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The urinary excretion of perfluorooctanoic acid (PFO) by male and female rats was investigated. Female rats excreted 76 ± 2.7 (SEM)% of a 2-mg dose of nonionic fluorine (as PFO) in the urine in 24-hr whereas male rats excreted only 9.2 ± 3.5% of the dose. The PFO clearance, inulin clearance, net excretion rate of PFO, and the glomerular filtration rate of PFO were measured. The effect of probenecid, an inhibitor of the organic acid transport system, on these measurements was also determined. In female rats the PFO clearance was severalfold greater than the inulin clearance and the clearance of PFO was markedly reduced by probenecid. Conversely, in male rats the PFO clearance was only a fraction of the inulin clearance and was virtually unaffected by probenecid. The data indicate that female rats are able to rapidly eliminate PFO in the urine by an active secretory mechanism which is inhibited by probenecid. In male rats this secretory mechanism is either absent or relatively inactive. This difference in PFO excretion by the male and female may explain the sex-related difference in PFO toxicity in which male rats are more susceptible to high doses than females.
Hanhijärvi et al. (Fri,) studied this question.