Environmental Health Perspectives最新文献

Background: Influenza remains a significant public health threat, with pandemic potential. Understanding environmental factors influencing virus spread and severity is critical, particularly as wildfires become more frequent and intense. While temperature and humidity's roles in virus seasonality and persistence are well understood, the impacts of air pollution-especially wildfire-specific particulate matter (PM_2.5)-on respiratory infections are less explored.

Objectives: This study aimed to investigate the association between wildfire PM_2.5 exposure and influenza or influenza-like illness (ILI) incidence. Specifically, we assessed (1) the long-term impact of PM_2.5 exposure during the preceding wildfire season on influenza/ILI risk in the following flu season, and (2) the effects of short-term PM_2.5 exposure during the active flu season.

Methods: We utilized ILI and influenza data from state health departments in six Western U.S. states (Arizona, Colorado, Montana, Nevada, Oregon, and Washington) from 2010 to 2019. We applied generalized linear distributed lag models to assess the impact of PM_2.5 exposure during the preceding wildfire season on influenza or ILI risk in the subsequent flu season, as well as the effect of short-term PM_2.5 exposure during the current flu season.

Results: Long-term exposure to wildfire PM_2.5 was associated with increased influenza risk in states with influenza data: Arizona ([Rate Ratio (RR) =1.061 (1.026-1.100)]), Colorado [RR=1.067 (1.056-1.078)], Montana [RR=1.038 (1.013-1.063)], and Oregon [RR=1.049 (1.041-1.057)], per 10 µg/m³ PM_2.5 increase. However, the states with only ILI data did not follow this pattern, revealing no observed effect in Nevada [RR=1.005 (0.920-1.097)] and a negative effect in Washington [RR=0.884 (0.842-0.919)]. Similarly, but to a lesser degree, short-term PM_2.5 exposure effects were noted in states with only influenza data, but not ILI data.

Discussion: Our findings underscore a positive association between wildfire-specific PM_2.5 and influenza risk in states with influenza data, suggesting a differential effect of PM_2.5 on respiratory infections. This study supports further investigation into causative mechanisms behind these correlations, particularly considering the increasing frequency of wildfires and the resulting air quality impacts. https://doi.org/10.1289/EHP16607.

Background: Dietary intake, especially foods of animal-origin, is an important source of per- and polyfluoroalkyl substances (PFAS) exposure to the general population. However, the distribution of legacy and emerging PFAS in different food categories is unclear, as well as their potential health risk for children.

Objectives: To investigate dietary sources of PFAS and evaluate the risk for 7-year-old children in Laizhou Wan, a region with high PFAS exposure in Shandong, China.

Methods: We sampled participants from the Laizhou Wan Birth Cohort study. We administered a dietary questionnaire to the parents of 7-year-old children and measured PFAS compounds in the serum of the children (n = 154) and meat and seafood samples (n = 45). We calculated the Mann-Whitney U test to compare serum PFAS levels between children who frequently consumed a specific type of marine fish or shrimp/shellfish and those who did not. Children's dietary PFAS intake was calculated through multiplying food consumption and PFAS concentrations, and health risks were assessed by comparing the intake of PFAS with health-based guideline values.

Results: In seafood, perfluorooctanic acid (PFOA) (0.52 ng/g wet weight (ww)), perfluoro-6-methylheptanesulfonic acid (iso-PFOS) (0.02 ng/g ww), and 6:2 chlorinated polyfluoroethersulfonic acid (0.06 ng/g ww) had the highest median concentrations among 10 linear PFAS, 8 branched isomers of PFOA and perfluorooctanesulfonic acid (PFOS), and 3 alternatives, respectively. Particularly, PFOA levels (median, 87.80 ng/g) in Zoarces slongatus (one type of marine fish), were approximately 10-100 times of those in other seafood species. Children who frequently consumed Zoarces slongatus had higher serum PFAS levels, especially PFOA, than those who did not. Seafood intake accounted for more than 80% of the total estimated daily intake of PFAS. The dietary estimated weekly intake values of four PFAS (PFOA, PFOS, perfluorononanoic acid, and perfluorohexanesulfonic acid) for children (7.4 ng/kg of body weight (bw)/week) exceeded the tolerable weekly intake (4.4 ng/kg bw/week) as recommended by the European Food Safety Authority.

Conclusion: Seafood was widely contaminated by both legacy PFAS and their alternatives in Laizhou Wan area. Intake of seafood, especially Zoarces slongatus, may contribute greatly to PFAS exposure in 7-year-old children. Avoiding intake of high PFAS polluted seafood may be an important strategy to protect local children. https://doi.org/10.1289/EHP15157.

Background: Triclosan, an antimicrobial chemical that was widely used in consumer products, may increase risk of allergic diseases in children, but prospective studies are needed to clarify the association.

Objectives: To elucidate the associations of time-varying urinary triclosan concentrations with eczema, allergic rhinitis, and wheeze.

Methods: In the HOME Study, a prospective pregnancy and birth cohort, we quantified urinary triclosan concentrations in mother-child pairs up to ten times between 16 weeks' gestation and age 12 years. Caregivers reported eczema, allergic rhinitis, and wheeze symptoms biannually until children were aged 6 years and again when they were aged 8- and 12 years. We used generalized estimating equations to estimate the covariate-adjusted association of gestational and childhood triclosan concentrations with the risk of reporting eczema, allergic rhinitis, or wheezing symptoms.

Results: Three hundred forty-seven mother-child dyads contributed >3,000 visits to the analysis of gestational exposures and >2,600 visits to childhood analyses. Each 2-fold higher childhood triclosan concentration was associated with a 1.23 (95% CI: 1.04, 1.46) and 1.12 (95% CI: 1.01, 1.25) times higher risk of reporting eczema and allergic rhinitis, respectively, but not wheezing (RR=0.98 [95% CI: 0.82, 1.16]). We did not observe modification by child sex. Associations of gestational triclosan with eczema, allergic rhinitis, or wheezing symptoms were null in the full sample. Child sex modified the association of gestational triclosan with allergic rhinitis and wheezing (p-interaction_Allergy: 0.02; p-interaction_Wheezing:0.10), with 1.09 (95% CI: 1.00, 1.19) and 0.91 (95% CI: 0.83, 1.00) times the risk of allergic rhinitis symptoms among males and females respectively.

Conclusion: Childhood urinary triclosan concentrations were associated with caregiver reported eczema, and more weakly with allergic rhinitis. Associations of gestational triclosan with allergic outcomes differed by child sex, suggesting heightened susceptibility to triclosan among males. https://doi.org/10.1289/EHP16710.

Background: Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child's ability to generate a well-regulated, protective immune response. T-cells coordinate with all immune cell types to orchestrate both cellular and antibody-mediated responses. While there is compelling evidence that PFAS alters immunity in humans, the specific effects of early life PFAS exposure on infant T-cell development are unreported. Because of their central role in immunity, altered T-cell development in infants would have implications on immune responses broadly and long-term.

Objectives: We seek to model longitudinal changes in the frequency of functionally distinct CD4+ T-cell subpopulations from birth through 12 months and their association with in-utero PFAS exposure.

Methods: Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant's first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, PFHXS and PFDA) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n=200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and pre-pregnancy body mass index.

Results: In-utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T-follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log₂-unit increase in PFOS was associated with lower Tfh [0.17% (95%CI: -0.30, -0.40)] and greater Th2 [0.27% (95%CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, PFHXS and PFDA. TEXT.

Discussion: Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated, protective immunity. Future studies into the role of PFAS-associated T-cell distribution and risk of adverse immune-related health outcomes in children are warranted. https://doi.org/10.1289/EHP16726.

Background: The field of environmental health sciences increasingly demands comprehensive and diverse datasets, particularly in response to emerging research areas such as climate change, mixtures, and exposomics. The data needed to address the complexity of environmental health research questions often extend beyond the boundaries of a single study or data resource. Traditional data management approaches struggle to harmonize the ever-expanding and heterogeneous data sources needed for research in the environmental health sciences. Harmonization may help address this issue as it involves aligning and standardizing various elements of data to allow comprehensive analysis, data pooling and interpretation across studies.

Objectives: The primary objective is to inform researchers about the transformative potential of embracing harmonization methodologies and to motivate contributions to ongoing efforts, thereby fostering advancements.

Methods: Using the Environmental Health Language Collaborative's Data Harmonization Use Case, we provide a practical illustration of existing data harmonization approaches, identify gaps, and emphasize future research and application directions. We selected two publicly available environmental epidemiology studies on the topic of childhood asthma and three studies on the topic of biomarkers of metals exposure during pregnancy and birth outcomes and applied several existing harmonization approaches to assess interoperability.

Discussion: Our process revealed the potential limitations of many existing harmonization approaches, with notable failures to identify common variables across independent datasets and lack of agreement between human and computer-based approaches. This use case identified various challenges with existing approaches, including reliance on often incomplete data documentation and large amounts of manual effort. To address these challenges, we recommend the continued advancement and dissemination of community data standards, the development of software and tools to facilitate harmonization through automation, and strategic efforts to promote engagement in data harmonization within the environmental health sciences community. Collaborative science is needed to advance our understanding of environmental contributors to health, and realizing the harmonization potential of our scientific data is a step toward improved collaboration. https://doi.org/10.1289/EHP15410.

Background: China is an important producer and consumer of per- and polyfluoroalkyl substances (PFAS), but there is limited understanding of longitudinal trends of PFAS in Chinese people.

Objectives: This study investigated decadal trends in PFAS and potential sources of exposure in the Dongfeng-Tongji cohort of Chinese people and explored potential misclassification bias.

Methods: We repeatedly measured serum PFAS (containing 11 perfluorocarboxylic acids (PFCAs), 9 perfluorosulfonic acids (PFSAs), 6 PFAS precursors, and 4 PFAS alternatives) in 648 samples (collected in 2008, 2013, and 2018) from 216 Chinese residents in Hubei Province. We used linear mixed effect model to examine trends in PFAS concentrations over survey time. We also assessed the potential exposure sources of PFAS using principal component analysis-multiple linear regression (PCA-MLR) model.

Results: Eleven PFAS were detected in at least 80% of the population, PFOS, PFOA, and 6:2CL-PFESA being the predominant PFAS. We found a slight decrease in linear-PFOS during the 10-year period; at the same time, the levels of PFOA doubled and the detection rate of short-chain PFCAs (PFBA, PFHpA) rose. 6:2CL-PFESA (China specific PFAS alternative) remained high for a decade. Similar correlation trends between PFAS were observed at three timepoints. Comparison of our findings with those from other studies suggests the study population was exposed to three potential sources of contamination, which may represent ingestion of contaminated diets, long-range transport of atmospheric PFAS, and exposures acquired from dust, drinking water, and daily commodities. We found that serum PFAS measurement at on timepoint was similar to levels over a 5-year period but not a 10-year period.

Discussion: Our study provides information on serum PFAS levels in Chinese retired workers in the Dongfeng-Tongji cohort, and highlights that the risk of exposure to novel PFCAs and PFAS alternatives deserves continued attention. For longitudinal studies with long-term follow-up (e.g. more than 5 years), relying only on a single baseline serum PFAS level may generate misclassification bias resulting in expected bias towards the null and affect the estimation of health effects. https://doi.org/10.1289/EHP15340.

Background: Toxicology in the 21^st Century (Tox21) assay data provide a valuable resource for the prediction of in vivo toxicity using machine learning models. However, the performances of these models previously developed using the pre-existing Tox21 assay data were less than ideal, likely due to insufficient coverage of the biological response space by the assay targets.

Objectives: This study aimed to assess whether expanding the Tox21 portfolio with new assays that probe under-represented targets/pathways related to unanticipated adverse drug effects could improve the predictive capacity of in vitro assay data for in vivo toxicity such as drug induced liver injury (DILI) and cardiotoxicity (DICT).

Methods: Models were constructed using data from the pre-existing panel of 36 assay targets and the expanded panel of 49 assay targets. A feature selection approach was used to determine the optimal number of assays needed for each model. The models were then applied to predict the potential hepatotoxicity and cardiotoxicity of compounds in the Tox21 10K compound library.

Results: For both DILI and DICT prediction, the best-performing models developed using the expanded assay panel required a smaller number of assays to achieve the same level of performance compared to those based on the pre-existing assays. Models constructed by combining both assay data (pre-existing + expanded) and chemical structure consistently outperformed those constructed based on assay data alone, but showed similar performance to those constructed based on chemical structure. The compounds predicted to have the highest toxic potential were experimentally verified to demonstrate the effectiveness of our models in identifying new potentially toxic compounds.

Discussion: The expansion of the Tox21 assay panel has significantly enhanced the predictive capacity of assay data for predicting DILI and DICT potential. This improvement underscores the importance of a diverse and comprehensive in vitro assay portfolio in advancing safety assessment. https://doi.org/10.1289/EHP16190.

Background: Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear.

Objective: To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, paternal quitting before pregnancy).

Methods: We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array.

Results: Maternal sustained smoking associated with differential DNA methylation (false discovery rate [FDR] <0.05) at 8,862 CpGs on the 450K (n=8,148) and did not differ by infant sex. We identified over 300 novel genes not previously identified in EWAS of smoking. No differential methylation was associated with maternal SHS, maternal former smoking, or paternal smoking around conception. However, cg24805739 (MED13L) was associated with paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n=3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues.

Conclusions: Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking and paternal smoking. https://doi.org/10.1289/EHP16303.

Background: Exposure to the ambient air pollutant ozone (O₃) is associated with adverse respiratory health outcomes. Rodent models have been used to identify mechanisms of response to O₃ but their utility has been questioned owing to species differences in physiologic response, most notably exposure-induced hypothermia, which renders rodents relatively resistant to O₃ compared to humans.

Objectives: First, to test whether a recombinant inbred mouse strain from the Collaborative Cross population, CC002/Unc, provides a sensitive model of ozone response by benchmarking it to the most commonly used inbred strain, C57BL/6J. Second, to identify the genetic basis of CC002/Unc's sensitivity.

Methods: We examined the responses of CC002/Unc and C57BL/6J mice to either acute (0.4 or 0.8 ppm O₃ x 4 hours) or repeated (0.8 ppm O₃ x 4 hours/day x 3 or 9 weekdays) O₃ exposure. Then, we mapped quantitative trait loci (QTL) for responses to 9 days of O₃ in a CC002/Unc x CC005/TauUnc (O₃-resistant) backcross population.

Results: CC002/Unc was far more responsive to acute O₃ than C57BL/6J, exhibiting significant inflammation following a single 0.4 ppm O₃ exposure and greater inflammation and injury after 0.8 ppm O₃. Enhanced sensitivity of CC002/Unc mice was associated with decreased breathing frequency and diminished hypothermic responses. Following repeated exposure, C57BL/6J lungs appeared normal, while CC002/Unc lungs had eosinophilic inflammation and centriacinar fibrosis. We identified five QTLs for airway eosinophilia, including a large-effect QTL on chromosome 11 that accounted for 18% of phenotypic variation and contains genes with plausible links to aberrant immune responses.

Discussion: The CC002/Unc strain provides an improved model to study the effects of acute and repeated O₃ exposure due to its enhanced sensitivity vs. C57BL/6J and more human-like thermoregulatory response. Further genetic analysis to pinpoint causal genes underlying CC002/Unc's susceptibility will provide new insights into mechanisms of O₃-induced lung disease. https://doi.org/10.1289/EHP15745.

Background: Several drinking water contaminants are known or suspected carcinogens; however, there are only a few investigations of drinking water exposures and ovarian cancer. We evaluated associations between regulated contaminants in community water systems (CWS) and ovarian cancer risk in the California Teachers Study, a prospective cohort of female California educators.

Methods: Participants were cancer-free, without bilateral oophorectomy, living in California at baseline (1995-1996) with geocoded addresses linked to a CWS (N=91,127, 92%), with follow-up through 2020 (mean=19.0 years). Among participants with a residential duration at enrollment of at least 10 years, we computed 15-year (1990-2005) averages of log2-transformed arsenic, nitrate, total trihalomethanes (TTHM) (N=59,881), and uranium concentrations (N=56,314). We estimated hazard ratios (HRs, 95% CIs) for all epithelial ovarian cancers (n=424) and the high-grade serous histotype (n=203), using Cox proportional hazards regression, adjusting for age, body mass index, menopause status, oral contraceptive use, and parity. We evaluated the mixture effect (per IQR in log2 concentrations), using quantile-based g-computation.

Results: Almost all women (>99%) had average exposures below regulatory limits for all contaminants. In single contaminant analyses, a doubling in average uranium concentrations was associated with all ovarian cancer (HR_perlog2=1.09, CI 1.02-1.16), whereas a doubling in nitrate was associated with the high-grade serous histotype (HR_perlog2=1.09, CI 1.02-1.17). Findings were similar in models adjusted for other contaminants. We observed positive but imprecise associations for arsenic and TTHM in single-contaminant and contaminant-adjusted analyses. HRs per increase in the mixture were 1.39 (1.00, 1.94) and 1.75 (1.09, 2.83), for all ovarian cancer and the high-grade serous histotype, respectively. Uranium was the largest contributor (55%) to the mixture effect for all ovarian cancer, and nitrate was the largest contributor (46%) for the high-grade serous histotype.

Conclusions: Novel associations between drinking water contaminants and ovarian cancer risk at levels below regulatory limits warrant further investigation. https://doi.org/10.1289/EHP16582.