Determinants of PFOA Serum Half-Life after End of Exposure: A Longitudinal Study on Highly Exposed Subjects in the Veneto Region

Abstract

Background: Perfluoroalkyl substances (PFAS) are widely used, ubiquitous, and highly persistent man-made chemicals. Groundwater of a vast area of the Veneto Region (northeastern Italy) was found to be contaminated by PFAS from a manufacturing plant active since the late 1960s. As a result, residents were overexposed to PFAS through drinking water until 2013, mainly to perfluorooctanoic acid (PFOA).

Objectives: The aim of the present study was to estimate the rates of decline in serum PFOA and their corresponding serum half-lives, while characterizing their determinants.

Methods: We investigated 5,860 subjects more than 14 years of age who enrolled in the second surveillance round of the regional health surveillance program. Two blood samples were collected between 2017 and 2022 (average time between measurements: 4 years). Serum PFOA excretion rates and half-lives were estimated based on linear mixed effect models, modeling subject-specific serum PFOA concentrations over time and correcting for background concentrations. For modeling determinants of half-life [age, sex, body mass index (BMI), smoking-habit, alcohol consumption, and estimated glomerular filtration rate (eGFR)], we added interaction terms between each covariate and the elapsed time between measurements. Perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) apparent half-lives were also estimated. A separate analysis was conducted in children ($n=480$). All analyses were stratified by sex.

Results: Median initial serum concentrations of PFOA was $49\text{ng}/\mathrm{mL}$ (range: 0.5-1,090), with a median reduction of 62.45%. The mean estimated PFOA half-life was 2.36 years [95% confidence interval (CI): 2.33, 2.40], shorter in women (2.04; 95% CI: 2.00, 2.08) compared to men (2.83; 95% CI: 2.78, 2.89). Half-lives varied when stratified by some contributing factors, with faster excretion rates in nonsmokers and nonalcohol drinkers (especially in males).

Conclusions: This study, to our knowledge the largest on PFOA half-life, provides precise estimates in young adults whose exposure via drinking water has largely ceased. For other PFAS, longer half-lives than reported in other studies can be explained by some ongoing exposure to PFAS via other routes. https://doi.org/10.1289/EHP13152.

Figure 1.

Distribution of half-lives (years) estimates in subjects $\ge 14$ years old, stratified by sex ($n=\mathrm{2,806}$ males; $n=\mathrm{2,941}$ females) (Table S1). Veneto Region, Italy (2017–2022). Half-lives more than 13 years (equivalent excretion constants $<0.05$) and $<1$ year (equivalent excretion constants $>0.75$) were excluded from the histogram.

Figure 2.

Stratified half-lives in males (A) and females (B). Mean half-lives and corresponding 95% CI in subjects $\ge 14$ years old, estimated adding the interaction of age with elapsed time and one by one an interaction term between each of the other covariate and elapsed time ($n=\mathrm{2,825}$ males; $n=\mathrm{2,944}$ females) (Table S2). Veneto Region, Italy (2017–2022). Note: AU, alcohol units; CI, confidence interval.