Hepatic and Renal Assessment of Acute Exposure to Inhaled Epichlorohydrin: Toxicological Evaluation and Exposure Modeling

Abstract

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 assessed at the termination of exposure and on days 1, 2, and 3 postexposure. Exposure to inhaled ECH caused no histopathological evidence of hepatic 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 weight 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 that 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) was decreased in young adult rats on day 0, and BUN was slightly increased in adult rats on days I, 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 levels to short-term toxicological threshold values, was conducted for three typical industrial sources of ECH pollution. The results of these analyses illustrated the interdependence of toxicological evaluation and exposure modeling in short-term non-cancer risk assessment and demonstrated the usefulness of AIAM in prioritizing chemicals for additional toxicological evaluation.