PNNL

Abstract

Perfluorooctanoic acid (PFOA) among other perfluorinated acids is becoming recognized as a ubiquitous environmental contaminant. PFOA is resistant to environmental degradation and appears to undergo no biotransformation in animals. Previous toxicokinetic studies in rodents have indicated that urinary excretion is the most important elimination pathway once PFOA has been absorbed. In some species, large sex related differences in urinary excretion have been reported that cause females to have much shorter blood or plasma elimination half-lives than males. Whether this phenomenon occurs in fish is unknown. Therefore, this study sought to determine the disposition of PFOA in male and female fathead minnows (Pimephales promelas) after a single oral dose of PFOA and subsequent euthanasia at various times until 336 hrs post-dosing. The PFOA concentration was then measured in plasma, gonads and fish carcass and the concentration-time profiles analyzed using toxicokinetic methods. The results indicated a clear sex difference in the elimination of PFOA. The plasma elimination half-life of PFOA in female minnows was 6.3 hrs while in male minnows it was 68.5 hrs. Pretreatment of female minnows with the synthetic androgen trenbolone, substantially delayed the elimination of PFOA, causing the elimination half-life to increase to 25.3 hrs. In males, pretreatment with the synthetic estrogen ethynylestradiol (EE2) had no effect on PFOA toxicokinetics. These results indicate sex differences in PFOA elimination in fathead minnows is at least partially associated with lower circulating androgen levels in females. Whether sex differences in PFOA elimination in minnows is attributable to differences in renal activity of organic anion transporters, as it appears to be for rodents, is unknown at present but clearly warrants further study.