Persistent organic pollutants and maternal glycemic outcomes in a diverse pregnancy cohort of overweight women.

BACKGROUND: Animal and human studies suggest certain persistent organic pollutants (POPs) may impact glucose metabolism; however, few epidemiologic studies have examined environmental determinants of glycemic outcomes during pregnancy. Our objective is to evaluate associations between exposures to individual and mixture of POPs and measures of prenatal fasting glucose, insulin, and insulin resistance during pregnancy in overweight women. METHODS: A cohort of overweight and obese pregnant women (N = 95) was recruited from California. Blood samples were collected during late first or second trimester (median = 16 weeks' gestation; range = 10-24 weeks). Exposures included serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs). Outcomes included serum concentrations of fasting plasma glucose, fasting plasma insulin, and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Generalized linear models were used to evaluate cross-sectional associations between individual and aggregate POPs and mean percent difference in fasting glucose, fasting insulin, and HOMA-IR. Bayesian kernel machine regression (BKMR) was used to assess the relative importance of each exposure to the association with our outcomes, using conditional and group posterior inclusion probabilities (PIPs). RESULTS: Study participants were racially/ethnically diverse and nearly half were below the federal poverty level. Across PBDEs and OH-PBDEs, the direction of associations with fasting glucose, fasting insulin and HOMA-IR were varied. A doubling of PCB-138, PCB-153, PCB-180, and ∑PCBs concentrations was associated with a 2.10% mmol/L (95%CI: 0.49%, 3.74%), 2.10% mmol/L (95%CI: -0.14%, 4.39%), 2.10% mmol/L (95%CI: 0.12%, 4.12%), and 2.81% mmol/L (95%CI: 0.38%, 5.31%) increase in fasting glucose, respectively. Exposure to individual PCBs was positively associated with both fasting insulin and HOMA-IR. All PFAS were inversely associated with fasting glucose, fasting insulin, and HOMA-IR. In BKMR models of fasting glucose, all four chemical classes were important contributors to the overall mixture, with PFASs identified as the most important contributor. DISCUSSION: Prenatal PCB exposure was positively associated while certain PBDE and PFAS analytes were inversely associated with fasting glucose concentrations in overweight women. Further examination of the relationship between POPs exposure and glycemic functioning in a larger study population of women during pregnancy is warranted.

A tiered approach to prioritizing registered pesticides for potential cancer hazard evaluations: implications for decision making.

BACKGROUND: Over 800 pesticides are registered for use in the United States. Human studies indicate concern that some pesticides currently in use in large quantities may also pose a carcinogenic hazard. Our objective is to identify candidates for future hazard evaluations among pesticides used in high volumes in the United States and also classified as potential carcinogens by U.S. Environmental Protection Agency (USEPA). We also identify data gaps where further research is needed. METHODS: We used a systematic, two-tiered review approach to prioritize pesticides. First, we identified currently registered pesticides classified by USEPA as "possible", "suggestive", or "likely" human carcinogens. Among these, we selected pesticides USEPA has listed as commonly used by volume in at least one sector (agriculture, home and garden, or industry, commercial, and/or government), and those without a published hazard evaluation in the past 5 years. Second, we searched primary literature databases for peer-reviewed human cancer studies reporting pesticide-specific data published since the last USEPA carcinogenicity evaluation for each pesticide, and created evidence maps of the number of studies meeting our criteria for each identified pesticide. No evaluation of study results or risk-of-bias assessments were conducted. RESULTS: We identified 18 pesticides meeting our selection criteria, 16 pesticides had information from human cancer studies published after their initial carcinogenicity review. Of these, eight pesticides had at least three studies for one or more cancer sites: carbaryl, dichloropropene, dimethoate, mancozeb, metolachlor, pendimethalin, permethrin, and trifluralin. A major limitation in the literature revealed a shortage of studies reporting risk estimates for individual pesticides, rather pesticides were grouped by chemical class. CONCLUSIONS: Our scoping report provides a map of the existing literature on real-world exposures and human cancer that has accumulated on pesticides classified as potential carcinogens by USEPA and used in high volumes. We also illustrate that several pesticides which are "data-rich" may warrant updated authoritative hazard evaluations. Our two-tiered approach and utilization of evidence mapping can be used to inform future decision-making to update cancer hazard evaluations.

An Approach to Assessing the Influence of Environmental and Occupational Cancer Hazard Identification on Policy Decision-Making.

BACKGROUND: Cancer hazard identification is critical to informing decisions on preventive actions. However, the influence of cancer hazard assessments on the creation of health-protective regulations is poorly understood. Although prior studies have measured the health and economic benefits of regulatory actions in general, we are not aware of efforts to explicitly study the influence of cancer hazard identification on policy decisions in the United States. OBJECTIVES: In this commentary, we present an approach to examine whether formal identification of a substance as a human carcinogen may prompt a regulatory action to reduce exposure to carcinogens and enhance public health. Further, we discuss the broader implications of cancer hazard identification on policy decision-making, including identifying gaps and providing recommendations. METHODS: Using the Report on Carcinogens (RoC) as a test case, we systematically searched U.S. federal and state databases for notices of regulations mentioning the RoC from 1995 to 2023. For each regulation, we extracted information on the carcinogen(s) regulated, the regulatory agency, the regulatory purpose, the economic sector exposure sources, and the analyzed public health benefits and costs. We created a publicly available, web-based interactive tool to visualize the data. DISCUSSION: U.S. regulatory agencies have been using cancer hazard evaluations, such as the RoC, for decades to inform public health policy actions to prevent or mitigate cancer risks. Specifically, nonregulatory cancer hazard assessments have been used to prioritize chemical evaluations, support regulatory-based assessments, and trigger regulatory action. Our approach showed that assessing the influence of cancer hazard identification on science-based public health policies is feasible, informative, and needed, and our study is a first step in this direction. We recommend expanding this approach to other cancer and noncancer hazard assessments to ultimately inform our understanding of the influence of hazard classifications on policymaking. https://doi.org/10.1289/EHP12681.

Indoor wood-burning from stoves and fireplaces and incident lung cancer among Sister Study participants.

BACKGROUND AND AIM: Epidemiological studies conducted mostly in low- and middle-income countries have found a positive association between household combustion of wood and lung cancer. However, most studies have been retrospective, and few have been conducted in the United States where indoor wood-burning usage patterns differ. We examined the association of exposure to indoor wood smoke from fireplaces and stoves with incident lung cancer in a U.S.-wide cohort of women. METHODS: We included 50,226 women without prior lung cancer participating in the U.S.-based prospective Sister Study. At enrollment (2003-2009), women reported frequency of use of wood-burning stoves and/or fireplaces in their longest-lived adult residence. Cox regression was used to estimate adjusted hazard ratios (HRadj) and 95 % confidence intervals (CI) for the association between indoor wood-burning fireplace/stove use and incident lung cancer. Lung cancer was self-reported and confirmed with medical records. RESULTS: During an average 11.3 years of follow-up, 347 medically confirmed lung cancer cases accrued. Overall, 62.3 % of the study population reported the presence of an indoor wood-burning fireplace/stove at their longest-lived adult residence and 20.6 % reported annual usage of ≥30 days/year. Compared to those without a wood-burning fireplace/stove, women who used their wood-burning fireplace/stove ≥30 days/year had an elevated rate of lung cancer (HRadj = 1.68; 95 % CI = 1.27, 2.20). In never smokers, positive associations were seen for use 1-29 days/year (HRadj = 1.64; 95 % CI = 0.87, 3.10) and ≥30 days/year (HRadj = 1.99; 95 % CI = 1.02, 3.89). Associations were also elevated across all income groups, in Northeastern, Western or Midwestern U.S. regions, and among those who lived in urban or rural/small town settings. CONCLUSIONS: Our prospective analysis of a cohort of U.S. women found that increasing frequency of wood-burning indoor fireplace/stove usage was associated with incident lung cancer, even among never smokers.

Cancer Hazard Evaluations for Contemporary Needs: Highlights From New National Toxicology Program Evaluations and Methodological Advancements.

The National Toxicology Program strives to raise awareness of cancer hazards in our environment. Identifying cancer hazards is key to primary prevention, informing public health decision making, and decreasing the global cancer burden. In December 2021, the US congressionally mandated 15th Report on Carcinogens was released, adding 8 new substances to the cumulative report. Chronic infection with Helicobacter pylori is listed as "known to be a human carcinogen." Antimony trioxide and 6 haloacetic acids found as water disinfection by-products-dichloroacetic acid, dibromoacetic acid, bromochloroacetic acid, tribromoacetic acid, bromodichloroacetic acid, chlorodibromoacetic acid-are listed as "reasonably anticipated to be a human carcinogen." A new dashboard provides interactive visualization and interrogation of the 256 listed substances, their uses, and associated cancers. Also, the National Toxicology Program recently published a Cancer Hazard Assessment Report on exposure scenarios associated with circadian disruption, concluding that persistent night shift work can cause breast cancer and certain lighting conditions may cause cancer. As highlighted in these reports and evaluations, we are evolving our approaches to meet contemporary challenges. These approaches include focusing on real-world exposures and advancing our methods to address challenges in cancer hazard assessments (eg, developing more structured approaches to evaluate mechanistic data and incorporating read-across approaches to assess chemicals lacking adequate human or animal cancer data). To promote public health, we provide information on environmental health disparities and disease prevention. Building on these efforts, we aim to continue our contributions to the war on cancer, declared 50 years ago.

Urinary polycyclic aromatic hydrocarbon metabolites and mortality in the United States: A prospective analysis.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous organic compounds associated with chronic disease in epidemiologic studies, though the contribution of PAH exposure on fatal outcomes in the U.S. is largely unknown. OBJECTIVES: We investigated urinary hydroxylated PAH metabolites (OH-PAHs) with all-cause and cause-specific mortality in a representative sample of the U.S. population. METHODS: Study participants were ≥20 years old from the National Health and Nutrition Examination Survey 2001-2014. Concentrations (nmol/L) of eight OH-PAHs from four parent PAHs (naphthalene, fluorene, phenanthrene, pyrene) were measured in spot urine samples at examination. We identified all-cause, cancer-specific, and cardiovascular-specific deaths through 2015 using the National Death Index. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ΣOH-PAHs and mortality endpoints. We assessed potential heterogeneity by age, gender, smoking status, poverty, and race/ethnicity. Additionally, we examined the overall mixture effect using quantile g-computation. RESULTS: In 9,739 eligible participants, there were 934 all-cause deaths, 159 cancer-specific deaths, and 108 cardiovascular-specific deaths (median 6.75 years follow-up). A log10 increase in ΣOH-PAHs was associated with higher all-cause mortality (HRadj = 1.39 [95%CI: 1.21, 1.61]), and possibly cancer-specific mortality (HRadj = 1.15 [95%CI: 0.79, 1.69]), and cardiovascular-specific mortality (HRadj = 1.49 [95%CI: 0.94, 2.33]). We observed substantial effect modification by age, smoking status, gender, and race/ethnicity across mortality endpoints. Risk of cardiovascular mortality was higher for non-Hispanic blacks and those in poverty, indicating potential disparities. Quantile g-computation joint associations for a simultaneous quartile increase in OH-PAHs were HRadj = 1.15 [95%CI: 1.02, 1.31], HRadj = 1.41 [95%CI: 1.05, 1.90], and HRadj = 0.98 [95%CI: 0.66, 1.47] for all-cause, cancer-specific, and cardiovascular-specific mortalities, respectively. DISCUSSION: Our results support a role for total PAH exposure in all-cause and cause-specific mortality in the U.S. population.

Challenges and recommendations on the conduct of systematic reviews of observational epidemiologic studies in environmental and occupational health.

Systematic reviews are powerful tools for drawing causal inference for evidence-based decision-making. Published systematic reviews and meta-analyses of environmental and occupational epidemiology studies have increased dramatically in recent years; however, the quality and utility of published reviews are variable. Most methodologies were adapted from clinical epidemiology and have not been adequately modified to evaluate and integrate evidence from observational epidemiology studies assessing environmental and occupational hazards, especially in evaluating the quality of exposure assessments. Although many reviews conduct a systematic and transparent assessment for the potential for bias, they are often deficient in subsequently integrating across a body of evidence. A cohesive review considers the impact of the direction and magnitude of potential biases on the results, systematically evaluates important scientific issues such as study sensitivity and effect modifiers, identifies how different studies complement each other, and assesses other potential sources of heterogeneity. Given these challenges of conducting informative systematic reviews of observational studies, we provide a series of specific recommendations based on practical examples for cohesive evidence integration to reach an overall conclusion on a body of evidence to better support policy making in public health.

A Prospective Analysis of Red and Processed Meat Consumption and Risk of Colorectal Cancer in Women.

BACKGROUND: Red and processed meats have been implicated as risk factors in the development of colorectal cancer in U.S. women, but associations with cooking practices are less well established. METHODS: Data are from the Sister Study, a cohort of women ages 35 to 74 years from the United States and Puerto Rico who have a sister diagnosed with breast cancer. Red and processed meat consumption, meat cooking practices, and intake of common meat products were collected at baseline using self-administered questionnaires (N = 48,704). Multivariable HRs (HRadj) and 95% confidence intervals (95% CI) were estimated. RESULTS: During a median 8.7 years' follow-up (range <1-12.7 years), 216 colorectal cancer cases were diagnosed. In categorical analyses, an increased risk of colorectal cancer was seen in the highest quartile of processed meat consumption compared with the lowest [HRadj = 1.52 (95% CI, 1.01-2.30); P trend = 0.02], and for specific meat products, including breakfast sausages [HRadj = 1.85 (95% CI, 1.30-2.64)] and bacon [HRadj = 1.46 (95% CI, 1.01-2.11)]. The HRadj for the highest quartile of red meat consumption was 1.04 (95% CI, 0.68-1.60), and little evidence of association was observed for cooking practices or doneness of red meat. We observed positive associations with specific red meat products when cooking methods were considered, for example, grilled/barbequed steaks [HRadj = 2.23 (95% CI, 1.20-4.14)] and hamburgers [HRadj = 1.98 (95% CI, 1.00-3.91)]. CONCLUSIONS: Higher reported daily intake of processed meats and consumption of barbecued/grilled red meat products were associated with increased risk of colorectal cancer in women. IMPACT: Variability in colorectal risk risk by meat type and cooking method should be considered when evaluating meat consumption.

Associations between sociodemographic characteristics and exposures to PBDEs, OH-PBDEs, PCBs, and PFASs in a diverse, overweight population of pregnant women.

Exposures to persistent organohalogen chemicals during pregnancy are associated with adverse health effects. Low-income, minority women with pre-existing co-morbidities may be particularly vulnerable to these exposures, but have historically been understudied. We aimed to characterize exposures to multiple chemical classes among a sample of ethnically diverse, lower income, overweight or obese pregnant women. Serum concentrations of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs) were measured in 98 pregnant women (California; 2011-2013). Aggregate exposures were evaluated using correlational clustering, a "chemical burden" score, and PCA. Associations between sociodemographic characteristics and individual and aggregate exposures were evaluated using multivariable linear regression. Clustering and PCA both produced four groupings: (PC1) PBDEs/OH-PBDEs, (PC2) PCBs, (PC3) PFNA/PFOA/PFDeA, (PC4) PFHxS/PFOS. Race/ethnicity and prepregnancy BMI were associated with PBDEs, OH-PBDEs and PC1. Maternal age was associated with PCBs and PC2. Parity was associated with PBDEs, OH-PBDEs and PC2. Poverty was negatively associated with PCBs, whereas food insecurity was positively associated with PFOS. We observed variations in sociodemographic profiles of exposures by chemical class and weak across-class correlations. These findings have implications for epidemiologic studies of chemical mixtures and for exposure reduction strategies.

Software Tools to Facilitate Systematic Review Used for Cancer Hazard Identification.

Objective and systematic methods to search, review, and synthesize published studies are a fundamental aspect of carcinogen hazard classification. Systematic review is a historical strength of the International Agency for Research on Cancer (IARC) Monographs Program and the United States National Toxicology Program (NTP) Office of the Report on Carcinogens (RoC). Both organizations are tasked with evaluating peer-reviewed, published evidence to determine whether specific substances, exposure scenarios, or mixtures pose a cancer hazard to humans. This evidence synthesis is based on objective, transparent, published methods that call for extracting and interpreting data in a systematic manner from multiple domains, including a) human exposure, b) epidemiological evidence, c) evidence from experimental animals, and d) mechanistic evidence. The process involves multiple collaborators and requires an extensive literature search, review, and synthesis of the evidence. Several online tools have been implemented to facilitate these collaborative systematic review processes. Specifically, Health Assessment Workplace Collaborative (HAWC) and Table Builder are custom solutions designed to record and share the results of the systematic literature search, data extraction, and analyses. In addition, a content management system for web-based project management and document submission has been adopted to enable access to submitted drafts simultaneously by multiple co-authors and to facilitate their peer review and revision. These advancements in cancer hazard classification have applicability in multiple systematic review efforts. https://doi.org/10.1289/EHP4224.

Using nature and outdoor activity to improve children's health.

Childhood obesity affects 17% or 12.5 million of America's children, contributing to the rise in children's health disparities. Type 2 diabetes, asthma, vitamin D deficiency, and attention-deficit/hyperactivity disorder have also increased over the past few decades. A shift toward a sedentary lifestyle is a major contributor to the decline in children's health. Children spend more time indoors using electronic media and less time engaged in outdoor unstructured play. This article reviews the current evidence of the mental and physical health benefits associated with unstructured, outdoor activities and time spent in a natural environment such as a park or other recreational area. Pediatric health care providers should recommend outdoor activities for children and refer families to safe and easily accessible outdoor areas. Pediatric health care providers can incorporate this simple, lifestyle-based intervention into anticipatory guidance.