Serum per- and polyfluoroalkyl substance concentrations and longitudinal change in post-infection and post-vaccination SARS-CoV-2 antibodies.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous throughout the United States. Previous studies have shown PFAS exposure to be associated with a reduced immune response. However, the relationship between serum PFAS and antibody levels following SARS-CoV-2 infection or COVID-19 vaccination has not been examined. We examined differences in peak immune response and the longitudinal decline of antibodies following SARS-CoV-2 infection and COVID-19 vaccination by serum PFAS levels in a cohort of essential workers in the United States. We measured serum antibodies using an in-house semi-quantitative enzyme-linked immunosorbent assay (ELISA). Two cohorts contributed blood samples following SARS-CoV-2 infection or COVID-19 vaccination. We used linear mixed regression models, adjusting for age, race/ethnicity, gender, presence of chronic conditions, location, and occupation, to estimate differences in immune response with respect to serum PFAS levels. Our study populations included 153 unvaccinated participants that contributed 316 blood draws over a 14-month period following infection, and 860 participants and 2451 blood draws over a 12-month period following vaccination. Higher perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) concentrations were associated with a lower peak antibody response after infection (p = 0.009, 0.031, 0.015). Higher PFOS, perfluorooctanoic acid (PFOA), PFHxS, and PFNA concentrations were associated with slower declines in antibodies over time after infection (p = 0.003, 0.014, 0.026, 0.025). PFOA, PFOS, PFHxS, and PFNA serum concentrations prior to vaccination were not associated with differences in peak antibody response after vaccination or with differences in decline of antibodies over time after vaccination. These results suggest that elevated PFAS may impede potential immune response to SARS-CoV-2 infection by blunting peak antibody levels following infection; the same finding was not observed for immune response to vaccination.

Serum per- and polyfluoroalkyl substance concentrations in four municipal US fire departments.

BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.

Comparison of Serum Per- and Polyfluoroalkyl Substances Concentrations in Incumbent and Recruit Firefighters and Longitudinal Assessment in Recruits.

OBJECTIVE: Firefighters are occupationally exposed to per- and polyfluoroalkyl substances (PFAS). This study objective was to compare serum PFAS concentrations in incumbent and recruit firefighters and evaluate temporal trends among recruits. METHODS: Serum PFAS concentrations were measured in 99 incumbent and 55 recruit firefighters at enrollment in 2015-2016, with follow-up 20 to 37 months later for recruits. Linear and logistic regression and linear mixed-effects models were used for analyses. Fireground exposure impact on PFAS concentrations was investigated using adjusted linear and logistic regression models. RESULTS: Incumbents had lower n-PFOA and PFNA than recruits and most PFAS significantly decreased over time among male recruits. No significant links were found between cumulative fireground exposures and PFAS concentrations. CONCLUSIONS: Serum PFAS concentrations were not increased in incumbent firefighters compared with recruits and were not associated with cumulative fireground exposures.

Per- and polyfluoroalkyl substances, epigenetic age and DNA methylation: a cross-sectional study of firefighters.

Background: Per- and polyfluoroalkyl substances (PFASs) are persistent chemicals that firefighters encounter. Epigenetic modifications, including DNA methylation, could serve as PFASs toxicity biomarkers. Methods: With a sample size of 197 firefighters, we quantified the serum concentrations of nine PFASs, blood leukocyte DNA methylation and epigenetic age indicators via the EPIC array. We examined the associations between PFASs with epigenetic age, site- and region-specific DNA methylation, adjusting for confounders. Results: Perfluorohexane sulfonate, perfluorooctanoate (PFOA) and the sum of branched isomers of perfluorooctane sulfonate (Sm-PFOS) were associated with accelerated epigenetic age. Branched PFOA, linear PFOS, perfluorononanoate, perfluorodecanoate and perfluoroundecanoate were associated with differentially methylated loci and regions. Conclusion: PFASs concentrations are associated with accelerated epigenetic age and locus-specific DNA methylation. The implications for PFASs toxicity merit further investigation.

Flame retardant exposure assessment: findings from a behavioral intervention study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) have been largely replaced by organophosphate flame retardants (OPFRs) and alternative brominated flame retardants (Alt-BFRs) to meet flammability requirements. Humans are ubiquitously exposed to some variety of flame retardants through contact with consumer products directly or through household dust. OBJECTIVES: To evaluate the effectiveness of house cleaning and hand washing practices to reduce exposure to flame retardants, we measured concentrations in dermal hand wipes and urinary metabolites before and after assignment to two consecutive interventions. METHODS: We selected 32 mother and child dyads from an existing cohort. This analysis focuses on mothers. Participants provided baseline measurements (urine, hand wipes, and questionnaires) and were then assigned for 1 week to either a house cleaning (including instruction on proper technique and cleaning supplies) or hand washing (including instruction on proper technique and soaps) intervention arm. For the second week, participants were assigned to the second intervention in addition to their initial assignment, thus all subjects both washed their hands and cleaned according to the intervention guidelines during week 2. We collected measurements at the end of weeks 1 and 2. RESULTS: We found reductions in urinary analytes after week 1 of house cleaning (BCIPHIPP and ip-DPHP), week 1 of hand washing (BCIPP, BCIPHIPP, and tbutyl-DPHP), and week 2 of combined interventions (BCIPHIPP and tbutyl-DPHP), compare to baseline. We found no significant decline in hand wipes in the entire sample but did find reductions after week 1 of house cleaning (BDE 209), week 1 of hand washing (TCEP), and week 2 of combined interventions (TDCIPP and BDE 209) in women with exposure above the median at baseline (verified through simulations). CONCLUSIONS: Exposure to individual flame retardants was reduced by about half, in some cases, by 1 week of increased hand washing, house cleaning to reduce dust, or combined activities.

Differential exposure to organophosphate flame retardants in mother-child pairs.

BACKGROUND: Humans are ubiquitously exposed to flame retardants, including organophosphate esters (OPEs), through direct contact with consumer products or exposure through household dust. Children are at increased risk because of their proximity to dust, hand-to-mouth activity, and the importance of childhood as a critical period in neurodevelopment. OBJECTIVES: To quantify differences in exposure levels between mothers and children (three to six years of age), we analyzed urinary metabolites of OPEs. We additionally assessed the ability of silicone wristbands (measuring ambient exposure) to predict urinary metabolite concentrations. METHODS: We selected 32 mother and child dyads from an existing cohort. Participants provided baseline urine samples and wore wristbands for one week. After the first week, they returned their wristbands and provided a second urine sample. During the second week, participants wore a second wristband that they returned at the end of week two with a third and final urine sample. RESULTS: We found significantly higher levels of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) (p < 0.001) and lower levels of bis(1-chloro-2-isopropyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) (p < 0.001) in children's urine samples compared to mothers' samples at baseline. We found that triphenylphosphate (TPHP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), and tris(1-chloro-2-propyl) phosphate (TCIPP) measured in wristbands predicted their respective metabolite levels in urine. CONCLUSION: Children had higher levels than mothers for two of six flame retardant metabolites measured in urine. Generally, wristband measurements positively predicted internal dose. As little is known about the health effects of OPEs on child development, future research is needed to determine the impact of differential exposure.