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 Dr. Levitt |
The proposed ban of its over-the-counter sales was based on controversial murine models suggesting that hydroquinone could act as a carcinogen, along with reports, also controversial, linking the product with exogenous ochronosis. The FDA's action was met with strong opposition from the largest user of hydroquinone, the aesthetic dermatologic community, which was adamant in its assertion of the product's safety, and, after the four-month period of public comment, no regulatory action was taken.
But the issue was never officially put to bed, and with hydroquinone bans currently on in the European Union, Japan and Australia, doctors and patients alike may be justified in wondering if hydroquinone remains on borrowed time in the U.S.
Among those making the strongest argument against extrapolation of the mouse studies at the crux of the FDA's concerns was Jacob Levitt, M.D., who published a critical review of the existing literature. He suggests that renal tumors described in previous studies are highly sex-, species- and strain-specific, and therefore weren't relative to humans. He concluded that cases of murine leukemia couldn't be expected to result from small topical doses of hydroquinone in humans."The studies showed that the strain of rats that developed kidney problems also developed the problems independently, even without hydroquinone exposure, because they were genetically predisposed to do so, so it was unfair to link their tumors to hydroquinone," says Dr. Levitt, an assistant clinical professor of dermatology at the Mount Sinai Medical Center in New York.
DATA DETOUR Not only did the studies fail to prove a carcinogenic link, but with respect to the liver they could, in fact, easily be read to suggest the opposite, he adds. "There was indeed a slight increase in benign adenomas in relation to hydroquinone exposure, but there was a decrease in malignant liver carcinomas, so you could argue that hydroquinone had a protective effect." Ultimately, he holds, the "systemic exposure to hydroquinone from routine topical application is no greater than that from quantities present in common foods."
Dr. Levitt also evaluated the FDA concern that hydroquinone could increase the risk for ochronosis, and found a remarkably low incidence rate in relation to hydroquinone usage.
As noted by Dr. Levitt in his paper, "A literature review of exogenous ochronosis and clinical studies employing hydroquinone (involving over 10,000 exposures under careful clinical supervision) reveal an incidence of exogenous ochronosis in the United States of 22 cases in more than 50 years."
Interestingly, the majority of ochronosis cases found were associated with lower — not higher — concentrations of hydroquinone (2 percent, as opposed to the prescription strength of 4 percent). This suggests overuse of the product at the consumer level may be a potential problem, and offers one bit of support for limiting its use to doctor-supervised prescriptions only.
"The way dermatologists use hydroquinone is to use it over a period of about three months and if it doesn't work, you stop," Dr. Levitt explains. "After six months or so, you'll probably get a plateau of effect anyway, and will also need to stop; but if people are using the product over-the-counter every day for 10 or 20 years, then there can be a problem and in that regard, I could defend keeping it as prescription only." Dr. Levitt notes that prior to its proposal for the ban, the FDA itself had already approved a hydroquinone-containing product, the melasma treatment Tri-Luma, a prescription-strength topical containing retinoid (0.5 percent tretinoin), steroid (0.01 percent fluocinolone acetonide) and hydroquinone (4 percent).
