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Background Ethylene oxide (EtO) is a carcinogenic gas used in chemical production and to sterilize medical equipment that has been linked to risk of breast and lymphohematopoietic cancers in a small number of occupational studies. We investigated the relationship between environmental EtO exposure and risk of these cancers. Methods Using the US Environmental Protection Agency’s Toxics Release Inventory, we estimated historical exposures for National Institutes of Health–AARP Diet and Health Study participants enrolled in 1995-1996. We constructed 2 metrics at 3, 5, and 10 km: 1) distance between residences and EtO-emitting facilities, weighted by the proportion of time the home was downwind of each facility, and 2) distance-weighted, wind direction–adjusted average airborne emissions index (AEI=∑[lbs EtO/km2]). We estimated risk (hazard ratio [HR], 95% confidence interval [CI]) of incident breast cancer (in situ and invasive) among postmenopausal women (n = 173 670) overall and by tumor estrogen receptor status and non-Hodgkin lymphoma in the full cohort (n = 451 945). Results We observed an increased risk of breast cancer associated with EtO-emitting facilities within 10 km (HR[≤10vs>10] = 1.05, 95% CI = 1.00 to 1.10) that appeared stronger for in situ (HR[≤10vs>10] = 1.13, 95% CI = 1.00 to 1.27) than invasive (HR[≤10vs>10] = 1.03, 95% CI = 0.97 to 1.09) disease. Risk of breast cancer in situ was also increased in the top AEI quartiles, and associations weakened with larger distances (HR[Q4vs0] = 1.60, 95% CI = 0.98 to 2.61; HR[Q4vs0] = 1.28, 95% CI = 0.92 to 1.79; HR[Q4vs0] = 1.25, 95% CI = 1.02 to 1.53 at 3, 5, and 10 km, respectively). No differences in breast cancer risk were observed by estrogen receptor status. We found no clear pattern of increased non-Hodgkin lymphoma risk. Conclusions A novel potential association between EtO emissions and risk of in situ, but not invasive, breast cancer warrants additional evaluation.

Disinfection byproducts (DBPs) andWe investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.Among postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen (Higher average concentrations of DBPs (95th percentile: TTHMWe report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.

PURPOSE. Outdoor light at night (LAN) can result in circadian disruption and hormone dysregulation and is a suspected risk factor for some cancers. Our study is the first to evaluate the association between LAN and risk of endometrial cancer, a malignancy with known relationship to circulating estrogen levels. METHODS. We linked enrollment addresses (1996) for 97,677 postmenopausal women in the prospective NIH-AARP cohort to satellite imagery of nighttime radiance to estimate LAN exposure. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (95%CI) for LAN quintiles and incident endometrial cancer overall (1,669 cases) and endometrioid adenocarcinomas (991 cases) through follow-up (2011). We tested for interaction with established endometrial cancer risk factors. RESULTS. We observed no association for endometrial cancer overall (HR(Q1vsQ5)=0.92; 95%CI=0.78–1.08; ptrend=0.67) or endometrioid adenocarcinoma (HR(Q1vsQ5)=1.01; 95%CI=0.82–1.24; ptrend=0.36). Although body mass index and menopause hormone therapy were both associated with risk, there was no evidence of interaction with LAN (pinteractions=0.52 and 0.50, respectively). CONCLUSION. Our study did not find an association between outdoor LAN and endometrial cancer risk, but was limited by inability to account for individual-level exposure determinants. Future studies should consider approaches to improve characterization of personal exposures to light.

Background: Insulin is fundamental in two conditions that are epidemic in the United States and globally: obesity and type II diabetes. Given insulin's established mechanistic involvement in energy balance and glucose tolerance, we examined its relationship to common health-related endpoints in a large population-based sample. Methods: The National Health and Nutrition Examination Survey is a cross-sectional study that uses a complex multistage probability design to obtain a representative sample of the United States population. Adult participants were included from 8 successive 2-year data waves (1999–2014), including 9,224 normal individuals, 7,699 prediabetic, and 3,413 diabetic subjects. The homeostatic model for insulin resistance (HOMA-IR) was available for 20,336 participants and its relationship with demographic, anthropometric, and clinical data was analyzed. We examined the relationship of HOMA-IR to 8 groups of outcome variables: general health, anthropometric/metabolic [waist size, body mass index (BMI)], cardiovascular (blood pressure), lipid [triglycerides, high-density lipoprotein (HDL)], hepatic [alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT)], hematologic [white blood cells (WBC), hemoglobin (Hgb), platelets], inflammatory (C-reactive protein), and nutritional (vitamins D and C, serum folate, and pyridoxine) variables. Results: HOMA-IR was generally strongly, monotonically, and highly significantly associated with adjusted outcomes in normal subjects, although clinical laboratory values were generally within normal bounds across insulin quartiles. In the normal subset, the odds ratio and 95% confidence interval for a quartile change in HOMA-IR for obesity (BMI > 30) was 3.62 (3.30–3.97), and for the highest quintile for the triglyceride/HDL the ratio was 2.00 (1.77–2.26), for GGT it was 1.40 (1.24–1.58), and for WBC it was 1.28 (1.16–1.40). The relationship of HOMA-IR to the various outcomes was broadly similar to that observed in prediabetics and diabetics with a few exceptions. Conclusions: HOMA-IR levels in a large sample of normal individuals are associated with poorer general health and adverse changes across a wide range of markers. A similar pattern of alterations is observed in prediabetic and diabetic samples. Impact: Clinically, checking insulin levels may be helpful to identify patients that merit further observation and are candidates for early interventions.

Longitudinal studies of environmental hazards often rely on exposure estimated at the participant’s enrollment residence. This could lead to exposure misclassification if participants move over time. METHODS: We evaluated residential mobility in the Iowa Women’s Health Study (age 55–69 years) over 19 years of follow-up (1986–2004). We assessed several environmental exposures of varying spatial scales at enrollment and follow-up addresses. Exposures included average nitrate concentrations in public water supplies, percent of agricultural land (row crops and pasture/hay) within 750 m, and the presence of concentrated animal feeding operations within 5 km. In comparison to gold standard duration–based exposures averaged across all residences, we evaluated the sensitivity and specificity of exposure metrics and attenuation bias for a hypothetical nested case–control study of cancer, which assumed participants did not move from their enrollment residence. RESULTS: Among 41,650 participants, 32% moved at least once during follow-up. Mobility was predicted by working outside the home, being a former/current smoker, having a higher education level, using a public drinking water supply, and town size of previous residence. Compared with duration-based exposures, the sensitivity and specificity of exposures at enrollment ranged from 94% to 99% and 97% to 99%, respectively. A hypothetical true odds ratio of 2.0 was attenuated 8% for nitrate, 9%–10% for agricultural land, and 6% for concentrated animal feeding operation exposures. CONCLUSIONS: Overall, we found low rates of mobility and mobility-related exposure misclassification in the Iowa Women’s Health Study. Misclassification and attenuation of hypothetical risk estimates differed by spatial variability and exposure prevalence.

Purpose: Few studies have investigated the relationship between risk of non-Hodgkin lymphoma (NHL) and residential proximity to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) emitted from industrial combustion and manufacturing sources. Methods: We evaluated this relationship among participants of the NIH-AARP Diet and Health Study, a prospective cohort (N = 548,845) in 6 states and 2 cities in the U.S. We linked geocoded enrollment addresses (1995–1996) with a U.S. Environmental Protection Agency database of 4,478 historical PCDD/F sources, which contained toxic equivalency quotient (TEQ) emissions estimates from 1995. Exposure metrics indicated presence/absence of any facility within 3 and 5km of participant homes, overall and by type of facility (e.g., coal-fired power plants, waste incinerators), which vary in emissions levels and constituency. We also calculated exposure as a distance- and toxicity-weighted average emissions index (AEI [g TEQ]). We used Cox regression to estimate associations (hazard ratios; HR and 95% confidence intervals; CI) with NHL and major subtypes, adjusting for and by strata of sociodemographic and lifestyle characteristics. Results: With 6,747 incident cases through 2011, we found no association between living near any or specific types of PCDD/F-emitting facilities and NHL risk. However, participants with an AEI >95th percentile within 5km had increased risk of NHL compared to unexposed (HR = 1.28; CI = 1.05–1.55; p-trend = 0.01). Specifically, we observed increased risk for lymphoplasmacytic lymphoma (HR = 2.98, CI = 1.16–7.63; p-trend = 0.03) and diffuse large B-cell lymphoma (HR = 1.65, CI = 1.11–2.46; p-trend = 0.01). Non-Hispanic blacks were nearly three times as likely as whites to live

Background Commercial databases can be used to identify participant addresses over time, but their quality and impact on environmental exposure assessment is uncertain. Objective To evaluate the performance of a commercial database to find residences and estimate environmental exposures for study participants. Methods We searched LexisNexis® for participant addresses in the Los Angeles Ultrafines Study, a prospective cohort of men and women aged 50–71 years. At enrollment (1995–1996) and follow-up (2004–2005), we evaluated attainment (address found for the corresponding time period) and match rates to survey addresses by participant characteristics. We compared geographically-referenced predictors and estimates of ultrafine particulate matter (UFP) exposure from a land use regression model using LexisNexis and survey addresses at enrollment. Results LexisNexis identified an address for 69% of participants at enrollment (N = 50,320) and 95% of participants at follow-up (N = 24,432). Attainment rate at enrollment modestly differed (≥5%) by age, smoking status, education, and residential mobility between surveys. The match rate at both survey periods was high (82–86%) and similar across characteristics. When using LexisNexis versus survey addresses, correlations were high for continuous values of UFP exposure and its predictors (rho = 0.86–0.92). Significance Time period and population characteristics influenced the attainment of addresses from a commercial database, but accuracy and subsequent estimation of specific air pollution exposures were high in our older study population.

Imputation of missing spatial attributes in health records may facilitate linkages to geo-referenced environmental exposures, but few studies have assessed geo-imputation impacts on epidemiologic inference. We imputed patient Census tracts in a case-crossover analysis of fine particulate matter (PM2.5) and respiratory hospitalizations in New York State (2000–2005). We observed non-significantly higher PM2.5 exposures, high accuracy of binary exposure assignment (89 to 99%), and marginally different hazard ratios (HRs) (−0.2 to 0.7%). HR differences were greater in urban versus rural areas. Given its efficiency and nominal influence on accuracy of exposure classification and measures of association, geo-imputation is a candidate method to address missing spatial attributes for health studies.

Young children are infected by a diverse variety of enteric pathogens in low-income, high-burden countries. Little is known about which conditions pose the greatest risk for enteric pathogen exposure and infection. Young children frequently play in residential public areas around their household, including areas contaminated by human and animal feces, suggesting these exposures are particularly hazardous. The objective of this study was to examine how the dose of six types of common enteric pathogens, and the probability of exposure to one or multiple enteric pathogens for young children playing at public play areas in Kisumu, Kenya is influenced by the type and frequency of child play behaviors that result in ingestion of soil or surface water. Additionally, we examine how pathogen doses and multi-pathogen exposure are modified by spatial variability in the number of public areas children are exposed to in their neighborhood. A Bayesian framework was employed to obtain the posterior distribution of pathogen doses for a certain number of contacts. First, a multivariate mixed effects tobit model was used to obtain the posterior distribution of pathogen concentrations, and their interdependencies, in soil and surface water, based upon empirical data of enteric pathogen contamination in three neighborhoods of Kisumu. Then, exposure doses were estimated using behavioral contact parameters from previous studies and contrasted under different exposure conditions. Pathogen presence and concentration in soil varied widely across local (< 25 meter radius area) and neighborhood-level scales, but pathogens were correlated among distinct surface water samples collected near to each other. Multi-pathogen exposure of children at public play areas was common. Pathogen doses and the probability of multi-pathogen ingestion increased with: higher frequency of environmental contact, especially for surface water; larger volume of soil or water ingested; and with play at multiple sites in the neighborhood versus single site play. Child contact with surface water and soil at public play areas in their neighborhood is an important cause of exposure to enteric pathogens in Kisumu, and behavioral, environmental, and spatial conditions are determinants of exposure., Author summary The enteric infections that cause diarrheal disease remain a leading cause of morbidity and mortality in young children in low-income settings where sanitation infrastructure is limited. The role of different exposure pathways in transmission of enteric pathogens to young children is unknown, but accurate information on relative risks posed by different pathways could improve how well intervention strategies are prioritized. New evidence reveals that young children often play at public areas in their neighborhood, including areas used for human and animal feces disposal, potentially exposing them to heavily contaminated environmental fomites. We describe a novel exposure assessment approach that examines how the dose of six different enteric pathogens, and the probability of exposure to multiple pathogens is influenced by behavioral, environmental, and spatial conditions in public areas of three low-income, urban neighborhoods of Kisumu, Kenya. We found that increased frequency of contact with the environment and volume of material ingested, especially for surface water, and increased contact with different neighborhood locations elevates dose and probability of multiple pathogen exposure. Our study demonstrates that playing in public areas poses a risk to children and provides new insights on how pathogen exposures vary across transmission pathways.

Some anthropogenic substances in drinking water are known or suspected endocrine disrupting compounds (EDCs), but EDCs are not routinely measured. We conducted a pilot study of 10 public drinking water utilities in Iowa, where common contaminants (e.g., pesticides) are suspected EDCs. Raw (untreated) and finished (treated) drinking water samples were collected in spring and fall and concentrated using solid phase extraction. We assessed multiple endocrine disrupting activities using novel mammalian cell-based assays that express nuclear steroid receptors (aryl hydrocarbon [AhR], androgenic [AR], thyroid [TR], estrogenic [ER] and glucocorticoid [GR]). We quantified each receptor’s activation relative to negative controls and compared activity by season and utility/sample characteristics. Among 62 samples, 69% had AhR, 52% AR, 3% TR, 2% ER, and 0% GR activity. AhR and AR activities were detected more frequently in spring (p = 0 .002 and < 0.001, respectively). AR activity was more common in samples of raw water (p = 0 .02) and from surface water utilities (p = 0 .05), especially in fall (p = 0 .03). Multivariable analyses suggested spring season, surface water, and nitrate and disinfection byproduct concentrations as determinants of bioactivity. Our results demonstrate that AR and AhR activities are commonly found in Iowa drinking water, and that their detection varies by season and utility/sample characteristics. Screening EDCs with cell-based bioassays holds promise for characterizing population exposure to diverse EDCs mixtures.

Globally, gastrointestinal (GI) infections by enteric pathogens are the second-leading cause of morbidity and mortality in children under five years of age (&le, 5 years). While GI pathogen exposure in households has been rigorously examined, there is little data about young children&rsquo, s exposure in public domains. Moreover, public areas in low-income settings are often used for other waste disposal practices in addition to human feces, such as trash dumping in areas near households. If young children play in public domains, they might be exposed to interrelated and highly concentrated microbial, chemical, and physical hazards. This study performed structured observations at 36 public areas in an internally displaced persons community that has transitioned into a formal settlement in Haiti. We documented how often young children played in public areas and quantified behaviors that might lead to illness and injury. Children &le, 5 years played at all public sites, which included infants who played at 47% of sites. Children touched and mouthed plastic, metal and glass trash, food and other objects from the ground, ate soil (geophagia) and drank surface water. They also touched latrines, animals, animal feces and open drainage canals. Hand-to-mouth contact was one of the most common behaviors observed and the rate of contact significantly differed among developmental stages (infants: 18/h, toddlers: 11/h and young children: 9/h), providing evidence that children could ingest trace amounts of animal/human feces on hands that may contain GI pathogens. These findings demonstrate that water, sanitation and hygiene interventions could be more effective if they consider exposure risks to feces in public domains. Furthermore, this research highlights the need for waste-related interventions to address the broader set of civil conditions that create unsafe, toxic and contaminated public environments where young children play.

The use of solid biomass fuels in cookstoves has been associated with chronic health impacts that disproportionately affect women worldwide. Solid fuel stoves that use wood, plant matter, and cow dung are commonly used for household cooking in rural Bangladesh. This study investigates the immediate effects of acute elevated cookstove emission exposures on pulmonary function. Pulmonary function was measured with spirometry before and during cooking to assess changes in respiratory function during exposure to cookstove emissions for 15 females ages 18–65. Cookstove emissions were characterized using continuous measurements of particulate matter (PM2.5—aerodynamic diameter