Health & Environmental Research Online (HERO)


PFHxS (355-46-4)


53 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Maternal serum concentrations of perfluoroalkyl substances and birth size in British boys

Authors: Marks, KJ; Cutler, AJ; Jeddy, Z; Northstone, K; Kato, K; Hartman, TJ (2019) International Journal of Hygiene and Environmental Health 222:889-895. HERO ID: 5081319

[Less] Per- and polyfluoroalkyl substances (PFAS) have been widely used in commercial and industrial manufacturing . . . [More] Per- and polyfluoroalkyl substances (PFAS) have been widely used in commercial and industrial manufacturing processes since the 1950s. Inverse associations between prenatal exposure to PFAS and birth size have been found in populations around the globe. This study examined the association of prenatal maternal serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) and birth size in British boys. The study included 457 mother-son dyads participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Birth weight (g), crown to heel length (cm), and head circumference (cm) were collected at delivery. PFAS were detected in all maternal serum samples during pregnancy (median: 30 weeks gestation (interquartile range: 12-33)). Median concentrations (interquartile range) were 13.8 ng/mL (11.0, 17.7), 3.0 ng/mL (2.3, 3.8), 1.9 ng/mL (1.4, 2.5), and 0.4 ng/mL (0.3, 0.5) for PFOS, PFOA, PFHxS, and PFNA, respectively. In multivariable linear regression models, inverse associations were detected between PFOS (continuous) and birth weight (β = -8.50 g, 95% CI = -15.93, -1.07 g), crown to heel length (β = -0.04 cm, 95% CI = -0.08, -0.01 cm), and head circumference (β = -0.02 cm, 95% CI = -0.04, -0.002 cm). In conclusion, prenatal exposure to high levels of PFOS may be associated with reduced birth size in male infants.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and the risk of hypertensive disorders of pregnancy

Authors: Huang, R; Chen, Q; Zhang, L; Luo, K; Chen, L; Zhao, S; Feng, L; Zhang, J (2019) Environmental Health: A Global Access Science Source 18:5. HERO ID: 5083564

[Less] BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been reported . . . [More] BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been reported to disrupt endocrine system and reproduction. However, epidemiological evidence on the association between PFAS and preeclampsia is inconsistent. We aimed to investigate the association between prenatal PFAS exposure and hypertensive disorders of pregnancy (HDP) in humans.

METHODS: PFAS were measured by liquid chromatography system coupled with tandem mass spectrometry in 687 umbilical cord plasma samples collected between 2011 and 2012 in Shanghai, China. Information on HDP including gestational hypertension and preeclampsia was abstracted from medical records. Multiple logistic regression was used to examine the association of each PFAS with gestational hypertension, preeclampsia, and overall HDP in separate models. Elastic net regression with logit link was used to identify independent associations between exposures and outcomes. Logistic regression was used to obtain the unpenalized estimates of the selected PFAS components for the associations with outcomes, adjusting for age, education level, pre-pregnancy BMI, parity, and mutual adjustment of selected PFAS.

RESULTS: The risk of gestational hypertension and preeclampsia was 3.3% and 2.8% in our subjects, respectively. Perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluoroundecanoic acid (PFUA) were associated with preeclampsia based on elastic net penalty regression. In the fully adjusted statistical model, women with a higher level of standardized ln-transformed PFBS had an increased odds of preeclampsia [adjusted odds ratio (AOR): 1.81, 95% confidence interval (CI): 1.03-3.17], and overall HDP (AOR: 1.64, 95% CI: 1.09-2.47).

CONCLUSIONS: Prenatal exposure to PFBS was positively associated with the risk of preeclampsia and overall HDP.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Associations of serum perfluoroalkyl substance and vitamin D biomarker concentrations in NHANES, 2003-2010

Authors: Etzel, TM; Braun, JM; Buckley, JP (2019) International Journal of Hygiene and Environmental Health 222:262-269. HERO ID: 5043582

[Less] Perfluoroalkyl substances (PFAS) are persistent endocrine disrupting chemicals found in industrial and . . . [More] Perfluoroalkyl substances (PFAS) are persistent endocrine disrupting chemicals found in industrial and commercial products. Previous research has shown that other endocrine disrupting chemicals such as phthalates and bisphenol A may alter circulating levels of vitamin D; however, no research has examined associations between PFAS and vitamin D biomarkers. We conducted a cross-sectional analysis of 7040 individuals aged 12 years and older participating in the 2003-2010 cycles of the United States National Health and Nutrition Examination Survey (NHANES). Concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and total 25-hydroxyvitamin D [25(OH)D] were measured in serum samples. We used multivariable linear regression to estimate covariate-adjusted differences in total 25(OH)D or prevalence odds of vitamin D deficiency per log2 change in PFAS concentrations. We also assessed potential effect measure modification by gender, age, and race/ethnicity. PFAS were detected in over 98% of the samples. In adjusted models, each 2-fold increase in PFOS was associated with 0.9 nmol/L (95% CI: 0.2, 1.5) lower total 25(OH)D concentrations, with associations significantly stronger among whites (β: -1.7; 95% CI: -2.6, -0.7) and individuals older than 60 years of age (β: -1.7; 95% CI: -2.9, -0.5). Each 2-fold increase in PFHxS was associated with 0.8 nmol/L (95% CI: 0.3, 1.3) higher total 25(OH)D, and this association was not modified by age, gender, and race/ethnicity. PFOA and PFNA were not associated with total 25(OH)D. When assessing prevalence odds of vitamin D deficiency, we observed similar patterns of association with PFAS concentrations. Our results suggest that some PFAS may be associated with altered vitamin D levels in the United States population, and associations may vary by chemical, age, and race/ethnicity. Prospective epidemiological studies are needed to confirm our findings and determine their implications for vitamin D-associated health outcomes in children and adults.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Characterization of age-based trends to identify chemical biomarkers of higher levels in children

Authors: Nguyen, VK; Colacino, JA; Arnot, JA; Kvasnicka, J; Jolliet, O (2019) Environment International 122:117-129. HERO ID: 5043339

[Less] BACKGROUND: Chemical biomarker concentrations are driven by complex interactions between . . . [More] BACKGROUND: Chemical biomarker concentrations are driven by complex interactions between chemical use patterns, exposure pathways, and toxicokinetic parameters such as biological half-lives. Criteria to differentiate legacy from current exposures are helpful for interpreting variation in age-based and time trends of chemical exposure and identifying chemicals to which children are highly exposed. A systematic approach is needed to study temporal trends for a wide range of chemicals in the US population.

OBJECTIVES: Using National Health and Nutrition Examination Survey (NHANES) data on measured biomarker concentrations for 141 chemicals from 1999 to 2014, we aim to 1) understand the influence of temporal determinants, in particular time trends, biological half-lives, and restriction dates on age-based trends, 2) systematically define an age-based pattern to identify chemicals with ongoing and high exposure in children, and 3) characterize how age-based trends for six Per- and Polyfluoroalkyl Substances (PFASs) are changing over time.

METHODS: We performed an integrated analysis of biological half-lives and restriction dates, compared distributions of chemical biomarker concentrations by age group, and then applied a series of regression models to evaluate the linear (βage) and nonlinear (βage2) relationships between age and chemical biomarker levels.

RESULTS: For restricted chemicals, a minimum persistence of 1 year in the human body is needed to observe substantial differences between the less exposed young population and historically exposed adults. We define a metric ( [Formula: see text] ) that identifies several phthalates, brominated flame retardants, pesticides, and metals such as lead and tungsten as elevated and ongoing exposures in children. While a substantial reduction in children's exposures was reflected in PFOS and PFOA, levels of PFNA and PFHxS in children were higher in 2013-2014 compared to those in 1999-2000.

CONCLUSIONS: Integrating a series of regression models with systemized stratified analyses by age group enabled us to define an age-based pattern to identify chemicals that are of higher levels in children.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Perfluoroalkyl substances (PFASs) and polychlorinated naphthalenes (PCNs) add to the chemical cocktail in peregrine falcon eggs

Authors: Vorkamp, K; Falk, K; Møller, S; Bossi, R; Rigét, FF; Sørensen, PB (2019) Science of the Total Environment 648:894-901. HERO ID: 5079652

[Less] A suite of perfluoroalkyl substances (PFASs) and polychlorinated naphthalenes (PCNs) were determined . . . [More] A suite of perfluoroalkyl substances (PFASs) and polychlorinated naphthalenes (PCNs) were determined in 41 peregrine falcon eggs collected in South Greenland between 1986 and 2014. Median concentrations of perfluorinated sulfonic acids (ΣPFSA) and perfluorinated carboxylic acids (ΣPFCA) were 303 ng/g dry weight (dw) (58 ng/g wet weight, ww) and 100 ng/g dw (19 ng/g ww), respectively, which was comparable to other studies. Perfluorooctane sulfonate (PFOS) accounted for 94% on average of all PFSAs, but did not show a significant time trend. Perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS) and perfluorodecane sulfonate (PFDS) showed non-linear decreases over the study period, while some long-chain PFCAs increased significantly. The PCN profile was dominated by the penta-, hexa- and tetrachlorinated congeners CN-52/60, CN-66/67 and CN-42. CN-54, an indicator of combustion, accounted for 2.4% of ΣPCN on average. All PCN congeners showed a decreasing tendency, which was significant for lipid-normalized concentrations of CN-53, CN-54 and CN-63. The ΣPCN median concentration was 21 ng/g lipid weight, which is in the high end of concentrations reported for bird eggs. The PCN and PFAS concentrations add to an already high contaminant burden and a complex chemical cocktail in the peregrine falcon population in Greenland, mainly reflecting contaminant exposure during migration and winter stays in Central and South America.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Do conventional cooking methods alter concentrations of per- and polyfluoroalkyl substances (PFASs) in seafood?

Authors: Taylor, MD; Nilsson, S; Bräunig, J; Bowles, KC; Cole, V; Moltschaniwskyj, NA; Mueller, JF (2019) Food and Chemical Toxicology 127:280-287. HERO ID: 5079808

[Less] Per-and poly-fluoroalkyl substances (PFASs) are bioaccumulative chemicals of emerging concern. Some . . . [More] Per-and poly-fluoroalkyl substances (PFASs) are bioaccumulative chemicals of emerging concern. Some PFASs accumulate in seafood, and can contribute to dietary exposure. Previous work has suggested cooking seafood decreases concentrations of neutral organic contaminants, however, previous studies dealing with PFASs have shown conflicting results. In this study, the potential changes of PFAS concentrations as a result of boiling, frying and baking are systematically examined. Blue Swimmer Crab (Portunus armatus), Dusky Flathead (Platycephalus fuscus) and School Prawn (Metapenaeus macleayi) were obtained from near a known PFAS point source and a reference location (affected by diffuse sources). Raw and cooked samples were analysed for commonly found PFASs. Of 23 target analytes, PFOS was the most frequently detected compound. PFOS, PFHxS and PFOA concentrations in School Prawn effectively doubled after boiling, and PFOS increased when Dusky Flathead was baked. There was no significant difference in PFOS concentration when Dusky Flathead was fried, or when the Blue Swimmer Crab was boiled. PFHxS and PFOA concentrations in Blue Swimmer Crab effectively halved after boiling. Increase in PFAS concentrations possibly arise from mass loss during the cooking process. Our data show that cooking does not consistently reduce PFAS concentrations, and cannot mitigate dietary exposure.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Cross-sectional study of the association between serum perfluorinated alkyl acid concentrations and dental caries among US adolescents (NHANES 1999-2012)

Authors: Puttige Ramesh, N; Arora, M; Braun, JM (2019) British Medical Journal Open 9:e024189. HERO ID: 5080517

[Less] STUDY OBJECTIVES: Perfluoroalkyl acids (PFAAs) are a class of anthropogenic and persistent . . . [More] STUDY OBJECTIVES: Perfluoroalkyl acids (PFAAs) are a class of anthropogenic and persistent compounds that may impact some biological pathways related to oral health. The objective of our study was to estimate the relationship between dental caries prevalence and exposure to four PFAA: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS) in a nationally representative sample of US adolescents.

SETTING/DESIGN: We analysed cross-sectional data from the National Health and Nutrition Examination Survey from 1999 to 2012 for 12-19-year-old US adolescents.

PARTICIPANTS: Of 10 856 adolescents aged 12 to 19 years who had a dental examination, we included 2869 with laboratory measurements for serum PFAA concentrations and complete covariate data in our study.

PRIMARY AND SECONDARY OUTCOME MEASURES: Dental caries prevalence was defined as the presence of decay or a restoration on any tooth surface, or the loss of a tooth due to tooth decay. We used multivariable logistic regression to estimate the covariate-adjusted association between serum PFAA concentrations and dental caries prevalence, accounting for the complex National Health and Nutrition Examination Survey design.

RESULTS: Of 2869 adolescents, 59% had one or more dental caries. We observed no associations between the prevalence of dental caries and serum concentrations of PFOA, PFOS or PFHxS. The adjusted odds of caries were 21% (OR 0.79; 95% CI 0.63 to 1.01), 15% (OR 0.85; 95% CI 0.67 to 1.08) and 30% (OR 0.7; 95% CI 0.55 to 0.90) lower among adolescents in the 2nd, 3rd and 4th serum PFNA concentration quartiles compared to adolescents in the first quartile, respectively. The linear trend for this association was not statistically significant.

CONCLUSION: PFOA, PFOS and PFHxS were not associated with prevalence of dental caries. The prevalence of caries was reduced with increasing serum PFNA concentrations; however, these results should be interpreted cautiously given that we were unable to adjust for several factors related to oral health.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Roles of gender and obesity in defining correlations between perfluoroalkyl substances and lipid/lipoproteins

Authors: Jain, RB; Ducatman, A (2019) Science of the Total Environment 653:74-81. HERO ID: 5080642

[Less] Data from National Health and Nutrition Examination Survey (NHANES) for 2005-2014 for those aged ≥20 years . . . [More] Data from National Health and Nutrition Examination Survey (NHANES) for 2005-2014 for those aged ≥20 years fasting for ≥8 h (N = 3629) were analyzed to evaluate the role that gender and obesity play in defining correlations between selected perfluoroalkyl substances (PFAS) and total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides. PFAS considered for analyses were: perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), perfluorohexane sulfonate (PFHxS), perfluoroundecanoic acid (PFUnDA), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-FOSAA). Gender and obesity stratified regression models were fitted to estimate associations between PFAS and lipid/lipoproteins with adjustments made for confounders. For obese males, but not for nonobese males, positive associations were found between TC and LDL with PFOA (β = 0.0519, p = 0.01 for TC and β = 0.0822, p = 0.03 for LDL), and PFNA (β = 0.0328, p = 0.03 for TC and β = 0.0679, p = 0.04 for LDL). For obese females, adjusted concentrations of TC increased with increase in the concentrations of PFDA (β = 0.0247, p = 0.048), PFNA (β = 0.0286, p = 0.04), and Me-PFOSAA (β = 0.0274, p = 0.02), and there was a positive association of LDL with PFOS (β = 0.0375, p = 0.04), PFDA (β = 0.0397, p = 0.047), and PFNA (β = 0.0593, p = 0.02). The findings, concerning the relationship of longer chain PFAS to serum lipids, suggest greater susceptibility to elevated TC and LDL cholesterol in the obese participants, with some differences between men and women. The key contributing modifiable risk for nonalcoholic steatosis is obesity, and, the development of nonalcoholic steatosis is recognized to be sexually dimorphic. The epidemiologic observation of a susceptible obese subgroup in our data is consistent with toxicology literature findings of disrupted cholesterol metabolism via induced steatosis following PFAS exposure. Gender differences affect serum concentration of PFAS during the reproductive years, and our data add a secondary question concerning whether they also affect the interaction between PFAS exposure and lipid handling in males and females.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Perfluoroalkyl substances are inversely associated with coronary heart disease in adults with diabetes

Authors: Honda-Kohmo, K; Hutcheson, R; Innes, KE; Conway, BN (2019) Journal of Diabetes and its Complications 33:407-412. HERO ID: 5080551

[Less] AIMS: Perfluoroalkyl substances (PFAS) are environmentally and biologically persistent . . . [More] AIMS: Perfluoroalkyl substances (PFAS) are environmentally and biologically persistent synthetic environmental contaminants linked to adverse health outcomes. Though null to modest inverse relationships between PFAS and coronary heart disease (CHD) have been reported, studies regarding relationships in high risk populations such as those with diabetes are sparse. We investigated the relationship of PFAS with CHD in persons with diabetes.

METHODS: Data on 5270 adults, aged ≥20 years, with diabetes were obtained from the C8 Health Project. Four PFAS were investigated separately: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA).

RESULTS: In logistic regression analyses adjusting for age, sex, diabetes duration, BMI, smoking, lipids, WBC, CRP, eGFR, uric acid, hemoglobin and iron, all PFAS were inversely associated with CHD, ORs (95% CIs): PFHxS; 0.72 (0.65-0.79), PFOA; 0.90 (0.81-0.96), PFOS; 0.90 (0.81-0.99), PFNA; 0.88 (0.76-1.02). Stratification by chronic kidney disease status revealed similar inverse relationships for those with and without chronic kidney disease.

CONCLUSIONS: In this cross-sectional study of over 5000 adults with diabetes, PFAS showed inverse associations with CHD. These findings may, if confirmed in future studies, provide new physiologic understanding of CHD prevention strategies.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis

Authors: Alderete, TL; Jin, R; Walker, DI; Valvi, D; Chen, Z; Jones, DP; Peng, C; Gilliland, FD; Berhane, K; Conti, DV; Goran, MI; Chatzi, L (2019) Environment International 126:445-453. HERO ID: 5080614

[Less] OBJECTIVE: To examine the prospective associations between exposure to perfluoroalkyl . . . [More] OBJECTIVE: To examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children.

METHODS: Forty overweight and obese Hispanic children (8-14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1-3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry. Multiple linear regression models were used to assess the association between baseline PFASs and changes in glucose homeostasis over follow-up. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with plasma PFASs concentrations. We performed a structural integrated analysis aiming to characterize the joint impact of all factors and to identify latent clusters of children with alterations in glucose homeostasis, based on their exposure and metabolomics profile.

RESULTS: Each ln (ng/ml) increase in PFOA and PFHxS concentrations was associated with a 30.6 mg/dL (95% CI: 8.8-52.4) and 10.2 mg/dL (95% CI: 2.7-17.7) increase in 2-hour glucose levels, respectively. A ln (ng/ml) increase in PFHxS concentrations was also associated with 17.8 mg/dL increase in the glucose area under the curve (95% CI: 1.5-34.1). Pathway enrichment analysis showed significant alterations of lipids (e.g., glycosphingolipids, linoleic acid, and de novo lipogenesis), and amino acids (e.g., aspartate and asparagine, tyrosine, arginine and proline) in association to PFASs exposure. The integrated analysis identified a cluster of children with increased 2-h glucose levels over follow up, characterized by increased PFAS levels and altered metabolite patterns.

CONCLUSIONS: This proof-of-concept analysis shows that higher PFAS exposure was associated with dysregulation of several lipid and amino acid pathways and longitudinal alterations in glucose homeostasis in Hispanic youth. Larger studies are needed to confirm these findings and fully elucidate the underlying biological mechanisms.