Perfluoroalkyl substance mixtures and cardio-metabolic outcomes in highly exposed male workers in the Veneto Region: a mixture-based approach

Abstract

BACKGROUND AND AIM: Perfluoroalkyl substances (PFAS) have been consistently associated with cardio-metabolic traits, associations of combined exposures to multiple PFAS with health outcomes in highly exposed populations have been poorly investigated. The aim of the present study was to examine these associations in male workers. METHODS: We considered a population of 232 male employees who had worked in a factory located in Trissino (Veneto, Italy), which produced PFAS and other chemicals during 1968-2018. Twelve serum PFAS were measured by HPLC-MS during 2018-2020; four (PFOA, PFOS, PFHxS and PFNA) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The associations between PFAS mixtures and each outcome were assessed through weighted quantile sum (WQS) regression model, taking into account potential confounders. RESULTS:Among the PFAS, PFOA was detected at the highest level, with a median concentration of 80.75 ng/mL and maximum levels up to 13,000 ng/mL. We observed that each quartile increase in the WQS index was associated with an increase in the levels of TC (β: 9.05, 95% IC: 2.04-16.05), LDL-C (β: 6.79, 95% IC: 0.51-13.07) and SBP (β: 2.64, 95% IC: 0.49-4.79). No effect of PFAS exposure on HDL cholesterol and DBP emerged. WQS analyses revealed a major contribution of PFNA and PFHxS for the cholesterol levels, although the main exposure was due to PFOA. PFOS and PFOA emerged as chemicals of concern regarding the association with SBP. CONCLUSIONS:We found strong positive association between a mixture of four PFAS and total cholesterol levels in particular. Within the mixture PFNA and PFHxS were the most influential. Further work will adjust for other possible confounding factors and apply other approaches to assess chemical mixtures. KEYWORDS: PFAS, Mixtures, Cardiovascular disease, Chemical exposures, Occupational exposures