BACKGROUND:Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent, widespread environmental contaminants, and some are endocrine disrupting. Studies of gynecologic cancers are limited; we evaluated ovarian cancer, a rare, often fatal malignancy. METHODS:This nested case-control study included 318 ovarian cancer cases and 472 individually matched female controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 10 US study centers (1993-2001). We looked at cases through 2016 and quantitated 8 PFAS in prediagnostic serum samples. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for continuous (log2-transformed) and categorized PFAS concentrations by using conditional logistic regression models, implicitly adjusting for matching factors (age, center, year of random assignment, year of blood draw, race and ethnicity) and adjusting for smoking, body mass index, family history of cancer, menopausal hormone therapy and oral contraceptive use, parity, and number of freeze-thaw cycles. RESULTS:We found a positive association with ovarian cancer for a doubling in 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) concentrations (OR for log2 = 1.24, 95% CI = 1.03 to 1.49) and 62% greater risk among those in the highest quartile (OR for quartile 4 vs quartile 1 = 1.62, 95% CI = 1.03 to 2.54; P for trend = .02). Perfluorooctane sulfonic acid (PFOS) was associated with increased risk (OR for log2 = 1.47, 95% CI = 1.05 to 2.06), with no quartile trend (P for trend = .79). Associations with perfluorononanoic acid (OR for log2 = 1.36, 95% CI = 0.95 to 1.95) and perfluorodecanoic acid (OR for log2 = 1.35, 95% CI = 0.94 to 1.95) were suggested, with nonmonotonic quartile trends (P for trend = .12 to .21). The MeFOSAA associations were strongest in women aged 55-59 years (OR for log 2 = 1.60, 95% CI = 1.13 to 2.27), more moderate in women aged 60-64 years (OR for log2 = 1.31, 95% CI = 0.90 to 1.90), and null among women 65 years of age and older (OR for log2 = 1.02, 95% CI = 0.73 to 1.43; P for heterogeneity = .22). Associations persisted in cases diagnosed 8 years or more after blood collection. CONCLUSIONS:These findings offer novel evidence for PFAS as ovarian cancer risk factors, particularly PFOS and MeFOSAA, a PFOS precursor.

Previous studies - primarily in high income countries - have shown that high prenatal temperatures are associated with adverse birth outcomes. However, these studies are mostly focused on average exposure across the full gestational period or short-term exposure immediately prior to delivery and may miss important sensitive windows of exposure in utero. Further, nearly all use ambient air temperature data, which neglect physiologically important interactions between air temperature and humidity. The Ghana Randomized Air Pollution and Health Study (GRAPHS) recruited pregnant individuals from 2013 to 2015 from communities in the Kintampo North Municipality and Kintampo South District of Ghana. We estimated daily maximum shaded wet bulb globe temperature (WBGTmax) and heat index (HImax) during pregnancy and examined associations with birth weight, birth length, head circumference, and incidence of low birth weight, preterm birth, and small for gestational age. Using linear regression analyses, trimester average models identified that higher WBGTmax in the first trimester was associated with larger head circumference; second trimester was associated with shorter birth length, lower birth weight and higher odds of preterm birth, and third trimester was associated with shorter gestational age and larger head circumference. Time-varying analyses using distributed lag nonlinear models find that, compared to the median, lower WBGTmax and HImax (25th percentile) during the first half of pregnancy was associated with higher birth weight and longer birth length. Compared to the median, lower WBGTmax and HImax (25th percentile) in the second half of pregnancy was associated with smaller head circumference while higher wet bulb globe temperature (75th percentile) was associated with larger head circumference. Overall, our study identified that higher WBGTmax and HImax are associated with pregnancy duration and newborn size. Given the overall trend in our study area of rising temperatures, these data suggest that adaptation strategies are urgently needed to protect child health.

Environmental epidemiologic studies using geospatial data often estimate exposure at a participant's residence upon enrollment, but mobility during the exposure period can lead to misclassification. We aimed to mitigate this issue by constructing residential histories for participants in the California Teachers Study through follow-up (1995-2018). Address records have been collected from the US Postal Service, LexisNexis, Experian, and California Cancer Registry. We identified records of the same address based on geo-coordinate distance (≤250 m) and street name similarity. We consolidated addresses, prioritizing those confirmed by participants during follow-up questionnaires, and estimating the duration lived at each address using dates associated with records (e.g., date-first-seen). During 23 years of follow-up, about half of participants moved (48%, including 14% out-of-state). We observed greater mobility among younger women, Hispanic/Latino women, and those in metropolitan and lower socioeconomic status areas. The cumulative proportion of in-state movers remaining eligible for analysis was 21%, 32%, and 41% at 5, 10, and 20 years post enrollment, respectively. Using self-reported information collected 10 years after enrollment, we correctly identified 94% of movers and 95% of non-movers as having moved or not moved from their enrollment address. This dataset provides a foundation for estimating long-term environmental exposures in diverse epidemiologic studies in this cohort. IMPACT: Our efforts in constructing residential histories for California Teachers Study participants through follow-up (1995-2018) benefit future environmental epidemiologic studies. Address availability during the exposure period can mitigate misclassification due to residential changes, especially when evaluating long-term exposures and chronic health outcomes. This can reduce differential misclassification among more mobile subgroups, including younger women and those from lower socioeconomic and urban areas. Our approach to consolidating addresses from multiple sources showed high accuracy in comparison to self-reported residential information. The residential dataset produced from this analysis provides a valuable tool for future studies, ultimately enhancing our understanding of environmental health impacts.

BACKGROUND:Volatile organic compounds (VOCs) are ubiquitous environmental pollutants. Exposure to VOCs is associated with cardiovascular disease risk factors, including elevated blood pressure in susceptible populations. However, research in the general population, particularly among nonsmoking adults, is limited. We hypothesized that higher VOC exposure is associated with higher blood pressure and hypertension, among nonsmokers. METHODS:We included 4 cycles of data (2011-2018) of nonsmoking adults (n=4430) from the National Health and Nutrition Examination Survey. Urinary VOC metabolites were measured by ultraperformance liquid chromatography-mass spectrometry, adjusted for urine dilution, and log-transformed. We estimated mean differences in blood pressure using linear models and prevalence ratio of stage 2 hypertension using modified Poisson models with robust standard errors. Models were adjusted for age, sex, race and ethnicity, education, body mass index, estimated glomerular filtration rate, and National Health and Nutrition Examination Survey cycle. RESULTS:Participants were 54% female, with a median age of 48 years, 32.3% had hypertension, and 7.9% had diabetes. The mean differences (95% CI) in systolic blood pressure were 1.61 (0.07-3.15) and 2.46 (1.01-3.92) mm Hg when comparing the highest with the lowest quartile of urinary acrolein (N-acetyl-S-[2-carboxyethyl]-L-cysteine) and 1,3-butadiene (N-acetyl-S-[3,4-dihydroxybutyl]-L-cysteine) metabolites. The prevalence ratios for hypertension were 1.06 (95% CI, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) when comparing the highest with lowest quartiles of urinary acrolein (N-acetyl-S-[2-carboxyethyl]-L-cysteine) and 1,3-butadiene (N-acetyl-S-[3,4-dihydroxybutyl]-L-cysteine), respectively. CONCLUSIONS:Exposure to VOCs may be a relevant yet understudied environmental contributor to cardiovascular disease risk in the nonsmoking, US population.

Purpose: Few studies have investigated the relationship between risk of non-Hodgkin lymphoma (NHL) and residential proximity to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) emitted from industrial combustion and manufacturing sources. Methods: We evaluated this relationship among participants of the NIH-AARP Diet and Health Study, a prospective cohort (N = 548,845) in 6 states and 2 cities in the U.S. We linked geocoded enrollment addresses (1995–1996) with a U.S. Environmental Protection Agency database of 4,478 historical PCDD/F sources, which contained toxic equivalency quotient (TEQ) emissions estimates from 1995. Exposure metrics indicated presence/absence of any facility within 3 and 5km of participant homes, overall and by type of facility (e.g., coal-fired power plants, waste incinerators), which vary in emissions levels and constituency. We also calculated exposure as a distance- and toxicity-weighted average emissions index (AEI [g TEQ]). We used Cox regression to estimate associations (hazard ratios; HR and 95% confidence intervals; CI) with NHL and major subtypes, adjusting for and by strata of sociodemographic and lifestyle characteristics. Results: With 6,747 incident cases through 2011, we found no association between living near any or specific types of PCDD/F-emitting facilities and NHL risk. However, participants with an AEI >95th percentile within 5km had increased risk of NHL compared to unexposed (HR = 1.28; CI = 1.05–1.55; p-trend = 0.01). Specifically, we observed increased risk for lymphoplasmacytic lymphoma (HR = 2.98, CI = 1.16–7.63; p-trend = 0.03) and diffuse large B-cell lymphoma (HR = 1.65, CI = 1.11–2.46; p-trend = 0.01). Non-Hispanic blacks were nearly three times as likely as whites to live <5 km of a facility, although we had limited power to evaluate heterogeneity in associations by race/ethnicity. Associations did not vary by age, smoking status, body mass index, or urbanicity of residence. Conclusions: Using an exposure metric accounting for distance and the toxicity of emissions, we found significant positive associations between residential exposure to high PCDD/F emissions and risk of NHL and two subtypes. Our results underscore the hazard for populations living near sources of these persistent organic pollutants.

BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) are widespread and environmentally persistent chemicals with immunotoxic properties. Children are prenatally exposed through maternal transfer of PFAS to cord blood, but no studies have investigated the relationship with childhood leukemia. METHODS:We measured maternal serum levels of 19 PFAS in first-trimester samples collected in 1986-2010 and evaluated associations with acute lymphoblastic leukemia in full-term offspring (aged younger than 15 years) for 400 cases and 400 controls in the Finnish Maternity Cohort, matched on sample year, mother's age, gestational age, birth order, and child's sex. We analyzed continuous and categorical exposures, estimating odds ratios (ORs) and 95% confidence intervals (CIs) via conditional logistic regression adjusted for maternal smoking and correlated PFAS (ρ ≥ ±0.3). We also stratified by calendar period, mean diagnosis age, and the child's sex. RESULTS:N-methyl-perfluorooctane sulfonamidoacetic acid was associated with acute lymphoblastic leukemia in continuous models (per each doubling in levels: ORperlog2 = 1.22, 95% CI = 1.07 to 1.39), with a positive exposure-response across categories (OR>90th percentile = 2.52, 95% CI = 1.33 to 4.78; Ptrend = .01). Although we found no relationship with perfluorooctane sulfonic acid overall, an association was observed in samples collected in 1986-1995, when levels were highest (median = 17.9 µg/L; ORperlog2 = 4.01, 95% CI = 1.62 to 9.93). A positive association with perfluorononanoic acid was suggested among first births (Pinteraction = .06). The N-methyl-perfluorooctane sulfonamidoacetic acid association was mainly limited to children diagnosed before age 5 years (Pinteraction = .02). We found no consistent patterns of association with other PFAS or differences by sex. CONCLUSIONS:These novel data offer evidence of a relationship between some PFAS and risk of the most common childhood cancer worldwide, including associations with the highest levels of perfluorooctanesulfonic acid and with a precursor, N-methyl-perfluorooctane sulfonamidoacetic acid.

BACKGROUND:Inorganic arsenic in drinking water (wAs) is linked to atherosclerosis and cardiovascular disease. However, risk is uncertain at lower levels present in US community water supplies (CWS), currently regulated at the federal maximum contaminant level of 10μg/L. OBJECTIVES:We evaluated the relationship between long-term wAs exposure from CWS and cardiovascular disease in the California Teachers Study cohort. METHODS:Using statewide health care administrative records from enrollment through follow-up (1995-2018), we identified fatal and nonfatal cases of ischemic heart disease (IHD) and cardiovascular disease (CVD). Participants' residential addresses were linked to a network of CWS boundaries and annual wAs concentrations (1990-2020). Most participants resided in areas served by a CWS (92%). Exposure was calculated as a time-varying, 10-year moving average up to a participant's event, death, or end of follow-up. Using Cox models, we estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the risk of IHD or CVD. We evaluated wAs exposure categorized by concentration thresholds relevant to regulation standards (<1.00, 1.00-2.99, 3.00-4.99, 5.00-9.99, ≥10μg/L) and continuously using a log2-transformation (i.e., per doubling). Models were adjusted for baseline age, neighborhood socioeconomic status, race/ethnicity, body mass index (BMI), and smoking status. We also stratified analyses by age, BMI, and smoking status. RESULTS:Our analysis included 98,250 participants, 6,119 IHD cases, and 9,936 CVD cases. The HRs for IHD at concentration thresholds (reference, <1μg/L) were 1.06 (95% CI: 1.00, 1.12), 1.05 (95% CI: 0.94, 1.17), 1.20 (95% CI: 1.02, 1.41), and 1.42 (95% CI: 1.10, 1.84) for 1.00-2.99μg/L, 3.00-4.99μg/L, 5.00-9.99μg/L, and ≥10μg/L, respectively. HRs for every doubling of wAs exposure were 1.04 (95% CI: 1.02, 1.06) for IHD and 1.02 (95% CI: 1.01, 1.04) for CVD. We observed statistically stronger risk among those ≤55 vs. >55 years of age at enrollment (pinteraction=0.006 and 0.012 for IHD and CVD, respectively). DISCUSSION:Long-term wAs exposure from CWS, at and below the regulatory limit, may increase cardiovascular disease risk, particularly IHD. https://doi.org/10.1289/EHP14410.

Diarrheal disease is the second leading cause of death among children under five in developing communities, despite active interventions to improve access to water, sanitation, and hygiene resources. Even interventions with high fidelity and compliance saw minimal improvements in health outcomes, necessitating a need for looking beyond traditionally targeted exposure pathways. This study focuses on the pathogen exposure a young child may receive while playing in the public spaces of informal settlements, where animal feces, human feces, and garbage are frequently observed. The study utilized 79 soil samples previously collected across ten cluster sites in Corail, Haiti and processed using DelAgua cultural assays and quantitative Polymerase Chain Reaction methods. Molecular assays screened for Aeromonas, Vibrio cholera, and several pathogenic Escherichia coli species. Behavioral observations of young children (<5 years old) were also conducted in overlapping areas with the environmental sampling to quantify frequency of risky and mitigating behaviors. Environmental and behavioral data were combined to obtain the posterior distribution of children’s pathogen exposure from playing in a public space for one hour. The model estimated that children have a likelihood of approximately 70% of being exposed to a pathogen during one hour of play and a greater than 30% chance of being exposed to multiple pathogens in the same period. While children and toddlers practice fewer risky behaviors compared to infants, they were shown to have higher likelihood of exposure and slightly higher pathogen dose per exposure. As anticipated, a high correlation between genes from the same E. coli species was observed in the model output. These findings demonstrate the need to consider public spaces as an important exposure pathway for young children for both future research and interventions.

Background:Volatile organic compounds (VOCs) are ubiquitous environmental pollutants. Exposure to VOCs is associated with cardiovascular disease (CVD) risk factors, including elevated blood pressure (BP) in susceptible populations. However, research in the general population, particularly among non-smoking adults, is limited. We hypothesized that higher VOC exposure is associated with higher BP and hypertension, among non-smokers. Methods:We included four cycles of data (2011-2018) of non-smoking adults (n=4,430) from the National Health and Nutrition Examination Survey (NHANES). Urinary VOC metabolites were measured by ultra-performance liquid chromatography-mass spectrometry, adjusted for urine dilution, and log-transformed. We estimated mean differences in BP using linear models and prevalence ratio of stage 2 hypertension using modified Poisson models with robust standard errors. Models were adjusted for age, sex, race and ethnicity, education, body mass index, estimated glomerular filtration rate and NHANES cycle. Results:Participants were 54% female, with a median age of 48 years, 32.3% had hypertension, and 7.9% had diabetes. The mean differences (95% CI) in systolic BP were 1.61 (0.07, 3.15) and 2.46 (1.01, 3.92) mmHg when comparing the highest to lowest quartile of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA) metabolites. The prevalence ratios (PR) for hypertension were 1.06 (1.02, 1.09) and 1.05 (1.01, 1.09) when comparing the highest to lowest quartiles of urinary acrolein (CEMA) and 1,3-butadiene (DHBMA), respectively. Conclusions:Exposure to VOCs may be relevant yet understudied environmental contributors to CVD risk in the non-smoking, US population.

BackgroundPollutants including metals/metalloids, nitrate, disinfection byproducts, and volatile organic compounds contaminate federally regulated community water systems (CWS) and unregulated domestic wells across the United States. Exposures and associated health effects, particularly at levels below regulatory limits, are understudied.ObjectiveWe described drinking water sources and exposures for the California Teachers Study (CTS), a prospective cohort of female California teachers and administrators.MethodsParticipants' geocoded addresses at enrollment (1995-1996) were linked to CWS service area boundaries and monitoring data (N = 115,206, 92%); we computed average (1990-2015) concentrations of arsenic, uranium, nitrate, gross alpha (GA), five haloacetic acids (HAA5), total trihalomethanes (TTHM), trichloroethylene (TCE), and tetrachloroethylene (PCE). We used generalized linear regression to estimate geometric mean ratios of CWS exposures across demographic subgroups and neighborhood characteristics. Self-reported drinking water source and consumption at follow-up (2017-2019) were also described.ResultsMedians (interquartile ranges) of average concentrations of all contaminants were below regulatory limits: arsenic: 1.03 (0.54,1.71) mu g/L, uranium: 3.48 (1.01,6.18) mu g/L, GA: 2.21 (1.32,3.67) pCi/L, nitrate: 0.54 (0.20,1.97) mg/L, HAA5: 8.67 (2.98,14.70) mu g/L, and TTHM: 12.86 (4.58,21.95) mu g/L. Among those who lived within a CWS boundary and self-reported drinking water information (2017-2019), approximately 74% self-reported their water source as municipal, 15% bottled, 2% private well, 4% other, and 5% did not know/missing. Spatially linked water source was largely consistent with self-reported source at follow-up (2017-2019). Relative to non-Hispanic white participants, average arsenic, uranium, GA, and nitrate concentrations were higher for Black, Hispanic and Native American participants. Relative to participants living in census block groups in the lowest socioeconomic status (SES) quartile, participants in higher SES quartiles had lower arsenic/uranium/GA/nitrate, and higher HAA5/TTHM. Non-metropolitan participants had higher arsenic/uranium/nitrate, and metropolitan participants had higher HAA5/TTHM.ImpactThough average water contaminant levels were mostly below regulatory limits in this large cohort of California women, we observed heterogeneity in exposures across sociodemographic subgroups and neighborhood characteristics. These data will be used to support future assessments of drinking water exposures and disease risk.

In the United States and globally, contaminant exposure in unregulated private-well point-of-use tapwater (TW) is a recognized public-health data gap and an obstacle to both risk-management and homeowner decision making. To help address the lack of data on broad contaminant exposures in private-well TW from hydrologically-vulnerable (al-luvial, karst) aquifers in agriculturally-intensive landscapes, samples were collected in 2018-2019 from 47 northeast Iowa farms and analyzed for 35 inorganics, 437 unique organics, 5 in vitro bioassays, and 11 microbial assays. Twenty- six inorganics and 51 organics, dominated by pesticides and related transformation products (35 herbicide-, 5 insecticide-, and 2 fungicide-related), were observed in TW. Heterotrophic bacteria detections were near ubiquitous (94 % of the samples), with detection of total coliform bacteria in 28 % of the samples and growth on at least one putative-pathogen selective media across all TW samples. Health-based hazard index screening levels were exceeded frequently in private-well TW and attributed primarily to inorganics (nitrate, uranium). Results support incorporation of residential treatment systems to protect against contaminant exposure and the need for increased monitoring of rural private-well homes. Continued assessment of unmonitored and unregulated private-supply TW is needed to model contaminant exposures and human-health risks.

Some dioxins are carcinogenic, but few studies have investigated the relationship between ambient polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) and risk of breast cancer. We evaluated associations between proximity-based residential exposure to industrial emissions of PCDD/F and breast cancer risk in a large U.S. cohort. Sister Study participants at enrollment (2003-2009) were followed for incident breast cancer through September 2018. After restricting to participants with ≥10 years of residential history prior to enrollment (n = 35,908), we generated 10-year distance- and toxic equivalency quotient (TEQ)-weighted average emissions indices (AEI [g TEQ/km2]) within 3, 5, or 10 km of participants' residences, overall and by facility type. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between AEI quartiles (vs. zero AEI) and risk of breast cancer [invasive or ductal carcinoma in situ]. There were 2670 incident breast cancer cases over 11 years (median) of follow-up. Breast cancer risk was increased for those in the highest quartile [Q] of AEI exposure within 3 km (HRQ4:1.18, 95% CI: 0.99,1.40, Ptrend = 0.03). The HR was higher for the 10-year AEI at 3 km from municipal solid waste facilities (HR ≥ median.vs.0:1.50, 95% CI: 0.98, 2.29; Ptrend = 0.07). Risk was higher among ever smokers (vs. never smokers) in the top quartile of the 3 km AEI (HRQ4:1.41, 95% CI:1.12,1.77, Ptrend = 0.003; Pinteraction = 0.03) and higher risk for ER negative tumors was suggested (HRQ4:1.47, 95% CI: 0.95, 2.28, Ptrend = 0.07, Pheterogeneity = 0.17). Our findings suggest that residential exposure to PCDD/F emissions may confer an increased risk of breast cancer.