CIR Reaches Verdicts on Butyl Myristate, HC Red No. 3 and More

Posted: June 17, 2008

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William Stott, PhD, representing the Alkanolamines Panel of the American Chemistry Council, reviewed the large body of data developed since the point 10 years ago when studies conducted by the NTP reported clear evidence that DEA and cocamide DEA were carcinogenic in male and female mice. The work has demonstrated that DEA affects mouse choline metabolism, which leads to cellular choline depletion, which leads to altered DNA methylation, which leads to altered gene expression (increased DNA synthesis and oncogene expression, reduced tumor suppressor gene expression and apotosis).

In work conducted at FDA and elsewhere, dermal penetration of DEA in personal care product vehicles was found to be significantly higher through mouse skin than either rat or human skin. In addition, the activity of choline oxidase, which is hundreds of times higher in the mouse compared to humans, suggesting that humans are resistant to choline deficiency — choline oxidase levels in the rat, however, are even higher than in the mouse. Overall, the available data support that DEA carcinogenesis in the mouse is related to choline depression and the effect is reversible and threshold-based. Given the known resistance in humans to choline deficiency, the data does not suggest a human health risk from the use of DEA and DEA fatty acids in cosmetic products.

Julie Skare, PhD, from the Procter & Gamble Company, provided an update on hair dye epidemiology, with a particular focus on the recent International Agency for Research on Cancer review (Baan et al. 2008, Carcinogenicity of some aromatic amines, organic dyes and related exposures, Lancet Oncology 9:322). She noted that the findings are not different from those in the 1993 IARC review, although there are three times as many studies of hair dye personal use and almost twice the number of hairdresser and barber occupational studies.

For occupations as a hairdresser and barber, the review group again concluded that occupational exposures are probably carcinogenic to humans, although no aspect of these occupations was identified as causal. For personal use of hair dyes, the IARC review concluded that the available epidemiology studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding a causal association between exposure and cancer. Limited animal studies can’t be interpreted as showing either the presence or absence of a carcinogenic effect. Overall, therefore, the IARC review group concluded that personal use of hair dyes was not classifiable as to its carcinogenicity in humans.

The IARC review group did specifically consider a report in press (now published) by Yawei Zhang, a member of the IARC working group (Zhang et al. 2008, Personal Use of Hair Dye and the Risk of Certain Subtypes of Non-Hodgkin Lymphoma, Am. J. Epidem. 167 (11) 1321-1331). This report presented pooled data from four previously published studies with detailed information on hair dye use. The authors reported an increased risk of Non-Hodgkin Lymphoma in women who started using hair dyes before 1980 but analysis by product type (permanent vs. non-permanent) or color (dark vs. light) were similar (when they were expected to be different — permanent > non-permanent and dark > light). The IARC working group noted that this absence of a clear pattern is an ongoing reason why the epidemiologic evidence was inadequate.