Subchronic toxicity studies on perfluorooctanesulfonate potassium salt in cynomolgus monkeys.
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.
Seacat
Andrew M
AM
3M Medical Department, Saint Paul, Minnesota 55133, USA.
Thomford
Peter J
PJ
Hansen
Kris J
KJ
Olsen
Geary W
GW
Case
Marvin T
MT
Butenhoff
John L
JL
D000284:Administration, Oral; D017738:Alkanesulfonic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005466:Fluorocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008136:Longevity / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D009929:Organ Size / Q000187:drug effects; D020675:Peroxisomes / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012074:Remission Induction; D018675:Toxicity Tests / Q000379:methods*
D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; D018809:Proliferating Cell Nuclear Antigen; C076994:perfluorooctane sulfonic acid