An Epidemiologic Investigation of Reproductive Hormones in Men with Occupational Exposure to Perfluorooctanoic Acid

Abstract

Perfluorooctanoic acid (PFOA), a potent synthetic surfactant used in industrial applications, is a peroxisome proliferator that has resulted in dose-related increases in hepatic, pancreatic acinar, and Leydig cell adenomas in laboratory animals. In addition, PFOA increased serum estradiol levels through the induction of hepatic aromatase activity. In 1993 and 1995, we conducted two cross-sectional studies of 111 and 80 production workers, respectively, and specifically measured their serum PFOA in relation to several reproductive hormones to determine whether such an effect occurs in humans. PFOA was not significantly associated with estradiol or testosterone in either year's study. A 10% increase in mean estradiol levels was observed among employees who had the highest levels of serum PFOA, although this association was confounded by body mass index. Neither was PFOA consistently associated with the other measured hormones. Our results provide reasonable assurance that, in this production setting, there were no significant hormonal changes associated with PFOA at the serum levels measured. Limitations of this investigation include its cross-sectional design, the few subjects exposed at the highest levels, and the lower levels of serum PFOA measured, compared with those levels reported to cause effects in laboratory animal studies.

Perfluorooctanesulfonate and other fluorochemicals in the serum of American Red Cross adult blood donors.

“…Changes in plasma cholecystokinin have not been observed in primates or humans exposed to APFO Olsen et al 2000). Hepatic toxicity, hypolipidemia, and abnormal hormone levels have not been associated with serum PFOA concentrations in APFO production workers whose serum levels have averaged 5 ppm with a range of and 0.1-114 ppm (Gilliland and Mandel 1996;Olsen et al 1998Olsen et al , 2000. A retrospective cohort mortality study of APFO production workers did not report statistically significant increased standardized mortality ratios for liver cancer, cirrhosis of the liver, or pancreas cancer, although an association was observed with prostate cancer mortality and nonspecific job duration of at least 10 years in the chemical plant (Gilliland and Mandel 1993).…”

Assessment of lipid, hepatic, and thyroid parameters with serum perfluorooctanoate (PFOA) concentrations in fluorochemical production workers

“…As a manufacturer and user of APFO until its phase-out beginning in 2000, the 3M Company (3M) has reported several periodic medical surveillance analyses of its fluorochemical production workers at its Antwerp, Belgium; Cottage Grove, MN; and Decatur, AL manufacturing facilities (Ubel et al 1980;Gilliland and Mandel 1996;Olsen et al 1998Olsen et al , 2000Olsen et al , 2003a. These analyses compared workers' clinical chemistry and hormone results in relation to their serum measurements of either PFOA or perfluorooctanesulfonate (PFOS, C 8 F 17 SO 3 -).…”

Serum levels of perfluorinated compounds and sperm Y:X chromosome ratio in two European populations and in Inuit from Greenland

“…Also, in rare minnow fish, PFOA exposure inhibited expression of genes responsible for thyroid hormone biosynthesis and also induced estrogen responsive genes [54]. Rats exposed to 25 mg PFOA/kg/day for 14 days developed Leydig cell hyperplasia and eventually also Leydig cell adenomas [55,56]. Male rats exposed to 5 or 10 mg of the PFAS perfluorododecanoic acid/kg/day for 14 days exhibited a decrease in testosterone levels and an increase in estradiol levels [57].…”