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

Abstract

Objectives Perfluorooctanoic acid (PFOA) results in peroxisome proliferator mediated effects in rats and mice resulting in hypolipidemia but not in monkeys. Counterintuitive modestly positive associations between PFOA and cholesterol levels in production workers have been inconsistently reported. The purpose of this assessment was to examine this association in male workers who manufactured or used PFOA at three facilities. Methods Subjects were male employee voluntary participants of a fluorochemical medical surveillance program who provided blood samples for serum measurement of PFOA (perfluorooctanoate) and various lipid, hepatic, and thyroid parameters. Statistical analyses included multiple and logistic regression and analysis of covariance. Results A total of 506 employees, who did not take cholesterol-lowering medications (93% of all male participants), were analyzed. Serum PFOA concentrations ranged from 0.007 to 92.03 lg/ml [arithmetic mean 2.21 lg/ml (95% confidence interval 1.66-2.77), median 1.10 lg/ml]. Adjusted for age, body mass index, and alcohol usage in regression analyses, PFOA was not statistically significantly (P > 0.05) associated with total cholesterol or low-density lipoproteins (LDL). High-density lipoproteins (HDL) were significantly negatively (P < 0.01) associated with PFOA for the three facilities combined but not by individual sites, indicating the overall result was likely a consequence of residual confounding due to different demographic profiles at these sites. Serum triglycerides were significantly positively associated with PFOA but not consistently by locations. There were no statistically significant associations observed between PFOA and hepatic enzymes for the three facilities combined although some modest positive associations were observed between PFOA and hepatic enzymes at one of the three facilities. Analyses of all locations showed no associations with TSH or T4 and PFOA. A negative association was observed for free T4 and positive association for T3; however, the findings were well within these assays' normal reference ranges. Conclusion There was no evidence that employees' serum PFOA concentrations were associated with total cholesterol or LDL. A negative association with HDL was explained by demographic differences across the three locations. Several explanations are offered for the inconsistent triglyceride associations with PFOA including both methodological as well as biological possibilities.

Consumption of Seafood, Serum Liver Enzymes, and Blood Levels of PFOS and PFOA in the Japanese Population

“…Exposure of Sprague-Dawley rats to PFOS and PFOA at a dose of 20 mg/kg resulted in hepatomegaly and severe histological changes of the liver, such as fatty degeneration, hepatocytic necrosis, and inflammatory cell infiltration 5) . Positive correlations of serum levels of PFOA with serum liver enzymes (γ -GTP, GOT or GPT) have been reported in several studies on fluorochemical workers with heavy exposure to PFOA or its related substance 32,33) but not in others 34,35) . Positive correlations were also observed between serum levels of PFOA or PFOS and hepatic enzymes (γ -GTP and/or GPT) in populations of the U.S. with high or background exposure to these PFCs 36,37) .…”

Environmental Thyroid Disruptors and Human Endocrine Health

“…Modest associations between PFOA and THs (negative for free T4 and positive for T3) were reported in 506 PFOA production workers across three production facilities (Olsen & Zobel, 2007); there were no associations between TSH or T4 and PFOA, and the free TH levels were within the normal reference range. On the other hand, Metzer et al (Metzer et al, 2010) recently determined whether increased serum PFOA or PFOS concentrations are associated with thyroid disease in a general adult US population sample (n = 3,974 individuals ≥ 20 years of age from NHANES waves 1999-2000 (n = 1,040), 2003-2004 (n = 1,454), and 2005-2006 (n = 1,480)).…”

“…The renal clearance of PFOA and PFOS is negligible in humans, leading to reported half-lives in blood serum of 3.8 and 5.4 years for PFOA and PFOS, respectively (Olsen et al, 2007).…”

“…Occupational exposure to PFOA reported in 2003 showed mean serum values of 1,780 ng/mL (range, 40-10,060 ng/mL) (Olsen et al, 2003a) and 899 ng/mL (range, 722-1,120 ng/mL) (Olsen et al, 2003b). Since then, voluntary industry reductions in production and use of other perfluorinated compounds, such as the US EPA-initiated PFOA Stewardship Program (US EPA, 2006), have contributed to a decreasing trend in human exposure for all perfluorinated compounds (Calafat et al, 2007;Olsen et al, 2007 Numerous studies have now shown PFAAs to impair thyroid homeostasis in animal studies. Depression of serum T4 and T3 in PFOS-exposed rats has been reported (Lau et al, 2003;Luebker et al, 2005;Seacat et al, 2003), without the concomitant increase in TSH that would be expected through feedback stimulation.…”

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

“…A study on male workers involved in ammonium perfluorooctanoate production showed that mean serum PFOA, measured in 1993, 1995 and 1997, was 5000 (SD 12200) ng/ml, 6800 (SD 16000) ng/ml and 6400 (SD 14300) ng/ml [31]. Another study looking at male volunteers from the 3M company workforce at three different locations found mean serum PFOA and PFOS concentrations at 2.21 (SD 6.40) µg/ml and 1.05 (SD 0.97) µg/ml respectively [32].…”