Implications of Insecticide-Treated Mosquito Net Fishing in Lower Income Countries

Introduction: Insecticide-treated mosquito nets (ITNs) are highly effective for the control of malaria. Yet widely distributed ITNs have been repurposed as fishing nets throughout the world.Objectives: Herein we present a synthesis of the current knowledge of ITN fishing and the toxicity of pyrethroids and discuss the potential implications of widespread fishing with ITNs. We further review effective management strategies in tropical fisheries to explore a framework for managing potential ITN fishing impacts.Discussion: Pyrethroids are toxic to fish and aquatic environments, and fishing with ITNs may endanger the health of fisheries. Furthermore, although human toxicity to the pyrethroid insecticides that impregnate ITNs is traditionally thought to be low, recent scientific advances have shown that pyrethroid exposure is associated with a host of human health issues, including neurocognitive developmental disorders, diabetes, and cardiovascular disease. Although it is known that ITN fishing is widespread, the implications for both fisheries and human communities is understudied and may be severe. https://doi.org/10.1289/EHP7001     

The Applications of Implementation Science in Water,Sanitation, and Hygiene (WASH) Research and Practice

Background: Delivery of high quality, at-scale, and sustained services is a major challenge in the water, sanitation, and hygiene (WASH) sector, made more challenging by a dearth of evidence-based models for adaption across contexts in low- and middle-income countries.Objective: We aim to describe the value of implementation science (IS) for the WASH sector and provide recommendations for its application.Methods: We review concepts from the growing field of IS—defined as the “scientific study of methods to promote the systematic uptake of research findings and other evidence-based practices into routine practice, and hence, to improve the quality and effectiveness of health services”—and we translate their relevance to WASH research, learning, and delivery.Discussion: IS provides a suite of methods and theories to systematically develop, evaluate, and scale evidence-based interventions. Though IS thinking has been applied most notably in health services delivery in high-income countries, there have been applications in low-income settings in fields such as HIV/AIDS and nutrition. Expanding the application of IS to environmental health, specifically WASH interventions, would respond to the complexity of sustainable service delivery. WASH researchers may want to consider applying IS guidelines to their work, including adapting pragmatic research models, using established IS frameworks, and cocreating knowledge with local stakeholders. https://doi.org/10.1289/EHP7762     

Participatory Research for Environmental Justice: A Critical Interpretive Synthesis

Background: Environmental health risks are disproportionately colocated with communities in poverty and communities of color. In some cases, participatory research projects have effectively addressed structural causes of health risk in environmental justice (EJ) communities. However, many such projects fail to catalyze change at a structural level.Objectives: This review employs Critical Interpretive Synthesis (CIS) to theorize specific elements of participatory research for environmental health that effectively prompt structural change in EJ communities.Methods: Academic database search was used to identify peer-reviewed literature describing participatory research with EJ communities to address environmental health. Synthetic constructs were developed iteratively related to study characteristics, design elements, and outcomes; and data were extracted for included records. Statistical analyses were performed to assess correlations between study design elements and structural change outcomes. Through critical, comparative, and contextual analyses of the “structural change” case study group and “non- structural change” group, informed by relevant theoretical literature, a synthesizing argument was generated.Results: From 505 total records identified, eligibility screening produced 232 case study articles, representing 154 case studies, and 55 theoretical articles for synthesis. Twenty-six case studies resulted in a structural change outcome. The synthesizing argument states that participatory research with EJ communities may be more likely to result in structural change when a) community members hold formal leadership roles; b) project design includes decision-makers and policy goals; and c) long term partnerships are sustained through multiple funding mechanisms. The assumption of EJ community benefit through research participation is critically examined.Discussion: Recommended future directions include establishing structural change as a goal of participatory research, employing participatory assessment of community benefit, and increased hiring of faculty of color at research institutions. The power, privilege, and political influence that academic institutions are able to leverage in partnership with EJ communities may be as valuable as the research itself. https://doi.org/10.1289/EHP6274     

Occurrence of Lead and Other Toxic Metals Derived from Drinking-Water Systems in Three West African Countries

Background: Exposure to toxic metals (TMs) such as lead can cause lifelong neurodevelopmental impairment and other adverse outcomes. TMs enter drinking water from human activity, geogenic contamination, and corrosion of water system components. Several studies report TM contamination in piped systems and private wells in high-income countries (HICs). However, few robust studies report on TM contamination in low- and middle-income countries (LMICs).Objectives: We characterized the occurrence and investigated sources of TM contamination in 261 rural water systems in three West African LMICs to inform prevention and management.Methods: Water samples were collected from 261 community water systems (handpumps and public taps) across rural Ghana, Mali, and Niger. Scrapings were collected from accessible components of a subset of these systems using a drill with acid-washed diamond-tipped bits. Samples were analyzed by inductively coupled plasma (ICP) mass spectrometry or ICP optical emission spectroscopy.Results: Of the TMs studied, lead most frequently occurred at levels of concern in sampled water system components and water samples. Lead mass fractions exceeded International Plumbing Code (IPC) recommended limits (0.25% wt/wt) for components in 82% (107/130) of systems tested; brass components proved most problematic, with 72% (26/36) exceeding IPC limits. Presence of a brass component in a water system increased expected lead concentrations in drinking-water samples by 3.8 times. Overall, lead exceeded World Health Organization (WHO) guideline values in 9% (24/261) of drinking-water samples across countries; these results are broadly comparable to results observed in many HICs. Results did not vary significantly by geography or system type.Discussion: Ensuring use of lead-free (<0.25%) components in new water systems and progressively remediating existing systems could reduce drinking-water lead exposures and improve health outcomes for millions. However, reflexive decommissioning of existing systems may deprive users of sufficient water for health or drive them to riskier sources. Because supply chains for many water system components are global, TM monitoring, prevention, and management may be warranted in other LMICs beyond the study area as well. https://doi.org/10.1289/EHP7804     

Quantitative Microbial Risk Assessment for Contaminated Private Wells in the Fractured Dolomite Aquifer of Kewaunee County,Wisconsin

Background: Private wells are an important source of drinking water in Kewaunee County, Wisconsin. Due to the region’s fractured dolomite aquifer, these wells are vulnerable to contamination by human and zoonotic gastrointestinal pathogens originating from land-applied cattle manure and private septic systems.Objective: We determined the magnitude of the health burden associated with contamination of private wells in Kewaunee County by feces-borne gastrointestinal pathogens.Methods: This study used data from a year-long countywide pathogen occurrence study as inputs into a quantitative microbial risk assessment (QMRA) to predict the total cases of acute gastrointestinal illness (AGI) caused by private well contamination in the county. Microbial source tracking was used to associate predicted cases of illness with bovine, human, or unknown fecal sources.Results: Results suggest that private well contamination could be responsible for as many as 301 AGI cases per year in Kewaunee County, and that 230 and 12 cases per year were associated with a bovine and human fecal source, respectively. Furthermore, Cryptosporidium parvum was predicted to cause 190 cases per year, the most out of all 8 pathogens included in the QMRA.Discussion: This study has important implications for land use and water resource management in Kewaunee County and informs the public health impacts of consuming drinking water produced in other similarly vulnerable hydrogeological settings. https://doi.org/10.1289/EHP7815     

Confronting Racism in Environmental Health Sciences: Moving the Science Forward for Eliminating Racial Inequities

Background: The twin pandemics of COVID-19 and systemic racism during 2020 have forced a conversation across many segments of our society, including the environmental health sciences (EHS) research community. We have seen the proliferation of statements of solidarity with the Black Lives Matter movement and commitments to fight racism and health inequities from academia, nonprofit organizations, governmental agencies, and private corporations. Actions must now arise from these promises. As public health and EHS scientists, we must examine the systems that produce and perpetuate inequities in exposure to environmental pollutants and associated health effects.Objectives: We outline five recommendations the EHS research community can implement to confront racism and move our science forward for eliminating racial inequities in environmental health.Discussion: Race is best considered a political label that promotes inequality. Thus, we should be wary of equating race with biology. Further, EHS researchers should seriously consider racism as a plausible explanation of racial disparities in health and consider structural racism as a factor in environmental health risk/impact assessments, as well as multiple explanations for racial differences in environmental exposures and health outcomes. Last, the EHS research community should develop metrics to measure racism and a set of guidelines on the use and interpretation of race and ethnicity within the environmental sciences. Numerous guidelines exist in other disciplines that can serve as models. By taking action on each of these recommendations, we can make significant progress toward eliminating racial disparities. https://doi.org/10.1289/EHP8186     

Developing a Flexible National Wastewater Surveillance System for COVID-19 and Beyond

Background: Wastewater testing offers a cost-effective strategy for measuring population disease prevalence and health behaviors. For COVID-19, wastewater surveillance addresses testing gaps and provides an early warning for outbreaks. As U.S. federal agencies build a National Wastewater Surveillance System around the pandemic, thinking through ways to develop flexible frameworks for wastewater sampling, testing, and reporting can avoid unnecessary system overhauls for future infectious disease, chronic disease, and drug epidemics.Objectives: We discuss ways to transform a historically academic exercise into a tool for epidemic response. We generalize lessons learned by a global network of wastewater researchers around validation and implementation for COVID-19 and opioids while also drawing on our experience with wastewater-based epidemiology in the United States.Discussion: Sustainable wastewater surveillance requires coordination between health and safety officials, utilities, labs, and researchers. Adapting sampling frequency, type, and location to threat level, community vulnerability, biomarker properties, and decisions that wastewater data will inform can increase the practical value of the data. Marketplace instabilities, coupled with a fragmented testing landscape due to specialization, may require officials to engage multiple labs to test for known and unknown threats. Government funding can stabilize the market, balancing commercial pressures with public good, and incentivize data sharing. When reporting results, standardizing metrics and contextualizing wastewater data with health resource data can provide insights into a community’s vulnerability and identify strategies to prevent health care systems from being overwhelmed. If wastewater data will inform policy decisions for an entire community, comparing characteristics of the wastewater treatment plant’s service population to those of the larger community can help determine whether the wastewater data are generalizable. Ethical protocols may be needed to protect privacy and avoid stigmatization. With data-driven approaches to sample collection, analysis, and interpretation, officials can use wastewater surveillance for adaptive resource allocation, pandemic management, and program evaluation. https://doi.org/10.1289/EHP8572     

COVID-19, the Built Environment,and Health

Background: Since the dawn of cities, the built environment has both affected infectious disease transmission and evolved in response to infectious diseases. COVID-19 illustrates both dynamics. The pandemic presented an opportunity to implement health promotion and disease prevention strategies in numerous elements of the built environment.Objectives: This commentary aims to identify features of the built environment that affect the risk of COVID-19 as well as to identify elements of the pandemic response with implications for the built environment (and, therefore, for long-term public health).Discussion: Built environment risk factors for COVID-19 transmission include crowding, poverty, and racism (as they manifest in housing and neighborhood features), poor indoor air circulation, and ambient air pollution. Potential long-term implications of COVID-19 for the built environment include changes in building design, increased teleworking, reconfigured streets, changing modes of travel, provision of parks and greenspace, and population shifts out of urban centers. Although it is too early to predict with confidence which of these responses may persist, identifying and monitoring them can help health professionals, architects, urban planners, and decision makers, as well as members of the public, optimize healthy built environments during and after recovery from the pandemic. https://doi.org/10.1289/EHP8888     

Knowledge Organization Systems for Systematic Chemical Assessments

Background: Although the implementation of systematic review and evidence mapping methods stands to improve the transparency and accuracy of chemical assessments, they also accentuate the challenges that assessors face in ensuring they have located and included all the evidence that is relevant to evaluating the potential health effects an exposure might be causing. This challenge of information retrieval can be characterized in terms of “semantic” and “conceptual” factors that render chemical assessments vulnerable to the streetlight effect.Objectives: This commentary presents how controlled vocabularies, thesauruses, and ontologies contribute to overcoming the streetlight effect in information retrieval, making up the key components of Knowledge Organization Systems (KOSs) that enable more systematic access to assessment-relevant information than is currently achievable. The concept of Adverse Outcome Pathways is used to illustrate what a general KOS for use in chemical assessment could look like.Discussion: Ontologies are an underexploited element of effective knowledge organization in the environmental health sciences. Agreeing on and implementing ontologies in chemical assessment is a complex but tractable process with four fundamental steps. Successful implementation of ontologies would not only make currently fragmented information about health risks from chemical exposures vastly more accessible, it could ultimately enable computational methods for chemical assessment that can take advantage of the full richness of data described in natural language in primary studies. https://doi.org/10.1289/EHP6994     

Development and Evaluation of a Holistic and Mechanistic Modeling Framework for Chemical Emissions,Fate, Exposure,and Risk

Background: Large numbers of chemicals require evaluation to determine if their production and use pose potential risks to ecological and human health. For most chemicals, the inadequacy and uncertainty of chemical-specific data severely limit the application of exposure- and risk-based methods for screening-level assessments, priority setting, and effective management.Objective: We developed and evaluated a holistic, mechanistic modeling framework for ecological and human health assessments to support the safe and sustainable production, use, and disposal of organic chemicals.Methods: We consolidated various models for simulating the PROduction-To-EXposure (PROTEX) continuum with empirical data sets and models for predicting chemical property and use function information to enable high-throughput (HT) exposure and risk estimation. The new PROTEX-HT framework calculates exposure and risk by integrating mechanistic computational modules describing chemical behavior and fate in the socioeconomic system (i.e., life cycle emissions), natural and indoor environments, various ecological receptors, and humans. PROTEX-HT requires only molecular structure and chemical tonnage (i.e., annual production or consumption volume) as input information. We evaluated the PROTEX-HT framework using 95 organic chemicals commercialized in the United States and demonstrated its application in various exposure and risk assessment contexts.Results: Seventy-nine percent and 97% of the PROTEX-HT human exposure predictions were within one and two orders of magnitude, respectively, of independent human exposure estimates inferred from biomonitoring data. PROTEX-HT supported screening and ranking chemicals based on various exposure and risk metrics, setting chemical-specific maximum allowable tonnage based on user-defined toxicological thresholds, and identifying the most relevant emission sources, environmental media, and exposure routes of concern in the PROTEX continuum. The case study shows that high chemical tonnage did not necessarily result in high exposure or health risks.Conclusion: Requiring only two chemical-specific pieces of information, PROTEX-HT enables efficient screening-level evaluations of existing and premanufacture chemicals in various exposure- and risk-based contexts. https://doi.org/10.1289/EHP9372     

Inequalities in Public Water Arsenic Concentrations in Counties and Community Water Systems across the United States, 2006–2011

Background: In the United States, nationwide estimates of public drinking water arsenic exposure are not readily available. We used the U.S. Environmental Protection Agency’s (EPA) Six-Year Review contaminant occurrence data set to estimate public water arsenic exposure. We compared community water system (CWS) arsenic concentrations during 2006–2008 vs. after 2009–2011, the initial monitoring period for compliance with the U.S. EPA’s 10μg/L arsenic maximum contaminant level (MCL).Objective: Our objective was to characterize potential inequalities in CWS arsenic exposure over time and across sociodemographic subgroups.Methods: We estimated 3-y average arsenic concentrations for 36,406 CWSs (98%) and 2,740 counties (87%) and compared differences in means and quantiles of water arsenic (via quantile regression) between both 3-y periods for U.S. regions and sociodemographic subgroups. We assigned CWSs and counties MCL compliance categories (High if above the MCL; Low if below) for each 3-y period.Results: From 2006–2008 to 2009–2011, mean and 95th percentile CWS arsenic (in micrograms per liter) declined by 10.3% (95% CI: 6.5%, 14.1%) and 11.5% (8.3%, 14.8%) nationwide, by 11.4% (4.7%, 18.1%) and 16.3% (8.1%, 24.5%) for the Southwest, and by 36.8% (7.4%, 66.1%) and 26.5% (12.1%, 40.8%) for New England, respectively. CWSs in the High/High compliance category (not MCL compliant) were more likely in the Southwest (61.1%), served by groundwater (94.7%), serving smaller populations (mean 1,102 persons), and serving Hispanic communities (38.3%).Discussion: Larger absolute declines in CWS arsenic concentrations at higher water arsenic quantiles indicate declines are related to MCL implementation. CWSs reliant on groundwater, serving smaller populations, located in the Southwest, and serving Hispanic communities were more likely to continue exceeding the arsenic MCL, raising environmental justice concerns. These estimates of public drinking water arsenic exposure can enable further surveillance and epidemiologic research, including assessing whether differential declines in water arsenic exposure resulted in differential declines in arsenic-associated disease. https://doi.org/10.1289/EHP7313     

Trends in Agricultural Triazole Fungicide Use in the United States, 1992–2016 and Possible Implications for Antifungal-Resistant Fungi in Human Disease

Background: The fungus Aspergillus fumigatus (A. fumigatus) is the leading cause of invasive mold infections, which cause severe disease and death in immunocompromised people. Use of triazole antifungal medications in recent decades has improved patient survival; however, triazole-resistant infections have become common in parts of Europe and are emerging in the United States. Triazoles are also a class of fungicides used in plant agriculture, and certain triazole-resistant A. fumigatus strains found causing disease in humans have been linked to environmental fungicide use.Objectives: We examined U.S. temporal and geographic trends in the use of triazole fungicides using U.S. Geological Survey agricultural pesticide use estimates.Discussion: Based on our analysis, overall tonnage of triazole fungicide use nationwide was relatively constant during 1992–2005 but increased >4-fold during 2006–2016 to 2.9 million kg in 2016. During 1992–2005, triazole fungicide use occurred mostly in orchards and grapes, wheat, and other crops, but recent increases in use have occurred primarily in wheat, corn, soybeans, and other crops, particularly in Midwest and Southeast states. We conclude that, given the chemical similarities between triazole fungicides and triazole antifungal drugs used in human medicine, increased monitoring for environmental and clinical triazole resistance in A. fumigatus would improve overall understanding of these interactions, as well as help identify strategies to mitigate development and spread of resistance. https://doi.org/10.1289/EHP7484     

Confounding by Socioeconomic Status in Epidemiological Studies of Air Pollution and Health: Challenges and Opportunities

Background: Despite a vast air pollution epidemiology literature to date and the recognition that lower-socioeconomic status (SES) populations are often disproportionately exposed to pollution, there is little research identifying optimal means of adjusting for confounding by SES in air pollution epidemiology, nor is there a strong understanding of biases that may result from improper adjustment.Objective: We aim to provide a conceptualization of SES and a review of approaches to its measurement in the U.S. context and discuss pathways by which SES may influence health and confound effects of air pollution. We explore bias related to measurement and operationalization and identify statistical approaches to reduce bias and confounding.Discussion: Drawing on the social epidemiology, health geography, and economic literatures, we describe how SES, a multifaceted construct operating through myriad pathways, may be conceptualized and operationalized in air pollution epidemiology studies. SES varies across individuals within the contexts of place, time, and culture. Although no single variable or index can fully capture SES, many studies rely on only a single measure. We recommend examining multiple facets of SES appropriate to the study design. Furthermore, investigators should carefully consider the multiple mechanisms by which SES might be operating to identify those SES indicators that may be most appropriate for a given context or study design and assess the impact of improper adjustment on air pollution effect estimates. Last, exploring model contraction and expansion methods may enrich adjustment, whereas statistical approaches, such as quantitative bias analysis, may be used to evaluate residual confounding. https://doi.org/10.1289/EHP7980     

Adopting a “Compound” Exposome Approach in Environmental Aging Biomarker Research: A Call to Action for Advancing Racial Health Equity

Background: In June 2020, the National Academies of Sciences, Engineering, and Medicine hosted a virtual workshop focused on integrating the science of aging and environmental health research. The concurrent COVID-19 pandemic and national attention on racism exposed shortcomings in the environmental research field’s conceptualization and methodological use of race, which have subsequently hindered the ability of research to address racial health disparities. By the workshop’s conclusion, the authors deduced that the utility of environmental aging biomarkers—aging biomarkers shown to be specifically influenced by environmental exposures—would be greatly diminished if these biomarkers are developed absent of considerations of broader societal factors—like structural racism—that impinge on racial health equity.Objectives: The authors reached a post-workshop consensus recommendation: To advance racial health equity, a “compound” exposome approach should be widely adopted in environmental aging biomarker research. We present this recommendation here.Discussion: The authors believe that without explicit considerations of racial health equity, people in most need of the benefits afforded by a better understanding of the relationships between exposures and aging will be the least likely to receive them because biomarkers may not encompass cumulative impacts from their unique social and environmental stressors. Employing an exposome approach that allows for more comprehensive exposure–disease pathway characterization across broad domains, including the social exposome and neighborhood factors, is the first step. Exposome-centered study designs must then be supported with efforts aimed at increasing the recruitment and retention of racially diverse study populations and researchers and further “compounded” with strategies directed at improving the use and interpretation of race throughout the publication and dissemination process. This compound exposome approach maximizes the ability of our science to identify environmental aging biomarkers that explicate racial disparities in health and best positions the environmental research community to contribute to the elimination of racial health disparities. https://doi.org/10.1289/EHP8392     

Aggressiveness and Metastatic Potential of Breast Cancer Cells Co-Cultured with Preadipocytes and Exposed to an Environmental Pollutant Dioxin: An in Vitro and in Vivo Zebrafish Study

Background: Breast cancer (BC) is a major public health concern, and its prognosis is very poor once metastasis occurs. The tumor microenvironment and chemical pollution have been suggested recently to contribute, independently, to the development of metastatic cells. The BC microenvironment consists, in part, of adipocytes and preadipocytes in which persistent organic pollutants (POPs) can be stored.Objectives: We aimed to test the hypothesis that these two factors (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an extensively studied, toxic POP and the microenvironment) may interact to increase tumor aggressiveness.Methods: We used a co-culture model using BC MCF-7 cells or MDA-MB-231 cells together with hMADS preadipocytes to investigate the contribution of the microenvironment and 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD on BC cells. Global differences were characterized using a high-throughput proteomic assay. Subsequently we measured the BC stem cell–like activity, analyzed the cell morphology, and used a zebrafish larvae model to study the metastatic potential of the BC cells.Results: We found that coexposure to TCDD and preadipocytes modified BC cell properties; moreover, it induced the expression of ALDH1A3, a cancer stem cell marker, and the appearance of giant cancer cells with cell-in-cell structures (CICs), which are associated with malignant metastatic progression, that we demonstrated in vivo.Discussion: The results of our study using BC cell lines co-cultured with preadipocytes and a POP and an in vivo zebrafish model of metastasis suggest that the interactions between BC cells and their microenvironment could affect their invasive or metastatic potential. https://doi.org/10.1289/EHP7102     

Using the Key Characteristics of Carcinogens to Develop Research on Chemical Mixtures and Cancer

Background: People are exposed to numerous chemicals throughout their lifetimes. Many of these chemicals display one or more of the key characteristics of carcinogens or interact with processes described in the hallmarks of cancer. Therefore, evaluating the effects of chemical mixtures on cancer development is an important pursuit. Challenges involved in designing research studies to evaluate the joint action of chemicals on cancer risk include the time taken to perform the experiments because of the long latency and choosing an appropriate experimental design.Objectives: The objectives of this work are to present the case for developing a research program on mixtures of environmental chemicals and cancer risk and describe recommended approaches.Methods: A working group comprising the coauthors focused attention on the design of mixtures studies to inform cancer risk assessment as part of a larger effort to refine the key characteristics of carcinogens and explore their application. Working group members reviewed the key characteristics of carcinogens, hallmarks of cancer, and mixtures research for other disease end points. The group discussed options for developing tractable projects to evaluate the joint effects of environmental chemicals on cancer development.Results and Discussion: Three approaches for developing a research program to evaluate the effects of mixtures on cancer development were proposed: a chemical screening approach, a transgenic model-based approach, and a disease-centered approach. Advantages and disadvantages of each are discussed. https://doi.org/10.1289/EHP8525     

The Parallel Transformations of Polycyclic Aromatic Hydrocarbons in the Body and in the Atmosphere

Background. Polycyclic aromatic hydrocarbons (PAHs) emitted from combustion sources are known to be mutagenic, with more potent species also being carcinogenic. Previous studies show that PAHs can undergo complex transformations both in the body and in the atmosphere, yet these transformation processes are generally investigated separately.Objectives. Drawing from the literature in atmospheric chemistry and toxicology, we highlight the parallel transformations of PAHs that occur in the atmosphere and the body and discuss implications for public health. We also examine key uncertainties related to the toxicity of atmospheric oxidation products of PAHs and explore critical areas for future research.Discussion. We focus on a key mode of toxicity for PAHs, in which metabolic processes (driven by cytochrome P450 enzymes), leads to the formation of oxidized PAHs that can damage DNA. Such species can also be formed abiotically in the atmosphere from natural oxidation processes, potentially augmenting PAH toxicity by skipping the necessary metabolic steps that activate their mutagenicity. Despite the large body of literature related to these two general pathways, the extent to which atmospheric oxidation affects a PAH’s overall toxicity remains highly uncertain. Combining knowledge and promoting collaboration across both fields can help identify key oxidation pathways and the resulting products that impact public health.Conclusions. Cross-disciplinary research, in which toxicology studies evaluate atmospheric oxidation products and their mixtures, and atmospheric measurements examine the formation of compounds that are known to be most toxic. Close collaboration between research communities can help narrow down which PAHs, and which PAH degradation products, should be targeted when assessing public health risks. https://doi.org/10.1289/EHP9984     

Pathological Cardiopulmonary Evaluation of Rats Chronically Exposed to Traffic-Related Air Pollution

Background: Traffic-related air pollution (TRAP) is made up of complex mixtures of particulate matter, gases and volatile compounds. However, the effects of TRAP on the cardiopulmonary system in most animal studies have been tested using acute exposure to singular pollutants. The cardiopulmonary effects and molecular mechanisms in animals that are chronically exposed to unmodified air pollution as a whole have yet to be studied. Additionally, sex-dependent toxicity of TRAP exposure has rarely been evaluated.Objectives: This study sought to assess the cardiopulmonary effect of chronic exposure to unmodified, real-world TRAP in both female and male rats.Methods: Four-week-old male and female rats were exposed to TRAP or filtered air for 14 months in a novel facility drawing air from a major freeway tunnel system in Northern California. Inflammation and oxidative stress markers were examined in the lung, heart, spleen, and plasma, and TRAP deposits were quantified in the lungs of both male and female rats.Results: Elemental analysis showed higher levels of eight elements in the female lungs and one element in the male lungs. Expression of genes related to fibrosis, aging, oxidative stress, and inflammation were higher in the rat hearts exposed to TRAP, with female rats being more susceptible than males. Enhanced collagen accumulation was found only in the TRAP-exposed female hearts. Plasma cytokine secretion was higher in both female and male rats, but inflammatory macrophages were higher only in TRAP-exposed male spleens.Discussion: Our results in rats suggest pathological consequences from chronic TRAP exposure, including sex differences indicating females may be more susceptible to TRAP-induced cardiac fibrosis. https://doi.org/10.1289/EHP7045     

Mining of Consumer Product Ingredient and Purchasing Data to Identify Potential Chemical Coexposures

Background: Chemicals in consumer products are a major contributor to human chemical coexposures. Consumers purchase and use a wide variety of products containing potentially thousands of chemicals. There is a need to identify potential real-world chemical coexposures to prioritize in vitro toxicity screening. However, due to the vast number of potential chemical combinations, this identification has been a major challenge.Objectives: We aimed to develop and implement a data-driven procedure for identifying prevalent chemical combinations to which humans are exposed through purchase and use of consumer products.Methods: We applied frequent itemset mining to an integrated data set linking consumer product chemical ingredient data with product purchasing data from 60,000 households to identify chemical combinations resulting from co-use of consumer products.Results: We identified co-occurrence patterns of chemicals over all households as well as those specific to demographic groups based on race/ethnicity, income, education, and family composition. We also identified chemicals with the highest potential for aggregate exposure by identifying chemicals occurring in multiple products used by the same household. Last, a case study of chemicals active in estrogen and androgen receptor in silico models revealed priority chemical combinations co-targeting receptors involved in important biological signaling pathways.Discussion: Integration and comprehensive analysis of household purchasing data and product-chemical information provided a means to assess human near-field exposure and inform selection of chemical combinations for high-throughput screening in in vitro assays. https://doi.org/10.1289/EHP8610     

Cold Spells and Cause-Specific Mortality in 47 Japanese Prefectures: A Systematic Evaluation

Background: Many studies have investigated the devastating health effects of heat waves, but less is known about health risks related to cold spells, despite evidence that extreme cold may contribute to a larger proportion of deaths.Objectives: We aimed to systematically investigate the association between cold spells and mortality in Japan.Methods: Daily data for weather conditions and 12 common causes of death during the 1972–2015 cold seasons (November–March) were obtained from 47 Japanese prefectures. Cold spells were defined as ≥2 consecutive days with daily mean temperatures ≤5th percentile for the cold season in each prefecture. Quasi-Poisson regression was combined with a distributed lag model to estimate prefecture-specific associations, and pooled associations at the national level were obtained through random-effects meta-analysis. The potential influence of cold spell characteristics (intensity, duration, and timing in season) on associations between cold spells and mortality was examined using a similar two-stage approach. Temporal trends were investigated using a meta-regression model.Results: A total of 18,139,498 deaths were recorded during study period. Mortality was significantly higher during cold spell days vs. other days for all selected causes of death. Mortality due to age-related physical debilitation was more strongly associated with cold spells than with other causes of death. Associations between cold spells and mortality from all causes and several more specific outcomes were stronger for longer and more intense cold spells and for cold spells earlier in the cold season. However, although all outcomes were positively associated with cold spell duration, findings for cold spell intensity and seasonal timing were heterogeneous across the outcomes. Associations between cold spells and mortality due to cerebrovascular disease, cerebral infarction, and age-related physical debility decreased in magnitude over time, whereas temporal trends were relatively flat for all-cause mortality and other outcomes.Discussion: Our findings may have implications for establishing tailored public health strategies to prevent avoidable cold spell–related health consequences. https://doi.org/10.1289/EHP7109