Subchronic Toxicity Studies on Perfluorooctanesulfonate Potassium Salt in Cynomolgus Monkeys

Abstract

This study was conducted to determine the earliest measurable response of primates to low-level perfluorooctanesulfonate (PFOS) exposure and to provide information to reduce uncertainty in human health risk assessment. Groups of male and female monkeys received 0, 0.03, 0.15, or 0.75 mg/kg/day potassium PFOS orally for 182 days. Recovery animals from each group, except the 0.03 mg/kg/day dose group, were monitored for one year after treatment. Significant adverse effects occurred only in the 0.75 mg/kg/day dose group and included compound-related mortality in 2 of 6 male monkeys, decreased body weights, increased liver weights, lowered serum total cholesterol, lowered triiodothyronine concentrations (without evidence of hypothyroidism), and lowered estradiol levels. Decreased serum total cholesterol occurred in the 0.75 mg/kg/day dose group at serum PFOS levels > 100 ppm. Hepatocellular hypertrophy and lipid vacuolation were present at term in the 0.75 mg/kg/day dose group. No peroxisomal (palmitoyl CoA oxidase) or cell proliferation (proliferating cell nuclear antigen immunohistochemistry) was detected. Complete reversal of clinical and hepatic effects and significant decreases in serum and liver PFOS occurred within 211 days posttreatment. Liver-to-serum PFOS ratios were comparable in all dose groups, with a range of 1:1 to 2:1. Serum concentrations associated with no adverse effects (0.15 mg/kg/day) were 82.6 +/- 25.2 ppm for males and 66.8 +/- 10.8 ppm for females. Comparison of serum PFOS concentrations associated with no adverse effect in this study to those reported in human blood samples (0.028 +/- 0.014 ppm) indicated an adequate margin of safety.

Perfluorooctane sulfonate (PFOS) affects hormone receptor activity, steroidogenesis, and expression of endocrine‐related genes in vitro and in vivo

“…Exposure to PFOS caused a reduction in serum T4 and T3 in rats and mice [18], and a decrease in serum T3 and estradiol levels in monkeys [27]. However, the mechanism of thyroid disruption still needs to be explored.…”

Brain region distribution and patterns of bioaccumulative perfluoroalkyl carboxylates and sulfonates in East Greenland polar bears (Ursus maritimus)

“…Adverse effect levels have been determined for PFOS in the serum of cynomolgus monkeys [40]. The blood of the present polar bears has also been analyzed (Supplemental Data, Table S6), and with that, we may be able to more easily compare how close current concentrations are to adverse effect levels.…”

Excretion of PFOA and PFOS in Male Rats During a Subchronic Exposure

“…Comparatively, PFOA has a faster rate of elimination than PFOS in rats, as well as other animals and even humans. For both genders of cynomolgus monkeys, an elimination half-life of about 20-30 days was found following dosing with PFOA , while a half-life of approximately 100-200 days was determined after exposure to PFOS (Seacat et al 2002). Based on recent monitoring of retired production workers, it has been demonstrated that both these perfluorochemicals have a relatively longer serum elimination half-life in humans (4.4 ± 3.6 years for PFOA vs. 8-9 years for PFOS) than in most mammals (Burris et al 2002;Olsen et al 2007).…”

“…Increasing numbers of studies have indicated the toxic effects caused by this kind of peroxisome proliferators in exposed laboratory animals (Seacat et al 2002;2003). PFOA and PFOS caused reductions in body weight, decreases in weight gain rate, and interference in lipid metabolism in rats (Lau et al 2007;Luebker et al 2002).…”