SUPPLEMENT

Camellia Sinesis

Hydroquinone & p-Hydroxyanisole

Methylisothiazolinone

CIR EXPERT PANEL MEETING

MARCH 17-18, 2014

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

(Main) 202-331-0651 (Fax) 202-331-0088 (Email) cirinfo@cir-safety.org (Website) www.cir-safety.org

Commitment & Credibility since 1976

MEMORANDOM

To: CIR Expert Panel and Liaisons

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

Date: March 14, 2014

Subject: Wave 3 Data Submitted for Camellia sinensis – Derived Ingredients

Attached is an IFRA Standard of “tea leaf absolute” that is based on a quantitative risk assessment for sensitization and limits tea leaf extract in products to 0.1% to 2.5%, depending on the product category.

Tea leaf absolute

84650-60-2

Camellia sinensis leaf extract Tea, ext. Tea sinensis absolute Thea chinensis ext. Thea sinensis ext.

Initial reviews: Current revision date: Implementation date:

Next review date

2006 For new submissions*: For existing fragrance compounds*: 2011

N/A

June 11 2007 June 11 , 2008

• This date applies to the supply of fragrance compounds (formulas) only, not to the finished products in the marketplace.

RECOMMENDATION: RESTRICTED

RESTRICTIONS: ~~F-""T~'t~ .. r--- <-T. ... ~ .... ~.r .. ·~"~__, ·~, oc;--., .,---=.-. _:;-, ~-~ ;=;)f'"'\ .... -:-u.,..,.:o;=~.-1"t""•·rP'f1,'...........-, ..... """"""'''_.,-;--,..----...~ .... -=-·.,_.- J

the -f!mslieCip~o.duct: (•:}' :. :•.\:·, · • ··. ·.:"'· ~·: :r.-'.J' . .., •• '-t::-..&1. ··.':..· ·, .· ,·. ~,._e.. ·- .. - ·- ~ ~ ,..._ 1 . ..____. - 1... - ._ J -~- .__ __..._ ~ ___ ._ -- :..;: ~~ ~

Category 1 See Note box (1) 0.01% Category 7 0.04%

Category 2 0.02% Category 8 0.5%

Category 3 0.07% Category 9 2.4%

Category 4 0.2% Category 10 2.5%

Category 5 0.1% Category 11 See Note Box (2)

Category 6 0.3% ~NOie;8(),(t~·~,~~'fJII~ ~--rc~·~-:. '- - · ~~ ~ · : ... -;,- ·. · .. ·· ~ :. · ~ ~ .~.-··.;.;~~- · · ·:~ · .... ~ ... · •. ~-a~ ~··· •'- o. 1.~~~2:: .. ! ~ ~-~·· ._:. "~~·~~-~..:_~_·:-~~~~ (1) IFRA would recommend that any material used to impart perfume or flavour in products intended for human ingestion should consist of ingredients that are in compliance with appropriate regulations for foods and food flavourings in the countries of planned distribution and, where these are lacking, with the recommendations laid down in the Code of Practice of IOFI (International Organisation of the Flavor Industry) (http://www.iofiorg.org/).

(2) Category 11 includes all non-skin contact or incidental skin contact products. Due to the negligible skin contact from these types of products there is no justification for a restriction of the concentration of this fragra_nc_e_in...:g:...re_d_ie_n_t i_n _th_e_fi~ni~sh_e_d..:.p_ro_d~uc_t. ___________ ---1

N/A

N/A

CRITICAL EFFECT: SENSITIZATION

IFRA Standard- Tea leaf absolute October 14, 2009 1/2

Tea leaf absolute

~ .. ,._ .. - .. - .. - --- i ;, -_.-.~" ~:':!._: --=- ... - .. ~ , ... ~ - - ·-. " _.=:-... - ' ' ...... - p -, ~---. • • • -=. -RIFM Sl,IM_!IIIA~IES: . :'. 1 ,., . , , . . . . . .. • . , -.. . .-. ·•:. :. • , !'---=- -~-~---'"'---- -·-··- ·---~-,......··--------~-·-· ---~---"'-~- ·--- "J:

Tea Leaf Absolute- Sensitization Potency Estimation Based on Weight of Evidence

Potency Classification

Based on Animal Data2

NOEL­HRIPT

(induction) (1Jglcm2

)

NOEL-HMT (induction) (tJg/cm2

)

LOEL1

(induction) (tJg/cm2

)

WoE NESIL3

(tJg/cm2)

Moderate 480 NA NA 480

are from RIFM and are listed in the RIFM Database. NOEL= No observed effect level; HRIPT = Human Repeat Insult Patch Test; HMT = Human Maximization Test; LOEL = lowest observed effect level; NA = Not Available.

1 Data derived from HRIPT or HMT. 2 Based on animal data using classification defined in ECETOC, Technical Report No. 87, 2003. 3 WoE NESIL limited to two significant figures. 4 1rritation was observed at higher concentrations; EC3 value not calculable

The RIFM Expert Panel reviewed the critical effect data for tea leaf absolute and based on the weight of evidence established the No Expected Sensitization Induction Level (NESIL) as 480 tJg/cm•. They recommend the limits for the 11 different product categories, which are the acceptable use levels of tea leaf absolute in the various product categories. These were derived from the application of the exposure-based quantitative risk assessment approach for fragrance ingredients, which is detailed in the QRA Expert Group Technical Dossier of March 15, 2006.

Gerberick, GF. et. al. (2001) Contact allergenic potency: Correlation of human and local lymph node assay data. American Journal of Contact Dermatitis, 12(3), 156-161 .

QRA Expert Group• (AM Api, DA Basketter, PA Cadby, M-F Cane, G Ellis, GF Gerberick, P Griem, PM McNamee, CA Ryan and R Safford), Dermal Sensitization Quantitative Risk Assessment (QRA) for Fragrance Ingredients, Technical Dossier, March 15, 2006, http://www.rifm.org/pub/publications.asp.

Research Institute for Fragrance Materials, Inc (1990). Delayed contact hypersensitivity study of tea leaf absolute in guinea pigs. RIFM report number 12409 (RIFM, Woodcliff Lake, NJ USA).

Research Institute for Fragrance Materials, Inc (2004 ). Repeated insult patch test of tea leaf absolute in human subjects. Unpublished report from Robertet Incorporated, Report number 44878 (RIFM, Woodcliff Lake, NJ USA).

Research Institute for Fragrance Materials, Inc (2005). Local Lymph Node Assay on tea leaf absolute. Unpublished report from Robertet Incorporated, Report number 47597 (RIFM, Woodcliff Lake, NJ USA).

IFRA Standard- Tea leaf absolute October 14, 2009 2/2

QRA INFORMATIONAL BOOKLET VERSION 6.0 • RIFM.

Table 1: SAF and Product Type Consumer Exposure Levels that Drive the IFRA QRA Category.

Category Product Type That Drives

IFRAQRA Consumer Category

SAF Exposure1 the Category Consumer Maximum Pragmatic Level

mg/cm2/day Exposure Level

Category 1 300 11.7 Lip Products

Not Necessary

Acceptable Exposure Level derived from QRA

Category 2 300 9.1 Deodorants/Antiperspirants

Not Necessary

Acceptable Exposure Level derived from QRA

Category 3 300 2.2 Hydroalcoholics for Not Necessary Shaved Skin Acceptable Exposure Level derived from QRA

Category 4 100 2.2 Hydroalcoholics for Not Necessary Unshaved Skin Acceptable Exposure Level derived from ORA

Category 5 100 4.2 Hand Cream

Not Necessary

Acceptable Exposure Level derived from ORA

Category 6 100 1.4 Mouthwash

Not Necessary

Acceptable Exposure Level derived from ORA

Category 7 300 4.4 Intimate Wipes

Not Necessary

Acceptable Exposure Level derived from ORA

Category 8 100 1.0 2% Hair Styling Aids The maximum concentration will not exceed 2% and may be

lower if determined by the ORA

Category 9 100 0.2 5% Rinse-off Hair Conditioners The maximum concentration will not exceed 5% and may be

lower if determined by the ORA.

Category 10 100 0.1 2.5%

Hard Surface Cleaners The maximum concentration will not exceed 2.5% and may be lower if determined by the ORA.

Category 11 10 0.00033 Due to the expected negligible skin exposure from such products the risk of induction of dermal sensitization through

Candles the normal formulation and use of such products is considered to be negligible. As such, the concentration of fragrance ingredient is not restricted in the finished product. .. , The Category Consumer Exposure Level (mg/cm /day) IS dnven by the product type 1n that category With the combined highest consumer

exposure level and highest Sensitization Assessment Factor (SAF). In order to identify the product type consumer exposure that drives the category consumer exposure please refer to the Technical Dossier, Table 9.

IFRA RIFM QRA Information Booklet V6.0 12 Last updated: July 5, 2011

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

(Main) 202-331-0651 (Fax) 202-331-0088 (Email) cirinfo@cir-safety.org (Website) www.cir-safety.org

Commitment & Credibility since 1976

MEMORANDOM

To: CIR Expert Panel and Liaisons

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

Date: March 14, 2014

Subject: Wave 3 Data for Hydroquinone and p-Hydroxyanisole

Attached is a letter submitted by the Women’s Voices for the Earth with comments on the draft reports on hydroquinone and p-hydroxyanisole. The two major concerns are that the VCRP does not reflect the true number of uses of these ingredients in nail products available to the general public and absorption of these ingredients by manicurists. The 2014 VCRP data on these two ingredients is also included.

P.O. BOX 8743, MISSOULA, MT 59807 • (406) 543-3747 • WWW.WOMENSVOICES.ORG

By email: cirinfo@cir-safety.org

February 24, 2014

To: Cosmetic Ingredient Review Expert Panel Members and Liaisons,

On behalf of Women’s Voices for the Earth, I read with interest the notes from the most recent CIR

meeting in December 2013 regarding the issue of assessing the safety of hydroquinone and p-

hydroxyanisole. In general, we are concerned about the presence of these chemicals in nail products,

particularly given the known tendency toward depigmentation and the fact that the significant majority

of manicurists who work with these products are women of color. We do not believe it is appropriate

to determine that these chemicals could be safely used in these products.

We also have additional information to offer on the current use of these chemicals in nail products

which we believe should be pertinent to your discussion of the matter.

1) The notes reflect that the current VCRP includes no reported uses of p-hydroxyanisole, and just

seven reported uses of hydroquinone in nail extenders.

In contrast, a 15 minute Google search identified several currently marketed products

containing p-hydroxyanisole, as well as additional products containing hydroquinone.

Specifically:

Products containing p-hydroxyanisole:

Mario Badescu Vitamin E Night Cream

http://www.mariobadescu.com/Vitamin-E-Night-Cream

Scarlight Scarguard MD

http://www.drugstore.com/scarguard-scarlight-md/qxp81227

(This product also contains hydroquinone as an active ingredient at 2%.)

Kiss Her by Kiss French Acrylic Sculpture Kit

http://www.walgreens.com/store/c/kiss-her-by-kiss-french-acrylic-sculpture-

kit/ID=prod4294346-product

Trans Design Instant No MMA Liquid Nail Monomer

http://transdesign.com/MSDS/INSTANT/Instant%20No%20MMA%20Liquid%20Monomer.pdf

(Ingredient listed by the synonym MEHQ at concentration of <10%)

2

Trans Design Instant MMA Nail Liquid

http://transdesign.com/MSDS/INSTANT/LIQUID.pdf

(Ingredient listed by the synonym 4-Methoxyphenol)

Nail Products containing hydroquinone:

Creative Nail Design: Solarnail Liquid

http://www.nailcrazy.com/Home/Brisa_Gel_files/L&PMaster_print.pdf

Creative Nail Design: RETENTION+

http://www.nailcrazy.com/Home/Brisa_Gel_files/L&PMaster_print.pdf

ASP (All Season Professional) Sculpture Kit

http://www.sallybeauty.com/nail-sculpture-kit/SBS-156392,default,pd.html

Beauty Secrets Acrylic Liquid

http://www.sallybeauty.com/secrets-acrylic-liquid/SBS-164434,es,pd.html

ASP Bonding Acrylic Liquid

http://www.sallybeauty.com/acrylic-nails/SBS-156618,es,pd.html?cm_vc=SEARCH

We understand that the CIR is aware of the shortfalls of the VCRP, in that it is a voluntary

program, so not all companies report, and not all existing products would be captured. For

some ingredients the information from the VCRP may be sufficient to give a general sense of

how commonly the chemical is used. However, in this case, the distinction between reporting

“no uses” of p-hydroxyanisole, and the truth that this ingredient is currently found in products is

significant. While certainly a Google search is also less than comprehensive for identifying

product ingredients, would the CIR consider taking this simple additional step in the future to

supplement their VCRP findings to get a more accurate picture of current chemical use?

2) As noted above, p-hydroxyanisole and hydroquinone are currently found in cosmetic products,

and specifically in nail products. We would like to point out that the nail products we identified

which contain these chemicals are not UV-cured gel nail products, but other types of nail

products mostly associated with acrylic nails. (But we are certainly concerned about the

potential impacts of UV-cured gel nail products containing these chemicals as well.) This

information appears to contradict the memo from the Nail Manufacturers Council which states

“The only type of monomer (with HQ or MEHQ as inhibitors) sold as cosmetics until recently,

were the cyanoacrylate glues.”

3

Hydroquinone and p-hydroxyanisole appear to be commonly used in acrylic nail products and

have been for some time. For example, an article printed in NAILS magazine in 2009 titled “The

Chemistry of Acrylics” contains this bullet on inhibitors used in acrylic nail products:

“Inhibitors: ingredients, typically hydroquinone, hydroquinone monomethyl ether (MEHQ), or

butylated hydroxytoluene, that keep the monomers from joining into polymer chains before they

are mixed with the powder, which would cause premature hardening.” (emphasis added)

http://www.nailsmag.com/article/82078/the-chemistry-of-acrylics

Additionally, we identified an MSDS for a gel nails product for LeChat Powder Gel Nail System,

dated in 1999, which contains both hydroquinone (<1%) and 4-methoxyphenol (<2%)(a

synonym for p-hydroxyanisole.)

http://www.professionalbeautymails.com/MSDS/LeChat/Powder%20Gel%20Nail%20System%2

0-%20Primer.pdf

3) While we are certainly concerned about the impact of these chemicals on salon workers, we

believe that consumers are also at risk from products sold for home use. We dispute the claim

made in the memo from the Nail Manufacturers Council that these chemicals are only found in

products “For Professional Use Only”. The memo states:

“There where (sic) kits which were intended for consumer use, but where (sic) too difficult for

untrained consumers to use. They are rarely found on any market today.”

In contrast , we found that the acrylic nail kit we identified, “Kiss Her by Kiss French Acrylic

Sculpture Kit” which contains p-hydroxyanisole is available for sale at Walgreens, Walmart, CVS,

Drugstore.com and Amazon.com, and thus easily found in the market today and available to

many consumers for home use.

4) Lastly, we question the CIR’s Safety Assessment of these chemicals with respect to nail

penetration. It appears that one argument for the safety of these chemicals in nail products is

that very little of the chemical will penetrate the nail. Unfortunately, there is no data available

showing this to be the case specifically for hydroquinone and p-hydroxyanisole. Instead the

assessment refers to a study using dibutyl phthalate as a surrogate indicating that there was

little absorption of this chemical on cadaver nails. This seems to us to be a poor example of a

surrogate, if the intent is to demonstrate lack of exposure. There is ample epidemiological

evidence that manicurists have significantly higher levels of urinary dibutyl phthalate

metabolites than the general population, and that there is a clear pre-shift/post-shift difference

in these levels as well. In addition, women who reported home use of nail polish also have

significantly elevated dibutyl phthalate metabolite levels compared to women who do not use

nail polish. (See abstracts of studies listed below.) While there may be little absorption

through the nail bed itself, clearly there is significant bodily exposure to dibutyl phthalate from

4

the use of nail products containing this chemical. It seems this would indicate that the CIR

should be concerned about other chemicals used in products which appear to only contact the

nail, but for which there must be additional exposure routes as well.

Kwapniewski R. et.al. Occupational Exposure to Dibutyl Phthalate among Manicurists. Journal of

Occupational and Environmental Medicine. 50(6): 705-11. June 2008.

http://www.ncbi.nlm.nih.gov/pubmed/18545098

Hines, CJ et.al. Urinary Phthalate Metabolite Concentrations among Workers in Selected

Industries: A Pilot Biomonitoring Study. Annals of Occupational Hygiene. 53(1):1-17 2009.

http://www.ncbi.nlm.nih.gov/pubmed/18948546

Buckley, JP, et.al. Consumer product exposures associated with urinary phthalate levels in

pregnant women. Journal of Exposure Science and Environmental Epidemiology. 22(5): 468-475

September 2012

http://www.ncbi.nlm.nih.gov/pubmed/22760436

Thank you for your consideration of these comments. We hope they will be of interest and

relevance to the discussion at your next meeting. Please don’t hesitate to contact me if there

are any questions regarding the information presented here.

Sincerely,

Alexandra Scranton Director of Science and Research Women’s Voices for the Earth alexs@womensvoices.org 406-543-3747

2014 VCRP on Hydroquinone and p-Hydroxyanisole

06A - Hair Dyes and Colors (all types requiring caution statements and patch tests) HYDROQUINONE

7

08D - Nail Extenders HYDROQUINONE 1 12A - Cleansing HYDROQUINONE 1 12F - Moisturizing HYDROQUINONE 2 12I - Skin Fresheners HYDROQUINONE 1 12J - Other Skin Care Preps HYDROQUINONE 6 18

08A - Basecoats and Undercoats P-HYDROXYANISOLE 3 08D - Nail Extenders P-HYDROXYANISOLE 2 5

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

(Main) 202-331-0651 (Fax) 202-331-0088 (Email) cirinfo@cir-safety.org (Website) www.cir-safety.org

Commitment & Credibility since 1976

Memorandum

To: CIR Expert Panel Members and Liaisons From: Christina L. Burnett, Senior Scientific Writer/Analyst Date: March 13, 2014 Subject: Wave 3 for Methylisothiazolinone (MI) Dr. Belsito has submitted an editorial article from Contact Dermatitis that makes a significant correction to the results of the LLNA that the Panel reviewed during the original assessment of MI in 2008. The article is attached to this e-mail package for your review.

WAVE3_pubdata

Roberts, DW. Methylisothiazolinone is categorised as a strong sensitiser in the Murine Local Lymph Node Assay. Contact Dermatitis. 2013; 69 (5): 262-263.