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Introduction: Per- and polyfluoroalkyl substances (PFAS) are prevalent environmental chemicals used extensively in consumer and industrial products. Distressing disruptions to sexual function are prevalent in reproductive-aged women, yet its etiology is incompletely characterized. PFAS could plausibly affect sexual function because they interfere with the production, metabolism, and secretion of reproductive hormones and have known neurotoxic properties. To our knowledge, however, no research to date has evaluated associations between PFAS exposure and female sexual function. Objective: To evaluate associations between PFAS biomarker concentrations and female sexual function. Methods: We used cross-sectional data from the Pregnancy Study Online (PRESTO; n=82), a preconception cohort study of female-identified pregnancy planners living in the United States or Canada, to estimate associations between PFAS biomarker concentrations and female sexual function, measured using 6 select items from the Female Sexual Function Index (FSFI). We summed scores from the FSFI items to create a sexual function score (range=0-30; median in PRESTO=22). Lower scores were indicative of worse sexual function. We measured concentrations of four PFAS (specifically PFOS, PFOA, PFNA, and PFHxS) in serum using isotope-dilution tandem mass spectrometry. We used multivariable linear regression to estimate mean differences in sexual function scores per interquartile range (IQR) increase in PFAS concentrations with 95% confidence intervals (CIs), adjusting for potential confounders. We stratified results by parity (parous vs. nulliparous) to evaluate the potential for effect modification by prior pregnancy, as placental transfer, menstruation, and lactation are known routes of PFAS elimination. Results: Median serum PFAS concentrations (ng/mL) were 1.3, 1.1, 0.3, and 0.7 for PFOS, PFOA, PFNA, and PFHxS, respectively. An IQR increase in PFHxS was associated with a 1.4-point decrease (95% CI -2.1, -0.6) in sexual function scores, reflecting a ~5% change. Among parous participants, there was a consistent trend of decreased sexual function scores per IQR increase in PFAS concentrations. The strongest association was observed for PFOS, where an IQR increase in serum concentration was associated with a 4.9-point decrease in sexual function scores (95% CI -9.1, -0.6). Conclusions: These preliminary findings indicate that higher serum PFAS concentrations are associated with decreased self-reported female sexual function. Prior research evaluating the relationship between environmental chemical exposures and sexual function have historically focused on male outcomes (e.g., semen quality). These fundings suggest value in expanding research focused on the sexual health consequences of endocrine disrupting chemicals to include female sexual function. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: LAW serves as a consultant to AbbVie, Inc. [ABSTRACT FROM AUTHOR]

Background: Female sexual function is important for sexual well-being, general health, fertility, and relationship satisfaction. Distressing impairments in sexual function, clinically recognized as female sexual dysfunction (FSD), can manifest as issues with interest/desire, arousal, orgasm, and pain during vaginal penetration. Some evidence suggests that exposure to endocrine-disrupting chemicals may adversely affect female sexual function, but associations for per- and polyfluoroalkyl substances (PFAS) have not been previously evaluated., Objective: We investigated associations between serum PFAS concentrations and female sexual function among U.S. pregnancy planners., Methods: We used cross-sectional data from participants from Pregnancy Study Online (PRESTO), a prospective preconception cohort study. Participants reported sexual function and distress at baseline on two validated measures: a modified version of the Female Sexual Function Index-6 (FSFI-6) and the Female Sexual Distress Scale (FSDS). We quantified PFAS serum concentrations in samples collected in the preconception period (i.e., at baseline) using solid phase extraction-high performance liquid chromatography-isotope-dilution-mass spectrometry. Participants reported sociodemographic information on structured baseline questionnaires. We included 78 participants with complete PFAS and sexual function data and fit multivariable linear regression models to estimate mean differences in FSFI-6 scores (β) or percent differences (%) in FSDS scores per interquartile range (IQR) increase in PFAS concentrations, adjusting for age, annual household income, years of education, parity, and body mass index. We further investigated effect measure modification by parity (parous vs. nulliparous) in stratified models., Results: An IQR increase in perfluorohexanesulfonic acid was associated with a 1.0-point decrease (95% CI = -1.8, -0.1) in reported FSFI-6 scores, reflecting poorer sexual function. PFAS were consistently associated with lower FSFI-6 scores among parous participants. PFAS were also associated, though imprecisely, with greater sexual distress., Conclusion: Some PFAS were associated with poorer sexual function among U.S. pregnancy planners, but future studies are needed to clarify the extent to which PFAS influences female sexual health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Persistent endocrine-disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants in the Study of Environment, Lifestyle, and Fibroids (n = 1394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale 4 (PSS-4) at baseline and every 20 months through 60 months (score range: 0-16); higher scores indicate higher stress. Endocrine-disrupting chemicals, including per- and polyfluoroalkyl substances, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit bayesian kernel machine regression and linear mixed-effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (eg, perfluorodecanoic acid, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, and other EDCs (eg PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women. This article is part of a Special Collection on Environmental Epidemiology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Uterine leiomyomata (UL; fibroids) are hormone-dependent neoplasms that can cause significant gynecologic morbidity. Studies have documented associations between concentrations of persistent endocrine-disrupting chemicals (EDCs) and UL incidence; however, few have assessed the effects of EDC mixtures on UL., Methods: In the Study of Environment, Lifestyle, and Fibroids, a prospective cohort study, participants attended study visits at baseline and approximately every 20 months for up to 10 years; at each visit, they completed questionnaires, provided blood samples, and underwent standardized ultrasound examinations. In baseline plasma samples (n = 1155), we quantified concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides using high-resolution mass spectrometry. We selected nine EDCs detected in >60 % of samples (4 PCBs, 4 PBDEs, and 2,2-bis(4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE)) and conducted probit Bayesian kernel machine regression with hierarchical variable selection to estimate effects of the EDC mixture and individual EDCs on UL incidence, adjusting for potential confounders., Results: During 10 years of follow-up, 32 % of participants developed ultrasound-detected UL. The EDC mixture was not appreciably associated with the probit of UL (β comparing all EDCs at their 75th vs. 50th percentile:= - 0.01, 95 % credible interval [CrI]: -0.11, 0.10). However, individual EDC concentrations were associated with UL in opposing directions: PCB138/158 was positively associated with UL (β for 25th-to-75th-percentile increase when all other chemicals were set to their 50th percentile = 0.18, 95 % CrI: -0.09, 0.44), whereas PBDE99 and p,p'-DDE were inversely associated with UL (β = -0.06, 95 % CrI: -0.21, 0.10 and β = -0.12, 95 % CrI: -0.34, 0.10, respectively). There was little evidence of interaction between EDCs., Conclusion: In this prospective ultrasound study, a mixture of persistent EDCs was not appreciably associated with incident UL during 10 years of follow-up, but individual EDCs were associated with UL in opposite directions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lauren A. Wise reports a consulting relationship with AbbVie Inc., and the Bill & Melinda Gates Foundation. LAW receives in-kind donations for primary data collection in Pregnancy Study Online (PRESTO), including home pregnancy tests (Swiss Precision Diagnostics) and fertility-tracking apps (Kindara.com). All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Studies have shown an association between hair product use and adverse health outcomes. Scientists have hypothesized that exposure to endocrine-disrupting chemicals (EDCs) drives these associations, but few studies have directly evaluated associations between hair product use and biomarkers of EDCs. Even more limited are studies of Black women, who frequently use EDC-containing products (e.g., hair relaxers)., Objective: We estimated associations between hair product use and EDC biomarker concentrations., Methods: We leveraged cross-sectional data from the Study of Environment, Lifestyle, and Fibroids, a cohort of females aged 23-34 years who self-identified as Black/African American from the Detroit-metropolitan area (USA; n = 425). On structured questionnaires, participants reported their past 24-h and past 12-month use of hair products, including relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food. We quantified urinary concentrations of 19 phthalate/phthalate alternative metabolites, 7 phenols, and 4 parabens using high performance liquid chromatography isotope dilution tandem mass spectrometry. EDC biomarker concentrations were creatinine-adjusted and natural log-transformed. We used multivariable linear regression to estimate mean percent differences in EDC biomarker concentrations and 95% confidence intervals (CIs) associated with hair product use, adjusting for sociodemographic confounders., Results: Hair product use was associated with greater concentrations of multiple EDC biomarkers. Notably, use of hair products in the previous 24 h (compared with non-use) was associated with 16.2% (95% CI = 0.7%, 35.9%), 35.0% (95% CI = 2.6%, 77.6%), and 32.3% (95% CI = 8.8%, 92.0%) higher concentrations of mono-isobutyl phthalate, methyl paraben, and ethyl paraben, respectively. Use of hair relaxers/straighteners/perms, styling products, moisturizers, oils, and hair food in the past 12 months was also associated with higher concentrations of multiple phthalate, phenol, and paraben biomarkers., Conclusion: Hair product use was associated with higher biomarker concentrations of multiple phthalates, phenols, and parabens. These findings suggest that hair products are potentially important exposure sources for hormonally-active chemicals among Black women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Motor function is critical for children's health, yet remains an understudied neurodevelopmental domain. Exposure to metals has been linked with motor function, but no study has examined the joint effects of metal mixtures., Methods: We evaluated cross-sectional associations between a metal mixture and motor function among 569 adolescents (10-14 years old) living near the ferroalloy industry. Concentrations of blood lead, hair manganese, hair copper, and hair chromium were quantified using inductively coupled plasma mass spectrometry. Neuropsychologists administered multiple fine motor function assessments: pursuit aiming, finger tapping, visual reaction time (VRT), and subtests from the Luria Nebraska battery. We estimated associations between motor function and the metal mixture using quantile-based g-computation and multivariable linear regression, adjusting for child age, sex, and socioeconomic status. We explored sex-specific associations in stratified models., Results: Associations between the metal mixture and motor function were mostly null but were modified by sex. We observed a beneficial association among females: a quartile increase in all metals in the mixture was associated with a 2.6% faster average response time on the VRT (95% confidence interval [CI] = -4.7%, -0.5%), driven by Cu and Cr. In contrast, this association was adverse among males ( ß = 1.5% slower response time [95% CI = -0.7%, 3.9%]), driven by Cu and Mn., Conclusions: Results suggest that males may be more susceptible to the adverse effects of metal exposure on motor function during adolescence than females. Future studies, particularly prospective study designs, are warranted to further understand the associations of metal mixtures with motor function., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products., Objective: We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity., Methods: We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23-35 years at enrollment (2010-2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL., Results: In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54-1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61-1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85-1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth., Impact Statement: In this prospective ultrasound study of 1158 Black females aged 23-35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals with neurotoxic properties. PFAS have been associated with depressive symptoms among women in some studies, but little research has evaluated the effects of PFAS mixtures. Further, no study has investigated interactions of PFAS-depression associations by perceived stress, which has been shown to modify the effects of PFAS on other health outcomes., Objective: In a prospective cohort study of reproductive-aged Black women, we investigated associations between PFAS and depressive symptoms and the extent to which perceived stress modified these associations., Methods: We analyzed data from 1499 participants (23-35 years) in the Study of Environment, Lifestyle, and Fibroids. We quantified concentrations of nine PFAS in baseline plasma samples using online solid-phase extraction-liquid chromatography-isotope dilution tandem mass spectrometry. Participants reported perceived stress via the Perceived Stress Scale (PSS-4; range = 0-16) at baseline and depressive symptoms via the Center for Epidemiologic Studies Depression Scale (CESD; range = 0-44) at the 20-month follow-up visit. We used Bayesian Kernel Machine Regression to estimate associations between PFAS concentrations, individually and as a mixture, and depressive symptoms, and to assess effect modification by PSS-4 scores, adjusting for confounders., Results: Baseline perfluorodecanoic acid concentrations were associated with greater depressive symptoms at the 20-month follow-up, but associations for other PFAS were null. The PFAS were not associated with depressive symptoms when evaluated as a mixture. The association between the 90th percentile (vs. 50th percentile) of the PFAS mixture with CES-D scores was null at the 10th (β = 0.03; 95 % CrI = 0.20, 0.25), 50th (β = 0.02; 95 % CrI = -0.16, 0.19), and 90th (β = 0.01; 95 % CrI = 0.18, 0.20) percentiles of PSS-4 scores, suggesting perceived stress did not modify the PFAS mixture., Conclusion: In this prospective cohort study, PFAS concentrations-assessed individually or as a mixture-were not appreciably associated with depressive symptoms, and there was no evidence of effect modification by perceived stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Results of studies investigating associations between individual endocrine-disrupting chemicals (EDCs) and incidence of uterine leiomyomata (UL), a hormone-dependent gynecological condition, have been inconsistent. However, few studies have evaluated simultaneous exposure to a mixture of EDCs with UL incidence., Methods: We conducted a case-cohort analysis (n = 708) of data from the Study of the Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. Participants were aged 23-35 years at enrollment, had an intact uterus, and identified as Black or African American. We measured biomarker concentrations of 21 non-persistent EDCs, including phthalates, phenols, parabens, and triclocarban, in urine collected at baseline, 20-month, and 40-month clinic visits. We ascertained UL incidence and characteristics using ultrasounds at baseline and approximately every 20 months through 60 months. We used probit Bayesian Kernel Machine Regression (BKMR-P) to evaluate joint associations between EDC mixtures with cumulative UL incidence. We estimated the mean difference in the probit of UL incidence over the study period, adjusting for baseline age, education, years since last birth, parity, smoking status and body mass index. We converted probit estimates to odds ratios for ease of interpretation., Results: We observed that urinary concentrations of the overall EDC mixture were inversely associated with UL incidence in the overall mixtures model, with the strongest inverse associations at the 70th percentile of all biomarkers compared with their 50th percentile (odds ratio = 0.59; 95% confidence interval: 0.36, 0.96). Strongest contributors to the joint association for the mixture were bisphenol S (BPS), ethyl paraben (EPB), bisphenol F (BPF) and mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), which each demonstrated inverse associations except for MECPP. There was suggestive evidence of an interaction between MECPP and EPB., Conclusion: In this prospective ultrasound study, we observed evidence of an inverse association between the overall mixture of urinary biomarker concentrations of non-persistent EDCs with UL incidence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Personal care products (PCPs) are sources of exposure to endocrine-disrupting chemicals (EDCs) among women, and socioeconomic status (SES) may influence these exposures. Black women have inequitable exposure to EDCs from PCP use, but no study has investigated how exposure to EDCs through PCPs may vary by SES, independent of race. Using data from the Study of Environment, Lifestyle, and Fibroids, a cohort of reproductive-aged Black women ( n = 751), we quantified associations between PCPs and urinary biomarker concentrations of EDC mixtures (i.e., phthalates, phenols, parabens) within SES groups, defined using k- modes clustering based on education, income, marital status, and employment. Information about PCP use and SES was collected through questionnaires and interviews. We used principal component analysis to characterize the EDC mixture profiles. Stratified linear regression models were fit to assess associations between PCP use and EDC mixture profiles, quantified as mean differences in PC scores, by SES group. Associations between PCP use and EDC mixture profiles varied by SES group; e.g., vaginal powder use was associated with a mixture of phenols among lower SES women, whereas this association was null for higher SES women. Findings suggest that SES influences PCP EDC exposure in Black women, which has implications for public health interventions.

Background: Exposure to environmental metals has been consistently associated with attention and behavioral deficits in children, and these associations may be modified by coexposure to other metals or iron (Fe) status. However, few studies have investigated Fe status as a modifier of a metal mixture, particularly with respect to attention-related behaviors., Methods: We used cross-sectional data from the Public Health Impact of Metals Exposure study, which included 707 adolescents (10-14 years of age) from Brescia, Italy. Manganese, chromium, and copper were quantified in hair samples, and lead was quantified in whole blood, using inductively coupled plasma mass spectrometry. Concentrations of Fe status markers (ferritin, hemoglobin, transferrin) were measured using immunoassays or luminescence assays. Attention-related behaviors were assessed using the Conners Rating Scales Self-Report Scale-Long Form, Parent Rating Scales Revised-Short Form, and Teacher Rating Scales Revised-Short Form. We employed Bayesian kernel machine regression to examine associations of the metal mixture with these outcomes and evaluate Fe status as a modifier., Results: Higher concentrations of the metals and ferritin were jointly associated with worse self-reported attention-related behaviors: metals and ferritin set to their 90th percentiles were associated with 3.0% [ β = 0.03 ; 95% credible interval (CrI): - 0.01 , 0.06], 4.1% ( β = 0.04 ; 95% CrI: 0.00, 0.08), and 4.1% ( β = 0.04 ; 95% CrI: 0.00, 0.08) higher T -scores for self-reported attention deficit/hyperactivity disorder (ADHD) index, inattention, and hyperactivity, respectively, compared with when metals and ferritin were set to their 50th percentiles. These associations were driven by hair manganese, which exhibited nonlinear associations with all self-reported scales. There was no evidence that Fe status modified the neurotoxicity of the metal mixture. The metal mixture was not materially associated with any parent-reported or teacher-reported scale., Conclusions: The overall metal mixture, driven by manganese, was adversely associated with self-reported attention-related behavior. These findings suggest that exposure to multiple environmental metals impacts adolescent neurodevelopment, which has significant public health implications. https://doi.org/10.1289/EHP12988.

Background: Metals, including lead (Pb), manganese (Mn), chromium (Cr) and copper (Cu), have been associated with neurodevelopment; iron (Fe) plays a role in the metabolism and neurotoxicity of metals, suggesting Fe may mediate metal-neurodevelopment associations. However, no study to date has examined Fe as a mediator of the association between metal mixtures and neurodevelopment., Objective: We assessed Fe status as a mediator of a mixture of Pb, Mn, Cr and Cu in relation to verbal learning and memory in a cohort of Italian adolescents., Methods: We used cross-sectional data from 383 adolescents (10-14 years) in the Public Health Impact of Metals Exposure Study. Metals were quantified in blood (Pb) or hair (Mn, Cr, Cu) using ICP-MS, and three markers of Fe status (blood hemoglobin, serum ferritin and transferrin) were quantified using luminescence assays or immunoassays. Verbal learning and memory were assessed using the California Verbal Learning Test for Children (CVLT-C). We used Bayesian Kernel Machine Regression Causal Mediation Analysis to estimate four mediation effects: the natural direct effect (NDE), natural indirect effect (NIE), controlled direct effect (CDE) and total effect (TE). Beta (β) coefficients and 95 % credible intervals (CIs) were estimated for all effects., Results: The metal mixture was jointly associated with a greater number of words recalled on the CVLT-C, but these associations were not mediated by Fe status. For example, when ferritin was considered as the mediator, the NIE for long delay free recall was null (β = 0.00; 95 % CI = -0.22, 0.23). Conversely, the NDE (β = 0.23; 95 % CI = 0.01, 0.44) indicated a beneficial association of the mixture with recall that operated independently of Fe status., Conclusion: An industry-relevant metal mixture was associated with learning and memory, but there was no evidence of mediation by Fe status. Further studies in populations with Fe deficiency and greater variation in metal exposure are warranted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Manganese (Mn) is a metal commonly found in drinking water, but the level that is safe for consumption is unknown. In the United States (U.S.), Mn is not regulated in drinking water and data on water Mn concentrations are temporally and spatially sparse., Objective: Examine temporal and spatial variability of Mn concentrations in repeated tap water samples in a case study of Holliston, Massachusetts (MA), U.S., where drinking water is pumped from shallow aquifers that are vulnerable to Mn contamination., Methods: We collected 79 residential tap water samples from 21 households between September 2018 and December 2019. Mn concentrations were measured using inductively coupled plasma mass spectrometry. We calculated descriptive statistics and percent of samples exceeding aesthetic (secondary maximum containment level; SMCL) and lifetime health advisory (LHA) guidelines of 50 µg/L and 300 µg/L, respectively. We compared these concentrations to concurrent and historic water Mn concentrations from publicly available data across MA., Results: The median Mn concentration in Holliston residential tap water was 2.3 µg/L and levels were highly variable (range: 0.03-5,301.8 µg/L). Mn concentrations exceeded the SMCL and LHA in 14% and 12% of samples, respectively. Based on publicly available data across MA from 1994-2022, median Mn concentration was 17.0 µg/L (N = 37,210; range: 1-159,000 µg/L). On average 40% of samples each year exceeded the SMCL and 9% exceeded the LHA. Samples from publicly available data were not evenly distributed between MA towns or across sampling years., Impact Statement: This study is one of the first to examine Mn concentrations in drinking water both spatially and temporally in the U.S. Findings suggest that concentrations of Mn in drinking water frequently exceed current guidelines and occur at concentrations shown to be associated with adverse health outcomes, especially for vulnerable and susceptible subpopulations like children. Future studies that comprehensively examine exposure to Mn in drinking water and its associations with children's health are needed to protect public health., (© 2023. The Author(s).)

Background: Metals may influence reproductive health, but few studies have investigated correlates of metal body burden among reproductive-aged women outside of pregnancy. Furthermore, while there is evidence of racial disparities in exposure to metals among U.S. women, there is limited research about correlates of metal body burden among Black women., Objective: To identify correlates of whole blood metal concentrations among reproductive-aged Black women., Methods: We analyzed cross-sectional data from a cohort of 1664 Black women aged 23-35 years in Detroit, Michigan, 2010-2012. We collected blood samples and questionnaire data. We measured concentrations of 17 metals in whole blood using inductively-coupled plasma-mass spectrometer-triple quadrupole and total mercury using Direct Mercury Analyzer-80. We used multivariable linear regression models to identify sociodemographic, environmental, reproductive, and dietary correlates of individual metal concentrations., Results: In adjusted models, age was positively associated with multiple metals, including arsenic, cadmium, and mercury. Education and income were inversely associated with cadmium and lead. Current smoking was strongly, positively associated with cadmium and lead. Alcohol intake in the past year was positively associated with arsenic, barium, copper, lead, mercury, vanadium, and zinc. Having pumped gasoline in the past 24 h was positively associated with cadmium, chromium, and molybdenum. Having lived in an urban area for the majority of residence in Michigan was positively associated with arsenic, lead, and nickel. Higher water intake in the past year was positively associated with several metals, including lead. Fish intake in the past year was positively associated with arsenic, cesium, and mercury. We also observed associations with body mass index, season, and other environmental, reproductive, and dietary factors., Significance: We identified potential sources of exposure to metals among reproductive-aged Black women. Our findings improve understanding of exposures to metals among non-pregnant reproductive-aged women, and can inform policies in support of reducing disparities in exposures., Impact Statement: There are racial disparities in exposures to metals. We analyzed correlates of blood metal concentrations among reproductive-aged Black women in the Detroit, Michigan metropolitan area. We identified sociodemographic, anthropometric, lifestyle, environmental, reproductive, and dietary correlates of metal body burden. Age was positively associated with several metals. Education and income were inversely associated with cadmium and lead, indicating socioeconomic disparities. We identified potential exposure sources of metals among reproductive-aged Black women, including smoking, environmental tobacco smoke, pumping gasoline, living in an urban area, and intake of alcohol, water, fish, and rice., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Manganese (Mn) is both an essential and toxic metal, and associations with neurodevelopment depend on exposure timing. Prospective data examining early life Mn with adolescent cognition are sparse., Methods: We enrolled 140 Italian adolescents (10-14 years old) from the Public Health Impact of Metals Exposure study. Mn in deciduous teeth was measured using laser ablation-mass spectrometry to represent prenatal, postnatal and early childhood exposure. The California Verbal Learning Test for Children (CVLT-C) was administered to assess adolescent verbal learning and memory. Multivariable regression models estimated changes in CVLT-C scores and the odds of making an error per doubling in dentine Mn in each exposure period. Multiple informant models tested for differences in associations across exposure periods., Results: A doubling in prenatal dentine Mn levels was associated with lower odds of making an intrusion error (OR = 0.23 [95% CI: 0.09, 0.61]). This beneficial association was not observed in other exposure periods. A doubling in childhood Mn was beneficially associated with short delay free recall: (ß = 0.47 [95% CI: -0.02, 0.97]), which was stronger in males (ß = 0.94 [95% CI: 0.05, 1.82]). Associations were null in the postnatal period., Conclusion: Exposure timing is critical for understanding Mn-associated changes in cognitive function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Manganese (Mn) is an essential nutrient and neurotoxicant, and the neurodevelopmental effects of Mn may depend on exposure timing. Less research has quantitatively compared the impact of Mn exposure on neurodevelopment across exposure periods., Methods: We used data from 125 Italian adolescents (10-14 years) from the Public Health Impact of Metals Exposure Study to estimate prospective associations of Mn in three early life exposure periods with adolescent attention-related behaviors. Mn was quantified in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry to represent prenatal (2nd trimester-birth), postnatal (birth ~1.5 years), and childhood (~1.5-6 years) exposure. Attention-related behavior was evaluated using the Conners Behavior Rating Scales in adolescence. We used multivariable linear regression models to quantify associations between Mn in each exposure period, and multiple informant models to compare associations across exposure periods., Results: Median tooth Mn levels (normalized to calcium) were 0.4 area under the curve (AUC) 55 Mn: 43 Ca × 10 4 , 0.1 AUC 55 Mn: 43 Ca × 10 4 , and 0.0006 55 Mn: 43 Ca for the prenatal, postnatal, and childhood periods. A doubling in prenatal tooth Mn levels was associated with 5.3% (95% confidence intervals [CI] = -10.3%, 0.0%) lower (i.e., better) teacher-reported inattention scores, whereas a doubling in postnatal tooth Mn levels was associated with 4.5% (95% CI = -9.3%, 0.6%) and 4.6% (95% CI = -9.5%, 0.6%) lower parent-reported inattention and attention deficit/hyperactivity disorder index scores, respectively. Childhood Mn was not beneficially associated with reported attention-related behaviors., Conclusion: Protective associations in the prenatal and postnatal periods suggest Mn is beneficial for attention-related behavior, but not in the childhood period., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Biomarker concentrations of metals are associated with neurodevelopment, and these associations may be modified by nutritional status (e.g., iron deficiency). No prior study on associations of metal mixtures with neurodevelopment has assessed effect modification by iron status., Objectives: We aimed to quantify associations of an industry-relevant metal mixture with verbal learning and memory among adolescents, and to investigate the modifying role of iron status on those associations., Methods: We used cross-sectional data from 383 Italian adolescents (10-14 years) living in proximity to ferroalloy industry. Verbal learning and memory was assessed using the California Verbal Learning Test for Children (CVLT-C), and metals were quantified in hair (manganese, copper, chromium) or blood (lead) using inductively coupled plasma mass spectrometry. Serum ferritin, a proxy for iron status, was measured using immunoassays. Covariate-adjusted associations of the metal mixture with CVLT subtests were estimated using Bayesian Kernel Machine Regression, and modification of the mixture associations by ferritin was examined., Results: Compared to the 50th percentile of the metal mixture, the 90th percentile was associated with a 0.12 standard deviation [SD] (95% CI = -0.27, 0.50), 0.16 SD (95% CI = -0.11, 0.44), and 0.11 SD (95% CI = -0.20, 0.43) increase in the number of words recalled for trial 5, long delay free, and long delay cued recall, respectively. For an increase from its 25th to 75th percentiles, copper was beneficially associated the recall trials when other metals were fixed at their 50th percentiles (for example, trial 5 recall: β = 0.31, 95% CI = 0.14, 0.48). The association between copper and trial 5 recall was stronger at the 75th percentile of ferritin, compared to the 25th or 50th percentiles., Conclusions: In this metal mixture, copper was beneficially associated with neurodevelopment, which was more apparent at higher ferritin concentrations. These findings suggest that metal associations with neurodevelopment may depend on iron status, which has important public health implications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose of Review: Exposure to environmental metals, like lead (Pb), manganese (Mn), and methylmercury (Me-Hg), has consistently been implicated in neurodevelopmental dysfunction. Recent research has focused on identifying modifying factors of metal neurotoxicity in childhood, such as age, sex, and co-exposures. Iron (Fe) status is critical for normal cognitive development during childhood, and current mechanistic, animal, and human evidence suggests that Fe status may be a modifier or mediator of associations between environmental metals and neurodevelopment. The goals of this review are to describe the current state of the epidemiologic literature on the role of Fe status (i.e., hemoglobin, ferritin, blood Fe concentrations) and Fe supplementation in the relationship between metals and children's neurodevelopment, and to identify research gaps., Recent Findings: We identified 30 studies in PubMed and EMBASE that assessed Fe status as a modifier, mediator, or co-exposure of associations of Pb, Me-Hg, Mn, copper (Cu), zinc (Zn), arsenic (As), or metal mixtures measured in early life (prenatal period through 8 years of age) with cognition in children. In experimental studies, co-supplementation of Fe and Zn was associated with better memory and cognition than supplementation with either metal alone. Several observational studies reported interactions between Fe status and Pb, Mn, Zn, or As in relation to developmental indices, memory, attention, and behavior, whereby adverse associations of metals with cognition were worse among Fe-deficient children compared to Fe-sufficient children. Only two studies quantified joint associations of complex metal mixtures that included Fe with neurodevelopment, though findings from these studies were not consistent. Findings support memory and attention as two possible cognitive domains that may be both vulnerable to Fe deficiency and a target of metals toxicity. Major gaps in the literature remain, including evaluating Fe status as a modifier or mediator of metal mixtures and cognition. Given that Fe deficiency is the most common nutritional deficiency worldwide, characterizing Fe status in studies of metals toxicity is important for informing public health interventions., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Some studies indicate that Black women have higher exposure to multiple non-persistent endocrine disrupting chemicals (EDCs) than white women, but little is known about correlates of exposure to EDC mixtures. Using baseline data from a prospective cohort study of reproductive-aged Black women (N = 751), we characterized profiles of EDC mixtures and identified correlates of exposure. At baseline, we quantified biomarkers of 16 phthalates, 7 phenols, 4 parabens, and triclocarban in urine and collected covariate data through self-administered questionnaires and interviews. We used principal component (PC) analysis and k-means clustering to describe EDC mixture profiles. Associations between correlates and PCs were estimated as the mean difference (β) in PC scores, while associations between correlates and cluster membership were estimated as the odds ratio (OR) of cluster membership. Personal care product use was consistently associated with profiles of higher biomarker concentrations of non-persistent EDCs. Use of nail polish, menstrual and vaginal products (e.g., vaginal powder, vaginal deodorant), and sunscreen was associated with a mixture of phthalate and some phenol biomarkers using both methods. Current vaginal ring use, a form of hormonal contraception placed inside the vagina, was strongly associated with higher concentrations of high molecular weight phthalate biomarkers (k-means clustering: OR = 2.42, 95% CI = 1.28, 4.59; PCA: β = -0.32, 95% CI = -0.71, 0.07). Several dietary, reproductive, and demographic correlates were also associated with mixtures of EDC biomarkers. These findings suggest that personal care product use, diet, and contraceptive use may be sources of exposure to multiple non-persistent EDCs among reproductive-aged Black women. Targeted interventions to reduce exposure to multiple EDCs among Black women are warranted., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Indoor spaces contain several classes of persistent organic chemicals, including per- and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs). However, concentrations of PFAS and persistent chemical mixtures and their associations with building characteristics on college campuses are understudied. We collected dust from 43 nonresidential spaces on four U.S. college campuses in 2016 and evaluated associations of room characteristics (carpeting, upholstered furniture, and years since last furnished) with dust concentrations of PFAS, PBDEs, PCBs, and OCPs. Nine PFAS, twelve PBDEs, two PCBs, and four OCPs were each detected in at least 75% of the spaces, including several chemicals (e.g., DDT) that have been banned for decades. Concentrations were correlated within and, in some cases, between chemical classes. Wall-to-wall carpeting (compared to rooms without wall-to-wall carpeting) was associated with higher concentrations of six individual PFAS and a mixture of PFAS, and the number of pieces of upholstered furniture was associated with increased concentrations of a mixture of PBDEs. These findings indicate that carpeting and furniture are current sources of PFAS and PBDEs, respectively. Building and finish materials should be carefully selected to avoid exposure to persistent chemicals., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Iron is needed for normal development in adolescence. Exposure to individual environmental metals (e.g., lead) has been associated with altered iron status in adolescence, but little is known about the cumulative associations of multiple metals with Fe status. We used data from the 2017-2018 National Health and Nutrition Examination Survey (NHANES) to examine associations between a metal mixture (lead, manganese, cadmium, selenium) and iron status in 588 U.S. adolescents (12-17 years). We estimated cumulative and interactive associations of the metal mixture with five iron status metrics using Bayesian Kernel Machine Regression (BKMR). Higher concentrations of manganese and cadmium were associated with lower log-transformed ferritin concentrations. Interactions were observed between manganese, cadmium, and lead for ferritin and the transferrin receptor, where iron status tended to be worse at higher concentrations of all metals. These results may reflect competition between environmental metals and iron for cellular uptake. Mixed metal exposures may alter normal iron function, which has implications for adolescent development., (© 2022 Wiley Periodicals LLC.)

Background: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure., Methods: We performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1499 Black women aged 23-35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010-2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95 % confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates., Results: PFHxS, PFOS, PFOA, and PFNA were detected in ≥97 % of women; PFDA in 86 %; MeFOSAA in 70 %; and PFUnDA in 52 %. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95 % CI) were observed between parity (≥3 vs. 0 births) and PFHxS (-34.7; -43.0, -25.1) and PFOA (-33.1; -39.2, -26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (-31.1; -37.8, -23.7), PFHxS (-24.2; -34.5, -12.3), and PFOS (-18.4; -28.3, -7.1); recent birth (<2 years ago vs. nulliparous) and PFOA (-33.1; -39.6, -25.8), PFHxS (-29.3; -39.0, -18.1), PFNA (-25.2; -32.7, -16.8), and PFOS (-18.3; -28.3, -6.9); and intensity of menstrual bleed (heavy vs. light) and PFHxS (-18.8; -28.3, -8.2), PFOS (-16.4; -24.9, -7.1), PFNA (-10.5; -17.8, -2.6), and PFOA (-10.0; -17.2, -2.1). Current use of depot medroxyprogesterone acetate (DMPA) was positively associated with PFOS (20.2; 1.4, 42.5), PFOA (16.2; 1.5, 33.0), and PFNA (15.3; 0.4, 32.4)., Conclusions: Reproductive factors that influence PFAS elimination showed strong associations with several PFAS (reduced concentrations with parity, recent birth, lactation, heavy menstrual bleeding; increased concentrations with DMPA use)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Black women are exposed to multiple endocrine-disrupting chemicals (EDCs), but few studies have examined their profiles of exposure to EDC mixtures. We identified biomarker profiles and correlates of exposure to EDC mixtures in a cross-sectional analysis of data from a prospective cohort study of 749 Black women aged 23-35 years. We quantified plasma concentrations of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), and per- and polyfluoroalkyl substances (PFAS) in nonfasting samples collected at baseline. Demographic, behavioral, dietary, and reproductive covariates were also collected at baseline. We used k- means clustering and principal component analysis (PCA) to describe concentration profiles of EDC mixtures (17 PCBs, 6 PBDEs, 4 OCPs, 6 PFAS), followed by multinomial logistic and multivariable linear regression to estimate mean differences in PCA scores (β) and odds ratios (ORs) of cluster membership with their respective 95% confidence intervals (CIs). Older age (per 1 year increase: β = 0.47, CI = 0.39, 0.54; OR = 1.27, CI = 1.20, 1.35), lower body mass index (per 1 kg/m 2 increase: β = -0.14, CI = -0.17, -0.12; OR = 0.91, CI = 0.89, 0.94), and current smoking (≥10 cigarettes/day vs never smokers: β = 1.37, CI = 0.20, 2.55; OR = 2.63, CI = 1.07, 6.50) were associated with profiles characterized by higher concentrations of all EDCs. Other behaviors and traits, including dietary factors and years since last birth, were also associated with EDC mixtures.

Objectives: The US National Toxicology Program (NTP) recently recommended in its Report on Carcinogens Monograph for Antimony Trioxide that antimony trioxide be listed as ' reasonably anticipated to be a human carcinogen ' based on sufficient evidence of carcinogenicity in experimental animals and supporting evidence from mechanistic studies. Our goal was to estimate the possible human cancer risk from occupational exposure to antimony trioxide., Methods: We selected data from 2-year inhalation studies in male and female mice conducted by the NTP and performed cancer dose-response analyses using cancer models and benchmark dose methods developed by the US Environmental Protection Agency. In these analyses, we generated benchmark doses and cancer slope factors for antimony trioxide, and then estimated human cancer risk under various exposure scenarios. Typical and worst-case inhalation scenarios in multiple occupational settings were used in risk estimation., Results: In typical case scenarios, the occupational cancer risk from antimony trioxide was estimated to be 0.025 (25 in 1000) for persons working with flame retardants in plastics and textiles for 40 years. Under worst-case scenarios, the occupational cancer risk was estimated to be 0.11 (110 in 1000) for persons working with flame retardants in plastics and textiles. At the current Occupational Safety and Health Administration Permissible Exposure Limit, the cancer risk for occupational inhalation exposure of antimony trioxide was estimated to be 0.096 (96 in 1000)., Conclusion: The risk estimates calculated in this study suggest that exposure to antimony trioxide at levels present in certain occupational settings results in a large increase in the risk of developing cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A new national cohort of Gulf War (GW) veterans of 1,318 participants was created from the Veterans Affairs Cooperative Studies Program 585 Gulf War Era Cohort and Biorepository (GWECB) pilot study. However, female veteran health outcomes have not been reported separately for those deployed versus nondeployed to the 1990-1991 GW. Methods: Using data from the cooperative studies program (CSP) #585 GWECB, this study examined whether excess prevalence and patterns of Gulf War Illness (GWI) symptoms were present among female veterans who served during the GW compared with female veterans who did not deploy to the GW (GW-Era). Results: A total of 301 women veterans participated in the survey (203 GW, 98 GW-era). Mean ages in 2016 were 53 years among GW women veterans and 54 years among GW-era women. Participant groups did not differ by age, race, ethnicity, or education, but GW women were more likely to have served in the army or navy and less likely to have served in the air force. Compared with GW-era women, GW-deployed women were significantly more likely to report 7 out of 34 symptoms related to cognitive, neurological, and mood problems and respiratory complaints when controlling for age, race, GW deployment, branch of service, and smoking status in logistic regression analyses. Ordered logistic regression was also used to estimate the association between the total number of self-reported symptoms and deployment status, age, race, branch of service, and smoking status. Results showed deployed GW veterans to have a nearly twofold risk of reporting more symptoms than GW-era women, with younger, nonwhite, army-enlisted GW women significantly more likely to report more total symptoms. Discussion: Twenty-five years after the war, GWECB women GW veterans continued to report a wide variety of symptoms at a significantly higher excess frequency prevalence than GW-era women. Our results showed at least a 14% excess frequency prevalence in all seven significantly different symptoms encompassing two out of the six Kansas GWI criteria, including neurological/mood/cognition, and respiratory domains. These results suggest that further study of these symptom domains is warranted in GW women veterans.