Selected Lesions of Dioxin in Laboratory Rodents

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) has been the subject of intensive investigations in laboratory animals during the last 2 decades. Toxicity studies have been conducted in several species of rodents and include several carcinogenicity studies as well as numerous mechanistic studies initiated to elucidate dioxin's mode of action, as both a carcinogen and a toxicant. Hepatotoxicity is a primary effect of dioxin. There has been an increase in hepatocellular tumors reported in both rats and mice exposed to dioxin. In addition to neoplastic changes, dioxin causes a spectrum of toxic changes in the liver. Additional neoplastic changes include subcutaneous fibrosarcomas and thyroid follicular cell tumors in both rats and mice and histiocytic sarcomas in mice. Dioxin causes devlopmental effects in the palate and kidney of mice. Changes in the female reproductive tract include ovarian atrophy, sertoliform hyperplasia, and Sertoli cell tumors. Dosing in utero results in gross malformations of the external genetalia. The effects of dioxin on the rodent model of endometriosis are described. In males, there are lowered sperm counts in the epididymis and minor testicular effects following gestational administration of dioxin. Both estrogenic and antiestrogenic-like effects have been ascribed to dioxin in laboratory animals; these activities are the result of dioxin-specific pathways resulting in the same end points as classic reproductive toxicants.