain WP2 uvrA was the only E. coli strain tested; doses up to 5,000 µg/plate), results were negative with and without metabolic activation.2 These statements are also applicable to Syntran® PC 5107 (polyacrylate-18 and polyacrylate-19).3 Polyacrylate-21 When Syntran® PC 5100 (composition data not provided) was evaluated for genotoxicity in the preceding Ames test (same strains, except strain WP2 uvrA was the only E. coli strain tested; doses up to 5,000 µg/plate), results were negative with and without metabolic activation.4 Genotoxicity data on polyacrylate-21 (Syntran® 5100CG) were not provided, and data on a closely related product (Syntran® PC 5100) were used to evaluate the genotoxicity of Syntran® 5100CG. It was noted that negative results would be expected for Syntran® 5100CG.



10

References

1. Toxicology Regulatory Services. Interpolymer cosmetic ingredient safety dossier. Syntran PC 5208 (polyacrylate-15). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2014. pp.1-2.

2. Toxicology Regulatory Services. Interpolymer cosmetic ingredient safety dossier on Syntran PC 5117 (polyacrylate-18 and polyacrylate-19). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2014.

3. Toxicology Regulatory Services. Interpolymer cosmetic ingredient safety dossier on Syntran PC 5107 (polyacrylate-18 and polyacrylate-19). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2014. pp.1-3.

4. Interpolymer. Cosmetic ingredient safety dossier on Syntran PC 5100CG (polyacrylate-21 and dimethylaminoethyl methacrylate copolymer). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2014. pp.1-3.

5. Toxicology Regulatory Services. Interpolymer cosmetic ingredient safety dossier. Suntran 5900 (polystyrene). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2013.

6. Evic France. Toxicological assessment report Syntran 5903 (styrene acrylates copolymer). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2005. pp.1-2.

7. Evic France. Toxicological assessment report on Syntran 5904 (styrene acrylates copolymer). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2005. pp.1-2.

8. Evic France. Toxicological assessment certificate referring to a complex ingredient intended to be used in cosmetic products. Suntran 5907 (styrene acrylates copolymer). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2009. pp.1-3.

9. Evic France. Toxicological assessment report on Syntran 5905 (styrene acrylates copolymer). Unpublished data submitted by the Personal Care Products Council on 4-21-2014. 2005. pp.1-2.

10. Personal Care Products Council. Information on ethylene/propylene/styrene copolymer and butylene/ethylene/styrene copolymer. Unpublished data submitted by the Personal Care Products Council on 4-24-2014. 2014. pp.1

11. Stillmeadow. Acute oral toxicity study. Trade name mixture containing 4-15% ethylene/propylene/styrene copolymer and 0.1-2.0% butylene/ethylene/styrene copolymer. Unpublished data submitted by the Personal Care Products Council on 4-24-2014. 1994. pp.1

12. Stillmeadow. Primary eye irritation study. Trade name mixture containing 4-15% ethylene/propylene/styrene copolymer and 0.1-2.0% butylene/ethylene/styrene copolymer. Unpublished data submitted by the Personal Care Products Council on 4-24-2014. 1992.

13. Stillmeadow. Primary dermal irritation study in rabbits. Trade name mixture containing 4-15% ethylene/propylene/styrene copolymer and 0.1-2.0% butylene/ethylene/styrene copolymer. Unpublished data submitted by the Personal Care Products Council on 4-24-2014. 1992. pp.1

14. Stephens & Associates. Human repeat insult patch test. Trade name mixture containing 4-15% ethylene/propylene/styrene copolymer and 0.1-2.0% butylene/ethylene/styrene copolymer. Unpublished data submitted by the Personal Care Products Council on 4-24-2014. 1994. pp.1



wave 2 alkyl phosphates alkyl polysiloxanes … phosphates alkyl polysiloxanes ceramides citrus peel...

Documents