Screening-level population risk assessment of nasal tumors in the US due to naphthalene exposure.

Several naphthalene Unit Risk Factors (URFs) were proposed by the US Environmental Protection Agency in 2004 using data on the development of olfactory epithelial neuroblastomas and nasal respiratory epithelial adenomas in rats, but these URFs may be inappropriate and unnecessarily conservative for estimating human cancer risks. The purpose of the present exercise was to perform a screening-level population risk assessment of the US population to compare the observed number of naphthalene-induced nasal tumors in the US to the number that would be predicted if the URFs for naphthalene were as proposed. Nine scenarios were evaluated to represent the range of exposures individuals have typically experienced. Results indicate that the total predicted burden of naphthalene-induced nasal tumors per year in the US (65,905 rare nasal tumors, of which 29,121 are olfactory epithelial neuroblastomas) is much greater than the number of these tumors actually observed per year (910 total nasal tumors, of which 66 are olfactory neuroblastomas) over the period 1973-2006. This suggests that using rat nasal tumor data to derive a naphthalene URF for humans should be re-evaluated.

A review of whole animal bioassays of the carcinogenic potential of naphthalene.

This report provides a summary of deliberations conducted under the charge for members of Module A participating in the Naphthalene State-of-the-Science Symposium (NS3), Monterey, CA, October 9-12, 2006. Whole animal bioassays have been performed by the National Toxicology Program in mice and rats to ascertain the carcinogenic potential of naphthalene by inhalation exposure. A statistically significant increased incidence of pulmonary alveolar/bronchiolar adenoma (a benign lesion), was observed among female mice; an observed increase among the males did not reach statistical significance. No nasal tumors were observed in either sex. A tumorigenic response was observed in both sexes of rats, in males an increased incidence of nasal respiratory epithelium adenoma (a benign rather than malignant lesion) and in females, olfactory epithelial neuroblastoma. Interpretations of these studies vary. On the one hand, evidence of extensive non-neoplastic response in both sexes of both species indicates cytotoxicity occurred at all doses, and strongly suggests that cytotoxicity played a significant role in the tumor responses observed in the target tissues. On the other hand, olfactory epithelial neuroblastoma has rarely been observed in NTP bioassays. This review seeks to develop a consensus understanding of the scientific evidence provided by these studies, taking into account that they have been used as the basis for quantitative human cancer risk assessment, and suggests scientific studies that, if performed, could resolve scientific uncertainties.