Serum concentrations of legacy, alternative, and precursor per- and polyfluoroalkyl substances: a descriptive analysis of premenopausal participants in the Canadian CARTaGENE cohort
The findings suggest that exposure to low levels of some alternative and precursor PFAS may be widespread in Canada and reinforce the role of pregnancy and breastfeeding as excretion pathways for legacy PFAS and support previous investigations demonstrating that exposure to some PFAS may be lower amongst financially disadvantaged populations.
Abstract
Human biomonitoring studies of per- and polyfluoroalkyl substances (PFAS) have typically focused on legacy PFAS. Data for alternative and precursor PFAS are emerging, but are still scarce. These data are critical for assessing exposure and human health risk.
We measured serum concentrations of 40 PFAS among 2,775 premenopausal participants from the CARTaGENE cohort (Phase A: 2009–2010; Phase B: 2013–2014). We examined differences in geometric mean serum concentrations of PFAS with > 60% detection, as well as the sum of 7 PFAS (Σ7PFAS), across categories of sociodemographic, lifestyle, and reproductive history characteristics.
Eight PFAS were detected in > 60% of participants. Geometric mean serum concentrations ranged from 0.03 µg/L (PFHpS and MeFOSAA) to 4.25 µg/L for PFOS and 8.00 µg/L for Σ7PFAS. The largest differences in serum PFAS concentrations were observed across reproductive history characteristics. Concentrations of PFOS, PFNA, PFOA, PFHxS, and the Σ7PFAS were monotonically lower with each additional child birthed, higher with increasing time since last pregnancy, and lower among those with a history of breastfeeding. The PFAS reducing effect of parity appeared to outweigh the bioaccumulative effect of age for most legacy PFAS. Concentrations of PFOS, PFNA, PFOA, PFHxS, PFDA, PFUnA and the Σ7PFAS were lower among participants with a reported household income below the Canadian low-income cut-off. Several alternative and precursor PFAS were detected in this population, including sulfonamidoacetic acids, sulfonamides, fluorotelomers, and fluoroethers, but serum concentrations were relatively low, with 95
th
percentiles < 0.5 µg/L.
This work contributes to expanding human biomonitoring data beyond legacy PFAS, and our findings suggest that exposure to low levels of some alternative and precursor PFAS may be widespread in Canada. These results also reinforce the role of pregnancy and breastfeeding as excretion pathways for legacy PFAS and support previous investigations demonstrating that exposure to some PFAS may be lower amongst financially disadvantaged populations.
BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a diverse group of organofluorine compounds used in industrial and consumer applications. The primary route of human exposure to PFAS is ingestion of contaminated food and drinking water, representing a significant and sometimes unavoidable exposure for many populations. Ecotoxicological and epidemiological studies have established associations between PFAS exposures and adverse health effects. Fetal and childhood development is a particularly susceptible window of exposure. OBJECTIVE: We characterized PFAS exposures for pregnant women in Suriname who identified as Indigenous or Tribal Peoples, and we examined regional variations in exposure patterns between urban, rural, and remote populations. METHODS: We measured 24 PFAS analytes in the blood serum of 100 pregnant Tribal and Indigenous women living in Suriname. Samples were collected from December 2016 to July 2019 and were purposively selected for laboratory analysis. We assessed differences in serum concentrations visually and statistically by location and ethnicity. RESULTS: Ten unique PFAS were detected in at least one sample. The median total PFAS across all participants was 1.05 ng/mL (IQR: 0.73–1.45 ng/mL). The most frequently detected PFAS were PFOS (DF = 100%, median concentration (x˜)=0.59ng/mL), PFOA (DF = 86%, x˜=0.15ng/mL), PFNA (DF = 84%, x˜=0.09ng/mL), PFUnDA (DF = 72%, x˜=0.09ng/mL), and PFHxS (DF = 71%, x˜=0.06ng/mL). Median total PFAS concentrations were highest for participants in the remote interior district, although differences among the districts were not statistically significant (p = 0.37) and should be interpreted cautiously due to limited statistical power. Indigenous Peoples tended to have higher total PFAS in their blood serum (x˜=1.25ng/mL) compared to Tribal Peoples (x˜=0.84ng/mL, p < 0.01), although we did not assess potential confounding variables. SIGNIFICANCE: Our analysis revealed mostly long-chain legacy PFAS with possibly different exposure risks for secluded interior communities compared to urban-coastal populations, indicating a need for contaminant source assessments. IMPACT: Our study adds to the growing literature around PFAS exposures for people living in remote areas. Suriname aims to reduce environmental contamination from persistent organic pollutants through the Stockholm Treaty. Our study provides data needed for policymakers and communities to make informed decisions about their environmental health.
Jenna K. Honan, Firoz Abdoel Wahid, Anisma R. Gokoel et al.· Journal of Exposure Science...· 0 citations
Background: The Milwaukee Angler Study was initiated in 2017 as part of the Biomonitoring of Great Lakes Populations Program (BGLP-III) to examine two adult populations at high risk of per- and polyfluoroalkyl substances (PFAS) exposure from consumption of PFAS-contaminated sportfish: licensed anglers near the Milwaukee Estuary Area of Concern (AOC) and Burmese refugees for whom fish is a dietary staple. Objective: This study seeks to provide a comprehensive examination of serum PFAS concentrations in these groups and investigate associations with locally caught fish consumption. Methods: Licensed urban anglers and Burmese refugees were independently recruited using population-specific sampling strategies. Participants completed questionnaires on demographics and fish consumption and provided biological specimens. Median and 95th percentile concentrations of seven PFAS were compared to 2017–2018 National Health and Nutrition Examination Survey (NHANES) data. Multivariable regression assessed associations between serum PFAS concentrations and self-reported local fish consumption from the Milwaukee AOC. Results: Among the 396 licensed angler participants, serum concentrations of three of the seven PFAS (PFOS, PFHxS, PFNA) were elevated compared to the U.S. population; PFOS, PFDA, PFHxS, PFNA, and total PFAS were significantly associated with increased local fish consumption when controlling for other demographic factors. Among the 103 Burmese refugee participants, four of the seven measured PFAS (PFOS, PFDA, PFUnDA, PFNA) were elevated compared to the U.S. population; PFOA, PFOS, PFDA, and total PFAS were associated with increased local fish consumption when controlling for other demographic factors. Significance: The results from this study support an association of local fish consumption with PFAS exposure among high-risk populations with varied demographic and local fish consumption practices in the Milwaukee Estuary AOC. Given that adherence to and awareness of state fish advisories can vary widely, our biomonitoring results underscore the importance of ongoing, tailored efforts to deliver culturally relevant public health interventions to the diverse populations surrounding the Great Lakes basin. Impact Statement: Building on the Biomonitoring of Great Lakes Populations program, this study adds PFAS-focused data from Milwaukee’s urban anglers and Burmese refugees, two understudied, high-exposure groups in the Milwaukee Estuary Area of Concern. By integrating detailed fish-consumption histories with serum PFAS and NHANES comparisons, the work directly informs Great Lakes Restoration Initiative goals and targeted fish-advisory interventions. These findings offer actionable evidence for exposure scientists, environmental epidemiologists, and public health practitioners.
T. Serio, Carrie Tomasallo, Xiaofei He et al.· Journal of Exposure Science...· 0 citations
Per and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with endocrine-disrupting and carcinogenic potential. However, their bioaccumulation profiles and clinical relevance in human breast cancer remain largely unexplored.
In this preliminary study we quantified the absolute concentrations of 33 PFAS congeners (ng/g) in paired tumour and adjacent non-tumorous tissues from 11 breast cancer patients (
n
= 11) using LC–MS/MS to evaluate their tissue distribution and clinical correlations.
The detection rates for six compounds (HFPOTA, PFOA, PFNA, PFUnDA, PFOS, and 6:2Cl-PFESA) were greater than 40%. In paired samples, several congeners showed higher concentrations in tumour than in adjacent non-tumorous tissue; using a two-sided exact Wilcoxon signed-rank test with Hodges–Lehmann effect sizes, tumour enrichment remained significant after Benjamini–Hochberg correction for HFPOTA (
q
= 0.041), PFNA (
q
= 0.047) and PFUnDA (
q
= 0.047). HFPOTA showed by far the highest tissue burden (median 654 ng/g). Clinically, PFOS concentrations were descriptively higher in Luminal B than in Luminal A tumours and were positively correlated with the proliferation marker Ki-67; a high 6:2Cl-PFESA–PR rank correlation was observed in four samples but was not statistically significant on the raw p-value (p ≈ 0.051) and is exploratory. Bioinformatic analyses indicated that computationally predicted shared target genes of PFAS and breast cancer are enriched in the PPAR signaling pathway, lipid metabolism, and steroid hormone biosynthesis.
Collectively, PFAS bioaccumulation was associated with breast cancer clinicopathological characteristics. Because the target genes are predicted rather than experimentally validated and the cohort is small (
n
= 11), these are exploratory, hypothesis-generating findings that require validation in larger cohorts. This study underscores the need to reassess the biosafety of novel PFAS alternatives and provides new insights into the environmental etiology of breast cancer.
Bei Sun, Zhanhua Gao, Xiyue Liu et al.· Frontiers in Public Health· 0 citations
Per- and polyfluoroalkyl substances (PFAS) are environmental contaminants associated with higher serum lipids, although primarily in cross-sectional studies, limiting causal inference. We aim to determine whether there is a causal relationship between PFAS and serum lipid levels by emulating a target trial of a hypothetical PFAS-reduction intervention using observational data. The target trial would enroll adults aged ≥20 years without prior cardiovascular, kidney, or liver disease, diabetes, or use of related medications. Participants would be randomly assigned to either PFAS-reduction counseling or no counseling, with adherence evaluated after 10 years, and then followed up after 10 years to assess effects on serum lipids. To emulate the target trial, we will use data from the Copenhagen City Heart Study on three successive clinical visits: baseline, follow-up, and outcome assessment visit, 10 years apart. Eligible participants meet the target trial criteria, have available blood samples for PFAS quantification at follow-up, and information on serum lipids at the outcome assessment. Intervention strategies will be evaluated based on observed reductions in PFAS concentrations between baseline and follow-up visit. Serum lipids are assessed at the outcome assessment visit. The emulation assumes exchangeability by adjusting for baseline and time-varying confounders using G-computation. This protocol explores applying the target trial emulation framework to improve causal inference in environmental epidemiology.
Georges Khoury, L. Deen, Lars Christian Lund et al.· Toxics· 0 citations
BACKGROUND
Low-level contamination of drinking water with per- and polyfluoroalkyl substances (PFAS) is widespread, yet the extent to which such concentrations contribute to human PFAS body burdens remains incompletely characterized.
OBJECTIVE
To synthesise evidence on the contribution of low-level PFAS in drinking water (defined as <100 ng/L for any individual PFAS) to PFAS concentrations in human blood.
METHODS
We systematically searched Embase, MEDLINE, and Scopus using predefined logic grids. Inclusion criteria were original human studies reporting both drinking water PFAS and blood/serum/plasma PFAS concentrations with a focus on low-level water exposures. Ten studies (n = 4576 participants; 4590 blood samples; 1297 water samples) met criteria. Data were extracted on populations, sampling frames, PFAS species and concentrations, and key findings.
RESULTS
Across studies from Sweden, China, USA, Germany, and Spain, "low-range" drinking water concentrations were associated with measurable increases in blood PFAS, with the most consistent and pronounced relationships observed for PFHxS. In children and high-consuming adults, water intake (≥7-8 cups/day or 1.8 Litres/day) and duration of residence on a supply amplified association. Evidence for contribution was most consistent at ~10-100 ng/L; below ~10 ng/L, associations were less consistent, though some data suggest PFHxS may influence serum levels even within this lower range. PFOA and PFOS showed weaker water-serum relationships at very low concentrations, compatible with greater contributions from legacy, non-water exposures. Heterogeneity in exposure assessment, timing, covariate control, and analytic reporting limited cross-study comparability.
SIGNIFICANCE
Even when drinking water PFAS concentrations are low, certain compounds-particularly PFHxS-can materially contribute to circulating PFAS, especially among children and high-water-consumption subgroups. These findings support compound-specific risk assessment, re-examination of default relative source contribution (RSC) assumptions for sensitive groups, and targeted monitoring that pairs household-level water measurements with biomonitoring. Standardized methods and longitudinal designs are needed to refine low-range concentration-response relationships and cumulative exposure estimates.
IMPACT STATEMENT
By summarising 10 epidemiologic studies that investigated the contribution of low-level PFAS in drinking water to PFAS concentrations in human blood using rigorous methodology, our review provides compelling evidence for a link between exposure to drinking water concentrations in the "low" range and measurable increases in blood PFAS. Additionally, it suggests even when drinking water PFAS concentrations are low, certain compounds-particularly PFHxS-can materially contribute to circulating PFAS, especially among children and high water consumption subgroups. Given the nature of this evidence, there is a need for compound-specific risk assessment, re-examination of default relative source contribution assumptions for sensitive groups, and targeted monitoring that pairs household-level water measurements with biomonitoring.
Y. Tefera, C. Shearer, M. Day et al.· Journal of Exposure Science...· 0 citations
It is suggested that higher plasma PFAS concentrations, particularly HFPO-DA, may be associated with more advanced TNM stage in colorectal cancer and warrant confirmation in larger prospective studies.
Ning Kang, Yang Zhao, Zhi Huang et al.· Frontiers in Toxicology· 1 citation
