Characterization of risk for general population exposure to perfluorooctanoate.
Perfluorooctanoate (PFOA), an environmentally and metabolically stable perfluorinated carboxylic acid, has been detected in the serum of children, adults and the elderly from the United States with the upper bound of the 95th percentile estimate in the range of 0.011-0.014 microg/mL (ppm). In this risk characterization, margins of exposure (MOE), which can provide a realistic perspective on potential for human risk, were determined by comparison of general population serum PFOA concentrations with serum concentrations from toxicological studies that are associated with the lower 95% confidence limit of a modeled 10 percent response or incidence level (LBMIC(10)) using USEPA BMDS software. The LBMIC(10) was estimated using surrogate data from other studies or pharmacokinetic relationships if serum PFOA data were not available. Modeled dose-responses (with resulting LBMIC(10) values) included post-natal effects in rats (29 microg/mL), liver-weight increase (23 microg/mL), and body-weight change (60 microg/mL) in rats and monkeys, and incidence of Leydig cell adenoma (125 microg/mL) in rats. MOE values based on the upper bound 95th percentile population serum PFOA concentration were large, ranging from 1600 (liver-weight increase) to 8900 (Leydig cell adenoma). These MOE values represent substantial protection of children, adults, and the elderly.
Butenhoff
John L
JL
Medical Department, 3M Company, Building 220-2E-02, St. Paul, MN 55144, USA. jlbutenhoff@mmm.com
Gaylor
David W
DW
Moore
John A
JA
Olsen
Geary W
GW
Rodricks
Joseph
J
Mandel
Jeffrey H
JH
Zobel
Larry R
LR
D000328:Adult; D000368:Aged; D000818:Animals; D000831:Animals, Newborn; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002210:Caprylates / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D005260:Female; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D007984:Leydig Cell Tumor / Q000139:chemically induced; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D008297:Male; D008954:Models, Biological; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D018570:Risk Assessment / Q000379:methods; D013736:Testicular Neoplasms / Q000139:chemically induced; D018675:Toxicity Tests
D002210:Caprylates; D005466:Fluorocarbons; C023036:perfluorooctanoic acid