U.S. Epa Inhalation Reference Concentration for Bromomethane

Abstract

The EPA inhalation reference concentration (RfC) for bromomethane was derived based on lesions observed in rat nasal epithelium from a chronic study. Reuzel et al. (1991) exposed Wistar rats to 0, 3, 30, or 90 ppm bromomethane for 6 h/day, 5 days/wk for up to 29 mo. Hyperplastic changes in the basal cells accompanied by degeneration in the olfactory epithelium in the dorso-medial part of the nasal cavity were observed in all exposed groups of both sexes at 29 mo of exposure. These changes were concentration-related in both incidence and severity and were statistically significant at 29 mo. The effect was not statistically significant in smaller groups of animals examined after 12 or 24 mo of exposure. This study identifies a lowest-observed-adverse-effect level (LOAEL) at 3 ppm in the rat. In the chronic National Toxicology Program (NTP) study (NTP, 1992), B6C3F1 mice were exposed to 0, 10, 33, or 100 ppm bromomethane for 6 h/day, 5 days/wk, for either 6, 15, or 24 mo. A statistically significant increase in the incidence of olfactory epithelial necrosis and metaplasia was seen in the nasal cavities of male and female mice exposed to 100 ppm. Mice exposed to lower concentrations did not exhibit significant increases in any of the lesions. Based on the results of this study, a LOAEL of 100 ppm and a no-observed-adverse-effect level (NOAEL) of 33 ppm was identified in mice. The RfC was based on the more sensitive effect from the rat study. The apparent 30-fold difference in the effect level between the 24- and 29-mo durations is surprising, because comparison of the effects after exposures ranging from 1 day to 24 mo shows similar effect levels. The LOAEL of 3 mg/m³ was adjusted to a continuous exposure scenario [LOAEL(ADI) = 2.08 mg/m³], and the human equivalent concentration was calculated to be 0.48 mg/m³. This value was divided by an uncertainty factor of 100, which includes intraspecies uncertainty, use of a LOAEL for a mild effect, and interspecies extrapolation. The resulting RfC is 5 μg/m³.