The Honorable Margaret Hamburg, M.D.
Food and Drug Administration
10903 New Hampshire Ave.
Building 1 Room 2217
Silver Spring, MD 20993-0002
Dr. Linda S. Birnbaum
National Institute of Environmental Health Sciences /
National Institutes of Health, and National Toxicology Program
P.O. Box 12233
Research Triangle Park, NC 27709
Re: Pressing Need to Expedite Photocarcinogenicity Assessment for Sunscreen Ingredient Retinyl Palmitate
Dear Commissioner Hamburg and Dr. Birnbaum:
We are writing to commend the scientists at the Center for Phototoxicology of the National Toxicology Panel (NTP) and Food and Drug Administration (FDA) National Center for Toxicological Research (NCTR) for outstanding research to help illuminate factors driving the rising skin cancer rates in the United States. We urge you to assess rapidly the data generated by the center’s investigation into whether retinyl palmitate, a vitamin A derivative and common ingredient in sunscreen products, is toxic and carcinogenic in the presence of sunlight.
Ten years ago FDA nominated retinyl palmitate for testing to determine whether the compound has photocarcinogenetic effects. That possibility was suggested by a series of studies conducted by FDA and academic scientists since 1985. In a document supporting the nomination, the National Toxicology Panel cited FDA’s concerns about the use of RP in skin care products (NTP 2000):
“Retinyl palmitate was selected by the [FDA’s] Center for Food Safety and Applied Nutrition for phototoxicity and photocarcinogenicity testing based on the increasingly widespread use of this compound in cosmetic retail products for use on sun-exposed skin, the biochemical and histological cutaneous alterations elicited by retinyl palmitate, and the association between topical application of retinoids and enhancement of photocarcinogenesis.”
Since that nomination, FDA researchers have published 17 studies and science reviews on the toxicity and chemistry of retinyl palmitate on the skin. According to FDA scientists, the study findings suggest that retinyl palmitate breaks down in sunlight to photomutagenic compounds, forms free radicals in the presence of UVA and UVB radiation and “[causes] events that affect a large segment of the chromosome” (e.g., Mei et al. 2005, 2006; Xei et al. 2006, see Addendum).
This research has culminated in the center’s completion of a one-year photocarcinogenicity study of retinyl palmitate. The study method, which is based on rodent testing, is currently the state-of-the-art technique for establishing whether a compound is carcinogenic in the presence of sunlight.
Key study data have been published on NTP’s website (NTP 2009), but your agencies’ final assessment of the work has not yet been made public.
Our review of the publicly available data suggests that your completion of this assessment could not be more urgent. The data show that tumors and lesions developed as much as 21 percent more rapidly in lab animals coated in a retinyl palmitate (RP)-laced cream (at concentrations of 0.1 percent to 0.5 percent), compared to control animals treated with an RP-free cream. Both groups were exposed to the equivalent of nine minutes of bright sunlight each day for up to a year. The differences are statistically significant and dose-dependent (EWG 2010).
The dramatically accelerated development of tumors and lesions in retinyl palmitate-treated animals, compared to untreated animals, has potentially significant implications for public health, which is why EWG raised concerns about the chemical in our 2010 review of sunscreen products (EWG 2010). Sunscreen makers have added retinyl palmitate and related forms of vitamin A to 41 percent of sunscreens on the market this year, according to EWG analysis of ingredient labels for nearly 500 products.
We are concerned that sunscreen industry consultants are attempting to downplay the relevance of the federal study. First, according to recent media reports, they disregard FDA’s body of research on retinyl palmitate. As well, they misstate the basic purpose of laboratory toxicity studies that rely on non-human animals. For instance, a dermatologist who consults for a wide range of prominent sunscreen companies was quoted as saying that it was “very premature to even cast doubt about the safety of this chemical,” on grounds that rodent studies are not applicable to humans.
As the FDA points out, “testing for photocarcinogenicity in humans is unethical; animal testing has been used as a surrogate.” As you well know, FDA, NTP and other scientific institutions are working to develop sorely needed non-animal methods for toxicity testing. Until reliable non-animal models are available, animal tests are established, state-of-the-art methods for evaluating toxicity. FDA acknowledges uncertainties in applying the test results to humans (FDA 2003). But given currently available methods, NTP cancer studies like the RP study conducted by the center are considered the “gold standard” for assessing human carcinogenicity risks (Ball 2009; Bucher 2002). FDA’s Guidance for Photosafety recommends the methods and species (hairless mouse) used by the center (FDA 2003). Scientists from the renowned MD Anderson Cancer Center have noted that “SKH1 [hairless] mice are the most widely used in dermatologic research… tumors induced in these mice resemble, both at the morphologic and molecular levels, UVR-induced skin malignancies in man” (Benavides 2009).
The literature shows that since 2002, FDA scientists have also studied retinyl palmitate with non-animal laboratory assays, including cellular and mechanistic studies, and with short-term animal studies. Your current study of the possible photocarcinogenicity of retinyl palmitate, using rodents, is based on a significant body of science that has deployed a variety of testing methods.
Some industry consultants may not be aware that the center’s testing is done in lieu of unethical human testing or that animals susceptible to cancer are selected to reduce the number of animals needed for testing. We are concerned that the broader dermatology community may not be fully aware of the relevance of the center’s important work.
As demonstrated by the media response to our report, the public and medical community are expressing immense interest in the safety of retinyl palmitate, especially in suncare products. With this letter we urge you to expedite the final review of the retinyl palmitate study data and provide guidance to consumers, physicians, and the industry about Vitamin A-based products.
Fully 10 years have passed since FDA scientists determined they had sufficient data to initiate research on the possible health hazards of retinyl palmitate, an effort that has culminated in the key photocarcinogenicity study now before us. EWG, like many scientists and health professionals around the country, is eagerly awaiting the final publication of your conclusions. We urge you to place high priority on its timely release. In the meantime, given the public health implications of the data you have published, and the industry’s use of RP in hundreds of suncare products before the government has completed its safety review, EWG is recommending that consumers avoid sunscreen containing retinyl palmitate.
Kenneth A. Cook
Copy: Dr. Paul Howard, Director, NTP/NCTR Center for Phototoxicology