Gender differences in pharmacokinetics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances in rats

Toxicokinetics of 8:2 fluorotelomer alcohol (8:2-FTOH) in male and female Hsd:Sprague Dawley SD rats after intravenous and gavage administration

“…PFOA was detected in the liver and kidney but not in the brain, consistent with previous studies [45,46]. Tissue:plasma ratios of 7:3-FTA in the liver and kidney were similar to those of PFOA in the same organs except in the brain where it was present in both males and females.…”

“…The plasma C max of PFOA and 7:3-FTA were 2- to 8-fold higher than the parent chemical 8:2 FTOH and reached T max much later than 8:2-FTOH. Females had a substantially shorter elimination half-life of PFOA than males, which has also been previously reported [27,[46], [47], [48]], resulting in lower C max and AUC after normalizing for dose (Table 3). The sex difference in PFOA half-life has been attributed to differences in renal resorption due to differences in expression of organic ion transporters [48,49].…”

Toxicokinetics of perfluorobutane sulfonate (PFBS), perfluorohexane-1-sulphonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in male and female Hsd:Sprague Dawley SD rats after intravenous and gavage administration

“…In this study, the male half-life of PFHxS was a little more than two weeks, while females displayed a half-life of around two days. Similarly, a previous report in Sprague-Dawley rats given 4 mg/kg PFHxS orally found females to have a half-life of around 2 days and males, 27 days [29]. For both PFBS and PFHxS, AUC and dose-adjusted AUC in plasma were lower and clearance was higher in females compared to males.…”

“…The longest chain PFSA, PFOS, had a half-life in the range of 33–40 days and did not display a sex difference in half-life after IV or gavage administration. Similarly, other studies have reported that the plasma half-life of PFOS was not different between sexes [29,30]. One report did find a sex difference in half-life: Charles River Sprague Dawley rats followed for 10 weeks after an oral dose of 2 or 15 mg/kg showed a 2-fold increase in half-life in females compared to males, 62 vs 38 days [15].…”

Evaluating thyroid hormone disruption: investigations of long-term neurodevelopmental effects in rats after perinatal exposure to perfluorohexane sulfonate (PFHxS)

“…In contrast, parental males had higher serum PFHxS levels, a different PFHxS distribution to organs, and showed clear signs of toxicity. The sex difference in adults is attributed to differential high expression of organic anion transporters in the kidneys of female rats that ensure efficient excretion of PFHxS into the urine [56][57][58] . Hence, male rats are exposed to much higher serum PFHxS levels than females.…”