Background: The chemical exposome includes exposure to numerous environmental and endogenous molecules, many of which have been linked to reproductive outcomes due to their endocrine-disrupting properties. As several breast cancer risk factors, including age and parity, are related to reproduction, it is imperative to investigate the interplay between such factors and the chemical exposome prior to conducting large scale exposome-based breast cancer studies.
Objective: This pilot study aimed to provide an overview of the chemical exposome in plasma samples from healthy women and identify associations between environmental exposures and three risk factors for breast cancer: age, parity, and age at menarche.
Material and methods: Plasma samples (n = 161), were selected based on reproductive history from 100 women participating in the Northern Sweden Health and Disease Study, between 1987 and 2006. Samples were analyzed by liquid chromatography high-resolution mass spectrometry (LC-HRMS) for 77 priority target analytes including contaminants and hormones, with simultaneous untargeted profiling of the chemical exposome and metabolome. Linear mixed effects models were applied to test associations between risk factors and chemical levels.
Results: Fifty-five target analytes were detected in at least one individual and over 94,000 untargeted features were detected across all samples. Among untargeted features, 430 could be annotated and were broadly classified as environmental (246), endogenous (167) or ambiguous (17). Applying mixed effect models to features detected in at least 70% of the samples (16,778), we found seven targeted analytes (including caffeine and various per- and poly-fluoroalkyl substances) and 38 untargeted features, positively associated with age. The directionality of these associations reversed for parity, decreasing with increasing births. Seven separate targeted analytes were associated with age at menarche.
Significance: This study demonstrates how a comprehensive chemical exposome approach can be used to inform future research prioritization regarding associations between known and unknown substances, reproduction, and breast cancer risk.
Impact statement: This study illustrates how chemical exposomics of long-term stored blood samples offers valuable insights to discover chemical exposures and their potential links to disease in humans, particularly those related to reproduction and breast cancer risk factors.
Background: Lead exposure remains a key problem for children during development. One treatment for lead poisoning is chelation - a topic that remains controversial with varied results. Bone lead serves as a marker of total body burden of lead and encompasses between 60-90% of lead storage in children.
Objective: In this study, we aimed to identify the change in bone lead as a result of chelation therapy in a group of lead poisoned children (blood lead >25 µg/dL).
Methods: Upon diagnosis with lead poisoning at Xinhua Hospital in Shanghai, China, children were recruited to our study, had their bone lead levels measured, and underwent one-week of intravenous, in-patient ethylenediaminetetraacetic acid chelation treatment. Up to three clinical visits with the same treatment protocol and bone lead measurements were completed over the two-year study. We measured biomarkers of lead exposure for children exposed via various potential sources, including home contaminants, local industrial emissions, traditional medicines, or lead cookware.
Results: We observed significant differences with bone lead after chelation therapy (p < 0.0001), even after calculating a conservative model for theoretical decay from known bone turnover (p = 0.01). The difference identified between our observed change in bone lead and literature established bone lead change significantly increased with more chelation treatments. A significant reduction in bone lead was observed following chelation treatment of children with lead poisoning - a difference that increased more with more chelation.
Significance: Study results indicate that chelation treatment is effective in reducing bone lead stores in children with initial blood lead levels greater than 25 µg/dL.
Impact statement: Lead exposure in children is a consistent problem - drastically impacting health across the life span. After exposure, lead stores in the bone of children serving as a potential endogenous source of exposure for years to decades. Our study demonstrated that chelation therapy, while reducing blood lead levels, additionally reduced bone lead levels. A reduction in bone lead would effectively reduce the potential for endogenous release of lead and restrict the damage done by lead exposure.
Background: Prenatal air pollution (AP) exposure has been linked to postpartum psychological functioning, impacting health outcomes in both women and children. Extant studies primarily focused on individual pollutants.
Objective: To assess the association between prenatal exposure to a mixture of seven AP components and postpartum psychological functioning using daily exposure data and data-driven statistical methods.
Methods: Analyses included 981 women recruited at 24.0 ± 9.9 weeks gestation and followed longitudinally. We estimated prenatal daily exposure levels for constituents of fine particles [elemental carbon (EC), organic carbon (OC), nitrate (NO3-), sulfate (SO42-), ammonium (NH4+)], nitrogen dioxide (NO2), and ozone (O3) using validated global 3-D chemical-transport models and satellite-based hybrid models based on residential addresses. Edinburgh Postnatal Depression Scale (EPDS) was administered to participants to derive a total EPDS score and the subconstruct scores for anhedonia and depressive symptoms. A distributed lag model (DLM) was employed within Bayesian Kernel Machine Regression (BKMR) to develop time-weighted exposure profile for each pollutant. These exposures were then input into a Weighted Quantile Sum (WQS) regression to estimate an overall mixture effect, adjusted for maternal age, education, race/ethnicity, season of delivery, and delivery year. Effect modification by race/ethnicity and fetal sex was also examined.
Results: Women were primarily Hispanic (51%) and Black (32%) reporting ≤12 years of education (58%). Prenatal exposure to an AP mixture was significantly associated with increased anhedonia subscale z-scores, particularly in Hispanics (β = 0.07, 95%CI = 0.004-0.13, per unit increase in WQS index). It was also borderline associated with increased total EPDS (β = 0.11, 95%CI = 0.00-0.22) and depressive symptom subscale (β = 0.09, 95%CI = -0.02 to 0.19) z-scores, particularly among Hispanic women who gave birth to a male infant. Sulfate (SO42-), O3 and OC were major contributors to these associations.
Impact: This study utilizes an advanced data-driven approach to examine the temporally- and mixture-weighted effects of prenatal air pollution exposure on postpartum psychological functioning. We found that exposure to a prenatal air pollution mixture predicted poorer postpartum psychological functioning, particularly anhedonia symptoms in Hispanic women. Findings underscore the importance of considering both exposure mixtures as well as potential modifying factors to better help identify particular pollutants that drive effects and susceptible populations, which can inform more effective intervention strategies.
Background: Knowledge of relationships between tropospheric ozone and mental and developmental health outcomes is currently inconclusive, with the largest knowledge gaps for children. This gap is important to address as evidence suggests that climate change will worsen ozone pollution.
Objective: We examine the association of average ozone exposure during the preconception period, and first, second and third trimesters of pregnancy on the odds of intellectual disability (ID) in Utah children.
Methods: For the period of 2002-2020, we assembled daily, tract-level ozone concentration data, data on ID case status, and data on cases' full siblings and population controls. We analyzed the data using generalized estimating equations.
Results: Ozone was positively associated with the odds of ID in cases vs. their siblings (in the preconception, first, second and third trimester exposure windows, all p < 0.05, n = 1042) and vs. population controls (only in the second trimester exposure window, p < 0.05, n = 5179). The strength of the association was largest during the second trimester in both analyses. A second trimester average ozone level increase of 10 ppb was associated with a 55.3% increase in the odds of ID relative to full siblings (95% confidence interval [CI]: 1.171-2.058) and a 22.8% increase in the odds of ID relative to population controls (CI: 1.054-1.431). Findings were robust to different subsets of sibling controls as well as several sensitivity analyses.
Significance: Results document that ozone has a measurable relationship with children's cognitive development in Utah.
Impact statement: Evidence suggests that climate change will worsen ozone pollution. The potential amplifying effect of climate change on ozone is more certain than it is for fine particulate matter. This means that ozone and health research will remain relevant into the future. Currently, several systematic reviews and meta-analyses have concluded that knowledge about ozone and cognitive health is insufficient, especially for children. Using two different study designs, we find that prenatal ozone exposure is associated with risk of intellectual disability in children.
Exposure science plays an essential role in the U.S. Environmental Protection Agency's (U.S. EPA) mission to protect human health and the environment. The U.S. EPA's Center for Public Health and Environmental Assessment (CPHEA) within the Office of Research and Development (ORD) provides the exposure science needed to characterize the multifaceted relationships between people and their surroundings in support of national, regional, local and individual-level actions. Furthermore, exposure science research must position its enterprise to tackle the most pressing public health challenges in an ever-changing environment. These challenges include understanding and confronting complex human disease etiologies, disparities in the social environment, and system-level changes in the physical environment. Solutions will sustainably balance and optimize the health of people, animals, and ecosystems. Our objectives for this paper are to review the role of CPHEA exposure science research in various recent decision-making contexts, to present current challenges facing U.S. EPA and the larger exposure science field, and to provide illustrative case examples where CPHEA exposure science is demonstrating the latest methodologies at the intersection of these two motivations. This blueprint provides a foundation for applying exposomic tools and approaches to holistically understand real-world exposures so optimal environmental public health protective actions can be realized within the broader context of a One Health framework. IMPACT STATEMENT: The U.S. EPA's Center for Public Health and Environmental Assessment exposure research priorities reside at the intersection of environmental decision contexts and broad public health challenges. The blueprint provides a foundation for advancing the tools and approaches to holistically understand real-world exposures so optimal environmental protection actions can be realized. A One Health lens can help shape exposure research for maximum impact to support solutions that are transdisciplinary and must engage multiple sectors.
Background: Exposure to ambient air pollution is associated with morbidity and mortality, making it an important public health concern. Emissions from motorized traffic are a common source of air pollution but evaluating the contribution of traffic-related air pollution (TRAP) emissions to health risks is challenging because it is difficult to disentangle the contribution of individual air pollution sources to exposure contrasts in an epidemiological study.
Objective: This paper describes a new framework to identify whether air pollution differences reflect contrasts in TRAP exposures. Because no commonly measured pollutant is entirely specific to on-road motor vehicles, this exposure framework combined information on pollutants, spatial scale (i.e., geographic extent), and exposure assessment methods and their spatial scale to determine whether the estimated effect of air pollution in a given study was related to differences in TRAP.
Methods: The exposure framework extended beyond the near-road environment to include differences in exposure to TRAP at neighborhood resolution ( ≤ 5 km) across urban, regional, and national scales. It also embedded a stricter set of criteria to identify studies that provided the strongest evidence that exposure contrasts were related to differences in traffic emissions.
Results: Application of the framework to the transparent selection of epidemiological studies for a systematic review produced insights on assessing and improving comparability of TRAP exposure measures, particularly for indirect measures such as distances from roads. It also highlighted study design challenges related to the duration of measurements and the structure of epidemiological models.
Impact statement: This manuscript describes a new exposure framework to identify studies of traffic-related air pollution, a case study of its application in an HEI systematic review, and its implications for exposure science and air pollution epidemiology experts. It identifies challenges and provides recommendations for the field going forward. It is important to bring this information to the attention of researchers in air pollution exposure science and epidemiology because applying the broader lessons learned will improve the conduct and reporting of studies going forward.
Background: Cooking-related emissions contribute to air pollutants in the home and may influence children's health outcomes.
Objective: In this pilot study, we investigate the effects of a cooking ventilation intervention in homes with gas stoves, including a video-based educational intervention and range hood replacement (when needed) in children's homes.
Methods: This was a pilot (n = 14), before-after trial (clinicaltrials.gov #NCT04464720) in homes in the San Francisco Bay Area that had a school-aged child, a gas stove, and either a venting range hood or over-the-range microwave/hood. Cooking events, ventilation use, and indoor air pollution were measured in homes for 2-4 weeks, and children completed respiratory assessments. Midway, families received this intervention: (1) education about the hazards of cooking-related pollutants and benefits of both switching to back burners and using the range hood whenever cooking and (2) ensuring the range hood met airflow and sound performance standards. The educational intervention was delivered via a video developed in conjunction with local youth.
Results: We found substantially increased use of back burners and slight increases in range hood use during cooking after intervening. Even though there was no change in cooking frequency or duration, these behavior changes resulted in decreases in nitrogen dioxide (NO2), including significant decreases in the total integrated concentration of NO2 over all cooking events from 1230 ppb*min (IQR 336, 7861) to 756 (IQR 84.0, 4210; p < 0.05) and NO2 collected on samplers over the entire pre- and post-intervention intervals from 10.4 ppb (IQR 3.5, 47.5) to 9.4 (IQR 3.0, 36.1; p < 0.005). There were smaller changes in PM2.5, and no changes were seen in respiratory outcomes.
Impact: This pilot before-after trial evaluated the use of a four-minute educational video to improve cooking ventilation in homes with gas stoves and one or more school-aged children. Participant behavior changed after watching the video, and there were decreases in indoor air pollutant concentrations in the home, some of which were significant. This brief video is now publicly available in English and Spanish (wspehsu.ucsf.edu/projects/indoor-air-quality), and this provides suggestive evidence of the utility of this simple intervention, which could be particularly beneficial for households that have children with asthma.