Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts.

Background: Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways. Objective: Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids. Methods: Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation. Results: PFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase. Conclusions: Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.

Associations between both legacy and alternative per- and polyfluoroalkyl substances and glucose-homeostasis: The Isomers of C8 health project in China.

BACKGROUND: Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. OBJECTIVES: To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. METHODS: We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. RESULTS: After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. CONCLUSIONS: Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

Associations of perfluorooctane sulfonate alternatives and serum lipids in Chinese adults.

BACKGROUND: Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), a group of perfluorooctane sulfonate (PFOS) alternatives, can be widely observed in humans and environmental matrices. However, associations between exposure to Cl-PFESAs and serum lipid levels in adults are unknown. OBJECTIVE: To explore the relationships between Cl-PFESA levels and serum lipid levels in adults. METHODS: We analyzed 1238 adults from the Isomers of C8 Health Project, a cross-sectional study conducted in China from July 2015 to October 2016. The average age of the participants was 61.98 ± 14.40 years. We quantified two select legacy per- and perfluoroalkyl substances [perfluorooctanoic acid (PFOA) and PFOS] and their alternatives (6:2 and 8:2 Cl-PFESAs). We also measured four serum lipids: low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). We used generalized linear models to estimate the associations between PFASs and serum lipids, with PFASs defined as either a categorical variable divided into quartiles or as a continuous variable. RESULTS: We found that 6:2 Cl-PFESA was positively associated with serum TC and LDL-C. For instance, LDL-C levels in the highest quartile of 6:2 Cl-PFESA exposure (Q4) were significantly higher than those in the lowest quartile (Q1) [ß: 0.19, 95% confidence interval (CI): 0.08, 0.30]. Further analysis showed that one ln-ng/mL increase in 6:2 Cl-PFESA exposure corresponded to a 0.10 mmol/L (95% CI: 0.05, 0.16) LDL-C increase, and that exposure to 8:2 Cl-PFESA was negatively correlated with HDL-C (ß: -0.03, 95% CI: -0.05, -0.01). TC had a similar relationship with both 6:2 Cl-PFESA and legacy PFASs. Participants with a BMI ≥ 25 kg/m2 exhibited a stronger association between 6:2 Cl-PFESA and TC. CONCLUSIONS: Our findings make the novel suggestion that exposure to Cl-PFESAs are adversely associated with serum lipid levels, and that such associations are also observed in legacy PFASs. Increased investigation into the effects of Cl-PFESAs exposure on human health is warranted.

Perfluoroalkyl substance exposure and urine CC16 levels among asthmatics: A case-control study of children.

BACKGROUND: Studies have reported an association between serum perfluoroalkyl substances (PFASs) and asthma. However, few studies have examined the possible associations between PFASs and the 16-kDa club cell secretory protein (Clara) (CC16) level, a prominent biomarker of asthma, among adolescents. METHODS: We recruited a total of 231 asthmatic children and 225 non-asthmatic controls in the Genetic and Biomarkers study for Childhood Asthma (GBCA) in northern Taiwan from 2009 to 2010. Structured questionnaires were administered by face-to-face interview. Urine CC16 was determined by an enzyme-link immunoassay kit. Multiple general linear models were employed to examine the associations between PFASs and urinary CC16 levels. RESULTS: Asthmatic participants had significantly higher serum PFAS concentrations overall than the healthy controls. After adjusting for confounding factors, urinary CC16 was significantly, negatively associated with PFASs, especially PFOS, PFOA, PFDA and PFNA, and especially among males, as follows: PFOS (ß = -0.003, 95% confidence interval [CI]: -0.004, -0.002), PFOA (ß = -0.045, 95% CI: -0.086, -0.004), and PFHxA (ß = -0.310, 95% CI: -0.455, -0.165) among asthmatic boys, and PFDA (ß = -0.126, 95%CI: -0.241, -0.012) and PFNA (ß = -0.329, 95% CI: -0.526, -0.132) among non-asthmatic boys. Among girls, PFDA (ß = -0.088, 95% CI: -0.172, -0.004), was the only PFAS significantly associated with CC16. Significant interaction effects (p < 0.15) on CC16 levels were found between asthma and PFOS, PFOA, PFBS and PFHxA in all participants. CONCLUSION: Our overall results showed that serum PFASs were significantly, inversely associated with CC16 levels. Associations were stronger among males.

Theory and practice in participatory research: lessons from the Native Elder Care Study.

Models for community-based participatory research (CBPR) urge academic investigators to collaborate with communities to identify and pursue research questions, processes, and outcomes valuable to both partners. The tribal participatory research (TPR) conceptual model suggests modifications to CBPR to fit the special needs of American Indian communities. This paper draws upon authors' collaboration with one American Indian tribe to recommend theoretical revision and practical strategies for conducting gerontological research in tribal communities. We rated the TPR model as a strong, specialized adaptation of participatory research principles. Although the need for some TPR mechanisms may vary, our experience recommends incorporating dissemination as a central TPR mechanism. Researchers and communities can expect well-crafted collaborative projects to generate particular types of positive project outcomes for both partners, but should prepare for both predictable and unique challenges.