OTC Coal Tar Skin Cancer Causation Data Lacking - FDA

The future of California Proposition 65 litigation against manufacturers, distributors and retailers of coal tar-containing dandruff shampoos, soaps and ointments could become clearer at a March 16 status conference in San Francisco state court.

While FDA concludes coal tar products do not increase the risk of skin cancer under conditions of use described in the OTC final monograph, and should not be required to carry additional warnings or restricted to Rx sale, the agency's Feb. 22 decision does not answer whether a Prop 65 warning would constitute "misbranding" under the FD&C Act.

Such a warning would state the product contains coal tar, "a chemical known to the state of California to cause cancer."

The agency's response to a citizen petition filed by Occupational Knowledge International also does not specifically address whether pharmaceutical-grade coal tar is the same as "crude" coal tar encompassed under the Prop 65 listing of carcinogenic "soots, tars and mineral oils."

FDA's safety review of the ingredient largely focused on medicinal-grade coal tar rather than other forms of the substance.

In examining published scientific articles, the agency excluded studies on occupational exposure because they did not involve pharmaceutical-grade coal tar, FDA notes. "Coal tar, at some exposures, has already been acknowledged to be carcinogenic. It would not be appropriate to extrapolate occupational data to humans using products under the conditions of use specified in the OTC drug product monograph," the agency opines.

FDA examined 11 published studies of topical applications of medicinal coal tar in humans and background incidence of skin cancer in psoriasis patients.

"While there are animal and human occupational exposure data to show that coal tar is carcinogenic, the data does not support that therapeutic use of coal tar in concentrations and formulations used in OTC drug products poses a risk of carcinogenicity," the agency concludes (¹ (Also see "Coal tar" - Pink Sheet, 26 Feb, 2001.)).

FDA notes the citizen petition largely was based on results from, and a quantitative risk assessment of, a dermal carcinogenicity bioassay conducted in mice at the Fraunhofer Institute of Toxicology in Germany. Nevertheless, the Fraunhofer data should not be used to calculate a "No Significant Risk Level" under conditions of OTC use because of several confounding factors in the study, the agency asserts.

The Fraunhofer study measured the incidence of skin tumors on mice from direct dermal application of coal tar. Doses were applied twice weekly for 78 weeks, and the study evaluated two different coal tar substances in a toluene vehicle.

"The agency believes that a quantitative risk assessment cannot be reasonably conducted using data from this study because of the presence of skin lesions, which likely changed the exposure to target sites and would confound extrapolation to humans," FDA says. "Analysis of systemic effects was confounded by secondary effects of skin infections and the entire study was confounded by the use of toluene due to its destructive effect on the skin of the mice in the study."

"In addition, it is not clear how the type of coal tar used in this study relates chemically to the types used in OTC drug products," the agency notes.

Furthermore, there are no reports in FDA's adverse event reporting system of carcinogenicity related to coal tar-containing products, the agency says. Of 25 AERs, "most...involved the skin or scalp (e.g., itching or burning), with a few allergic-type reactions."

Trial in the Prop 65 litigation had been postponed pending FDA's decision, but a new trial date could be set at the upcoming status conference.

While the California Attorney General's office iterated FDA's decision will not affect the Prop 65 case, OKI Executive Director Perry Gottesfeld, a plaintiff in the litigation, contended the case "received a boost" from the agency's recognition of "animal and human occupational exposure data" demonstrating carcinogenicity.

However, defendants are likely to view FDA's decision as bolstering their arguments that carcinogenicity warnings on coal-tar containing products sold in California are unnecessary. Defendants also may continue to push for summary judgment on grounds the requested warnings are federally preempted.

More than 20 defendants originally were named in the litigation, including drug distributor Bergen Brunswig, Whitehall-Robins, which markets Denorex, Johnson & Johnson's Neutrogena division and Tegrin marketer Reedco, a subsidairy of GlaxoSmithKline's Block Drug.