A 2-year inhalation rat and mouse
cancer study by the National Toxicology Program (NTP) on
1-bromopropane, a brominated
solvent most commonly used as a vapor degreaser, showed significant increase in
tumors in the lung of female mice and in the large intestine of male and female rats. The most sensitive endpoint was lung
tumors in female mice. Mice of both sexes had
hyperplasia and
inflammation of the nose and showed regeneration of lung tissue. The NTP assumed that these
tumors were due to genotoxic effects and that a linear dose-response relationship was appropriate. It is plausible that, similar to
chloroform,
hyperplasia and
inflammation are required as initial events for
tumor development. If true, then a threshold-based model may be more appropriate for
1-bromopropane. To test this hypothesis, a 28-day repeat dose inhalation Big Blue® Assay was conducted using female transgenic B6C3F1 mice. The target exposure concentrations and the exposure regimen were identical to those used by the NTP. Results demonstrated no elevation in mutant frequency of the cII transgene in lung, colon, or liver. Positive controls produced statistically significant increases in mutant frequencies across all tested tissues. These results demonstrate that
1-bromopropane does not induce cII mutants in lungs, colon, or liver under the testing conditions. These data have important ramifications in the quantitative evaluation of
tumor results for this chemical and support a mechanism of action where a threshold for carcinogenicity is plausible.