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Background: Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites. OBJECTIVE: We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS. Methods: Information about lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999- 2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk. Results: Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [rate ratios (RR) = 1.24; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile ([RR.sub.Q4] = 1.20; 95% CI: 0.95, 1.52; p-trend = 0.19), particularly among those Discussion: We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms. https://doi.org/10.1289/EHP13684, Introduction Atrazine is a chlorinated-triazine herbicide used to control broadleaf and grassy weeds in various crops such as corn, sorghum, sugar cane, conifers, turf grasses, and bioenergy plants. (1) According [...]

BackgroundPopulation studies support the adverse associations of air pollution exposures with child behavioral functioning and cognitive performance, but few studies have used spatiotemporally resolved pollutant assessments.ObjectivesWe investigated these associations using more refined exposure assessments in 1,967 mother-child dyads from three U.S. pregnancy cohorts in six cities in the ECHO-PATHWAYS Consortium.MethodsPre- and postnatal nitrogen dioxide (NO2) and particulate matter (PM) ≤2.5μm in aerodynamic diameter (PM2.5) exposures were derived from an advanced spatiotemporal model. Child behavior was reported as Total Problems raw score using the Child Behavior Checklist at age 4-6 y. Child cognition was assessed using cohort-specific cognitive performance scales and quantified as the Full-Scale Intelligence Quotient (IQ). We fitted multivariate linear regression models that were adjusted for sociodemographic, behavioral, and psychological factors to estimate associations per 2-unit increase in pollutant in each exposure window and examined modification by child sex. Identified critical windows were further verified by distributed lag models (DLMs).ResultsMean NO2 and PM2.5 ranged from 8.4 to 9.0 ppb and 8.4 to 9.1 μg/m3, respectively, across pre- and postnatal windows. Average child Total Problems score and IQ were 22.7 [standard deviation (SD): 18.5] and 102.6 (SD: 15.3), respectively. Children with higher prenatal NO2 exposures were likely to have more behavioral problems [β: 1.24; 95% confidence interval (CI): 0.39, 2.08; per 2 ppb NO2], particularly NO2 in the first and second trimester. Each 2-μg/m3 increase in PM2.5 at age 2-4 y was associated with a 3.59 unit (95% CI: 0.35, 6.84) higher Total Problems score and a 2.63 point (95% CI: -5.08, -0.17) lower IQ. The associations between PM2.5 and Total Problems score were generally stronger in girls. Most predefined windows identified were not confirmed by DLMs.DiscussionOur study extends earlier findings that have raised concerns about impaired behavioral functioning and cognitive performance in children exposed to NO2 and PM2.5 in utero and in early life. https://doi.org/10.1289/EHP10248.

BACKGROUND: Glyphosate is the most commonly used herbicide worldwide and has been implicated in the development of certain hematologic cancers. Although mechanistic studies in human cells and animals support the genotoxic effects of glyphosate, evidence in human populations is scarce. OBJECTIVES: We evaluated the association between lifetime occupational glyphosate use and mosaic loss of chromosome Y (mLOY) as a marker of genotoxicity among male farmers. METHODS: We analyzed blood-derived DNA from 1,606 farmers [greater than or equal to]50 years of age in the Biomarkers of Exposure and Effect in Agriculture study, a subcohort of the Agricultural Health Study. mLOY was detected using genotyping array intensity data in the pseudoautosomal region of the sex chromosomes. Cumulative lifetime glyphosate use was assessed using self-reported pesticide exposure histories. Using multivariable logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between glyphosate use and any detectable mLOY (overall mLOY) or mLOY affecting [greater than or equal to]10% of cells (expanded mLOY). RESULTS: Overall, mLOY was detected in 21.4% of farmers, and 9.8% of all farmers had expanded mLOY. Increasing total lifetime days of glyphosate use was associated with expanded mLOY [highest vs. lowest quartile; OR = 1.75 (95% CI: 1.00, 3.07), [p.sub.trend] = 0.03] but not with overall mLOY; the associations with expanded mLOY were most apparent among older ([greater than or equal to]70 years of age) men [OR = 2.30 (95% CI: 1.13, 4.67), [p.sub.trend] = 0.01], never smokers [OR = 2.32 (95% CI: 1.04, 5.21), [p.sub.trend] = 0.04], and nonobese men [OR = 2.04 (95% CI: 0.99, 4.19), [p.sub.trend] =0.03]. Similar patterns of associations were observed for intensity-weighted lifetime days of glyphosate use. DISCUSSION: High lifetime glyphosate use could be associated with mLOY affecting a larger fraction of cells, suggesting glyphosate could confer genotoxic or selective effects relevant for clonal expansion. As the first study to investigate this association, our findings contribute novel evidence regarding the carcinogenic potential of glyphosate and require replication in future studies. https://doi.org/10.1289/EHP12834, Introduction Glyphosate is a broad-spectrum, post-emergent herbicide used in both agricultural and nonagricultural settings worldwide. (1) Since it was first registered for use in 1974, glyphosate has become the most [...]

BackgroundPesticide exposure is associated with many long-term health outcomes; the potential underlying mechanisms are not well established for most associations. Epigenetic modifications, such as DNA methylation, may contribute. Individual pesticides may be associated with specific DNA methylation patterns but no epigenome-wide association study (EWAS) has evaluated methylation in relation to individual pesticides.ObjectivesWe conducted an EWAS of DNA methylation in relation to several pesticide active ingredients.MethodsThe Agricultural Lung Health Study is a case-control study of asthma, nested within the Agricultural Health Study. We analyzed blood DNA methylation measured using Illumina's EPIC array in 1,170 male farmers of European ancestry. For pesticides still on the market at blood collection (2009-2013), we evaluated nine active ingredients for which at least 30 participants reported past and current (within the last 12 months) use, as well as seven banned organochlorines with at least 30 participants reporting past use. We used robust linear regression to compare methylation at individual C-phosphate-G sites (CpGs) among users of a specific pesticide to never users.ResultsUsing family-wise error rate (p

Background: The presence of contaminants in cannabis presents a potential health hazard to recreational users and susceptible patients with medical conditions. Because of the federally illegal status of cannabis, there are no unified regulatory guidelines mitigating the public health risk of cannabis contaminants. Objective: To inform further research and provide solutions to the public health risk of cannabis contaminants at a national level, we examined the current landscape of state-level contaminant regulations, and cannabis contaminants of concern, as well as patient populations susceptible to contaminants. Methods: We examined the regulatory documents for medical and recreational cannabis in all legalized U.S. jurisdictions and compiled a complete list of regulated contaminants, namely, pesticides, inorganics, solvents, microbes, and mycotoxins. We data mined the compliance testing records of 5,654 cured flower and 3,760 extract samples that accounted for ~ 6% of California's legal cannabis production in 2020- 2021. We also reviewed the publicly available medical cannabis use reports to tabulate the susceptible patient populations. Results: As of 18 May 2022, 36 states and the District of Columbia listed a total of 679 cannabis contaminants as regulated in medical or recreational cannabis, including 551 pesticides, 74 solvents, 12 inorganics, 21 microbes, 5 mycotoxins, and 16 other contaminants. Different jurisdictions showed significant variations in regulated contaminants and action levels ranging up to four orders of magnitude. A failure rate of 2.3% was identified for flowers and 9.2% for extracts in the California samples. Insecticides and fungicides were the most prevalent categories of detected contaminants, with boscalid and chlorpyrifos being the most common. The contaminant concentrations fell below the regulatory action levels in many legalized jurisdictions, indicating a higher risk of contaminant exposure. Cannabis use reports indicated usage in several patient populations susceptible to contamination toxicity, including cancer (44,318) and seizure (21,195) patients. Discussion: Although individual jurisdictions can implement their policies and regulations for legalized cannabis, this study demonstrates the urgent need to mitigate the public health risk of cannabis contamination by introducing national-level guidelines based on conventional risk assessment methodologies and knowledge of patients' susceptibility in medical use. https://doi.org/10.1289/EHP11206, Introduction The broader use and state-level legalization of cannabis have gained significant public interest and support in recent years. Approximately half of all U.S. adults have reported that they have [...]

Background: In low- and middle-income countries, burning biomass indoors for cooking or heating has been associated with poorer lung function. In high-income countries, wood, a form of biomass, is commonly used for heating in rural areas with increasing prevalence. However, in these settings the potential impact of chronic indoor woodsmoke exposure on pulmonary function is little studied. Objective: We evaluated the association of residential wood burning with pulmonary function in case-control study of asthma nested within a U.S. rural cohort. Methods: Using sample weighted multivariable linear regression, we estimated associations between some and frequent wood burning, both relative to no exposure, in relation to forced expiratory volume in 1 s (FE[V.sub.1]), forced vital capacity (FVC), their ratio (FE[V.sub.1]/FVC), and fractional exhaled nitric oxide (FeNO). We examined effect modification by smoking or asthma status. Results: Among all participants and within smoking groups, wood burning was not appreciably related to pulmonary function. However, in individuals with asthma (n = 1,083), frequent wood burning was significantly associated with lower FE[V.sub.1] [[beta]: -164 mL; 95% confidence interval (CI): -261, -66 mL], FVC ([beta]: -125 mL; 95% CI: -230, -20 mL), and FE[V.sub.1]/FVC ([beta]: -2%; 95% CI: -4, -0.4%), whereas no appreciable association was seen in individuals without asthma (n = 1,732). These differences in association by asthma were statistically significant for FE[V.sub.1] ([p.sub.interaction] = 0.0044) and FE[V.sub.1]/FVC ([p.sub.interaction] = 0.049). Frequent wood burning was also associated with higher FeNO levels in all individuals (n = 2,598; b: 0.1 ln(ppb); 95% CI: 0.02, 0.2), but associations did not differ by asthma or smoking status. Discussion: Frequent exposure to residential wood burning was associated with a measure of airway inflammation (FeNO) among all individuals and with lower pulmonary function among individuals with asthma. This group may wish to reduce wood burning or consider using air filtration devices. https://doi.org/10.1289/EHP10734, Introduction For low- and middle-income countries, burning biomass in the home is well understood to pollute household air, increase airway-related disease, and negatively impact lung function. (1-3) Exposure to household [...]

Background: By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection byproducts, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants. Objectives: In this study, we investigated the combined effect on bladder cancer risk contributed by TTHMs, bladder cancer susceptibility variants identified through genome-wide association studies, and variants in several candidate genes. Methods: We analyzed data from two large case-control studies--the New England Bladder Cancer Study (n/n = 989 cases/1,162 controls), a population-based study, and the Spanish Bladder Cancer Study (n/n = 706 cases/772 controls), a hospital-based study. Because of differences in exposure distributions and metrics, we estimated effects of THMs and genetic variants within each study separately using adjusted logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CI) with and without interaction terms, and then combined the results using meta-analysis. Results: Of the 16 loci showing strong evidence of association with bladder cancer, rs907611 at 11p15.5 [leukocyte- specific protein 1 (LSP1 region)] showed the strongest associations in the highest exposure category in each study, with evidence of interaction in both studies and in metaanalysis. In the highest exposure category, we observed OR= 1.66 (95% CI: 1.17, 2.34, p- trend = 0.005) for those with the rs907611-GG genotype and p-interaction = 0.02. No other genetic variants tested showed consistent evidence of interaction. Discussion: We found novel suggestive evidence for a multiplicative interaction between a putative bladder carcinogen, TTHMs, and genotypes of rs907611. Given the ubiquitous exposure to THMs, further work is needed to replicate and extend this finding and to understand potential molecular mechanisms. https://doi.org/10.1289/EHP9895, Introduction Worldwide, bladder cancer ranks as the ninth most common incident cancer and the 13th in mortality, with ~400,000 cases diagnosed each year. (1) Approximately 75% of incident cases occur [...]

Background: Some pesticides are immunotoxic and have been associated with an increased risk of immune-mediated diseases. The risk of shingles, the clinical reactivation of varicella-zoster virus, increases with aging and immunosuppression; little is known about its associations with pesticides. OBJECTIVE: We examined the use of agricultural pesticides in relation to incident shingles in a prospective cohort of licensed pesticide applicators. Methods: The study sample included 12,820 (97% male) farmers (enrolled in 1993-1997 in North Carolina and Iowa), who were followed for a median of 12 y (interquartile range: 11-13). Shingles was self-reported at enrollment and at follow-up. We evaluated ever-use of 48 agricultural pesticides reported at study enrollment in relation to shingles risk and considered exposure-response for intensity-weighted lifetime days (IWLDs) of use. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models, adjusting for state, and allowing estimates to vary by median attained age (60 y). Results: Incident shingles was reported by 590 participants. Associations were positive (HRs >1.2) for ever- vs. never- use of eight insecticides, three fumigants, two fungicides, and five herbicides, and exposure-response trends were seen across increasing quartiles (Q3 and Q4>Q1) or tertiles (T3 and T2 > T1) of IWLDs for four insecticides [permethrin (crops), coumaphos, malathion, and lindane], two fumigants (carbon tetrachloride/carbon disulfide and methyl bromide), and three herbicides [alachlor, trifluralin ( Conclusions: Several specific pesticides were associated with increased risk of shingles in farmers, especially at higher levels of cumulative use. These novel findings, if replicated in other populations, could have broader implications for the potential effects of pesticides on vaccine efficacy and susceptibility to other infections. https://doi.org/10.1289/EHP7797, Introduction Incidence of herpes zoster (commonly known as shingles), the symptomatic loss of latency of varicella-zoster virus (VZV), is estimated at 3-5 cases/1,000-person years in the United States, with unexplained [...]

BACKGROUND: Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer. However, few prospective studies have investigated links to specific pesticides. OBJECTIVE: We evaluated the lifetime use of individual pesticides and the incidence of RCC. METHODS: We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993-1997) and the end of follow-up (2014-2015). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures. RESULTS: There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged R[R.sub.IWD Tertile 3] = 2.92 (95% CI: 1.65, 5.17; [p.sub.trend] = 0.001)], with similar risk estimates for lagged exposure [20-y lag R[R.sub.IWD Tertile 3] = 3.37 (95% CI: 1.83, 6.22; [p.sub.trend] = 0.001)]. In 20-y lagged analyses, we also found exposure--response associations with chlorpyrifos [R[R.sub.IWD Quartile 4] = 1.68 (95% CI: 1.05, 2.70; [p.sub.trend] = 0.01)], chlordane [R[R.sub.IWD Tertile 3] = 2.06 (95% CI: 1.10, 3.87; [p.sub.trend] = 0.02)], atrazine [R[R.sub.IWD Quartile 4] = 1.43 (95% CI: 1.00, 2.03; [p.sub.trend] = 0.02)], cyanazine [R[R.sub.IWD Quartile 4] = 1.61 (95% CI: 1.03, 2.50; [p.sub.trend] = 0.02)], and paraquat [R[R.sub.IWD >Median] = 1.95 (95% CI: 1.03,3.70; [p.sub.trend] = 0.04)]. CONCLUSIONS: This is, to our knowledge, the first prospective study to evaluate RCC risk in relation to various pesticides. We found evidence of associations with RCC for four herbicides (2,4,5-T, atrazine, cyanazine, and paraquat) and two insecticides (chlorpyrifos and chlordane). Our findings provide insights into specific chemicals that may influence RCC risk among pesticide applicators. Confirmation of these findings and investigations of the biologic plausibility and potential mechanisms underlying the observed associations are warranted. https://doi.org/10.1289/EHP6334, Introduction The incidence of renal cell carcinoma (RCC), the most common form of kidney cancer, has been steadily increasing in the United States for several decades (Noone et al. 2018; [...]

Background: Farmers have a higher incidence of multiple myeloma, and there is suggestive evidence of an elevated prevalence of its precursor, monoclonal gammopathy of undetermined significance (MGUS), relative to the general population. Pesticide exposures are suspected to play a role; however, the biologic plausibility for associations with multiple myeloma remains unclear. Objectives: Our objectives were to examine the prevalence of MGUS and evaluate associations with a wide range of pesticides in a large sample of farmers. Methods: We obtained sera and assessed MGUS among 1,638 male farmers [greater than or equal to] 50 years of age in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate associations with MGUS for recent use (within the 12 months before phlebotomy) and cumulative intensity-weighted lifetime days of use of specific pesticides. Results: The age-standardized MGUS prevalence was significantly elevated among AHS farmers (7.7%) compared with demographically similar men in the National Health and Nutrition Examination Survey (2.8%) or Olmsted County, Minnesota (3.8%; p < 0.001). Recent use of permethrin was associated with MGUS [recent use vs. no recent use, OR = 1.82 (95% CI: 1.06, 3.13)], especially among those who had also used it in the past [recent and past use vs. never use, OR = 2.49 (95% CI: 1.32, 4.69)]. High intensity-weighted lifetime use of the organochlorine insecticides aldrin and dieldrin was associated with MGUS relative to those who never used either of these pesticides [OR = 2.42 (95% CI: 1.29, 4.54); ptiend = 0.006]. We also observed a positive association with high lifetime use of petroleum oil/distillates as an herbicide, as well as an inverse association with fonofos use. Discussion: This is the largest investigation of MGUS in farmers and the first to identify an association with MGUS for permethrin, a pyrethroid insecticide previously associated with multiple myeloma. Given the continued widespread use of permethrin in various residential and commercial settings, our findings may have important implications for exposed individuals in the general population. https://doi.org/10.1289/EHP6960, Introduction An excess in the incidence of multiple myeloma (MM), an aggressive plasma cell malignancy, has been consistently observed in studies of farmers and other agricultural workers conducted over the [...]

BACKGROUND: The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled between 1993 and 1997- EPTC (S-ethyl-N, N-thipropylthiocarbamate) is a [...]

Background: The occupation of farming has been associated with rheumatoid arthritis (RA); pesticides may account for this association, but there are few studies. Objectives: We investigated associations between RA and use of pesticides in the Agricultural Health Study. Methods: The study sample was drawn from male pesticide applicators enrolled in 1993-1997 who provided questionnaire data at baseline and at least once during follow-up (over a median 18 y; interquartile range 16-19). Incident RA cases (n = 220), confirmed by physicians or by self-reported use of disease-modifying antirheumatic drugs, were compared with noncases (n = 26,134) who did not report RA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for enrollment age, state, smoking pack-years, and education. We evaluated the association of RA with the use of 46 pesticides and across 4 levels (never use and tertiles) of lifetime days of use for 16 pesticides with OR [greater than or equal to] 1.2 for ever use. Results: Incident RA was associated with ever use of fonofos (OR = 1.70; 95% CI: 1.22, 2.37), carbaryl (OR = 1.51; 95% CI: 1.03, 2.23), and chlorimuron ethyl (OR = 1.45; 95% CI: 1.01, 2.07) compared with never use. Statistically significant exposure-response trends in association with RA were observed for lifetime days of use of atrazine [[OR.sub.tertile3] = 1.62 (95% CI: 1.09, 2.40); [P.sub.trend] = 0.01] and toxaphene [[OR.sub.tertile3] = 2.42 (95% CI: 1.03, 5.68); [P.sub.trend] = 0.02]. Exposure-response was nonlinear for fonofos [[OR.sub.tertile1 = 2.27 (95% CI: 1.44, 3.57); [OR.sub.tertile2] = 0.98 (95% CI: 0.54, 1.80); [OR.sub.tertile3] = 2.10 (95% CI: 1.32, 3.36); [P.sub.trend] = 0.005] and suggestive for carbaryl ([P.sub.trend] = 0.053). Conclusions: Our results provide novel evidence of associations between exposure to some pesticides and RA in male farmers. https://doi.org/10.1289/EHP1013, Introduction Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease (McInnes and Schett 2011) that affects 0.5-1% of the world's adult population (Alamanos and Drosos 2005), with higher rates in [...]

BACKGROUND: Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence. OBJECTIVE: We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina. METHODS: Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking (smoking status and pack-years), sex, and lifetime days of use of any pesticides. Results: Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p = 0.049) and borderline for lifetime days (p = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence. CONCLUSIONS: These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted., Introduction Lung cancer is the leading cause of cancer related death in the United States (American Cancer Society 2017) and in the world (Torre et al. 2015). Lung cancer mortality [...]

BACKGROUND: Growing evidence suggests that pesticide use may contribute to respiratory symptoms. Objective: We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers. METHODS: Using the 2005-2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by [greater than or equal to] 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent. RESULTS: In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure-response models with up to five exposure categories, we saw evidence of an exposure-response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin. Conclusions: These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects., Introduction Worldwide, more than 5 billion pounds of pesticide active ingredients are used annually (U.S. EPA 2011a). Pesticides represent a diverse group of chemical and physical agents that have varying [...]

BACKGROUND: Increased pesticide concentrations in house dust in agricultural areas have been attributed to several exposure pathways, including agricultural drift, para-occupational, and residential use. OBJECTIVE: To guide future exposure assessment efforts, we quantified relative contributions of these pathways using meta-regression models of published data on dust pesticide concentrations. METHODS: From studies in North American agricultural areas published from 1995 to 2015, we abstracted dust pesticide concentrations reported as summary statistics [e.g., geometric means (GM)]. We analyzed these data using mixed-effects meta-regression models that weighted each summary statistic by its inverse variance. Dependent variables were either the log-transformed GM (drift) or the log-transformed ratio of GMs from two groups (para-occupational, residential use). RESULTS: For the drift pathway, predicted GMs decreased sharply and nonlinearly, with GMs 64% lower in homes 250 m versus 23 m from fields (interquartile range of published data) based on 52 statistics from seven studies. For the para-occupational pathway, GMs were 2.3 times higher [95% confidence interval (CI): 1.5, 3.3; 15 statistics, five studies] in homes of farmers who applied pesticides more recently or frequently versus less recently or frequently. For the residential use pathway, GMs were 1.3 (95% CI: 1.1, 1.4) and 1.5 (95% CI: 1.2, 1.9) times higher in treated versus untreated homes, when the probability that a pesticide was used for the pest treatment was 1-19% and ≥ 20%, respectively (88 statistics, five studies). CONCLUSION: Our quantification of the relative contributions of pesticide exposure pathways in agricultural populations could improve exposure assessments in epidemiologic studies. The metaregression models can be updated when additional data become available. http://dx.doi.org/10.1289/EHP426, Introduction Adults living in agricultural areas may be exposed to pesticides from several occupational and environmental sources and pathways (Arbuckle et al. 2006; Curl et al. 2002; Deziel et al. [...]

BACKGROUND: We have recently shown that biomarker levels of selected metals are higher in Asians than in other U.S. ethnic groups, with important differences within selected Asian subgroups. Much of this difference may be dietary in origin; however, this is not well established. OBJECTIVE: We evaluated dietary intake of toxic metals as a source of increased biomarker levels of metals among U.S. Asians. METHODS: We estimated daily food consumption and dietary intake of arsenic, cadmium, lead, and mercury by combining 24-hr dietary intake recall data from the 2011-2012 National Health and Nutrition Examination Survey (NHANES) with data from the USDA Food Composition Intake Database and FDA Total Dietary Study. We analyzed associations between dietary metal intake and biomarker levels of the metals using linear regression. Further, estimated food consumption and metal intake levels were compared between Asians and other racial/ethnic groups (white, black, Mexican American, and other Hispanic) and within three Asian subgroups (Chinese, Indian Asian, and other Asians). RESULTS: Significant associations (p < 0.05) were found between biomarker levels and estimated dietary metal intake for total and inorganic arsenic and mercury among Asians. Asians had the highest daily fish and rice consumption across the racial/ethnic groups. Fish was the major contributor to dietary mercury and total arsenic intake, whereas rice was the major contributor to inorganic arsenic dietary intake. Fish consumption across the Asian subgroups varied, with Asian Indians having lower fish consumption than the other Asian subgroups. Rice consumption was similar across the Asian subgroups. CONCLUSIONS: We confirmed that estimated dietary intake of arsenic (total and inorganic) and mercury is significantly associated with their corresponding biomarkers in U.S. Asians, using nationally representative data. In contrast, estimated dietary intake of cadmium and lead were not significantly associated with their corresponding biomarker levels in U.S. Asians. http://dx.doi.org/10.1289/EHP28, Introduction Biomarker levels of toxic metals/metalloids (hereafter, simply referred to as 'metals'), such as arsenic, cadmium, lead, and mercury, are higher among the Asian population than other racial/ethnic groups in [...]

From climate change to hydraulic fracturing, and from drinking water safety to wildfires, environmental challenges are changing. The United States has made substantial environmental protection progress based on media-specific and single pollutant risk-based frameworks. However, today's environmental problems are increasingly complex and new scientific approaches and tools are needed to achieve sustainable solutions to protect the environment and public health. In this article, we present examples of today's environmental challenges and offer an integrated systems approach to address them. We provide a strategic framework and recommendations for advancing the application of science for protecting the environment and public health. We posit that addressing 21st century challenges requires transdisciplinary and systems approaches, new data sources, and stakeholder partnerships. To address these challenges, we outline a process driven by problem formulation with the following steps: a) formulate the problem holistically, b) gather and synthesize diverse information, c) develop and assess options, and d) implement sustainable solutions. This process will require new skills and education in systems science, with an emphasis on science translation. A systems-based approach can transcend media--and receptor-specific bounds, integrate diverse information, and recognize the inextricable link between ecology and human health., Background Environmental and public health scientists and decision-makers are addressing new and complex environmental challenges that impact human well-being and ecological health. Energy demands have increased, and sources and approaches [...]

BACKGROUND: Nitrate is a drinking water contaminant arising from agricultural sources, and it is a precursor in the endogenous formation of N-nitroso compounds (NOC), which are possible bladder carcinogens. OBJECTIVES: We investigated the ingestion of nitrate and nitrite from drinking water and diet and bladder cancer risk in women. METHODS: We identified incident bladder cancers among a cohort of 34,708 postmenopausal women in Iowa (1986-2010). Dietary nitrate and nitrite intakes were estimated from a baseline food frequency questionnaire. Drinking water source and duration were assessed in a 1989 follow-up. For women using public water supplies (PWS) > 10 years (n = 15,577), we estimated average nitrate (N[O.sub.3]-N) and total trihalomethane (TTHM) levels and the number of years exceeding one-half the maximum contaminant level (N[O.sub.3]-N: 5 mg/L, TTHM: 40 pg/mL) from historical monitoring data. We computed hazard ratios (HRs) and 95% confidence intervals (CIs), and assessed nitrate interactions with TTHM and with modifiers of NOC formation (smoking, vitamin C). RESULTS: We identified 258 bladder cancer cases, including 130 among women > 10 years at their PWS. In multivariable-adjusted models, we observed nonsignificant associations among women in the highest versus lowest quartile of average drinking water nitrate concentration (HR = 1.48; 95% CI: 0.92, 2.40; [p.sub.trend] = 0.11), and we found significant associations among those exposed [greater than or equal to] 4 years to drinking water with > 5 mg/L N[O.sub.3]-N (HR = 1.62; 95% CI: 1.06, 2.47; [P.sub.trend] = 0.03) compared with women having 0 years of comparable exposure. TTHM adjustment had little influence on associations, and we observed no modification by vitamin C intake. Relative to a common reference group of never smokers with the lowest nitrate exposures, associations were strongest for current smokers with the highest nitrate exposures (HR = 3.67; 95% CI: 1.43, 9.38 for average water N[O.sub.3]-N and HR = 3.48; 95% CI: 1.20, 10.06 and [greater than or equal to] 4 years > 5 mg/L, respectively). Dietary nitrate and nitrite intakes were not associated with bladder cancer. CONCLUSIONS: Long-term ingestion of elevated nitrate in drinking water was associated with an increased risk of bladder cancer among postmenopausal women. http://dx.doi.org/10.1289/EHP191, Introduction Urinary bladder cancer is the sixth most common malignancy in the United States, with an incidence among men that is 4 times greater than that in women [National Cancer [...]

BACKGROUND: Diesel exhaust is a known lung carcinogen. Farmers use a variety of dieselized equipment and thus may be at increased risk of lung cancer, but farm exposures such as endotoxins may also be protective for lung cancer. Objectives: We evaluated the relative risk of incident lung cancer, including histological subtype, from enrollment (1993-1997) to 2010-2011 in relation to farm equipment use in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators and spouses in Iowa and North Carolina, USA. METHODS: Farm equipment use was reported by 21,273 farmers and 29,840 spouses. Rate ratios (RRs) were estimated separately for farmers and spouses with Poisson regression models adjusted for smoking and other confounders. We conducted stratified analyses by exposure to animals or stored grain, a surrogate for endotoxin exposure. RESULTS: Daily diesel tractor use (vs. no use) was positively associated with lung cancer in farmers (RR = 1.48; 95% CI: 0.87, 2.50; 35 exposed, 32 unexposed cases), particularly adenocarcinoma (RR = 3.39; 95% CI: 1.23, 9.33; 12 exposed, 7 unexposed cases). The association of adenocarcinoma with daily (vs. low/no) use of diesel tractors was stronger for farmers with no animal or stored grain exposures (RR = 6.23; 95% CI: 2.25, 17.25; 5 exposed, 18 unexposed cases) than among farmers with these exposures (RR = 1.19; 95% CI: 0.51, 2.79; 7 exposed, 27 unexposed cases) (p-interaction = 0.05). CONCLUSIONS: This study provides preliminary evidence of an increased risk of lung adenocarcinoma among daily drivers of diesel tractors and suggests that exposure to endotoxins may modify the impact of diesel exposure on lung cancer risk. Confirmation of these findings with more exposed cases and more detailed exposure information is warranted. http://dx.doi.org/10.1289/ehp.1409238, Introduction Diesel exhaust has recently been classified by the International Agency for Research on Cancer as a lung carcinogen based primarily on epidemiological findings in miners and truck drivers and [...]

BACKGROUND: Organochlorine (OC) insecticides and polychlorinated biphenyls (PCBs) have been shown to have estrogenic, antiestrogenic, or antiandrogenic properties; as a result, the impact of exposure to these compounds and risk of hormonal cancers, such as prostate cancer, is a concern. OBJECTIVES: We conducted a nested case--control study, using prospectively collected serum, to estimate associations between OC exposures and metastatic prostate cancer in a population-based cohort from Norway. METHODS: Sera from 150 cases and 314 controls matched on date of blood draw, age at blood draw, and region was used to determine concentrations of 11 OC pesticide metabolites and 34 PCB congeners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for quartiles of lipid-corrected metabolite levels were calculated using conditional logistic regression. RESULTS: Metastatic prostate cancer was two times as likely among men with serum concentrations of oxychlordane in the highest quartile compared with those in the lowest quartile (OR = 2.03; 95% CI: 1.03, 4.03; p-trend 0.05). Elevated but nonsignificant ORs were estimated for the highest versus lowest quartile of heptachlor epoxide, HCB, and mirex, although these exposures were correlated with oxychlordane. Findings for specific PCB congeners showed a significant inverse association between natural log-transformed lipid-adjusted PCB 44 and metastatic prostate cancer (OR = 0.74; 95% CI: 0.56, 0.97; p-trend = 0.02). CONCLUSIONS: Our study highlights the importance of estimating associations with specific OC chemicals and suggests a possible role of OC insecticides and PCBs in the etiology of metastatic prostate cancer. http://dx.doi.org/10.1289/ehp.1408245, Introduction Organochlorines (OCs) are a diverse group of persistent synthetic compounds that have been used as pesticides (mostly insecticides) and for various industrial and commercial applications. OC insecticides were widely [...]

Background: Olfactory impairment (OI) is common among older adults and independently predicts all-cause mortality and the risk of several major neurodegenerative diseases. Pesticide exposure may impair olfaction, but empirical evidence is lacking. Objective: We aimed to examine high pesticide exposure events (HPEEs) in relation to self-reported OI in participants in the Agricultural Health Study (AHS). Methods: We conducted multivariable logistic regression to examine the associations between HPEEs reported at enrollment (1993-1997) and self-reported OI at the latest AHS follow-up (2013-2015) among 11,232 farmers, using farmers without HPEEs as the reference or unexposed group. Results: A total of 1,186 (10.6%) farmers reported OI. A history of HPEEs reported at enrollment was associated with a higher likelihood of reporting OI two decades later {odds ratio (OR) = 1.49 [95% confidence interval (CI): 1.28, 1.73]}. In the analyses on the HPEE involving the highest exposure, the association appears to be stronger when there was a >4-h delay between HPEE and washing with soap and water [e.g., OR = 2.07 (95% CI: 1.48, 2.89) for 4-6 h vs. OR = 1.39 (95% CI: 1.11, 1.75) for Conclusions: HPEEs may cause long-lasting olfactory deficit. Future studies should confirm these findings with objectively assessed OI and also investigate potential mechanisms. https://doi.org/10.1289/EHP3713, Introduction The human sense of smell decreases with age. Olfactory impairment (OI), or poor sense of smell, is an understudied public health problem among older adults. OI affects up to [...]

BACKGROUND: Human exposure to phenols, including bisphenol A and parabens, is widespread. Evidence suggests that paternal exposure to environmental chemicals may adversely affect reproductive outcomes. OBJECTIVES: We evaluated associations of paternal phenol urinary concentrations with fertilization rate, embryo quality, implantation, and live birth. METHODS: Male-female couples who underwent in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a prospective study of environmental determinants of fertility and pregnancy outcomes were included. The geometric mean of males' specific gravity-adjusted urinary phenol concentrations measured before females' cycle was quantified. Associations between male urinary phenol concentrations and fertilization rate, embryo quality, implantation, and live birth were investigated using generalized linear mixed models to account for multiple cycles per couple. RESULTS: Couples (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations were not associated with fertilization or live birth following IVF. In adjusted models, compared with the lowest quartile of methyl paraben, paternal concentrations in the second quartile were associated with decreased odds of live birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82). CONCLUSIONS: To our knowledge, these are some of the first data on the association of paternal urinary phenol concentrations with reproduction and pregnancy outcomes. Although these results do not preclude possible adverse effects of paternal paraben exposures on such outcomes, given the modest sample size, further understanding could result from confirmation using a larger and more diverse population. http://dx.doi.org/10.1289/ehp.1408605, Introduction Humans experience ubiquitous exposure to phenols, including bisphenol A (BPA) and parabens. The National Report on Human Exposure to Environmental Chemicals [Centers for Disease Control and Prevention (CDC) 2013], [...]

BACKGROUND: Women living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities. OBJECTIVE: Our objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas. METHODS: We evaluated the following nonoccupational exposure pathways: paraoccupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal). RESULTS: Among 35 publications identified (published 1995-2013), several reported significant or suggestive (p < 0.1) associations between paraoccupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified. CONCLUSIONS: Evidence supported the importance of paraoccupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies. http://dx.doi.org/10.1289/ehp.1408273, Introduction Most evidence for health effects of pesticides in adults comes from studies of occupationally exposed men (McDuffie 1994, 2005). Relatively less is known about pesticide-related health effects in women, [...]