HEPATIC AND RENAL ASSESSMENT OF ACUTE EXPOSURE TO INHALED EPICHLOROHYDRIN - TOXICOLOGICAL EVALUATION AND EXPOSURE MODELING

To examine the hepatic and renal effects of acute exposure to inhaled epichlorohydrin (ECH), male F344 rats were exposed either to 0 or 100 ppm ECH by inhalation for 4 h. Hepatic and renal toxicity were assesse d at the termination of exposure and on days 1, 2, and 3 postexposure. Exposure to inhaled ECH caused no histopathological evidence of hepat ic or renal toxicity and had no effect on serum indicators of hepatic toxicity, or hepatic cytochrome P-450 and glutathione concentrations. Exposure to inhaled ECH resulted in an increase in relative kidney wei ght in rats that were either 65 +/- 2 days old or 73 +/- 2 days old on the day of inhalation exposure (young adult rats) but not in rats tha t were 96 +/- 2 days old on the day of inhalation exposure (adult rats ), and a decrease in absolute and relative liver weight in adult rats but not young adult rats. Blood urea nitrogen/creatinine (BUN/CREAT) w as decreased in young adult rats on day 0, and BUN was slightly increa sed in adult rats on days 1, 2 and 3. These observations indicate that acute exposure to 100 ppm ECH did not produce consistent alterations in indicators of hepatic and renal toxicity. Ambient impact assessment modeling (AIAM), a methodology for estimation of exposure over short time periods and comparison of these predicted ambient concentration l evels to short-term toxicological threshold values, was conducted for three typical industrial sources of ECH pollution. The results of thes e analyses illustrated the interdependence of toxicological evaluation and exposure modeling in short-term noncancer risk assessment and dem onstrated the usefulness of AIAM in prioritizing chemicals for additio nal toxicological evaluation.