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Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Non-targeted analysis (NTA) has made critical contributions in the fields of environmental chemistry and environmental health. One critical bottleneck is the lack of available analytical standards for most chemicals in the environment. Our study aims to explore a novel approach that integrates measurements of equilibrium partition ratios between organic solvents and water (KSW) to predictions of molecular structures. These properties can be used as a fingerprint, which with the help of a machine learning algorithm can be converted into a series of functional groups (RDKit fragments), which can be used to search chemical databases. We conducted partitioning experiments using a chemical mixture containing 185 chemicals in 10 different organic solvents and water. Both a liquid chromatography quadrupole time-of-flight mass spectrometer (LC-QTOF MS) and a LC-Orbitrap MS were used to assess the feasibility of the experimental method and the accuracy of the algorithm at predicting the correct functional groups. The two methods showed differences in log KSW with the QTOF method showing a mean absolute error (MAE) of 0.22 and the Orbitrap method 0.33. The differences also culminated into errors in the predictions of RDKit fragments with the MAE for the QTOF method being 0.23 and for the Orbitrap method being 0.31. Our approach presents a new angle in structure elucidation for NTA and showed promise in assisting with compound identification.

BackgroundNontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.ObjectivesWe characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco.MethodsWe collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures.ResultsWe detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between -0.1 and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS (coefficient=0.9, 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [OR=1.33 (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [OR=1.28 (95% CI: 0.90, 1.86)].DiscussionWe identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. https://doi.org/10.1289/EHP11546.

BackgroundDifferential risks for adverse pregnancy outcomes may be influenced by prenatal chemical exposures, but current exposure methods may not fully capture data to identify harms and differences.MethodsWe collected maternal and cord sera from pregnant people in Fresno and San Francisco, and screened for over 2420 chemicals using LC-QTOF/MS. We matched San Francisco participants to Fresno participants (N = 150) and compared detection frequencies. Twenty-six Fresno participants wore silicone wristbands evaluated for over 1500 chemicals using quantitative chemical analysis. We assessed whether living in tracts with higher levels of pollution according to CalEnviroScreen correlated with higher numbers of chemicals detected in sera.ResultsWe detected 2167 suspect chemical features across maternal and cord sera. The number of suspect chemical features was not different by city, but a higher number of suspect chemicals in cosmetics or fragrances was detected in the Fresno versus San Francisco participants' sera. We also found high levels of chemicals used in fragrances measured in the silicone wristbands. Fresno participants living in tracts with higher pesticide scores had higher numbers of suspect pesticides in their sera.ConclusionsMultiple exposure-assessment approaches can identify exposure to many chemicals during pregnancy that have not been well-studied for health effects.

BackgroundExposure to per- and poly-fluoroalkyl substances (PFAS) remains an important public health issue due to widespread detection and persistence in environmental media, slow metabolism in humans, and influences on physiological processes such as neurological signaling. Maternal depression is highly prevalent during pregnancy and postpartum and is potentially sensitive to PFAS. The health risks associated with PFAS may be further amplified in historically marginalized communities, including immigrants.ObjectiveEvaluate maternal concentrations of PFAS in association with depression scores during pregnancy and whether effects differ between US born and immigrant women.MethodsOur study sample included 282 US born and 235 immigrant pregnant women enrolled in the Chemicals in Our Bodies prospective birth cohort based in San Francisco, CA. We measured 12 PFAS in serum samples collected in the second trimester and depressive symptom scores were assessed using the Center for Epidemiologic Studies Depression Scale. Associations were estimated using linear regression, adjusting for maternal age, education, pre-pregnancy body mass index, and parity. Associations with a PFAS mixture were estimated using quantile g-computation.ResultsIn adjusted linear regression models, a twofold increase in two PFAS was associated with higher depression scores in the overall sample, and this association persisted only among immigrant women (β [95 % confidence interval]: perfluorooctane sulfonic acid (2.7 [0.7-4.7]) and methyl-perfluorooctane sulfonamide acetic acid (2.9 [1.2-4.7]). Quantile g-computation indicated that simultaneously increasing all PFAS in the mixture by one quartile was associated with increased depressive symptoms among immigrant women (mean change per quartile increase = 1.12 [0.002, 2.3]), and associations were stronger compared to US born women (mean change per quartile increase = 0.09 [-1.0, 0.8]).ConclusionsFindings provide new evidence that PFAS are associated with higher depression symptoms among immigrant women during pregnancy. Results can inform efforts to address environmental factors that may affect depression among US immigrants.

BackgroundPer- and poly-fluoroalkyl substances (PFAS) are commonly detected in a variety of foods and food packaging materials. However, few studies have examined diet as a potential source of PFAS exposure during pregnancy. In the present cross-sectional study, we examined prenatal PFAS levels in relation to self-reported consumption of meats, dairy products, and processed foods during pregnancy.MethodsParticipants were enrolled in the Chemicals in Our Bodies study, a demographically diverse pregnancy cohort in San Francisco, CA (N = 509). Diet was assessed using a self-reported interview questionnaire administered during the second trimester. Participants were asked on average how many times a day, week, or month they ate 11 different foods since becoming pregnant. Responses were categorized as at least once a week or less than once a week and foods were grouped into three categories: processed foods, dairy products, and meats. Twelve PFAS (ng/mL) were measured in second trimester serum samples. We investigated relationships between consumption of individual dairy products, meats, and processed foods and natural log-transformed PFAS using separate linear regression models adjusted for maternal age, education, race/ethnicity, and nativity.ResultsSeven PFAS were detected in ≥65% of participants. Consumption of dairy milk and cheese at least once per week was moderately associated with elevated levels of perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDeA) relative to those who ate dairy products less than once week. The strongest associations observed were with PFDeA for dairy milk (β = 0.2, 95% confidence interval [CI] = 0.02, 0.39) and PFNA for cheese (β = 0.22, 95% CI = 0.02, 0.41). Eating fish, poultry, and red meat at least once per week was associated with higher levels of perfluoroundecanoic acid, PFDeA, PFNA, and perflucorooctane sulfonic acid.ConclusionsResults indicate that consumption of animal products may contribute to elevated prenatal PFAS levels.

BackgroundExposure to environmental chemicals during pregnancy adversely affects maternal and infant health, and identifying socio-demographic differences in exposures can inform contributions to health inequities.MethodsWe recruited 294 demographically diverse pregnant participants in San Francisco from the Mission Bay/Moffit Long (MB/ML) hospitals, which serve a primarily higher income population, and Zuckerberg San Francisco General Hospital (ZSFGH), which serves a lower income population. We collected maternal and cord sera, which we screened for 2420 unique formulas and their isomers using high-resolution mass spectrometry using LC-QTOF/MS. We assessed differences in chemical abundances across socioeconomic and demographic groups using linear regression adjusting for false discovery rate.ResultsOur participants were racially diverse (31% Latinx, 16% Asian/Pacific Islander, 5% Black, 5% other or multi-race, and 43% white). A substantial portion experienced financial strain (28%) and food insecurity (20%) during pregnancy. We observed significant abundance differences in maternal (9 chemicals) and cord sera (39 chemicals) between participants who delivered at the MB/ML hospitals versus ZSFGH. Of the 39 chemical features differentially detected in cord blood, 18 were present in pesticides, one per- or poly-fluoroalkyl substance (PFAS), 21 in plasticizers, 24 in cosmetics, and 17 in pharmaceuticals; 4 chemical features had unknown sources. A chemical feature annotated as 2,4-dichlorophenol had higher abundances among Latinx compared to white participants, those delivering at ZSFGH compared to MB/ML, those with food insecurity, and those with financial strain. Post-hoc QTOF analyses indicated the chemical feature was either 2,4-dichlorophenol or 2,5-dichlorophenol, both of which have potential endocrine-disrupting effects.ConclusionsChemical exposures differed between delivery hospitals, likely due to underlying social conditions faced by populations served. Differential exposures to 2,4-dichlorophenol or 2,5-dichlorophenol may contribute to disparities in adverse outcomes.

BackgroundOxidative stress from excess reactive oxygen species (ROS) is a hypothesized contributor to preterm birth. Per- and polyfluoroalkyl substances (PFAS) exposure is reported to generate ROS in laboratory settings, and is linked to adverse birth outcomes globally. However, to our knowledge, the relationship between PFAS and oxidative stress has not been examined in the context of human pregnancy.ObjectiveTo investigate the associations between prenatal PFAS exposure and oxidative stress biomarkers among pregnant people.MethodsOur analytic sample included 428 participants enrolled in the Illinois Kids Development Study and Chemicals In Our Bodies prospective birth cohorts between 2014 and 2019. Twelve PFAS were measured in second trimester serum. We focused on seven PFAS that were detected in >65 % of participants. Urinary levels of 8-isoprostane-prostaglandin-F2α, prostaglandin-F2α, 2,3-dinor-8-iso-PGF2α, and 2,3-dinor-5,6-dihydro-8-iso-PGF2α were measured in the second and third trimesters as biomarkers of oxidative stress. We fit linear mixed-effects models to estimate individual associations between PFAS and oxidative stress biomarkers. We used quantile g-computation and Bayesian kernel machine regression (BKMR) to assess associations between the PFAS mixture and averaged oxidative stress biomarkers.ResultsLinear mixed-effects models showed that an interquartile range increase in perfluorooctane sulfonic acid (PFOS) was associated with an increase in 8-isoprostane-prostaglandin-F2α (β = 0.10, 95 % confidence interval = 0, 0.20). In both quantile g-computation and BKMR, and across all oxidative stress biomarkers, PFOS contributed the most to the overall mixture effect. The six remaining PFAS were not significantly associated with changes in oxidative stress biomarkers.ConclusionsOur study is the first to investigate the relationship between PFAS exposure and biomarkers of oxidative stress during human pregnancy. We found that PFOS was associated with elevated levels of oxidative stress, which is consistent with prior work in animal models and cell lines. Future research is needed to understand how prenatal PFAS exposure and maternal oxidative stress may affect fetal development.

While important advances have been made in high-resolution mass spectrometry (HRMS) and its applications in non-targeted analysis (NTA), the number of identified compounds in biological and environmental samples often does not exceed 5% of the detected chemical features. Our aim was to develop a computational pipeline that leverages data from HRMS but also incorporates physicochemical properties (equilibrium partition ratios between organic solvents and water; Ksolvent-water) and can propose molecular structures for detected chemical features. As these physicochemical properties are often sufficiently different across isomers, when put together, they can form a unique profile for each isomer, which we describe as the "physicochemical fingerprint". In our study, we used a comprehensive database of compounds that have been previously reported in human blood and collected their Ksolvent-water values for 129 partitioning systems. We used RDKit to calculate the number of RDKit fragments and the number of RDKit bits per molecule. We then developed and trained an artificial neural network, which used as an input the physicochemical fingerprint of a chemical feature and predicted the number and types of RDKit fragments and RDKit bits present in that structure. These were then used to search the database and propose chemical structures. The average success rate of predicting the right chemical structure ranged from 60 to 86% for the training set and from 48 to 81% for the testing set. These observations suggest that physicochemical fingerprints can assist in the identification of compounds with NTA and substantially improve the number of identified compounds.

BackgroundPrenatal exposure to individual per‑ and poly‑fluoroalkyl substances (PFAS) and psychosocial stressors have been associated with reductions in fetal growth. Studies suggest cumulative or joint effects of chemical and non-chemical stressors on fetal growth. However, few studies have examined PFAS and non-chemical stressors together as a mixture, which better reflects real life exposure patterns. We examined joint associations between PFAS, perceived stress, and depression, and fetal growth using two approaches developed for exposure mixtures.MethodsPregnant participants were enrolled in the Chemicals in Our Bodies cohort and Illinois Kids Development Study, which together make up the ECHO.CA.IL cohort. Seven PFAS were previously measured in 2nd trimester maternal serum samples and were natural log transformed for analyses. Perceived stress and depression were assessed using self-reported validated questionnaires, which were converted to t-scores using validated methods. Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to assess joint associations between PFAS, perceived stress and depression t-scores and birthweight z-scores (N = 876).ResultsIndividual PFAS, depression and perceived stress t-scores were negatively correlated with birthweight z-scores. Using quantile g-computation, a simultaneous one quartile increase in all PFAS, perceived stress and depression t-scores was associated with a slight reduction in birthweight z-scores (mean change per quartile increase = -0.09, 95% confidence interval = -0.21,0.03). BKMR similarly indicated that cumulative PFAS and stress t-scores were modestly associated with lower birthweight z-scores. Across both methods, the joint association appeared to be distributed across multiple exposures rather than due to a single exposure.ConclusionsOur study is one of the first to examine the joint effects of chemical and non-chemical stressors on fetal growth using mixture methods. We found that PFAS, perceived stress, and depression in combination were modestly associated were lower birthweight z-scores, which supports prior studies indicating that chemical and non-chemical stressors are jointly associated with adverse health outcomes.

BackgroundPrenatal exposure to per- and poly-fluoroalkyl substances (PFAS) and psychosocial stressors has been associated with adverse pregnancy outcomes, including preterm birth. Previous studies have suggested that joint exposure to environmental chemical and social stressors may be contributing to disparities observed in preterm birth. Elevated corticotropin-releasing hormone (CRH) during mid-gestation may represent one biologic mechanism linking chemical and nonchemical stress exposures to preterm birth.MethodsUsing data from a prospective birth cohort (N = 497), we examined the cross-sectional associations between five individual PFAS (ng/mL; PFNA, PFOA, PFOS, PFHxS, and Me-PFOSA-AcOH) and CRH (pg/mL) using linear regression. PFAS and CRH were measured during the second trimester in serum and plasma, respectively. Coefficients were standardized to reflect change in CRH associated with an interquartile range (IQR) increase in natural log-transformed PFAS. We additionally examined if the relationship between PFAS and CRH was modified by psychosocial stress using stratified models. Self-reported depression, stressful life events, perceived stress, food insecurity, and financial strain were assessed using validated questionnaires during the second trimester and included as binary indicators of psychosocial stress.ResultsAn IQR increase in PFNA was associated with elevated CRH (β = 5.17, 95% confidence interval [CI] = 1.79, 8.55). Increased concentrations of PFOA were also moderately associated with CRH (β = 3.62, 95% CI = -0.42, 7.66). The relationship between PFNA and CRH was stronger among women who experienced stressful life events, depression, food insecurity, and financial strain compared to women who did not experience these stressors.ConclusionsThis cross-sectional study is the first to examine the relationship between PFAS exposure and CRH levels in mid-gestation. We found that these associations were stronger among women who experienced stress, which aligns with previous findings that chemical and nonchemical stressor exposures can have joint effects on health outcomes.

BackgroundPer- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures.MethodsStudy participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110 second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes.ResultsT/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman ρ = 0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase = 0.03, 95% confidence interval [CI] = -0.03, 0.08) and maternal telomere length (mean change per quartile increase = 0.03 (95% CI = -0.03, 0.09). When restricted to maternal-fetal paired samples (N = 76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase = 0.16, 95% CI = 0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase = 0.11 [95% CI = 0.01, 0.22]). No associations were observed with maternal telomere length among paired samples.ConclusionsOur findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.

BackgroundPer- and poly-fluoroalkyl substances (PFAS) are commonly detected in a variety of foods and food packaging materials. However, few studies have examined diet as a potential source of PFAS exposure during pregnancy. In the present cross-sectional study, we examined prenatal PFAS levels in relation to self-reported consumption of meats, dairy products, and processed foods during pregnancy.MethodsParticipants were enrolled in the Chemicals in Our Bodies study, a demographically diverse pregnancy cohort in San Francisco, CA (N = 509). Diet was assessed using a self-reported interview questionnaire administered during the second trimester. Participants were asked on average how many times a day, week, or month they ate 11 different foods since becoming pregnant. Responses were categorized as at least once a week or less than once a week and foods were grouped into three categories: processed foods, dairy products, and meats. Twelve PFAS (ng/mL) were measured in second trimester serum samples. We investigated relationships between consumption of individual dairy products, meats, and processed foods and natural log-transformed PFAS using separate linear regression models adjusted for maternal age, education, race/ethnicity, and nativity.ResultsSeven PFAS were detected in ≥65% of participants. Consumption of dairy milk and cheese at least once per week was moderately associated with elevated levels of perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDeA) relative to those who ate dairy products less than once week. The strongest associations observed were with PFDeA for dairy milk (β = 0.2, 95% confidence interval [CI] = 0.02, 0.39) and PFNA for cheese (β = 0.22, 95% CI = 0.02, 0.41). Eating fish, poultry, and red meat at least once per week was associated with higher levels of perfluoroundecanoic acid, PFDeA, PFNA, and perflucorooctane sulfonic acid.ConclusionsResults indicate that consumption of animal products may contribute to elevated prenatal PFAS levels.

Non-targeted analysis (NTA), including both suspect screening analysis (SSA) and unknown compound analysis, has gained increasing popularity in various fields for its capability in identifying new compounds of interests. Current major challenges for NTA SSA are that (1) tremendous effort and resources are needed for large-scale identification and confirmation of suspect chemicals and (2) suspect chemicals generally show low matching rates during identification and confirmation processes. To narrow the gap between these challenges and smooth implementation of NTA SSA methodology in the biomonitoring field, we present a thorough SSA workflow for the large-scale screen, identification, and confirmation of industrial chemicals that may pose adverse health effects in pregnant women and newborns. The workflow was established in a study of 30 paired maternal and umbilical cord serum samples collected at delivery in the San Francisco Bay area. By analyzing LC-HRMS and MS/MS data, together with the assistance of a combination of resources including online MS/MS spectra libraries, online in silico fragmentation tools, and the EPA CompTox Chemicals Dashboard, we confirmed the identities of 17 chemicals, among which monoethylhexyl phthalate, 4-nitrophenol, tridecanedioic acid, and octadecanedioic acid are especially interesting due to possible toxicities and their high-volume use in industrial manufacturing. Similar to other previous studies in the SSA field, the suspect compounds show relatively low MS/MS identification (16%) and standard confirmation (8%) rates. Therefore, we also investigated origins of false positive features and unidentifiable suspected features, as well as technical obstacles encountered during the confirmation process, which would promote a better understanding of the flaw of low confirmation rate and encourage gaining more effective tools for tackling this issue in NTA SSA.

Non-targeted analysis (NTA), including both suspect screening analysis (SSA) and unknown compound analysis, has gained increasing popularity in various fields for its capability in identifying new compounds of interests. Current major challenges for NTA SSA are that (1) tremendous effort and resources are needed for large-scale identification and confirmation of suspect chemicals and (2) suspect chemicals generally show low matching rates during identification and confirmation processes. To narrow the gap between these challenges and smooth implementation of NTA SSA methodology in the biomonitoring field, we present a thorough SSA workflow for the large-scale screen, identification, and confirmation of industrial chemicals that may pose adverse health effects in pregnant women and newborns. The workflow was established in a study of 30 paired maternal and umbilical cord serum samples collected at delivery in the San Francisco Bay area. By analyzing LC-HRMS and MS/MS data, together with the assistance of a combination of resources including online MS/MS spectra libraries, online in silico fragmentation tools, and the EPA CompTox Chemicals Dashboard, we confirmed the identities of 17 chemicals, among which monoethylhexyl phthalate, 4-nitrophenol, tridecanedioic acid, and octadecanedioic acid are especially interesting due to possible toxicities and their high-volume use in industrial manufacturing. Similar to other previous studies in the SSA field, the suspect compounds show relatively low MS/MS identification (16%) and standard confirmation (8%) rates. Therefore, we also investigated origins of false positive features and unidentifiable suspected features, as well as technical obstacles encountered during the confirmation process, which would promote a better understanding of the flaw of low confirmation rate and encourage gaining more effective tools for tackling this issue in NTA SSA.

Recent technological advances in mass spectrometry have enabled us to screen biological samples for a very broad spectrum of chemical compounds allowing us to more comprehensively characterize the human exposome in critical periods of development. The goal of this study was three-fold: (1) to analyze 590 matched maternal and cord blood samples (total 295 pairs) using non-targeted analysis (NTA); (2) to examine the differences in chemical abundance between maternal and cord blood samples; and (3) to examine the associations between exogenous chemicals and endogenous metabolites. We analyzed all samples with high-resolution mass spectrometry using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) in both positive and negative electrospray ionization modes (ESI+ and ESI-) and in soft ionization (MS) and fragmentation (MS/MS) modes for prioritized features. We confirmed 19 unique compounds with analytical standards, we tentatively identified 73 compounds with MS/MS spectra matching, and we annotated 98 compounds using an annotation algorithm. We observed 103 significant associations in maternal and 128 in cord samples between compounds annotated as endogenous and compounds annotated as exogenous. An example of these relationships was an association between three poly and perfluoroalkyl substances (PFASs) and endogenous fatty acids in both the maternal and cord samples indicating potential interactions between PFASs and fatty acid regulating proteins.

Recent technological advances in mass spectrometry have enabled us to screen biological samples for a very broad spectrum of chemical compounds allowing us to more comprehensively characterize the human exposome in critical periods of development. The goal of this study was three-fold: (1) to analyze 590 matched maternal and cord blood samples (total 295 pairs) using non-targeted analysis (NTA); (2) to examine the differences in chemical abundance between maternal and cord blood samples; and (3) to examine the associations between exogenous chemicals and endogenous metabolites. We analyzed all samples with high-resolution mass spectrometry using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) in both positive and negative electrospray ionization modes (ESI+ and ESI-) and in soft ionization (MS) and fragmentation (MS/MS) modes for prioritized features. We confirmed 19 unique compounds with analytical standards, we tentatively identified 73 compounds with MS/MS spectra matching, and we annotated 98 compounds using an annotation algorithm. We observed 103 significant associations in maternal and 128 in cord samples between compounds annotated as endogenous and compounds annotated as exogenous. An example of these relationships was an association between three poly and perfluoroalkyl substances (PFASs) and endogenous fatty acids in both the maternal and cord samples indicating potential interactions between PFASs and fatty acid regulating proteins.

BackgroundPer- and polyfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are endocrine disrupting chemicals with widespread exposures across the U.S. given their abundance in consumer products. PFAS and PBDEs are associated with reproductive toxicity and adverse health outcomes, including certain cancers. PFAS and PBDEs may affect health through alternations in telomere length. In this study, we examined joint associations between prenatal exposure to PFAS, PBDEs, and maternal and newborn telomere length using mixture analyses, to characterize effects of cumulative environmental chemical exposures.MethodsStudy participants were enrolled in the Chemicals in Our Bodies (CIOB) study, a demographically diverse cohort of pregnant people and children in San Francisco, CA. Seven PFAS (ng/mL) and four PBDEs (ng/g lipid) were measured in second trimester maternal serum samples. Telomere length (T/S ratio) was measured in delivery cord blood of 292 newborns and 110 second trimester maternal whole blood samples. Quantile g-computation was used to assess the joint associations between groups of PFAS and PBDEs and newborn and maternal telomere length. Groups considered were: (1) all PFAS and PBDEs combined, (2) PFAS, and (3) PBDEs. Maternal and newborn telomere length were modeled as separate outcomes.ResultsT/S ratios in newborn cord and maternal whole blood were moderately correlated (Spearman ρ = 0.31). In mixtures analyses, a simultaneous one quartile increase in all PFAS and PBDEs was associated with a small increase in newborn (mean change per quartile increase = 0.03, 95% confidence interval [CI] = -0.03, 0.08) and maternal telomere length (mean change per quartile increase = 0.03 (95% CI = -0.03, 0.09). When restricted to maternal-fetal paired samples (N = 76), increasing all PFAS and PBDEs combined was associated with a strong, positive increase in newborn telomere length (mean change per quartile increase = 0.16, 95% CI = 0.03, 0.28). These associations were primarily driven by PFAS (mean change per quartile increase = 0.11 [95% CI = 0.01, 0.22]). No associations were observed with maternal telomere length among paired samples.ConclusionsOur findings suggest that PFAS and PBDEs may be positively associated with newborn telomere length.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) and organophosphate flame retardants (OPFRs) are chemicals that may contribute to placenta-mediated complications and adverse maternal-fetal health risks. Few studies have investigated these chemicals in relation to biomarkers of effect during pregnancy. We measured 12 PFASs and four urinary OPFR metabolites in 132 healthy pregnant women during mid-gestation and examined a subset with biomarkers of placental development and disease (n = 62). Molecular biomarkers included integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and matrix metalloproteinase-1 (MMP1). Morphological endpoints included potential indicators of placental stress and the extent of cytotrophoblast (CTB)-mediated uterine artery remodeling. Serum PFASs and urinary OPFR metabolites were detected in ∼50%-100% of samples. The most prevalent PFASs were perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonic acid (PFOS), with geometric mean (GM) levels of ∼1.3-2.8 (95% confidence limits from 1.2-3.1) ng/ml compared to ≤0.5 ng/ml for other PFASs. Diphenyl phosphate (DPhP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) were the most prevalent OPFR metabolites, with GMs of 2.9 (95% CI: 2.5-3.4) and 3.6 (95% CI: 2.2-3.1) ng/ml, respectively, compared to

Our proof-of-concept study develops a suspect screening workflow to identify and prioritize potentially ubiquitous chemical exposures in matched maternal/cord blood samples, a critical period of development for future health risks. We applied liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF/MS) to perform suspect screening for ∼3500 industrial chemicals on pilot data from 30 paired maternal and cord serum samples (n = 60). We matched 662 suspect features in positive ionization mode and 788 in negative ionization mode (557 unique formulas overall) to compounds in our database, and selected 208 of these for fragmentation analysis based on detection frequency, correlation in feature intensity between maternal and cord samples, and peak area differences by demographic characteristics. We tentatively identified 73 suspects through fragmentation spectra matching and confirmed 17 chemical features (15 unique compounds) using analytical standards. We tentatively identified 55 compounds not previously reported in the literature, the majority which have limited to no information about their sources or uses. Examples include (i) 1-(1-acetyl-2,2,6,6-tetramethylpiperidin-4-yl)-3-dodecylpyrrolidine-2,5-dione (known high production volume chemical) (ii) methyl perfluoroundecanoate and 2-perfluorooctyl ethanoic acid (two PFAS compounds); and (iii) Sumilizer GA 80 (plasticizer). Thus, our workflow demonstrates an approach to evaluating the chemical exposome to identify and prioritize chemical exposures during a critical period of development.

BackgroundPrenatal exposure to per- and poly-fluoroalkyl substances (PFAS) and psychosocial stressors has been associated with adverse pregnancy outcomes, including preterm birth. Previous studies have suggested that joint exposure to environmental chemical and social stressors may be contributing to disparities observed in preterm birth. Elevated corticotropin-releasing hormone (CRH) during mid-gestation may represent one biologic mechanism linking chemical and nonchemical stress exposures to preterm birth.MethodsUsing data from a prospective birth cohort (N = 497), we examined the cross-sectional associations between five individual PFAS (ng/mL; PFNA, PFOA, PFOS, PFHxS, and Me-PFOSA-AcOH) and CRH (pg/mL) using linear regression. PFAS and CRH were measured during the second trimester in serum and plasma, respectively. Coefficients were standardized to reflect change in CRH associated with an interquartile range (IQR) increase in natural log-transformed PFAS. We additionally examined if the relationship between PFAS and CRH was modified by psychosocial stress using stratified models. Self-reported depression, stressful life events, perceived stress, food insecurity, and financial strain were assessed using validated questionnaires during the second trimester and included as binary indicators of psychosocial stress.ResultsAn IQR increase in PFNA was associated with elevated CRH (β = 5.17, 95% confidence interval [CI] = 1.79, 8.55). Increased concentrations of PFOA were also moderately associated with CRH (β = 3.62, 95% CI = -0.42, 7.66). The relationship between PFNA and CRH was stronger among women who experienced stressful life events, depression, food insecurity, and financial strain compared to women who did not experience these stressors.ConclusionsThis cross-sectional study is the first to examine the relationship between PFAS exposure and CRH levels in mid-gestation. We found that these associations were stronger among women who experienced stress, which aligns with previous findings that chemical and nonchemical stressor exposures can have joint effects on health outcomes.

Our proof-of-concept study develops a suspect screening workflow to identify and prioritize potentially ubiquitous chemical exposures in matched maternal/cord blood samples, a critical period of development for future health risks. We applied liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF/MS) to perform suspect screening for ∼3500 industrial chemicals on pilot data from 30 paired maternal and cord serum samples (n = 60). We matched 662 suspect features in positive ionization mode and 788 in negative ionization mode (557 unique formulas overall) to compounds in our database, and selected 208 of these for fragmentation analysis based on detection frequency, correlation in feature intensity between maternal and cord samples, and peak area differences by demographic characteristics. We tentatively identified 73 suspects through fragmentation spectra matching and confirmed 17 chemical features (15 unique compounds) using analytical standards. We tentatively identified 55 compounds not previously reported in the literature, the majority which have limited to no information about their sources or uses. Examples include (i) 1-(1-acetyl-2,2,6,6-tetramethylpiperidin-4-yl)-3-dodecylpyrrolidine-2,5-dione (known high production volume chemical) (ii) methyl perfluoroundecanoate and 2-perfluorooctyl ethanoic acid (two PFAS compounds); and (iii) Sumilizer GA 80 (plasticizer). Thus, our workflow demonstrates an approach to evaluating the chemical exposome to identify and prioritize chemical exposures during a critical period of development.

BackgroundAnimal and human studies suggest certain persistent organic pollutants (POPs) may impact glucose metabolism; however, few epidemiologic studies have examined environmental determinants of glycemic outcomes during pregnancy. Our objective is to evaluate associations between exposures to individual and mixture of POPs and measures of prenatal fasting glucose, insulin, and insulin resistance during pregnancy in overweight women.MethodsA cohort of overweight and obese pregnant women (N = 95) was recruited from California. Blood samples were collected during late first or second trimester (median = 16 weeks' gestation; range = 10-24 weeks). Exposures included serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs). Outcomes included serum concentrations of fasting plasma glucose, fasting plasma insulin, and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Generalized linear models were used to evaluate cross-sectional associations between individual and aggregate POPs and mean percent difference in fasting glucose, fasting insulin, and HOMA-IR. Bayesian kernel machine regression (BKMR) was used to assess the relative importance of each exposure to the association with our outcomes, using conditional and group posterior inclusion probabilities (PIPs).ResultsStudy participants were racially/ethnically diverse and nearly half were below the federal poverty level. Across PBDEs and OH-PBDEs, the direction of associations with fasting glucose, fasting insulin and HOMA-IR were varied. A doubling of PCB-138, PCB-153, PCB-180, and ∑PCBs concentrations was associated with a 2.10% mmol/L (95%CI: 0.49%, 3.74%), 2.10% mmol/L (95%CI: -0.14%, 4.39%), 2.10% mmol/L (95%CI: 0.12%, 4.12%), and 2.81% mmol/L (95%CI: 0.38%, 5.31%) increase in fasting glucose, respectively. Exposure to individual PCBs was positively associated with both fasting insulin and HOMA-IR. All PFAS were inversely associated with fasting glucose, fasting insulin, and HOMA-IR. In BKMR models of fasting glucose, all four chemical classes were important contributors to the overall mixture, with PFASs identified as the most important contributor.DiscussionPrenatal PCB exposure was positively associated while certain PBDE and PFAS analytes were inversely associated with fasting glucose concentrations in overweight women. Further examination of the relationship between POPs exposure and glycemic functioning in a larger study population of women during pregnancy is warranted.

BackgroundInfants whose mothers experience greater psychosocial stress and environmental chemical exposures during pregnancy may face greater rates of preterm birth, lower birth weight, and impaired neurodevelopment.MethodsECHO.CA.IL is composed of two cohorts, Chemicals in Our Bodies (CIOB; n = 822 pregnant women and n = 286 infants) and Illinois Kids Development Study (IKIDS; n = 565 mother-infant pairs), which recruit pregnant women from San Francisco, CA and Urbana-Champaign, IL, respectively. We examined associations between demographic characteristics and gestational age, birth weight z-scores, and cognition at 7.5 months across these two cohorts using linear models. We also examined differences in biomarkers of exposure to per- and polyfluoroalkyl substances (PFAS), measured in second-trimester serum, and psychosocial stressors by cohort and participant demographics.ResultsTo date, these cohorts have recruited over 1300 pregnant women combined. IKIDS has mothers who are majority white (80%), whereas CIOB mothers are racially and ethnically diverse (38% white, 34% Hispanic, 17% Asian/Pacific Islander). Compared to CIOB, median levels of PFOS, a specific PFAS congener, are higher in IKIDS (2.45 ng/mL versus 1.94 ng/mL), while psychosocial stressors are higher among CIOB. Across both cohorts, women who were non-white and single had lower birth weight z-scores relative to white women and married women, respectively. Demographic characteristics are not associated with cognitive outcomes at 7.5 months.ConclusionsThis profile of the ECHO.CA.IL cohort found that mothers and their infants who vary in terms of socioeconomic status, race/ethnicity, and geographic location are similar in many of our measures of exposures and cognitive outcomes. Similar to past work, we found that non-white and single women had lower birth weight infants than white and married women. We also found differences in levels of PFOS and psychosocial stressors based on geographic location.

BackgroundInfants whose mothers experience greater psychosocial stress and environmental chemical exposures during pregnancy may face greater rates of preterm birth, lower birth weight, and impaired neurodevelopment.MethodsECHO.CA.IL is composed of two cohorts, Chemicals in Our Bodies (CIOB; n = 822 pregnant women and n = 286 infants) and Illinois Kids Development Study (IKIDS; n = 565 mother-infant pairs), which recruit pregnant women from San Francisco, CA and Urbana-Champaign, IL, respectively. We examined associations between demographic characteristics and gestational age, birth weight z-scores, and cognition at 7.5 months across these two cohorts using linear models. We also examined differences in biomarkers of exposure to per- and polyfluoroalkyl substances (PFAS), measured in second-trimester serum, and psychosocial stressors by cohort and participant demographics.ResultsTo date, these cohorts have recruited over 1300 pregnant women combined. IKIDS has mothers who are majority white (80%), whereas CIOB mothers are racially and ethnically diverse (38% white, 34% Hispanic, 17% Asian/Pacific Islander). Compared to CIOB, median levels of PFOS, a specific PFAS congener, are higher in IKIDS (2.45 ng/mL versus 1.94 ng/mL), while psychosocial stressors are higher among CIOB. Across both cohorts, women who were non-white and single had lower birth weight z-scores relative to white women and married women, respectively. Demographic characteristics are not associated with cognitive outcomes at 7.5 months.ConclusionsThis profile of the ECHO.CA.IL cohort found that mothers and their infants who vary in terms of socioeconomic status, race/ethnicity, and geographic location are similar in many of our measures of exposures and cognitive outcomes. Similar to past work, we found that non-white and single women had lower birth weight infants than white and married women. We also found differences in levels of PFOS and psychosocial stressors based on geographic location.

BackgroundPolybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function.MethodsTo evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy (n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion-integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and metalloproteinase-1 (MMP1)-and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues-leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall's tau correlation and linear regression methods.ResultsPBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE concentrations and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive).ConclusionsWe found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.

BackgroundPerfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are used in consumer products for their water repellent and flame retardant properties, respectively. However, there is widespread prenatal exposure and concern about their potential harm to the developing fetus. Here, we utilized data from a demographically diverse cohort of women in San Francisco, CA to examine associations between prenatal exposure to PFAS and PBDEs with gestational age and birth weight for gestational age z-scores.MethodsWomen included in this analysis were enrolled in the Chemicals in our Bodies (CIOB) cohort study (N = 506). PFAS and PBDEs were measured in serum obtained during the second trimester of pregnancy. Linear regression models were used to calculate crude and adjusted β coefficients for the association between PFAS and PBDE concentrations in tertiles and gestational age and birth weight z-scores. Individual PFAS and PBDE concentrations, as well as their sums, were examined in separate models.ResultsThe highest compared to lowest tertile of BDE-47 was associated with shorter gestational age (β = - 0.49, 95% confidence interval [CI] = - 0.95, - 0.02). Additionally, exposure to BDE-47 and BDE-99 in the middle tertile was also associated with a reduction in birth weight z-scores (β = - 0.26, 95% CI = -0.48, - 0.04; β = - 0.25, 95% CI = -0.47, - 0.04, respectively) compared to those in the lowest tertile of exposure. No consistent associations were observed between increasing PFAS concentrations and gestational age or birth weight z-scores.DiscussionAmong a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy and birth weight z-scores. However, most PFAS congeners were not associated with adverse birth outcomes. PFAS and PBDE concentrations were lower in our cohort relative to other studies. Future research should assess the effects of emerging and persistent PFAS and PBDEs on birth outcomes, as some congeners are being phased out and replaced by chemically similar structures.

BackgroundPerfluoroalkyl substances (PFAS) and polybrominated diphenyl ethers (PBDEs) are used in consumer products for their water repellent and flame retardant properties, respectively. However, there is widespread prenatal exposure and concern about their potential harm to the developing fetus. Here, we utilized data from a demographically diverse cohort of women in San Francisco, CA to examine associations between prenatal exposure to PFAS and PBDEs with gestational age and birth weight for gestational age z-scores.MethodsWomen included in this analysis were enrolled in the Chemicals in our Bodies (CIOB) cohort study (N = 506). PFAS and PBDEs were measured in serum obtained during the second trimester of pregnancy. Linear regression models were used to calculate crude and adjusted β coefficients for the association between PFAS and PBDE concentrations in tertiles and gestational age and birth weight z-scores. Individual PFAS and PBDE concentrations, as well as their sums, were examined in separate models.ResultsThe highest compared to lowest tertile of BDE-47 was associated with shorter gestational age (β = - 0.49, 95% confidence interval [CI] = - 0.95, - 0.02). Additionally, exposure to BDE-47 and BDE-99 in the middle tertile was also associated with a reduction in birth weight z-scores (β = - 0.26, 95% CI = -0.48, - 0.04; β = - 0.25, 95% CI = -0.47, - 0.04, respectively) compared to those in the lowest tertile of exposure. No consistent associations were observed between increasing PFAS concentrations and gestational age or birth weight z-scores.DiscussionAmong a diverse group of pregnant women in the San Francisco Bay Area, we found non-linear associations between prenatal exposure to PBDEs during the second trimester of pregnancy and birth weight z-scores. However, most PFAS congeners were not associated with adverse birth outcomes. PFAS and PBDE concentrations were lower in our cohort relative to other studies. Future research should assess the effects of emerging and persistent PFAS and PBDEs on birth outcomes, as some congeners are being phased out and replaced by chemically similar structures.

Prenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal-fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014-16). Maternal-fetal PBDE levels were compared to population characteristics using censored Kendall's tau correlation and linear regression. PBDEs were commonly detected in all biomatrices. Before lipid adjustment, wet-weight levels of all four PBDE congeners were highest in the fetal liver (p  Latina/Hispanic > Non-Hispanic White > Asian/Pacific Islander/Other; p

Non-targeted analysis provides a comprehensive approach to analyze environmental and biological samples for nearly all chemicals present. One of the main shortcomings of current analytical methods and workflows is that they are unable to provide any quantitative information constituting an important obstacle in understanding environmental fate and human exposure. Herein, we present an in silico quantification method using mahine-learning for chemicals analyzed using electrospray ionization (ESI). We considered three data sets from different instrumental setups: (i) capillary electrophoresis electrospray ionization-mass spectrometry (CE-MS) in positive ionization mode (ESI+), (ii) liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) in ESI+ and (iii) LC-QTOF/MS in negative ionization mode (ESI-). We developed and applied two different machine-learning algorithms: a random forest (RF) and an artificial neural network (ANN) to predict the relative response factors (RRFs) of different chemicals based on their physicochemical properties. Chemical concentrations can then be calculated by dividing the measured abundance of a chemical, as peak area or peak height, by its corresponding RRF. We evaluated our models and tested their predictive power using 5-fold cross-validation (CV) and y randomization. Both the RF and the ANN models showed great promise in predicting RRFs. However, the accuracy of the predictions was dependent on the data set composition and the experimental setup. For the CE-MS ESI+ data set, the best model predicted measured RRFs with a mean absolute error (MAE) of 0.19 log units and a cross-validation coefficient of determination (Q2) of 0.84 for the testing set. For the LC-QTOF/MS ESI+ data set, the best model predicted measured RRFs with an MAE of 0.32 and a Q2 of 0.40. For the LC-QTOF/MS ESI- data set, the best model predicted measured RRFs with a MAE of 0.50 and a Q2 of 0.20. Our findings suggest that machine-learning algorithms can be used for predicting concentrations of nontargeted chemicals with reasonable uncertainties, especially in ESI+, while the application on ESI- remains a more challenging problem.

BACKGROUND:Polybrominated diphenyl ether (PBDE) exposures have been associated with adverse pregnancy outcomes. A hypothesized mechanism is via alterations in placental development and function. However, we lack biomarkers that can be used as early indicators of maternal/fetal response to PBDE exposures and/or perturbations in placental development or function. METHODS:To evaluate the relationship between PBDE levels and placental biomarkers during mid-gestation of human pregnancy (n = 62), we immunolocalized three molecules that play key roles in cytotrophoblast (CTB) differentiation and interstitial/endovascular uterine invasion-integrin alpha-1 (ITGA1), vascular endothelial-cadherin (CDH5), and metalloproteinase-1 (MMP1)-and assessed three morphological parameters as potential indicators of pathological alterations using H&E-stained tissues-leukocyte infiltration, fibrinoid deposition, and CTB endovascular invasion. We evaluated associations between placental PBDE levels and of biomarkers of placental development and disease using censored Kendall's tau correlation and linear regression methods. RESULTS:PBDEs were detected in all placental samples. We observed substantial variation in antigen expression and morphological endpoints across placental regions. We observed an association between PBDE concentrations and immunoreactivity of endovascular CTB staining with anti-ITGA1 (inverse) or interstitial CTBs staining with anti-CDH5 (positive). CONCLUSIONS:We found several molecular markers that may be sensitive placental indicators of PBDE exposure. Further, this indicates that placental biomarkers of development and disease could be useful barometers of exposure to PBDEs, a paradigm that could be extended to other environmental chemicals and placental stage-specific antigens.

Many California nail salon workers are low-income Vietnamese women of reproductive age who use nail products daily that contain androgen-disrupting phthalates, which may increase risk of male reproductive tract abnormalities during pregnancy. Yet, few studies have characterized phthalate exposures among this workforce. To characterize individual metabolites and cumulative phthalates exposure among a potentially vulnerable occupational group of nail salon workers, we collected 17 post-shift urine samples from Vietnamese workers at six San Francisco Bay Area nail salons in 2011, which were analyzed for four primary phthalate metabolites: mono-n-butyl-, mono-isobutyl-, mono(2-Ethylhexyl)-, and monoethyl phthalates (MnBP, MiBP, MEHP, and MEP, respectively; μg/L). Phthalate metabolite concentrations and a potency-weighted sum of parent compound daily intake (Σandrogen-disruptor, μg/kg/day) were compared to 203 Asian Americans from the 2011-2012 National Health and Nutritional Examination Survey (NHANES) using Student's t-test and Wilcoxin signed rank test. Creatinine-corrected MnBP, MiBP, MEHP (μg/g), and cumulative phthalates exposure (Σandrogen-disruptor, μg/kg/day) levels were 2.9 (p < 0.0001), 1.6 (p = 0.015), 2.6 (p < 0.0001), and 2.0 (p < 0.0001) times higher, respectively, in our nail salon worker population compared to NHANES Asian Americans. Levels exceeded the NHANES 95th or 75th percentiles among some workers. This pilot study suggests that nail salon workers are disproportionately exposed to multiple phthalates, a finding that warrants further investigation to assess their potential health significance.

Exposures to persistent organohalogen chemicals during pregnancy are associated with adverse health effects. Low-income, minority women with pre-existing co-morbidities may be particularly vulnerable to these exposures, but have historically been understudied. We aimed to characterize exposures to multiple chemical classes among a sample of ethnically diverse, lower income, overweight or obese pregnant women. Serum concentrations of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs) were measured in 98 pregnant women (California; 2011-2013). Aggregate exposures were evaluated using correlational clustering, a "chemical burden" score, and PCA. Associations between sociodemographic characteristics and individual and aggregate exposures were evaluated using multivariable linear regression. Clustering and PCA both produced four groupings: (PC1) PBDEs/OH-PBDEs, (PC2) PCBs, (PC3) PFNA/PFOA/PFDeA, (PC4) PFHxS/PFOS. Race/ethnicity and prepregnancy BMI were associated with PBDEs, OH-PBDEs and PC1. Maternal age was associated with PCBs and PC2. Parity was associated with PBDEs, OH-PBDEs and PC2. Poverty was negatively associated with PCBs, whereas food insecurity was positively associated with PFOS. We observed variations in sociodemographic profiles of exposures by chemical class and weak across-class correlations. These findings have implications for epidemiologic studies of chemical mixtures and for exposure reduction strategies.

Exposures to persistent organohalogen chemicals during pregnancy are associated with adverse health effects. Low-income, minority women with pre-existing co-morbidities may be particularly vulnerable to these exposures, but have historically been understudied. We aimed to characterize exposures to multiple chemical classes among a sample of ethnically diverse, lower income, overweight or obese pregnant women. Serum concentrations of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs) were measured in 98 pregnant women (California; 2011-2013). Aggregate exposures were evaluated using correlational clustering, a "chemical burden" score, and PCA. Associations between sociodemographic characteristics and individual and aggregate exposures were evaluated using multivariable linear regression. Clustering and PCA both produced four groupings: (PC1) PBDEs/OH-PBDEs, (PC2) PCBs, (PC3) PFNA/PFOA/PFDeA, (PC4) PFHxS/PFOS. Race/ethnicity and prepregnancy BMI were associated with PBDEs, OH-PBDEs and PC1. Maternal age was associated with PCBs and PC2. Parity was associated with PBDEs, OH-PBDEs and PC2. Poverty was negatively associated with PCBs, whereas food insecurity was positively associated with PFOS. We observed variations in sociodemographic profiles of exposures by chemical class and weak across-class correlations. These findings have implications for epidemiologic studies of chemical mixtures and for exposure reduction strategies.

Many California nail salon workers are low-income Vietnamese women of reproductive age who use nail products daily that contain androgen-disrupting phthalates, which may increase risk of male reproductive tract abnormalities during pregnancy. Yet, few studies have characterized phthalate exposures among this workforce. To characterize individual metabolites and cumulative phthalates exposure among a potentially vulnerable occupational group of nail salon workers, we collected 17 post-shift urine samples from Vietnamese workers at six San Francisco Bay Area nail salons in 2011, which were analyzed for four primary phthalate metabolites: mono-n-butyl-, mono-isobutyl-, mono(2-Ethylhexyl)-, and monoethyl phthalates (MnBP, MiBP, MEHP, and MEP, respectively; μg/L). Phthalate metabolite concentrations and a potency-weighted sum of parent compound daily intake (Σandrogen-disruptor, μg/kg/day) were compared to 203 Asian Americans from the 2011-2012 National Health and Nutritional Examination Survey (NHANES) using Student's t-test and Wilcoxin signed rank test. Creatinine-corrected MnBP, MiBP, MEHP (μg/g), and cumulative phthalates exposure (Σandrogen-disruptor, μg/kg/day) levels were 2.9 (p < 0.0001), 1.6 (p = 0.015), 2.6 (p < 0.0001), and 2.0 (p < 0.0001) times higher, respectively, in our nail salon worker population compared to NHANES Asian Americans. Levels exceeded the NHANES 95th or 75th percentiles among some workers. This pilot study suggests that nail salon workers are disproportionately exposed to multiple phthalates, a finding that warrants further investigation to assess their potential health significance.

Prenatal polybrominated diphenyl ether (PBDE) exposures are a public health concern due to their persistence and potential for reproductive and developmental harm. However, we have little information about the extent of fetal exposures during critical developmental periods and the variation in exposures for groups that may be more highly exposed, such as communities of color and lower socioeconomic status (SES). To characterize maternal-fetal PBDE exposures among potentially vulnerable groups, PBDE levels were examined in the largest sample of matched maternal serum, placenta, and fetal liver tissues during mid-gestation among a geographically, racially/ethnically, and socially diverse population of pregnant women from Northern California and the Central Valley (n = 180; 2014-16). Maternal-fetal PBDE levels were compared to population characteristics using censored Kendall's tau correlation and linear regression. PBDEs were commonly detected in all biomatrices. Before lipid adjustment, wet-weight levels of all four PBDE congeners were highest in the fetal liver (p  Latina/Hispanic > Non-Hispanic White > Asian/Pacific Islander/Other; p

Background Many California nail salon workers are low-income Vietnamese women of reproductive age who use nail products daily that contain androgen-disrupting phthalates which may increase risk of male reproductive tract abnormalities during pregnancy. Yet, few studies have characterized phthalate exposures among this workforce. Objective To characterize individual metabolites and cumulative phthalates exposure among a potentially vulnerable occupational group of nail salon workers. Study Design We collected 17 post-shift urine samples from Vietnamese workers at six San Francisco Bay Area nail salons in 2011, which were analyzed for four primary phthalate metabolites: mono- n -butyl-, mono-isobutyl-, mono(2-ethylhexyl)-, and monoethyl phthalates (MnBP, MiBP, MEHP, and MEP, respectively) (μg/L). Phthalate metabolite concentrations and a potency-weighted sum of parent compound daily intake (Σandrogen-disruptor, μg/kg/day) were compared to 203 Asian Americans from the 2011– 12 National Health and Nutritional Examination Survey (NHANES) using Student’s t-test and Wilcoxin signed rank test. Results Creatinine-corrected MnBP, MiBP, MEHP (μg/g), and cumulative phthalates exposure (Σandrogen-disruptor, μg/kg/day) levels were 2.9 ( p < 0.0001), 1.6 ( p = 0.015), 2.6 ( p < 0.0001), and 2.0 ( p < 0.0001) times higher, respectively, in our nail salon worker population compared to NHANES Asian Americans. Levels exceeded the NHANES 95 th or 75 th percentiles among some workers. Conclusion This pilot study suggests that nail salon workers are disproportionately exposed to multiple phthalates, a finding that warrants further investigation to assess their potential health significance.

PurposePolybrominated diphenyl ethers (PBDEs) are among the most persistent and pervasive global environmental contaminants. Their toxic and endocrine-disrupting properties have made them a focus of concern for breast cancer. Our objective was to evaluate the risk of breast cancer associated with serum PBDE levels in a case-control study nested within the California Teachers Study.MethodsParticipants were 902 women with invasive breast cancer (cases) and 936 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed between 2011 and 2015. Blood samples were collected from cases an average of 35 months after diagnosis. PBDEs were measured in serum using automated solid phase extraction and gas chromatography/high resolution mass spectrometry. Statistical analyses were restricted to the three congeners with detection frequencies ≥75%: 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',6-pentabromodiphenyl ether (BDE-100), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CI) for each BDE congener, adjusting for serum lipids and other potential confounders.ResultsThe OR for each of the three BDE congeners was close to unity with a CI that included one. Analyses stratified by menopausal status, tumor hormone responsiveness, BMI, and changes in body weight yielded similarly null results.ConclusionsOur findings provide no evidence that serum levels of BDE-47, BDE-100 or BDE-153 are associated with breast cancer risk. These results should be interpreted in the context of study limitations which include the reliance on PBDE measurements that may not represent pre-diagnostic, early-life or chronic exposures and a lack of information on genetic polymorphisms and other factors which may affect endogenous estrogen levels.

PurposePolybrominated diphenyl ethers (PBDEs) are among the most persistent and pervasive global environmental contaminants. Their toxic and endocrine-disrupting properties have made them a focus of concern for breast cancer. Our objective was to evaluate the risk of breast cancer associated with serum PBDE levels in a case-control study nested within the California Teachers Study.MethodsParticipants were 902 women with invasive breast cancer (cases) and 936 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed between 2011 and 2015. Blood samples were collected from cases an average of 35 months after diagnosis. PBDEs were measured in serum using automated solid phase extraction and gas chromatography/high resolution mass spectrometry. Statistical analyses were restricted to the three congeners with detection frequencies ≥75%: 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',6-pentabromodiphenyl ether (BDE-100), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CI) for each BDE congener, adjusting for serum lipids and other potential confounders.ResultsThe OR for each of the three BDE congeners was close to unity with a CI that included one. Analyses stratified by menopausal status, tumor hormone responsiveness, BMI, and changes in body weight yielded similarly null results.ConclusionsOur findings provide no evidence that serum levels of BDE-47, BDE-100 or BDE-153 are associated with breast cancer risk. These results should be interpreted in the context of study limitations which include the reliance on PBDE measurements that may not represent pre-diagnostic, early-life or chronic exposures and a lack of information on genetic polymorphisms and other factors which may affect endogenous estrogen levels.

Despite gradual legislative efforts to phase out flame retardants (FRs) from the marketplace, polybrominated diphenyl ethers (PBDEs) are still widely detected in human maternal and fetal tissues, eg, placenta, due to their continued global application in consumer goods and inherent biological persistence. Recent studies in rodents and human placental cell lines suggest that PBDEs directly cause placental toxicity. During pregnancy, trophoblasts play key roles in uterine invasion, vascular remodeling, and anchoring of the placenta-fetal unit to the mother. Thus, to study the potential consequences of PBDE exposures on human placental development, we used an in vitro model: primary villous cytotrophoblasts (CTBs). Following exposures, the endpoints that were evaluated included cytotoxicity, function (migration, invasion), the transcriptome, and the methylome. In a concentration-dependent manner, common PBDE congeners, BDE-47 and -99, significantly reduced cell viability and increased death. Upon exposures to sub-cytotoxic concentrations (≤ 5 µM), we observed BDE-47 accumulation in CTBs with limited evidence of metabolism. At a functional level, BDE-47 hindered the ability of CTBs to migrate and invade. Transcriptomic analyses of BDE-47 effects suggested concentration-dependent changes in gene expression, involving stress pathways, eg, inflammation and lipid/cholesterol metabolism as well as processes underlying trophoblast fate, eg, differentiation, migration, and vascular morphogenesis. In parallel assessments, BDE-47 induced low-level global increases in methylation of CpG islands, including a subset that were proximal to genes with roles in cell adhesion/migration. Thus, using a primary human CTB model, we showed that PBDEs induced alterations at cellular and molecular levels, which could adversely impact placental development.

Background Many California nail salon workers are low-income Vietnamese women of reproductive age who use nail products daily that contain androgen-disrupting phthalates which may increase risk of male reproductive tract abnormalities during pregnancy. Yet, few studies have characterized phthalate exposures among this workforce. Objective To characterize individual metabolites and cumulative phthalates exposure among a potentially vulnerable occupational group of nail salon workers. Study Design We collected 17 post-shift urine samples from Vietnamese workers at six San Francisco Bay Area nail salons in 2011, which were analyzed for four primary phthalate metabolites: mono- n -butyl-, mono-isobutyl-, mono(2-ethylhexyl)-, and monoethyl phthalates (MnBP, MiBP, MEHP, and MEP, respectively) (μg/L). Phthalate metabolite concentrations and a potency-weighted sum of parent compound daily intake (Σandrogen-disruptor, μg/kg/day) were compared to 203 Asian Americans from the 2011– 12 National Health and Nutritional Examination Survey (NHANES) using Student’s t-test and Wilcoxin signed rank test. Results Creatinine-corrected MnBP, MiBP, MEHP (μg/g), and cumulative phthalates exposure (Σandrogen-disruptor, μg/kg/day) levels were 2.9 ( p < 0.0001), 1.6 ( p = 0.015), 2.6 ( p < 0.0001), and 2.0 ( p < 0.0001) times higher, respectively, in our nail salon worker population compared to NHANES Asian Americans. Levels exceeded the NHANES 95 th or 75 th percentiles among some workers. Conclusion This pilot study suggests that nail salon workers are disproportionately exposed to multiple phthalates, a finding that warrants further investigation to assess their potential health significance.

BackgroundPer- and poly- fluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Their potential as breast carcinogens is unclear. Our objective was to evaluate the risk of breast cancer associated with serum PFAS concentrations in a nested case-control study within the California Teachers Study.MethodsParticipants were 902 women with invasive breast cancer (cases) and 858 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed during 2011-2015, an average of 35 months after case diagnosis. PFASs were measured using automated online SPE-HPLC-MS/MS methods. Statistical analyses were restricted to six PFASs with detection frequencies ≥ 95%: PFOA (Perfluorooctanoic acid), PFNA (Perfluorononanoic acid), PFUnDA (Perfluoroundecanoic acid), PFHxS (Perfluorohexane sulfonic acid), PFOS (Perfluorooctane sulfonic acid), and MeFOSAA (2-(N-Methyl-perfluorooctane sulfonamido) acetic acid. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs), estimating the breast cancer risk associated with each PFAS.ResultsFor all cases of invasive breast cancer, none of the adjusted ORs were statistically significant but marginally significant ORs

BackgroundPer- and poly- fluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Their potential as breast carcinogens is unclear. Our objective was to evaluate the risk of breast cancer associated with serum PFAS concentrations in a nested case-control study within the California Teachers Study.MethodsParticipants were 902 women with invasive breast cancer (cases) and 858 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed during 2011-2015, an average of 35 months after case diagnosis. PFASs were measured using automated online SPE-HPLC-MS/MS methods. Statistical analyses were restricted to six PFASs with detection frequencies ≥ 95%: PFOA (Perfluorooctanoic acid), PFNA (Perfluorononanoic acid), PFUnDA (Perfluoroundecanoic acid), PFHxS (Perfluorohexane sulfonic acid), PFOS (Perfluorooctane sulfonic acid), and MeFOSAA (2-(N-Methyl-perfluorooctane sulfonamido) acetic acid. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs), estimating the breast cancer risk associated with each PFAS.ResultsFor all cases of invasive breast cancer, none of the adjusted ORs were statistically significant but marginally significant ORs

BackgroundEndocrine-disrupting chemicals (EDCs) can target immune and metabolic pathways. However, few epidemiologic studies have examined the influence of EDCs on measures of inflammation and cellular aging during pregnancy and postpartum.ObjectiveWe investigated associations between prenatal exposures to polybrominated diphenyl ethers (PBDEs), hydroxylated PBDE metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and per- and polyfluorochemicals (PFASs) with repeated biomarker measurements of inflammation and cellular aging in women during pregnancy and the postpartum period.MethodologyOverweight or obese pregnant women were recruited from the San Francisco Bay area (n = 103) during their first or second trimester of pregnancy. Blood samples were collected from participants at baseline (median 16 weeks gestation) and at three and nine months postpartum. Serum concentrations of PBDEs, OH-PBDEs, PCBs, and PFASs were measured at baseline. Inflammation biomarkers (interleukin 6 [IL-6], interleukin 10 [IL-10], and tumor necrosis factor [TNF-α]) and leukocyte telomere length (LTL), a biomarker of cellular aging, were measured at all three time points. Associations between serum chemical concentrations and repeated measures of IL-6, IL-10, TNF-α, and LTL were examined using linear mixed models. We also examined the potential for effect modification by time (visit) and obesity.ResultsIn adjusted models, we observed positive relationships between PBDEs and pro-inflammatory cytokines (IL-6 and TNF-α). A doubling in ∑PBDEs was associated with a 15.26% (95% CI 1.24, 31.22) and 3.74% (95% CI -0.19, 7.82) increase in IL-6 and TNF-α, respectively. Positive associations were also observed for PFASs and IL-6. A two-fold increase in ∑PFASs was associated with a 20.87% (95% CI 3.46, 41.22) increase in IL-6. 5-OHBDE-47 was inversely associated with anti-inflammatory cytokine IL-10. Some EDC-outcome associations, including those of PBDEs with TNF-α, were stronger during pregnancy (compared to three or nine months postpartum) and among obese (compared to overweight) women (p-interaction

BackgroundHuman fetal exposures to polybrominated diphenyl ethers (PBDEs) and their metabolites (OH-PBDEs) are unique from adults, and in combination with a different metabolic profile, may make fetal development more sensitive to adverse health outcomes from these exposures. However, we lack data to characterize human fetal PBDE exposures and the metabolic factors that can influence these exposures.ObjectiveWe examined differences between 2nd trimester maternal and fetal exposures to PBDEs and OH-PBDEs. We also characterized fetal cytochrome P450 (CYP) mRNA expression and its associations with PBDE exposures.MethodsWe collected paired samples of maternal serum and fetal liver (n=86) with a subset having matched placenta (n=50). We measured PBDEs, OH-PBDEs, and mRNA expression of CYP genes (e.g. CYP1A1, -2E1, -2J2, -2C9) in all samples. As a sensitivity analysis, we measured PBDEs and OH-PBDEs in umbilical cord serum from a subset (n=22).ResultsBDE-47 was detected in ≥96% of all tissues. Unadjusted ∑PBDEs concentrations were highest in fetal liver (geometric mean (GM)=0.72ng/g), whereas lipid-adjusted concentrations were highest in cord serum (111.12ng/g lipid). In both cases, fetal concentrations were approximately two times higher than maternal serum levels (GM=0.33ng/g or 48.75ng/g lipid). ΣOH-PBDEs were highest in maternal and cord sera and 20-200 times lower than PBDE concentrations. In regression models, maternal BDE-47 explained more of the model variance of liver than of placenta BDE-47 concentrations (adjusted R2=0.79 vs 0.48, respectively). In adjusted logistic regression models, ∑PBDEs were positively associated with expression of CYP2E1 and -2J2 (placenta), and -1A1 (liver) (p

BackgroundHuman fetal exposures to polybrominated diphenyl ethers (PBDEs) and their metabolites (OH-PBDEs) are unique from adults, and in combination with a different metabolic profile, may make fetal development more sensitive to adverse health outcomes from these exposures. However, we lack data to characterize human fetal PBDE exposures and the metabolic factors that can influence these exposures.ObjectiveWe examined differences between 2nd trimester maternal and fetal exposures to PBDEs and OH-PBDEs. We also characterized fetal cytochrome P450 (CYP) mRNA expression and its associations with PBDE exposures.MethodsWe collected paired samples of maternal serum and fetal liver (n=86) with a subset having matched placenta (n=50). We measured PBDEs, OH-PBDEs, and mRNA expression of CYP genes (e.g. CYP1A1, -2E1, -2J2, -2C9) in all samples. As a sensitivity analysis, we measured PBDEs and OH-PBDEs in umbilical cord serum from a subset (n=22).ResultsBDE-47 was detected in ≥96% of all tissues. Unadjusted ∑PBDEs concentrations were highest in fetal liver (geometric mean (GM)=0.72ng/g), whereas lipid-adjusted concentrations were highest in cord serum (111.12ng/g lipid). In both cases, fetal concentrations were approximately two times higher than maternal serum levels (GM=0.33ng/g or 48.75ng/g lipid). ΣOH-PBDEs were highest in maternal and cord sera and 20-200 times lower than PBDE concentrations. In regression models, maternal BDE-47 explained more of the model variance of liver than of placenta BDE-47 concentrations (adjusted R2=0.79 vs 0.48, respectively). In adjusted logistic regression models, ∑PBDEs were positively associated with expression of CYP2E1 and -2J2 (placenta), and -1A1 (liver) (p

Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants. Technical mixtures PentaBDE and OctaBDE were phased out in 2004 through voluntary and regulatory actions with DecaBDE remaining in limited use until 2013. Biomonitoring studies have shown widespread presence of PBDEs in the US and worldwide population. While some studies suggest that human serum concentrations are declining over time, it is unclear whether this trend will continue. Our objective was to examine temporal trends of PentaBDEs and their hydroxylated metabolites (OH-PBDEs) between 2008 and 2014 in populations of ethnically diverse, pregnant women residing in Northern California (n = 111). Serum samples were collected and analyzed by high resolution mass spectrometry for five PentaBDE congeners and two OH-PBDEs. We found widespread exposures in participants from all three time points (2008/09, 2011/12, 2014). Temporal patterns varied substantially by congener. BDE-47, -99 and the OH-PBDEs decreased between 2008/09-2011/12 but plateaued between 2011/12-2014. In contrast, BDE-100 decreased across all years, BDE-153 decreased in the latter years, and BDE-28 decreased initially and then increased. These findings indicate that while policies to remove PBDEs from the marketplace have successfully lead to declines in exposures to some PBDE congeners, human exposures to these legacy pollutants could plateau and remain ubiquitous in human populations.

BackgroundHuman fetal exposures to polybrominated diphenyl ethers (PBDEs) and their metabolites (OH-PBDEs) are unique from adults, and in combination with a different metabolic profile, may make fetal development more sensitive to adverse health outcomes from these exposures. However, we lack data to characterize human fetal PBDE exposures and the metabolic factors that can influence these exposures.ObjectiveWe examined differences between 2nd trimester maternal and fetal exposures to PBDEs and OH-PBDEs. We also characterized fetal cytochrome P450 (CYP) mRNA expression and its associations with PBDE exposures.MethodsWe collected paired samples of maternal serum and fetal liver (n=86) with a subset having matched placenta (n=50). We measured PBDEs, OH-PBDEs, and mRNA expression of CYP genes (e.g. CYP1A1, -2E1, -2J2, -2C9) in all samples. As a sensitivity analysis, we measured PBDEs and OH-PBDEs in umbilical cord serum from a subset (n=22).ResultsBDE-47 was detected in ≥96% of all tissues. Unadjusted ∑PBDEs concentrations were highest in fetal liver (geometric mean (GM)=0.72ng/g), whereas lipid-adjusted concentrations were highest in cord serum (111.12ng/g lipid). In both cases, fetal concentrations were approximately two times higher than maternal serum levels (GM=0.33ng/g or 48.75ng/g lipid). ΣOH-PBDEs were highest in maternal and cord sera and 20-200 times lower than PBDE concentrations. In regression models, maternal BDE-47 explained more of the model variance of liver than of placenta BDE-47 concentrations (adjusted R2=0.79 vs 0.48, respectively). In adjusted logistic regression models, ∑PBDEs were positively associated with expression of CYP2E1 and -2J2 (placenta), and -1A1 (liver) (p

After several decades of widespread use, some per- and polyfluoroalkyl substances (PFASs) were phased-out of use due to concerns raised by their persistent, bioaccumulative, and toxic properties. Our objective was to evaluate temporal trends in serum PFAS levels among 1257 middle-aged and older California women (ages 40-94) during a four year period, beginning approximately 5-10 years after these phase-outs began. An online SPE-HPLC-MS/MS was used to measure 10 long-chain PFASs in serum from blood collected cross-sectionally during 2011-2015 from a subset of participants in the California Teachers Study. Results from multivariable linear regression analyses indicated that serum concentrations of nearly all PFASs declined on average 10% to 20% per year. Serum levels of perfluorohexanesulfonic acid (PFHxS) did not significantly decline. With the exception of PFHxS, the downward trend in serum concentrations was evident for all PFASs across all ages, although declines were comparatively steeper among the oldest women. These findings suggest that the phase-out of some common PFASs has resulted in reduced human exposures to them. The lack of a decline for PFHxS suggests that these exposures may be ongoing and underscores the importance of continued biomonitoring and research efforts to elucidate current pathways of exposure.

Triphenyl phosphate (TPhP) is a flame retardant additive frequently found in consumer products and household dust. We administered 170μg of TPhP in maternal food from gestational day 8.5 to weaning and evaluated metabolic phenotypes of 3.5 month old male and female rats, and weight-matched males up to 6 months, to assess the development of obesity and type 2 diabetes mellitus (T2DM), respectively. Perinatal TPhP exposure increased body and fat mass in 3.5 month old male and female rats, while leptin and cumulative energy intake were elevated in males and females, respectively. Independent of body mass, perinatal TPhP exposure accelerated T2DM onset in males and increased plasma non-esterified- fasting fatty acids. These observations suggest that perinatal exposure to TPhP exacerbates the development of obesity in male and female UCDavis-T2DM rats and accelerates T2DM onset in male UCD-T2DM rats.