Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort DOI Creative Commons
Donghai Liang, Kaitlin R. Taibl, Anne L. Dunlop

et al.

Environmental Science & Technology, Journal Year: 2023, Volume and Issue: 57(43), P. 16206 - 16218

Published: Oct. 19, 2023

Prenatal exposure to single chemicals belonging the per- and polyfluoroalkyl substances (PFAS) family is associated with biological perturbations in mother, fetus, placenta, plus adverse health outcomes. Despite our knowledge that humans are exposed multiple PFAS, potential joint effects of PFAS on metabolome remain largely unknown. Here, we leveraged high-resolution metabolomics identify metabolites metabolic pathways perturbed by a mixture during pregnancy. Targeted assessment perfluorooctanoic acid (PFOA), perfluorononanoic (PFNA), perfluorooctanesulfonic (PFOS), perfluorohexanesulfonic (PFHxS), along untargeted profiling, were conducted nonfasting serum samples collected from pregnant African Americans at 6–17 weeks gestation. We estimated overall effect partial using quantile g-computation single-chemical linear regression. All models adjusted for maternal age, education, parity, early pregnancy body mass index, substance use, gestational sample collection. Our analytic included 268 participants was socioeconomically diverse, majority receiving public insurance (78%). observed 13.3% detected features (n = 1705, p < 0.05), which more than any chemicals. There consistent association indicative systemic inflammation oxidative stress (e.g., glutathione, histidine, leukotriene, linoleic acid, prostaglandins, vitamins A, C, D, E metabolism) across all metabolome-wide studies. Twenty-six validated against authenticated compounds (p 0.05). Based weights, PFNA contributed most γ-aminobutyric (GABA), tyrosine, uracil. In one first studies its kind, demonstrate feasibility utility methods designed mixtures conjunction assess human metabolome. identified pronounced Taken together, findings illustrate integrating environmental analyses high-throughput elucidate molecular mechanisms underlying health.

Language: Английский

Pilot-Scale Thermal Destruction of Per- and Polyfluoroalkyl Substances in a Legacy Aqueous Film Forming Foam DOI
Erin P. Shields, Jonathan D. Krug,

William R. Roberson

et al.

ACS ES&T Engineering, Journal Year: 2023, Volume and Issue: 3(9), P. 1308 - 1317

Published: June 1, 2023

The destruction of per- and polyfluoroalkyl substances (PFAS) is critical to ensure effective remediation PFAS contaminated matrices. hazardous chemicals within incinerators other thermal treatment processes has historically been determined by calculating the efficiency (DE) or removal (DRE). While high DEs, >99.99%, are deemed acceptable for most compounds, many can be converted at low temperatures resulting in DEs without full mineralization potential release remaining fluorocarbon portions environment. Many these products incomplete combustion (PICs) greenhouse gases, have unknown toxicity, some react create new perfluorocarboxylic acids. Experiments using aqueous film forming foam (AFFF) a pilot-scale research combustor varied environment determine if indicate mineralization. Several operating conditions above 1090 °C resulted few detectable fluorinated PIC emissions. However, several below 1000 produced > 99.99% quantifiable mg/m3 emission concentrations nonpolar PICs. These results suggest that DE alone may not best indication total destruction, additional characterization warranted.

Language: Английский

Citations

33
PFAS Exposures and the Human Metabolome: A Systematic Review of Epidemiological Studies DOI
Sandra India Aldana, Meizhen Yao, Vishal Midya

et al.

Current Pollution Reports, Journal Year: 2023, Volume and Issue: 9(3), P. 510 - 568

Published: June 29, 2023

Language: Английский

Citations

33
Toxic effects of per- and polyfluoroalkyl substances on sperm: Epidemiological and experimental evidence DOI Creative Commons

Zhangbei Sun,

Yiqian Wen,

Binhui Wang

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 20, 2023

As emerging organic contaminants, per- and polyfluoroalkyl substances (PFASs) have aroused worldwide concern due to their environmental persistence, ubiquitous presence, bioaccumulation, potential toxicity. It has been demonstrated that PFASs can accumulate in human body cause multiple adverse health outcomes. Notably, detected the semen of human, posing a hazard male fecundity. This article reviews evidence about toxic effects exposure on reproduction, focusing sperm quality. Epidemiological studies showed PFASs, such as perfluorooctanoic acid (PFOA) perfluorooctane sulfonic (PFOS), were adversely associated with parameters humans, including count, morphology motility. Experimental results also confirmed PFAS led testicular epididymal damage, therefore impairing spermatogenesis The mechanisms reproductive toxicity may be involved blood-testosterone barrier destruction, apoptosis, testosterone synthesis disorder, membrane lipid composition alteration, oxidative stress Ca 2+ influx sperm. In conclusion, this review highlighted threat spermatozoa.

Language: Английский

Citations

29
Metabolic perturbations in pregnant rats exposed to low-dose perfluorooctanesulfonic acid: An integrated multi-omics analysis DOI Creative Commons

Guoqi Yu,

Jinguo Wang, Yongjie Liu

et al.

Environment International, Journal Year: 2023, Volume and Issue: 173, P. 107851 - 107851

Published: Feb. 26, 2023

Emerging epidemiological evidence has linked per- and polyfluoroalkyl substances (PFAS) exposure could be to the disturbance of gestational glucolipid metabolism, but toxicological mechanism is unclear, especially when at a low level. This study examined metabolic changes in pregnant rats treated with relatively dose perfluorooctanesulfonic acid (PFOS) through oral gavage during pregnancy [gestational day (GD): 1–18]. We explored molecular mechanisms underlying perturbation. Oral glucose tolerance test (OGTT) biochemical tests were performed assess homeostasis serum lipid profiles Sprague-Dawley (SD) randomly assigned starch, 0.03 0.3 mg/kg·bw·d groups. Transcriptome sequencing combined non-targeted metabolomic assays further identify differentially altered genes metabolites liver maternal rats, determine their correlation phenotypes. Results transcriptome showed that expressed PFOS related several pathways, such as peroxisome proliferator-activated receptors (PPARs) signaling, ovarian steroid synthesis, arachidonic insulin resistance, cholesterol unsaturated fatty bile secretion. The untargeted metabolomics identified 164 158 differential groups, respectively under negative ion mode Electrospray Ionization (ESI-), which enriched pathways α-linolenic glycolysis/gluconeogenesis, glycerolipid glucagon signaling pathway, glycine, serine threonine metabolism. Co-enrichment analysis indicated may disturb metabolism glycerolipid, linoleic acid, biosynthesis, threonine. key involved included down-regulated Ppp1r3c Abcd2, up-regulated Ogdhland Ppp1r3g, increased glycerol 3-phosphate lactosylceramide identified. Both them significantly associated fasting blood (FBG) Our findings provide mechanistic clues for clarifying toxicity human, susceptible population women.

Language: Английский

Citations

29
Plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease DOI Creative Commons
Linda Dunder, Samira Salihović, Peter Lind

et al.

Environment International, Journal Year: 2023, Volume and Issue: 177, P. 107979 - 107979

Published: May 24, 2023

Per- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic cardiometabolic effects in both experimental epidemiological studies, but with conflicting results. The aim of the present study was investigate potential associations between plasma PFAS levels preselected proteomic biomarkers previously inflammation, metabolism cardiovascular disease. Three (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic (PFOA) perfluorohexane (PFHxS)) were measured by non-targeted metabolomics 249 proximity extension assay (PEA) from 2,342 individuals within Epidemiology for Health (EpiHealth) Sweden (45–75 years old, 50.6 % men). After adjustment age sex, 92% significant PFOS concentrations proteins inverse (p < 0.0002, Bonferroni-adjusted). results not as clear PFOA PFHxS, still 80% 64 being inverse. age, smoking, education, exercise habits alcohol consumption, epidermal growth factor receptor (EGFR), paraoxonase type 3 (PON3) remained positively associated all three PFAS, while resistin (RETN) urokinase plasminogen activator surface (uPAR) showed PFAS. Our findings imply that exposure is cross-sectionally altered disease middle-aged humans.

Language: Английский

Citations

27
Untargeted metabolomics and machine learning unveil the exposome and metabolism linked with the risk of early pregnancy loss DOI

Yixuan Shi,

Keyi Li,

Ran Ding

et al.

Journal of Hazardous Materials, Journal Year: 2025, Volume and Issue: 488, P. 137362 - 137362

Published: Jan. 31, 2025

Language: Английский

Citations

1
Associations of prenatal metal exposure with child neurodevelopment and mediation by perturbation of metabolic pathways DOI Creative Commons

Ya Jie Xie,

Han Xiao, Dan Zheng

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 1, 2025

Prenatal exposure to metals has been associated with impaired neurodevelopment in children, but the detailed molecular mechanisms remain largely unknown. Based on Wuhan Healthy Baby Cohort, China (N = 1088), eleven were measured maternal urine during early pregnancy (13.1 ± 1.1 weeks) and metabolomics profiling was conducted cord blood. Neurodevelopment evaluated using Bayley Scales of Infant Development 2-year-old children obtain mental development index (MDI) psychomotor (PDI). After false discovery rate correction, higher urinary levels manganese, nickel, aluminum, rubidium, gallium, summary score only significantly lower MDI scores. The weighted quantile sum metal mixture showed a significant inverse association PDI scores, aluminum contributing most associations. Histidine, beta-alanine, purine, pyrimidine metabolism mediated above associations, suggesting that disturbances amino acids, neurotransmitter neuroendocrine may be important mediators children. linked underlying are unclear. Here, authors show neurotransmitters, mediate association.

Language: Английский

Citations

1
Global Exposure to Per- and Polyfluoroalkyl Substances and Associated Burden of Low Birthweight DOI

Xiarui Fan,

Song Tang, Ying Wang

et al.

Environmental Science & Technology, Journal Year: 2022, Volume and Issue: 56(7), P. 4282 - 4294

Published: March 16, 2022

Low birthweight (LBW) is a worldwide public health concern, while the global burden of LBW attributable to endocrine-disrupting chemicals, such as per- and polyfluoroalkyl substances (PFAS), has not yet been evaluated. Here, we established large dataset for biomonitoring seven representative congeners PFAS by examining data from 2325 publications. Global exposure perfluorooctanesulfonic acid (PFOS) was highest, followed perfluorohexanesulfonic (PFHxS) perfluorooctanoic (PFOA). Spatiotemporal varied considerably, with daily intake estimated in range 0.01–1.7 ng/kg/day. Moreover, decreasing trends PFOS, PFHxS, PFOA were noted most regions world over past two decades, but observed other long carbon chains, especially East Asia. Furthermore, that human contributed approximately 461,635 (95% confidence interval: 57,418 854,645) cases per year during predominantly Asian regions. Although our estimation may be constrained uncertainties dose–response curve availability, this study unveiled might contributor prevalence 2000–2019, supporting continuous actions mitigate contamination.

Language: Английский

Citations

33
Cumulative maternal and neonatal effects of combined exposure to a mixture of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) during pregnancy in the Sprague-Dawley rat DOI Creative Commons
Justin M. Conley,

Christy Lambright,

Nicola Evans

et al.

Environment International, Journal Year: 2022, Volume and Issue: 170, P. 107631 - 107631

Published: Nov. 12, 2022

Globally, biomonitoring data demonstrate virtually all humans carry residues of multiple per- and polyfluoroalkyl substances (PFAS). Despite pervasive co-exposure, limited mixtures-based in vivo PFAS toxicity research has been conducted. Perfluorooctanoic acid (PFOA) perfluorooctane sulfonic (PFOS) are commonly detected human environmental samples both produce adverse effects laboratory animal studies, including maternal offspring when orally administered during pregnancy lactation. To evaluate the combined exposure to PFOA PFOS, we exposed pregnant Sprague-Dawley rats from gestation day 8 (GD8) postnatal 2 (PND2) (10-250 mg/kg/d) or PFOS (0.1-5 individually characterize dose response curve parameters, followed by a variable-ratio mixture experiment with constant (2 mixed increasing doses (3-80 mg/kg/d). The study design was intended to: 1) shift curves for endpoints shared 2) allow comparison addition (DA) (RA) model predictions, 3) conduct relative potency factor (RPF) analysis endpoints, 4) avoid overt toxicity. Maternal serum liver concentrations were consistent between individual chemical experiments. Combined significantly shifted towards at lower compared PFOA-only these well predicted addition. For amenable analyses, DA produced equivalent better estimates observed than RA. All evaluated accurately RPF approaches except gestational weight gain, which less-than-additive results mixture. Data support hypothesis cumulative on co-exposure additive predictive effects.

Language: Английский

Citations

31
Bioaccumulation and impact of maternal PFAS offloading on egg biochemistry from wild-caught freshwater turtles (Emydura macquarii macquarii) DOI Creative Commons
David J. Beale, Sandra Nilsson, Utpal Bose

et al.

The Science of The Total Environment, Journal Year: 2022, Volume and Issue: 817, P. 153019 - 153019

Published: Jan. 11, 2022

Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic contaminants that pervasive in the environment. Toxicity resulting from elevated PFAS concentrations wildlife has been studied, yet evidence of their accumulation, developmental toxicity maternal offloading egg-laying species is limited. Here we show freshwater short-necked turtles (Emydura macquarii macquarii) exposed to biological impact on oviducal eggs. Total were determined serum adult females harvested eggs collected euthanised low high levels compared against turtle a suitable reference site. Multi-omics assays utilised explore biochemical egg albumen, yolk eggshell using range metabolomics, lipidomics, proteomics techniques. Eggshells also screened for metals by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Analysis female demonstrated transference 1.6 5.3 times higher impacted eggs, respectively, concentrations. Oviducal comprised >90% bioaccumulated load. Multi-omic analysis dissected fractions illustrated significantly purine metabolism metabolites, which tied potential dysfunctional processes. The yolks depleted lipids lipid quality growth development. eggshells lower calcium, important immune response proteins, glycerophosphoethanolamines (PE) histidine metabolites weakened physical structure. Further investigation needed establish rate quantify hatchling success fully demonstrate PFAS-developmental linkages.

Language: Английский

Citations

30