Paraben Study Is Not Based On Sound Science, Consultants Maintain

A British study finding a high level of parabens in breast tumor samples was not conducted "in a manner that reflects sound science," according to consultants for the Cosmetic, Toiletry & Fragrance Association.

ToxLogic President Robert Golden, PhD, and Center for Toxicology & Environmental Health Senior Toxicologist Jay Gandy, PhD, outlined concerns with the study protocol in a letter to the editor published in the July/August issue of the Journal of Applied Toxicology. The letter is one of three published in the journal raising concerns.

The original study by Philippa Darbre, MD, University of Reading, et al., was published in the January issue of the journal, recommended additional studies evaluating the potential connection between the cosmetic preservatives and breast cancer (¹ (Also see "Methylparaben Accumulation Noted In UK Breast Tumor Study" - Pink Sheet, 19 Jan, 2004.), p. 14). A corresponding editorial by Philip Harvey, MD, Covance Labs, et al., further explored a link between estrogenic ingredients used in underarm products and breast cancer.

The study did not include control tissues, when a finding of equal paraben levels in normal breast tissue would have negated the central finding of the study, the CTFA consultants maintain. They also question whether laboratory contamination was prevalent.

Another concern is the use of paraben-containing drugs to treat breast cancer, such as exemestane, which should have been controlled in the study by reference to breast tumor tissue from patients not treated with the drugs, the letter states.

The study also failed to address existing epidemiological data indicating a lack of association between underarm deodorants and breast cancer, including research by the National Cancer Institute, the letter says. Further, the majority of underarm products sold in the U.S. and the UK do not contain parabens, the consultants note, citing CTFA.

The authors add that only some parabens, including isobutylparaben and n-butylparaben, have demonstrated weak in vivo estrogenic activity, noting methylparaben accounted for 62% of the parabens found in the breast tumor tissues in the study.

A second letter funded by CTFA and written by New York Medical College Department of Pathology professors Alan Young, PhD, and Gary Williams, MD, says the Darbre hypothesis that absorbed parabens from underarm cosmetics might contribute to breast cancer is "untenable" and the supporting paper is "seriously flawed on a number of counts."

The letter questions the nature and handling of the breast tumor samples, suggesting that acquisition and storage procedures could have contributed to paraben levels and pointing out it is unclear whether the samples were benign or malignant or had normal tissue associated with them.

In addition, the study does not include background information on the subjects, such as their age and whether they use underarm cosmetics formulated with parabens, information vital to ascertaining routes of exposure, the authors maintain.

British Cosmetic, Toiletry & Perfumery Association Director General Christopher Flower, PhD, submitted a third letter on the subject, pointing out the study suffered from a number of shortcomings. Methyl-paraben, the paraben found in the highest levels in the study, has "little or no reported estrogenic potency," he says, claiming the researchers should have investigated alternative sources of paraben exposure.

In a response published in the journal, Darbre et al. maintain the goal of the research was to determine "whether parabens can be detected in human breast tissue," not to demonstrate whether paraben exposure is linked to breast cancer. "Nowhere in the manuscript was any claim made that the presence of parabens had caused the breast cancer," the retort says.

Darbre et al. defended the use of blank values and the statistical method used to compensate for them, noting the issue was openly acknowledged in the paper. In response to the critique regarding the types of parabens found in the tissue, the researchers note that the remaining 38% of the parabens found in the tissue were ethylparaben, n-propylparaben, n-butylparaben and isobutylparaben, two of which have been shown to have in vitro uterotrophic activity, while other parabens have demonstrated in vivo estrogenic activity.

Darbre et al. also questioned the claim by CTFA that the majority of underarm products sold do not contain parabens, citing a published study reporting that out of 215 cosmetic products, 99% of leave-on products and 77% of rinse-off products are formulated with parabens.