Subchronic Inhalation Toxicity and Neurotoxicity Assessment of Cumene in Fischer 344 Rats

Male and female Fischer 344 rats were exposed to cumene vapor at 0, 100, 500, and 1,200 ppm for 6 h per day, 5 days per week, for 13 weeks; a satellite group received a single 6-h exposure. A subsequent 13-week study with a 4-week recovery period was conducted at 0, 50, 100, 500, and 1,200 ppm. Following the single exposure, the functional observational battery was altered at 500 and 1,200 ppm through 6 h postexposure. In the subchronic studies, there were no exposure-related changes in the functional observational battery, auditory brain stem response, brain measurements, or nervous system histopathology. Motor activity decreases seen only in male rats exposed to 500 or 1,200 ppm in the first study were not replicated in the second study. The 500-and/or 1,200-ppm groups showed transient decreases in body weight gain and food consumption, an increase in water consumption, and changes in several hematologic and clinical chemistry parameters. There were no exposure-related ophthalmologic findings or effects on spermatogenesis. Weights of liver, kidneys, and adrenal glands were increased in the 500- and 1,200-ppm groups. Renal proximal tubular cell hypertrophy, hyperplasia, and hyaline drop formation were observed in the male rats at 500 and 1,200 ppm. In conclusion, exposure to cumene vapor resulted in mild toxicity at 1,200 ppm, minimal effects at 500 ppm, and no observable effects at 50 and 100 ppm. Cumene vapor exposure was neither neurotoxic nor ototoxic in these studies.