The potential toxicity of the mesit

The potential toxicity of the mesityl oxide was evaluated using a combined repeated dose and reproductive/developmental toxicity screening test. The test consisted of four phases: pre-mating (14 days), mating (1-14 days), gestation (21-22 days), and early lactation (4 days). Male and female Sprague-Dawley rats were exposed to mean chamber vapor concentrationsof 0, 31, 103, or 302 ppm of the test substance (target concentrations of 0, 30, 100, or 300 ppm) for six hrs/day, 7 days/week for a total of 36 to 49 exposures for female rats (through Day 20 of gestation) and 49 exposures for male rats. Parameters examined consisted of body weight, body weight change, feed consumption, organ weights, gross pathology, histopathology, hematology, clinical chemistry, reproductive performance, and litter data. No mortality of adult animals was observed during the study. An exposure-dependent reduction (p =< 0.05) in feed consumption, and a corresponding reduction in mean body weight were observed during the pre-mating phase for male and female rats from all testsubstance exposure groups, and during the first week of the gestation phase for the high-and mid-exposure female rats. During exposure, effects of the test substance consisted of a transient reduction in activity for the high- and mid-exposure groups, and partially closed eyes for the high-exposure group. An increased incidence of post-exposure porphyrin nasal discharge was observed for all test substance exposure groups with the incidence-being slightly higer for the female rats when compared to the male rats. Additionally, post-exposure sialorrhea vas observed for 3 of 12 high-exposure male rats. These clinical signs were indicative of the irritating nature of the vaporized test substanse. A slight reduction in mean serum creatinine levels for all male exposure groups was not considered biologically significant since organ toxicity is associated with increases rather than decrease in serum creatinine level. No exposure-related changes were seen at necropsy for male or female rats. Histopathology revealed exposure-dependent changes in the olfactory and respiratory epithelium of the nasal passages which were characterized by the presence of sero-cellular exudates, chronic focal inflammation, and focal metaplasia of the respiratory and olfactory epithelium of the nasal passages. These changes are a common response to an irritating vapor. No other exposure-related changes were observed during histopathology examinations. In summary, exposure to 302, 103, or 31 ppm of the test substance was associated with a concentration-dependent lower feed consumption, body weight, and body weight gain; clinical abnormalities and nasal passage pathology in the test groups were consistent with exposure to an irritating vapor. Thus, a lowest-observed-adverse-effect level (LOAEL) for toxicity was determined to be 31 ppm based on effects on feed consumption, body weights, body weight gain, and nasal passage histopathology.