© 1981 Oxford University Press
research-article |
A Thirteen Week Repeated Inhalation Study of Ethylene Dibromide in Rats,1,,2
Toxicology Research Laboratory, Health and Environmental Sciences U.S.A., Dow Chemical U.S.A., Midland, MI 48640
A Thirteen Week Repeated Inhalation Study of Ethylene Dibromide in Rats. Nitschke, K.D., Kociba, R.J., Keyes, D.G. and McKenna, M.J. (1981). Fundam. Appl. Toxicol. 1:437–442. Male and female CDF (F 344) rats were exposed to 0, 3, 10 or 40 ppm ethylene dibromide (EDB), 6 hours/ day, 5 days/week for 13 weeks for a total of 67–68 exposures in 95–96 days. Scheduled sacrifices occurred after 1,6, and 13 weeks of exposure. Additional rats were held for a recovery period of 88–89 days and subsequently necropsied. Rats exposed to 3 ppm EDB showed no consistent effect in any parameter measured. At 10 ppm, EDB caused slight epithelial hyperplasia of the nasal turbinates in animals necropsied after 1, 6 or 13 weeks of exposure; however, 88 days after the last exposure to EDB, nasal turbinate changes were not observed. Rats exposed to 40 ppm EDB exhibited a decrease in body weight gain throughout the 13-week exposure period, an increase in liver and kidney weights after 6 and 13 weeks of exposure, and hyperplasia and nonkeratinizing squamous metaplasia of the respiratory epithelium of the nasal turbinates. After a recovery period of 88 days, there was a reversion to normal of the nasal turbinates in 19 of 20 rats and only an isolated focus of hyperplasia of the nasal epithelium in the one remaining rat. It is believed that this observation would have returned to control limits if allowed a slightly longer recovery period. The most sensitive response associated with repeated subchronic exposure of rats to 10 or 40 ppm EDB involves pathologic changes in the respiratory epithelium of the nasal turbinates. These changes regressed during a subsequent postexposure phase with no indication of a progression of the lesions. Since exposure of rats to 3 ppm EDB elicited no discernible response in any of the tissues examined, 3 ppm was defined as the no-observable-effect level.