An Analysis of the National Toxicology Program′s (NTP) Technical Report (NTP TR 421) on the Toxicology and Carcinogenesis Studies of Talc

Abstract

The NTP toxicology and carcinogenicity studies of nonasbestiform, cosmetic-grade talc (the NTP Talc Report) were conducted by exposing male and female F344/N rats and B6C3F1 mice to target aerosol concentrations of 0, 6, and 18 mg/m 3 talc for 6 hr daily, 5 days per week. Based on results of the high dose, the Report concluded that talc caused lung tumors in female rats and pheochromocytomas in male and female rats, and there was no evidence of carcinogenic activity in mice. A thorough evaluation of lung toxicity revealed that talc-induced lung tumors occurred only in the group of animals that exhibited the most profound degree of chronic toxicity, However, these data were presented as empirical observations rather than discussed in a manner that would relate them to the risk assessment implications of the bioassay, i.e., relevant data were collected but not "used." In addition, the evaluation of the pheochromocytomas was inadequate because it failed to place sufficient emphasis on the spontaneous incidence of this tumor in rats, These deficiencies caused the author to vote against the conclusions presented in the Talc Report when it was reviewed by the NTP Board of Scientific Counselors, The appropriate conclusions are (1) the data do not indicate that the pheochromocytomas were treatment-related; (2) the maximum tolerated dose (MTD) was exceeded in the female rats exposed to the high dose; and (3) talc is not expected to cause lung tumors under conditions of exposure that fail to result in marked chronic lung toxicity.