Half-Life of Serum Elimination of Perfluorooctanesulfonate,Perfluorohexanesulfonate, and Perfluorooctanoate in Retired Fluorochemical Production Workers

Abstract

BackgroundThe presence of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHS), and perfluorooctanoate (PFOA) has been reported in humans and wildlife. Pharmacokinetic differences have been observed in laboratory animals.ObjectiveThe purpose of this observational study was to estimate the elimination half-life of PFOS, PFHS, and PFOA from human serum.MethodsTwenty-six (24 male, 2 female) retired fluorochemical production workers, with no additional occupational exposure, had periodic blood samples collected over 5 years, with serum stored in plastic vials at −80°C. At the end of the study, we used HPLC-mass spectrometry to analyze the samples, with quantification based on the ion ratios for PFOS and PFHS and the internal standard 18O2-PFOS. For PFOA, quantitation was based on the internal standard 13C2-PFOA.ResultsThe arithmetic mean initial serum concentrations were as follows: PFOS, 799 ng/mL (range, 145–3,490); PFHS, 290 ng/mL (range, 16–1,295); and PFOA, 691 ng/mL (range, 72–5,100). For each of the 26 subjects, the elimination appeared linear on a semi-log plot of concentration versus time; therefore, we used a first-order model for estimation. The arithmetic and geometric mean half-lives of serum elimination, respectively, were 5.4 years [95% confidence interval (CI), 3.9–6.9] and 4.8 years (95% CI, 4.0–5.8) for PFOS; 8.5 years (95% CI, 6.4–10.6) and 7.3 years (95% CI, 5.8–9.2) for PFHS; and 3.8 years (95% CI, 3.1–4.4) and 3.5 years (95% CI, 3.0–4.1) for PFOA.ConclusionsBased on these data, humans appear to have a long half-life of serum elimination of PFOS, PFHS, and PFOA. Differences in species-specific pharmacokinetics may be due, in part, to a saturable renal resorption process.

Bias in half-life estimates using log concentration regression in the presence of background exposures, and potential solutions

“…(1), provided that the covariates have constant multiplicative effects on serum concentrations over time. 7 Studies of post-shift workers, 2,5 retired workers, 4 fasting subjects, 6 and subjects undergoing exposure interventions 7,9 have used regression of log biomarker concentrations on time to estimate elimination rate constants and corresponding half-lives for environmental contaminants. However, Eq.…”

“…A previous study of a retired US occupational cohort reported an average PFOA half-life estimate of 3.8 years from 5 years of follow-up with a baseline median serum PFOA concentration of 408 ng/ml and up to eight measurements per participant. 4 All three PFOA half-life estimates relied on some form of log concentration regression. By how much might these PFOA half-life study estimates be overestimated because of background exposures?…”

Excretion of PFOA and PFOS in Male Rats During a Subchronic Exposure

“…For both genders of cynomolgus monkeys, an elimination half-life of about 20-30 days was found following dosing with PFOA , while a half-life of approximately 100-200 days was determined after exposure to PFOS (Seacat et al 2002). Based on recent monitoring of retired production workers, it has been demonstrated that both these perfluorochemicals have a relatively longer serum elimination half-life in humans (4.4 ± 3.6 years for PFOA vs. 8-9 years for PFOS) than in most mammals (Burris et al 2002;Olsen et al 2007). …”

Structure–activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor

“…Besides, the negligible renal clearance of PFCs leads to a possibility of long-term exposure in human. For example, as one of the most concerned PFCs, PFOS is present in the blood of general population at a level of about 20 ppb and an estimated half-life of nearly 5.4 years (Calafat et al 2007;Olsen et al 2007). Because of the characteristics of wide distribution and high stability, there has been a great concern as to PFCs' potential harmful effects on human health (Steenland et al 2010).…”