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 microg/ml [arithmetic mean 2.21 microg/ml (95% confidence interval 1.66-2.77), median 1.10 microg/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.