Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study.

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.

Hair product use and urinary biomarker concentrations of non-persistent endocrine disrupting chemicals among reproductive-aged Black women.

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.

A multi-environmental source approach to explore associations between metals exposure and olfactory identification among school-age children residing in northern Italy.

BACKGROUND: Metal exposures can adversely impact olfactory function. Few studies have examined this association in children. Further, metal exposure occurs as a mixture, yet previous studies of metal-associated olfactory dysfunction only examined individual metals. Preventing olfactory dysfunctions can improve quality of life and prevent neurodegenerative diseases with long-term health implications. OBJECTIVE: We aimed to test the association between exposure to a mixture of 12 metals measured in environmental sources and olfactory function among children and adolescents residing in the industrialized province of Brescia, Italy. METHODS: We enrolled 130 children between 6 and 13 years old (51.5% females) and used the "Sniffin' Sticks" test to measure olfactory performance in identifying smells. We used a portable X-ray fluorescence instrument to determine concentrations of metals (arsenic (As), calcium, cadmium (Cd), chromium, copper, iron, manganese, lead (Pb), antimony, titanium, vanadium and zinc) in outdoor and indoor deposited dust and soil samples collected from participants' households. We used an extension of weighted quantile sum (WQS) regression to test the association between exposure to metal mixtures in multiple environmental media and olfactory function adjusting for age, sex, socio-economic status, intelligence quotient and parents' smoking status. RESULTS: A higher multi-source mixture was significantly associated with a reduced Sniffin' Sticks identification score (ß = -0.228; 95% CI -0.433, -0.020). Indoor dust concentrations of Pb, Cd and As provided the strongest contributions to this association (13.8%, 13.3% and 10.1%, respectively). The metal mixture in indoor dust contributed more (for 8 metals out of 12) to the association between metals and olfactory function compared to soil or outdoor dust. IMPACT STATEMENT: Among a mixture of 12 metals measured in three different environmental sources (soil, outdoor and indoor dust), we identified Pb, Cd and As measured in indoor dust as the main contributors to reduced olfactory function in children and adolescents residing in an industrialized area. Exposure to indoor pollution can be effectively reduced through individual and public health interventions allowing to prevent the deterioration of olfactory functions. Moreover, the identification of the factors that can deteriorate olfactory functions can be a helpful instrument to improve quality of life and prevent neurodegenerative diseases as long-term health implications.

Per- and polyfluoroalkyl substances (PFAS), perceived stress, and depressive symptoms in a prospective cohort study of black women.

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 (ß = 0.03; 95 % CrI = 0.20, 0.25), 50th (ß = 0.02; 95 % CrI = -0.16, 0.19), and 90th (ß = 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.

Non-persistent endocrine disrupting chemical mixtures and uterine leiomyomata in the study of environment, lifestyle and fibroids (SELF).

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.

Personal Care Products, Socioeconomic Status, and Endocrine-Disrupting Chemical Mixtures in Black Women.

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.

An Industry-Relevant Metal Mixture, Iron Status, and Reported Attention-Related Behaviors in Italian Adolescents.

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% [ß=0.03; 95% credible interval (CrI): -0.01, 0.06], 4.1% (ß=0.04; 95% CrI: 0.00, 0.08), and 4.1% (ß=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.

Assessing the mediating role of iron status on associations between an industry-relevant metal mixture and verbal learning and memory in Italian adolescents.

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 (ß) 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 (ß = 0.00; 95 % CI = -0.22, 0.23). Conversely, the NDE (ß = 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.

Early-life manganese exposure during multiple developmental periods and adolescent verbal learning and memory.

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.

A prospective ultrasound study of cigarette smoking and uterine leiomyomata incidence and growth.

BACKGROUND: Uterine leiomyomata (fibroids) are common, benign neoplasms that contribute substantially to gynecologic morbidity. Some existing epidemiologic studies indicate that cigarette smoking is associated with lower uterine leiomyomata risk. However, no prospective studies have systematically screened an entire study population for uterine leiomyomata using transvaginal ultrasound or evaluated the association between cigarette smoking and uterine leiomyomata growth. OBJECTIVE: This study aimed to examine the association between cigarette smoking and uterine leiomyomata incidence and growth in a prospective ultrasound study. STUDY DESIGN: We enrolled 1693 residents from the Detroit metropolitan area into the Study of Environment, Lifestyle, and Fibroids during 2010 to 2012. Eligible participants were aged 23 to 34 years, had an intact uterus but no previous diagnosis of uterine leiomyomata, and self-identified as Black or African American. We invited participants to complete a baseline visit and 4 follow-up visits over approximately 10 years. At each visit, we used transvaginal ultrasound to assess uterine leiomyomata incidence and growth. Participants provided extensive self-reported data throughout follow-up including exposures to active and passive cigarette smoking in adulthood. We excluded participants who did not return for any follow-up visits (n=76; 4%). We fit Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals for the association between time-varying smoking history and incidence rates of uterine leiomyomata. We fit linear mixed models to estimate the percentage difference and 95% confidence intervals for the association between smoking history and uterine leiomyomata growth. We adjusted for sociodemographic, lifestyle, and reproductive factors. We interpreted our results based on magnitude and precision rather than binary significance testing. RESULTS: Among 1252 participants without ultrasound evidence of uterine leiomyomata at baseline, uterine leiomyomata were detected in 394 participants (31%) during follow-up. Current cigarette smoking was associated with a lower uterine leiomyomata incidence rate (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Associations were stronger among participants who had smoked for longer durations (≥15 years vs never: hazard ratio, 0.49; 95% confidence interval, 0.25-0.95). The hazard ratio for former smokers was 0.78 (95% confidence interval, 0.50-1.20). Among never smokers, the hazard ratio for current passive smoke exposure was 0.84 (95% confidence interval, 0.65-1.07). Uterine leiomyomata growth was not appreciably associated with current (percent difference, -3%; 95% confidence interval, -13% to 8%) or former (percent difference, -9%; 95% confidence interval, -22% to 6%) smoking. CONCLUSION: We provide evidence from a prospective ultrasound study that cigarette smoking is associated with lower uterine leiomyomata incidence.

Associations of an industry-relevant metal mixture with verbal learning and memory in Italian adolescents: The modifying role of iron status.

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: ß = 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.

Early life manganese exposure and reported attention-related behaviors in Italian adolescents.

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) 55Mn:43Ca × 104, 0.1 AUC 55Mn:43Ca × 104, and 0.0006 55Mn:43Ca 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.

Waxing activity as a potential source of exposure to per- and polyfluoroalkyl substances (PFAS) and other environmental contaminants among the US ski and snowboard community.

BACKGROUND: Skiers and snowboarders apply waxes and solvents to their equipment to enhance glide across the snow. Waxing results in exposures to per- and polyfluoroalkyl substances (PFAS) and particulate matter, which have been associated with adverse health effects among professional wax technicians in Scandinavia. However, little is known about exposure among people who participate at other levels of sport, including recreationally, in other regions. OBJECTIVE: We sought to characterize wax-related exposures among US skiers and snowboarders who participate across numerous levels of sport to expand scientific understanding of environmental health risks among this population. METHODS: We used an anonymous electronic survey to evaluate wax-related exposures among US cross-country and downhill skiers and snowboarders. Specifically, we assessed (Fang et al., 2020): duration of time involved with each sport in any role (Freberg et al., 2013), intensity of wax-related exposures based on time spent in waxing areas, wax use, and wax type (Rogowski et al., 2007), frequency of fluorinated wax application, and (Freberg et al., 2010) use of exposure interventions. RESULTS: Participants tended to be long-term winter sports enthusiasts (e.g., median downhill skiing duration: 31 years). Nearly all (92%) participants personally applied some wax to their skis/snowboards and most applied waxes containing PFAS (67%) and solvents (62%). Ski professionals waxed the most pairs of skis with fluorinated waxes annually (median (IQR): 20 (1, 100)), though individuals participating recreationally also applied fluorinated waxes regularly. Exposure interventions were not widely used. SIGNIFICANCE: Waxing activities may pose significant risk of exposure to PFAS and other environmental contaminants among the US ski and snowboard community. Efforts are needed to reduce these exposures through changes to wax use patterns and broader adoption of exposure reduction strategies.

Correlates of whole blood metal concentrations among reproductive-aged Black women.

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.

Environmental Metal Exposure, Neurodevelopment, and the Role of Iron Status: a Review.

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.

Associations of a metal mixture with iron status in U.S. adolescents: Evidence from the National Health and Nutrition Examination Survey.

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.

Correlates of non-persistent endocrine disrupting chemical mixtures among reproductive-aged Black women in Detroit, Michigan.

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 (ß) 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: ß = -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.

Bayesian kernel machine regression-causal mediation analysis.

Greater understanding of the pathways through which an environmental mixture operates is important to design effective interventions. We present new methodology to estimate natural direct and indirect effects and controlled direct effects of a complex mixture exposure on an outcome through a mediator variable. We implement Bayesian Kernel Machine Regression (BKMR) to allow for all possible interactions and nonlinear effects of (1) the co-exposures on the mediator, (2) the co-exposures and mediator on the outcome, and (3) selected covariates on the mediator and/or outcome. From the posterior predictive distributions of the mediator and outcome, we simulate counterfactuals to obtain posterior samples, estimates, and credible intervals of the mediation effects. Our simulation study demonstrates that when the exposure-mediator and exposure-mediator-outcome relationships are complex, BKMR-Causal Mediation Analysis performs better than current mediation methods. We applied our methodology to quantify the contribution of birth length as a mediator between in utero co-exposure to arsenic, manganese, and lead, and children's neurodevelopmental scores, in a prospective birth cohort in Bangladesh. Among younger children, we found a negative (adverse) association between the metal mixture and neurodevelopment. We also found evidence that birth length mediates the effect of exposure to the metal mixture on neurodevelopment for younger children. If birth length were fixed to its 75th percentile value, the harmful effect of the metal mixture on neurodevelopment is attenuated, suggesting nutritional interventions to help increase fetal growth, and thus birth length, could potentially block the harmful effect of the metal mixture on neurodevelopment.