Induction of Leydig Cell Adenomas by Ammonium Perfluorooctanoate: A Possible Endocrine-Related Mechanism. Cook, J.C., Murray, S.M., Frame, S.R., and Hurtt, M.E. (1991). Toxicol. Appl. Pharmacol. 000, 000-000. Ammonium perfluorooctanoate (C8) produced an increased incidence of Leydig cell adenomas in Crl:CD(trademark)BR (CD) rats fed 300 ppm for two years. A hormonal (non-genotoxic) mechanism was examined since C8 was negative in short-term tests for genotoxicity. Adult made CD rats were gavaged with either 0, 1, 10, 25, or 50 mg/kg C8 for 14 days. In addition, a control group was pair-fed to the 50 mg/kg C8 group. A dose-dependent decrease in body and relative accessory sex organ (ASO) weights was seen, with the relative ASO weights of the 50 mg/kg group significantly less than the pair-fed control. Serum estradiol levels were elevated in the 10, 25, and 50 mg/kg C8-treated animals. Estradiol levels were 2.7-fold greater in the 50 mg/kg C8 group when compared to the pair-fed control. The increase in serum estradiol levels occurred at the same dose levels as the increase in hepatic Beta-oxidation activity. A statistically significant downward trend with dose was seen in serum testosterone levels when compared with the ad libitum control.