Male reproductive system parameters in a two-generation reproduction study of ammonium perfluorooctanoate in rats and human relevance

Ammonium perfluorooctanoate (ammonium PFOA) is an industrial surfactant that has been used primarily as a processing aid in the manufacture of fluoropolymers. The environmental and metabolic stability of PFOA together with its presence in human blood and long elimination half-life have led to extensive toxicological studies in laboratory animals. Two recent publications based on observations from the Danish general population have reported: (1) a negative association between serum concentrations of PFOA in young adult males and their sperm counts and (2) a positive association among women with time to pregnancy. A two-generation reproduction study in rats was previously published (2004) in which no effects on functional reproduction were observed at doses up to 30 mg ammonium PFOA/kg body weight. The article contained the simple statement: “In males, fertility was normal as were all sperm parameters”. In order to place the recent human epidemiological data in perspective, herein we provide the detailed male reproductive parameters from that study, including sperm quality and testicular histopathology. Sperm parameters in rats from the two-generation study in all ammonium PFOA treatment groups were unaffected by treatment with ammonium PFOA. These observations reflected the normal fertility observations in these males. No evidence of altered testicular and sperm structure and function was observed in ammonium PFOA-treated rats whose mean group serum PFOA concentrations ranged up to approximately 50,000 ng/mL. Given that median serum PFOA in the Danish cohorts was approximately 5 ng/mL, it seems unlikely that concentrations observed in the general population, including those recently reported in Danish general population, could be associated causally with a real decrement in sperm number and quality.