Subchronic and developmental toxicity studies of n-butyl propionate vapor in rats

Two inhalation studies were conducted to evaluate the possible subchronic and developmental toxic effects of n-butyl propionate. In the subchronic study, Sprague-Dawley rats (15/sex/group) were exposed to 0, 250, 750, or 1500 ppm vapor for 6 h/d, 5 d/wk for 13 wk. Five of the rats per sex per group were held after the final exposure for an 8-wk recovery period. Standard parameters of subchronic toxicity were measured throughout the study, and at the end of exposure and recovery periods, necropsies were performed, organs weighed, and tissues processed for microscopic examination. Exposure did not produce marked treatment-related deaths or adversely affect clinical signs, hematology, clinical chemistries, organ weights, or the histology of major visceral organs. The only systemic toxic effects were significant decreases in body weight, body weight gain, and feed consumption that occurred in 1500 ppm group rats. Morphologic changes were limited to the nasal cavity as evidenced by a concentration-related increased incidence and severity of olfactory epithelium degeneration in rats of the 750 and 1500 ppm groups. These degenerative microscopic alterations were primarily confined to the olfactory epithelium within the dorsal portion of the medial meatus, with lesser involvement of the olfactory mucosae overlying the tips of some of the adjacent ethmoturbinates. Both the systemic and nasal cavity effects appeared reversible after exposure ceased. In the developmental toxicity study, pregnant Sprague-Dawley rats (24/group) were exposed to 0, 500, 1000, or 2000 ppm vapor for 6 h/d on gestation d 6-15 and sacrificed on gestation d 20. All treatment-group dams exhibited significant reductions in body weight, body weight gain, and feed consumption. Gestational parameters were equivalent across all groups and there were no treatment-related developmental or teratogenic effects. The no-observed-adverse effects levels (NOAELs) determined for nbutyl propionate were 250 ppm for subchronic toxicity (based on the olfactory epithelium degeneration) and 22000 ppm for developmental toxicity (no developmental effects at top dose tested). Under the conditions of this study, a NOAEL was not determined for maternal toxicity.