Stimulation by Oestradiol of the Urinary Excretion of Perfluorooctanoic Acid in the Male rat

Abstract

The urinary excretion of perfluorooctanoic acid (PFOA) was studied in male Wistar rats after castration and oestradiol administration as well as in intact females and males. During the first 24 hr females excreted 72 +/- 5% (N = 6) of a single intraperitoneal dose of PFOA (50 mg/kg) in urine whereas the intact males excreted only 9 +/- 4% (N = 6). After castration followed by oestradiol administration (500 micrograms/kg every 2nd day for 14 days), the males excreted PFOA in urine in similar amounts as the females (68 +/- 14% at 24 hr, N = 10). Oestradiol treatment of non-castrated males produced similar results (61 +/- 19% at 24 hr, N = 10). Also castration without oestradiol administration significantly enhanced the renal PFOA excretion, but not as effectively as oestradiol treatment. After 96 hr, the concentration of PFOA in serum of intact males was 17-40 times higher than in the serum of other groups. PFOA was similarly bound by the proteins in the serum of females and males. Phase II metabolism of PFOA was not shown either in males or females.

Peer Reviewed: Perfluorochemical Surfactants in the Environment

“…This difference is explained by rapid elimination of PFOA in female rat urine relative to that of males. Sex-related differences in the pharmacokinetics of PFOA are not evident in mice, monkeys, and dogs (31).…”

Age effect on perfluorooctanoate (PFOA) plasma concentration in post-weaning rats following oral gavage with ammonium perfluorooctanoate (APFO)

“…Following intravenous administration, the half-lives for male and female rats were 5.6 and 0.08 days, respectively (Ohmori et al, 2003). Many investigators have reported similar sex-dependent differences in elimination in rats (Davis et al, 1991;Hanhijärvi et al, 1982;Kojo et al, 1986;Kudo et al, 2001Kudo et al, , 2002Kudo and Kawashima, 2003;Ophaug and Singer, 1980;Vanden Heuvel et al, 1991;Ylinen et al, 1989).…”

“…Elimination is down regulated by testosterone in both female and castrated male rats Kudo et al, 2001Kudo et al, , 2002 and up regulated by estradiol in male rats (Ylinen et al, 1989). All of the above studies were conducted on sexually mature rats.…”

13‐Week Dietary Toxicity Study of Ammonium Perfluorooctanoate (APFO) in Male Rats

“…rat is frequently used in safety evaluation studies as a representative of a rodent species. Male rats were used since the compound is cleared less quickly by male rats (Kojo et al, 1986;Ylinen et al, 1989) and effects in male rats have been demonstrated at lower doses than in females (Griffith and Long, 1980;Kennedy et al, 2004).…”