Evaluation of Hepatotoxic and Nephrotoxic Effects of Hexachlorobenzene, DDT , and p,p′‐ DDE in Rats

ABSTRACT Persistent organic pollutants such as hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT), and its major metabolite p,p′‐dichlorodiphenyldichloroethylene (p,p′‐DDE) are lipophilic organochlorine pesticides that persist in the environment and bioaccumulate in tissues. We aimed to evaluate the hepatic and renal effects of subchronic low‐dose oral exposure to HCB, DDT, and p,p′‐DDE in male rats using serum biochemistry and histopathology. Thirty‐two male Sprague–Dawley rats were randomly assigned to control, HCB, DDT, and p,p′‐DDE groups ( n = 8/group). Animals received 5 mg/kg of each compound or vehicle (corn oil) by oral gavage every other day for 5 weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin, blood urea nitrogen (BUN), and creatinine were measured. Liver and kidney tissues were examined histologically and injury was quantified by a semi‐quantitative histopathological H‐score. Exposure did not significantly alter ALT, AST, total bilirubin, BUN or creatinine. However, ALP activity was significantly decreased in the DDT‐ and p,p′‐DDE‐treated groups ( p < 0.05). Histopathology showed marked renal alterations in the HCB and DDT groups, including glomerular deformation, narrowed Bowman's space, and tubular disorganization, and the renal H‐score was significantly higher than control in both groups ( p < 0.001). Hepatic architecture and H‐score were similar in all groups. Low‐dose subchronic exposure to HCB and DDT was associated with quantifiable renal histopathological alterations in the absence of parallel biochemical abnormalities, which may reflect early, subclinical nephrotoxicity. DDT and p,p′‐DDE selectively reduced serum ALP activity. These findings suggest that more sensitive endpoints than serum biomarkers may be required to detect organ injury associated with organochlorine pesticide exposure.