Alkoxyresorufin Metabolism in White-Footed Mice at Relevant Environmental Concentrations of Aroclor 1254

Abstract

Recent investigations have detected polychlorinated biphenyl (PCB) body burdens in wild white-footed mice (Peromyscus Ieucopus) captured at hazardous waste sites. Insufficient information is currently available to interpret the toxicological significance of these body burdens. In an effort to provide this information, we investigated hepatic changes and PCB body burdens in whitefooted mice following a 21-day dietary exposure to a PCB mixture, Aroclor 1254. Dietary concentrations tested were 0, 2.5, 25, 50, and 100 mg Aroclor 1254/kg diet (reported as ppm). Liver weights were significantly increased at all concentrations except 2.5 ppm. Ethoxyresorufin O-dealkylase (EROD) activity, an aryl hydrocarbon hydroxylase-type substrate, was significantly increased at all PCB concentrations, but the dose-response tended to plateau above 25 ppm. Pentoxyresorufin O-dealkylase (PROD) activity, a putative phenobarbital-type substrate, was significantly increased in a dose-dependent manner at 25 ppm PCB and above, with no plateau response. Pentobarbital sleep time was significantly decreased at 25 ppm, but not at 2.5 ppm. Results indicate white-footed mice undergo a mixed-type in duction pattern following exposure to Aroclor 1254, with EROD the most sensitive indicator of PCB exposure. This investigation identified a no observed effect concentration for liver weights and PROD activity at 2.5 ppm in the diet which is equivalent to a body burden of 2.0 mg Aroclor 1254/kg wet wt of mice; the no observed effect concentration for EROD is below these levels. These results support the use of EROD, PROD, and liver weight as biomarkers of PCB exposure in field-captured rodents.