EWG Comments to FDA on Nano-Scale Ingredients in Cosmetics

A Survey of Ingredients in 25,000 Personal Care Products Reveals Widespread Use of Nano-Scale Materials, Not Assessed for Safety, in Everyday Products

October 2006

Comments to U.S. Food and Drug Administration
Docket: FDA Regulated Products Containing Nanotechnology Materials
Docket number: 2006N-0107

Environmental Working Group
Washington, D.C.

The Environmental Working Group is a non-profit public health and environmental research and advocacy organization based in Washington, DC. We have conducted research on the safety of ingredients in personal care products for the past six years. Among our projects in this area is an online consumer tool that we update annually called Skin Deep, an interactive safety assessment that currently contains nearly 15,000 personal care products and their 7,000 constituent ingredients (www.cosmeticdatabase.com).

We have completed an in-depth survey of the use of nano-scale materials in personal care products, with findings derived from a systematic evaluation of ingredient labels, directions, and package details from the more than 25,000 products being uploaded for our next annual Skin Deep update. These products represent about one-quarter of the approximately 100,000 personal care products FDA estimates to be on the market (FR 2006). Our search encompassed common nano-scale ingredient terms such as micronized, fullerenes, the prefix "nano," quantum dots, and liposomes. We also searched product ingredient listings against a comprehensive database of chemicals now commercially available in nano sizes (Nanowerk 2006).

Our research reveals the widespread use of nano-scale ingredients in everyday personal care products. Our results represent the most comprehensive list of such products compiled to date.

We identified nearly 9,800 products containing nano-scale ingredients or ingredients that may contain a nano-scale fraction.¹ These include 256 products containing one or more of 57 different types of nano-scale or micronized ingredients, and 9,509 additional products containing ingredients that are commercially available in nano sizes, but nearly all of which have no label information on particle size whatsoever. These products include those regulated as cosmetics and as drugs, such as sunscreen, as detailed below:

• 256 products with one or more of 57 different types of small-scale ingredients listed on the label or package (Table 1 and Table 2), including products with "nanodelivery systems," 23 forms of "micronized" ingredients, and 3 products containing carbon-based, nano-scale "wire cages" known as fullerenes, among other types of nano-scale materials.
  
  These products include 27 sunscreens that specifically note the use of micronized or nano-scale zinc oxide or titanium dioxide (Table 2). Neither of these two sunscreen ingredients have been comprehensively reviewed for safety in their micronized or nano-scale form by FDA. The European Union's Scientific Committee on cosmetics denied approval for micronized zinc oxide as a sunscreen in 2003, citing a lack of data on skin absorption and inhalation, and studies showing the ingredient to be potentially toxic in the presence of light (SCCNFP 2003, SCCP 2005).
• 9,509 products (over one-third of all personal care products assessed by EWG) contain ingredients that are commercially available in nano-scale forms (Table 3). This includes 250 sunscreens containing titanium dioxide or zinc oxide (Table 4), and containing gold, silver, iron oxide, zeolite, and liposomes, miniscule fatty balls used to deliver ingredients deeper into the skin (Table 3). Nearly all of these products fail to note whether the listed ingredient is conventional or nano-scale.

Widespread use, unknown risks. Our research indicates that the cosmetics industry uses nano-scale ingredients routinely, even though exposures and potential risks are poorly understood. We understand that FDA is still conducting basic safety studies on these personal care product ingredients, necessitated by the unique properties FDA highlights in the announcement for their October 10, 2006 public meeting on nanotechnology: "due to their small size and extremely high ratio of surface area to volume, nanotechnology materials often have chemical or physical properties that are different from those of their larger counterparts," including "increased chemical and biological activity." FDA recently presented a summary of ongoing research the agency is conducting to evaluate the penetration and toxicity in vitro and in mice and pigs of quantum dots and zinc oxide and titanium dioxide nanoparticles, with tests to define pharmacokinetics, toxicogenomics, photocytotoxicity, and photocarcinogenicity (FDA 2006b).

But while FDA conducts basic research to substantiate the safety of nano-scale ingredients, the widespread use of these chemicals in products continues. FDA cannot require the cosmetics industry to test ingredients or products. FDA regulations do, however, require manufacturers to post a warning label on products containing ingredients that haven't been adequately substantiated for safety. The implementing regulations for the Federal Food, Drug, and Cosmetic Act (FD&CA) at 21 C.F.R. 740.10(a) read: "Each ingredient used in a cosmetic product and each finished cosmetic product shall be adequately substantiated for safety prior to marketing. Any such ingredient or product whose safety is not adequately substantiated prior to marketing is misbranded unless it contains the following conspicuous statement on the principal display panel: Warning—The safety of this product has not been determined."

None of the products we assessed bears this warning label. This omission can mean one of two things: either manufacturers believe they do have the data needed to substantiate safety of nano-scale ingredients, or they are using ingredients with unknown risks and failing to post the required warning label. Either way, we recommend that FDA take the logical actions that follow—requesting safety studies of the industry, and enforcing requirements for a warning label if such studies aren't produced.

New initiative will reveal available safety data. Through the industry's trade association, the Cosmetic, Toiletry, and Fragrance Association (CTFA), the cosmetics industry is initiating a new program called the Consumer Commitment Code that will shed light on what the industry itself knows about the safety of nano-scale materials (CTFA 2006). The Code includes a dossier program to make safety information more easily accessible to FDA through what CTFA is calling a "Safety Information Summary." Companies would provide this summary to FDA upon request. According to one media report, the Safety Information Summary would include raw material specifications, which presumably would include information on particle size (Laas 2006). A Safety Information Summary would also presumably include a summary of safety information, including available penetration and toxicity studies for nano-scale materials, which would also, presumably, be available to FDA upon request.

Most importantly, according to media reports, the Safety Information Summary would include a statement that the product's safety has been substantiated. CTFA's chief scientist notes that such a statement would require that a product's ingredients had been assessed by the industry's expert panel (the Cosmetic Ingredient Review, or CIR), by FDA, or by the regulatory body of another country. According to the industry newsletter The Rose Sheet, "key elements of the code include companies' commitment to using ingredients that have been substantiated for safety either by FDA or the Cosmetic Ingredient Review Expert Panel" (Laas 2006).

However, none of the nano-scale materials currently used in cosmetics have been substantiated for safety in cosmetics by the FDA or the Cosmetic Ingredient Review Expert Panel. By restricting their 600 member companies to the use of assessed ingredients only, CTFA seems to be endorsing a moratorium on nano-scale materials in cosmetics.

And if not, CTFA would instead be saying that it believes all nano-scale materials to be identical to conventional materials with respect to exposure potential and toxicity. Although this finding would be contrary to existing, publicly available studies, if companies have supporting safety data, it would finally be available to FDA through the industry's new Safety Information Summaries.

The bottom line is that through CTFA's new Consumer Commitment Code, FDA can either look forward to nano-scale materials being removed from cosmetics altogether, or to the public release of industry safety studies that justify the continued, safe use of these ingredients in personal care products.

Recommendations. Our recommendations to FDA include the following:

• FDA should establish, through a public process, a definition for adequate substantiation of safety for cosmetic ingredients, including nano-scale materials. We have proposed the following definition that would require specific consideration of the effect of particle size on exposure and toxicity:
  The safety of personal care and cosmetic products must be substantiated through peer-reviewed scientific publications or publicly available industry studies, to a reasonable certainty of no harm from aggregate exposures to the product and its component ingredients including impurities, taking into account factors that may increase toxicity or penetration of the product or its component chemicals through the skin, including the presence of penetration enhancers and the effects of particle size including nanoparticles, and including all anticipated cosmetic exposures and all other exposures for which there is reliable information, taking into consideration vulnerable populations such as infants and pregnant women. Safety cannot be substantiated in the absence of data.
  Safety substantiation for a cosmetic product must explicitly account for risks posed by impurities, ingredient degradates, and reaction products of ingredients, and must be based on an assessment of risk that incorporates 1) information about product use patterns including among vulnerable populations such as infants and pregnant women; and 2) analysis of the cumulative effects of ingredients, impurities, ingredient degradates, and reaction products of ingredients with common health effects or target organs. In the case of threshold effects, an additional ten-fold margin of safety shall be applied in assessments of risk for pre- and post-natal toxicity for infants and pregnant women. A different margin of safety may be used only if, on the basis of reliable data, such a margin will be safe for infants and pregnant women.


• FDA should request from the cosmetics industry all available studies on nano-scale materials used to adequately substantiate ingredient and product safety, including but not limited to all studies in the industry's new Safety Information Summaries in addition to the information recently submitted to FDA by CTFA on nano-scale sunscreen ingredients. FDA should review these studies and make determinations on the safety of nano-scale ingredients in personal care products, and should require warning labels on products which cannot be substantiated for safety.


• FDA should identify the presence of nano-scale materials in all personal care products. As a first step, FDA should require companies to submit information on particle size for ingredients entered into the Agency's Voluntary Cosmetic Registration Program product database. Under the CTFA's Consumer Commitment Code, CTFA member companies will be bound to give FDA their product formulations through this database; particle size should be required data. Because both absorption and toxicity are a function of particle size, collection of such information should be a key element of FDA's product safety evaluations. With these data, the Administration can monitor when and if commercial ingredients are introduced that fall outside the range of particle sizes for existing studies used to substantiate ingredient safety.


• And finally, FDA should act on the petition requesting amendment of its regulations for products composed of engineered nanoparticles generally and sunscreen drug products composed of engineered nanoparticles specifically, submitted earlier this year by the International Center for Technology Assessment.

Notes

¹ The upperbound limit of particle size for nano-scale materials has been variously defined as ranging from between 100 and 200 nanometers. FDA has not developed its own formal definition of nano-scale. The agency participated in the National Nanotechnology Institute's development of a definition setting an upperbound particle size of 100 nanometers (FDA 2006a). Other sources reference an upperbound size of 200 nanometers for nano-scale materials, including the National Cancer Institute (NCI 2006) and various pharmaceutical companies (e.g., Elan 2006, Ames Laboratory 2006). For the purposes of this document, when particle size distribution information is available, we define materials as containing a nano-scale fraction if at least some portion of the material includes particles 200 nanometers or less in diameter.

Appendix

Table 1
Nano-scale and micronized ingredients in personal care products.

Table 2
256 personal care products with nano-scale or micronized ingredients.

Table 3
Ingredients in personal care products that are commercially available at a nano scale.

Table 4
200 sunscreen products containing zinc oxide and titanium dioxide, with no indication on product lables if ingredients are nano-scale, micronized, or conventional.

References

Ames Laboratory. 2006. Cellular drug delivery from the inside out. Mesoporous nanospheres focus of Ames Laboratory research. 29 Mar 2006. Available online at: http://www.ameslab.gov/final/News/2006rel/nanoparticles.htm. Accessed: 17 Oct 2006.

CTFA (Cosmetic, Toiletry, and Fragrance Association). 2006. CTFA Launches Package of Consumer-Oriented Industry Initiatives at 2006 Annual Meeting. Press release 06-07. 2 Mar 2006. Available online at: http://www.ctfa.org/Template.cfm?template=/
ContentManagement/ContentDisplay.cfm&ContentID=3753.

Elan. 2006. NanoCrystal® Technology. Available online at: http://www.elan.com/EDT/nanocrystal_technology/default.asp. Accessed: 17 Oct 2006.

FDA (U.S. Food and Drug Administration). 2006a. FDA and Nanotechnology Products. Frequently Asked Questions (FAQs). Available online at: http://www.fda.gov/nanotechnology/faqs.html. Accessed: 17 Oct 2006.

FDA (U.S. Food and Drug Administration). 2006. FDA Considerations for Regulation of Nanomaterial Containing Products. Presentation by Nakissa Sadrieh, Ph.D., Office of Pharmaceutical Science, CDER, FDA. Available online at http://www.fda.gov/nanotechnology/.

FR (Federal Register). 2006. Department of Health and Human Services. Food and Drug Administration. Notice - Agency Information Collection Activities; Proposed Collection; Comment Request; Cosmetic Labeling Regulations. Vol 71, No 11, p 2947. 18 January 2006.

Laas, Molly. 2006. "CTFA Moves Forward With Implementation Of Consumer Commitment Code." The Rose Sheet. Vol 27, No 039, p6. 25 Sept 2006.

Nanowerk. 2006. Nanomaterial Database of 1,352 nanoparticles from 93 suppliers. Available online at http://www.nanowerk.com/phpscripts/n_dbsearch.php.

NCI (National Cancer Institute). 2006. Nanoscale "Cell Within A Cell" Delivers Multiple Therapies that Kill Tumors. NCI Alliance for Nanotechnology in Cancer. Available online at: http://nano.cancer.gov/news_center/nanotech_news_2005-08-01a.asp. Accessed: 17 Oct 2006.

SCCNP (The Scientific Committee on Cosmetic Products and Non-Food Products Intended for Consumers). 2003. Opinion concerning zinc oxide. OLIPCA n S 76. Adopted by the SCCNFP during the 24th plenary meeting of 24-25 June 2003.

SCCP (The Scientific Committee on Consumer Products). 2005. Statement on zinc oxide used in sunscreen. Adopted by the SCCP during the 5th plenary meeting of 20 September 2005.