Pheochromocytoma in rats: a weak link in the assessment of talc carcinogenicity?

This Letter to the Editor addresses the recent step by the International Agency for Research on Cancer (IARC) to reclassify pure talc from Group 2B "Possibly carcinogenic to humans" to Group 2A "Probably carcinogenic to humans". This change was made by IARC not based on any new data, but by reassessing previous studies, including an inhalation study on rats and mice performed in the 1980s under the auspices of the National Toxicology Program (NTP). The NTP study, however, found evidence of tumorigenicity in rats only, but not in mice. This contradicts the toxicological principle of "at least two species" for extrapolating carcinogenicity status from animals to humans. Benign and malignant pheochromocytoma, a rare condition identified in the adrenal medulla of rats in multiple NTP studies, played a special role in the IARC talc reclassification, being evaluated as the "unusual" finding requiring a precautionary approach. The Letter argues that combined benign, malignant, and complex pheochromocytoma in rats is irrelevant for the assessment of talc carcinogenicity in humans. However, with the exclusion of pheochromocytoma argumentation, the need for talc reclassification appears to be highly questionable.