Effects of inhalation exposure to propylene oxide on respiratory tract, reproduction and development in rats

Nasal, respiratory, reproductive and developmental toxicities of propylene oxide (PO) were examined by exposing male and female Sprague-Dawley rats to PO vapor by inhalation at a concentration of 0 (control), 125, 250, 500 or 1,000 ppm for 6 h/d, 7 d/wk, during a 5- to 6-wk period, including premating, mating and postmating or gestation. The inhalation exposure to 1,000 ppm PO seriously affected parental survival, the upper and lower respiratory tract, male and female reproductive systems, motor function, and fetal survival and development, whereas the exposure to 500 ppm or less primarily caused nasal lesions without any sign of reproductive or developmental toxicity. Because atrophy of the olfactory epithelium in the male rats exposed to 250 ppm was the most sensitive endpoint for PO toxicity, the NOAEL was determined to be 125 ppm for the nasal endpoint. An additional inhalation experiment was carried out to further examine developmental toxicity by exposing pregnant rats to 0, 125, 250, 500, 750 or 1,000 ppm PO during a 2-wk period of gestation, Day 6 through Day 19. The 2-wk inhalation experiment revealed that reduced fetal body weights and delayed ossification occurred in association with significantly reduced body weights of the dams exposed to 750 and 1,000 ppm, whereas neither fetal death nor teratogenicity occurred at those two exposure levels. It was concluded that the developmental toxicity of fetal death was manifested at parentally toxic exposure levels above 500 ppm, a level which seriously affected parental survival, the upper and lower respiratory tracts and reproductive system.