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Background: Because of unique exposures, studies among farmers may yield insights into the relationship between allergies and non-Hodgkin lymphoid (NHL) neoplasms. We evaluated farm characteristics, allergic symptoms and conditions, and risk of NHL including specific subtypes in the Agricultural Health Study, a prospective cohort of farmers and spouses from North Carolina and Iowa.Methods: We identified 710 incident cases of NHL (including chronic lymphocytic leukemia and multiple myeloma) among 82,370 participants with baseline data on crop and animal exposures, including 454 cases among 52,850 participants with baseline data on recent allergy symptoms (rhinitis) and living on a farm during childhood. HR and 95% confidence intervals (CI) were calculated using multivariable-adjusted proportional hazards models.Results: We observed reduced risks of NHL among farmers and spouses with rhinitis at baseline (HR, 0.63; 95% CI, 0.51–0.79), related to growing soybeans (HR, 0.80; 95% CI, 0.67–0.96), and among farmers who handled stored grains or hay (HR, 0.66; 95% CI, 0.52–0.82). Growing up on a farm was associated with increased NHL risk (HR, 1.51; 95% CI, 1.15–1.98). Results did not differ significantly by NHL subtype.Conclusions: Both the reduced risk of NHL among those with allergy symptoms and specific farm exposures in adulthood, and the increased risk among those who grew up on a farm suggest that the host immune response to agricultural allergens may influence NHL development.Impact: This prospective study is, to our knowledge, the first to investigate the relationship between allergy symptoms and NHL risk in farmers; confirmation of these findings in other farming populations is warranted. Cancer Epidemiol Biomarkers Prev; 24(3); 587–94. ©2015 AACR.

The GuLF STUDY is investigating health outcomes associated with oil spill-related chemical exposures among workers involved in the spill response and clean-up following the Deepwater Horizon disaster. Due to the lack of dermal exposure measurements, we estimated dermal exposures using a deterministic model, which we customized from a previously published model. Workers provided information on the frequency of contact with oil, tar, chemical dispersants applied to the oil spill and sea water, as well as the use of protective equipment, by job/activity/task. Professional judgment by industrial hygienists served as a source of information for other model variables. The model estimated dermal exposures to total hydrocarbons (THC), benzene, ethylbenzene, toluene, xylene, n-hexane (BTEX-H), polycyclic aromatic hydrocarbons (PAHs), and dispersants in GuLF DREAM units (GDUs). Arithmetic means (AMs) of THC exposure estimates across study participants ranged from 0.9) for most of the substances in oil but were lower for some of the substances in tar. These data were linked to the study participants to allow investigation of adverse health effects that may be related to dermal exposures.

Objectives Our objectives were to (i) determine correlations between measurements of THC and of BTEX-H, (ii) apply these linear relationships to predict BTEX-H from measured THC, (iii) use these correlations as informative priors in Bayesian analyses to estimate exposures. Methods We used a Bayesian left-censored bivariate framework for all 3 objectives. First, we modeled the relationships (i.e. correlations) between THC and each BTEX-H chemical for various overarching groups of measurements using linear regression to determine if correlations derived from linear relationships differed by various exposure determinants. We then used the same linear regression relationships to predict (or impute) BTEX-H measurements from THC when only THC measurements were available. Finally, we used the same linear relationships as priors for the final exposure models that used real and predicted data to develop exposure estimate statistics for each individual exposure group. Results Correlations between measurements of THC and each of the BTEX-H chemicals (n = 120 for each of BTEX, 36 for n-hexane) differed substantially by area of the Gulf of Mexico and by time period that reflected different oil-spill related exposure opportunities. The correlations generally exceeded 0.5. Use of regression relationships to impute missing data resulted in the addition of >23 000 n-hexane and 541 observations for each of BTEX. The relationships were then used as priors for the calculation of exposure statistics while accounting for censored measurement data. Conclusions Taking advantage of observed relationships between THC and BTEX-H allowed us to develop robust exposure estimates where a large amount of data were missing, strengthening our exposure estimation process for the epidemiologic study.

The GuLF Study is investigating adverse health effects from work on the response and clean-up after the Deepwater Horizon explosion and oil release. An essential and necessary component of that study was the exposure assessment. Bayesian statistical methods and over 135 000 measurements of total hydrocarbons (THC), benzene, ethylbenzene, toluene, xylene, and n-hexane (BTEX-H) were used to estimate inhalation exposures to these chemicals for >3400 exposure groups (EGs) formed from three exposure determinants: job/activity/task, location, and time period. Recognized deterministic models were used to estimate airborne exposures to particulate matter sized 2.5 µm or less (PM2.5) and dispersant aerosols and vapors. Dermal exposures were estimated for these same oil-related substances using a model modified especially for this study from a previously published model. Exposures to oil mist were assessed using professional judgment. Estimated daily THC arithmetic means (AMs) were in the low ppm range (

In the GuLF Study, a study investigating possible adverse health effects associated with work on the oil spill response and clean-up (OSRC) following the Deepwater Horizon disaster in the Gulf of Mexico, we used a job-exposure matrix (JEM) approach to estimate exposures. The JEM linked interview responses of study participants to measurement data through exposure groups (EGs). Here we describe a systematic process used to develop transparent and precise EGs that allowed characterization of exposure levels among the large number of OSRC activities performed across the Gulf of Mexico over time and space. EGs were identified by exposure determinants available to us in our measurement database, from a substantial body of other spill-related information, and from responses provided by study participants in a detailed interview. These determinants included: job/activity/task, vessel and type of vessel, weathering of the released oil, area of the Gulf of Mexico, Gulf coast state, and time period. Over 3000 EGs were developed for inhalation exposure and applied to each of 6 JEMs of oil-related substances (total hydrocarbons, benzene, toluene, ethylbenzene, total xylene, and n-hexane). Subsets of those EGs were used for characterization of exposures to dispersants, particulate matter, and oil mist. The EGs allowed assignment to study participants of exposure estimates developed from measurement data or from estimation models through linkage in the JEM for the investigation of exposure-response relationships.

ObjectivesOccupational asbestos exposure is causally linked to mesothelioma. However, whether exposure to only chrysotile asbestos is associated with mesothelioma risk, and the heterogeneity in risk by different fibre types/lengths remains unclear. We investigated whether mesothelioma risk differs among workers exposed to only chrysotile asbestos compared with chrysotile and ≥1 amphibole (ie, amosite, tremolite, anthophyllite and crocidolite) over the working lifetime.MethodsWe analysed next-of-kin interview data including occupational histories for 580 white men (176 cases and 404 controls) from a case–control study of mesothelioma conducted in the USA in 1975–1980. Asbestos exposure was determined by an occupational hygienist using a job-exposure matrix and exposure categories included chrysotile only and nine chrysotile–amphibole mixtures. Logistic regression models were used to estimate the ORs and 95% CIs of mesothelioma, comparing each asbestos category to the unexposed group, adjusted for age at death and data source. Analysis of contrasts was used to assess overall heterogeneity and pair-wise differences in risk.ResultsExposure to long and short chrysotile only was associated with increased mesothelioma risk compared with the unexposed (OR=3.8 (95% CI 1.3 to 11.2)). The complex mixture of extra-long amosite, short and long chrysotile, tremolite and anthophyllite was associated with the highest risk (OR=12.8 (95% CI 4.1 to 40.2)). There was evidence for overall heterogeneity among the asbestos exposure categories (p heterogeneity=0.02). However, the lower risk observed for exposure to chrysotile only compared with the complex mixture was not significant (p difference=0.10).ConclusionsOur findings suggest that policies aimed at regulating asbestos should target both pure chrysotile and mixtures that include amphibole.

Background The 2010 Deepwater Horizon (DWH) oil spill involved thousands of workers and volunteers to mitigate the oil release and clean-up after the spill. Health concerns for these participants led to the initiation of a prospective epidemiological study (GuLF STUDY) to investigate potential adverse health outcomes associated with the oil spill response and clean-up (OSRC). Characterizing the chemical exposures of the OSRC workers was an essential component of the study. Workers on the four oil rig vessels mitigating the spill and located within a 1852 m (1 nautical mile) radius of the damaged wellhead [the Discoverer Enterprise (Enterprise), the Development Driller II (DDII), the Development Driller III (DDIII), and the HelixQ4000] had some of the greatest potential for chemical exposures. Objectives The aim of this paper is to characterize potential personal chemical exposures via the inhalation route for workers on those four rig vessels. Specifically, we presented our methodology and descriptive statistics of exposure estimates for total hydrocarbons (THCs), benzene, toluene, ethylbenzene, xylene, and n-hexane (BTEX-H) for various job groups to develop exposure groups for the GuLF STUDY cohort. Methods Using descriptive information associated with the measurements taken on various jobs on these rig vessels and with job titles from study participant responses to the study questionnaire, job groups [unique job/rig/time period (TP) combinations] were developed to describe groups of workers with the same or closely related job titles. A total of 500 job groups were considered for estimation using the available 8139 personal measurements. We used a univariate Bayesian model to analyze the THC measurements and a bivariate Bayesian regression framework to jointly model the measurements of THC and each of the BTEX-H chemicals separately, both models taking into account the many measurements that were below the analytic limit of detection. Results Highest THC exposures occurred in TP1a and TP1b, which was before the well was mechanically capped. The posterior medians of the arithmetic mean (AM) ranged from 0.11 ppm (‘Inside/Other’, TP1b, DDII; and ‘Driller’, TP3, DDII) to 14.67 ppm (‘Methanol Operations’, TP1b, Enterprise). There were statistical differences between the THC AMs by broad job groups, rigs, and time periods. The AMs for BTEX-H were generally about two to three orders of magnitude lower than the THC AMs, with benzene and ethylbenzene measurements being highly censored. Conclusions Our results add new insights to the limited literature on exposures associated with oil spill responses and support the current epidemiologic investigation of potential adverse health effects of the oil spill.

Insecticide use has been linked to increased risk of non‐Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self‐reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B‐cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype‐specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20‐2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17‐2.16: FL, SLL) and DDT (OR = 1.36, 1.06‐1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (P trend = 1.7 × 10−4), chlordane (P trend = 1.0 × 10−3) and DDT (P trend = 4.2 × 10−3), however, the exposure‐response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45‐9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75‐16.53; P trend = 3.6 × 10−3). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure., What's new? Insecticides are persistent environmental pollutants that have been linked to increased risk of non‐Hodgkin lymphoma (NHL). Although NHL encompasses a heterogeneous group of malignancies, few studies have examined subtype‐specific associations for insecticide exposure. Analyzing data from population‐based case‐control studies of lymphatic cancers, the authors of this study show that lindane, chlordane, and DDT are associated with increased risk of multiple NHL subtypes. Analyses further uncovered a novel link between increased follicular lymphoma risk and pyrethrum use. None of the insecticides investigated, however, were associated with all NHL subtypes, suggesting a role for etiologic heterogeneity in pesticide exposure and NHL risk.

Background The herbicide dicamba has been commonly used agriculturally and residentially. Recent approval of genetically engineered dicamba-resistant crops is expected to lead to increased dicamba use, and there has been growing interest in potential human health effects. A prior analysis in the Agricultural Health Study (AHS) suggested associations between dicamba and colon and lung cancer. We re-evaluated dicamba use in the AHS, including an additional 12 years and 2702 exposed cancers. Methods The AHS is a prospective cohort of pesticide applicators in Iowa and North Carolina. At enrollment (1993–1997) and follow-up (1999–2005), participants reported dicamba use. Exposure was characterized by cumulative intensity-weighted lifetime days, including exposure lags of up to 20 years. We estimated relative risks (RR) and 95% confidence intervals (CI) using multivariable Poisson regression for incident cancers diagnosed from enrollment through 2014/2015. Results Among 49 922 applicators, 26 412 (52.9%) used dicamba. Compared with applicators reporting no dicamba use, those in the highest quartile of exposure had elevated risk of liver and intrahepatic bile duct cancer (nexposed = 28, RRQ4 = 1.80, CI: 1.26–2.56, Ptrend < 0.001) and chronic lymphocytic leukaemia (CLL, nexposed = 93, RRQ4 = 1.20, CI: 0.96–1.50, Ptrend = 0.01) and decreased risk of myeloid leukaemia (nexposed = 55, RRQ4 = 0.73, CI: 0.51–1.03, Ptrend = 0.01). The associations for liver cancer and myeloid leukaemia remained after lagging exposure of up to 20 years. Conclusions With additional follow-up and exposure information, associations with lung and colon cancer were no longer apparent. In this first evaluation of liver and intrahepatic bile duct cancer, there was an association with increasing use of dicamba that persisted across lags of up to 20 years.

Background: During the 2010 Deepwater Horizon (DWH) disaster, controlled burning was conducted to remove oil from the water. Workers near combustion sites were potentially exposed to increased fine particulate matter [with aerodynamic diameter ≤2.5μm (PM2.5)] levels. Exposure to PM2.5 has been linked to decreased lung function, but to our knowledge, no study has examined exposure encountered in an oil spill cleanup. Objective: We investigated the association between estimated PM2.5 only from burning/flaring of oil/gas and lung function measured 1–3 y after the DWH disaster. Methods: We included workers who participated in response and cleanup activities on the water during the DWH disaster and had lung function measured at a subsequent home visit (n=2,316). PM2.5 concentrations were estimated using a Gaussian plume dispersion model and linked to work histories via a job-exposure matrix. We evaluated forced expiratory volume in 1 s (FEV1; milliliters), forced vital capacity (FVC; milliliters), and their ratio (FEV1/FVC; %) in relation to average and cumulative daily maximum exposures using multivariable linear regressions. Results: We observed significant exposure–response trends associating higher cumulative daily maximum PM2.5 exposure with lower FEV1 (p-trend=0.04) and FEV1/FVC (p-trend=0.01). In comparison with the referent group (workers not involved in or near the burning), those with higher cumulative exposures had lower FEV1 [−166.8mL, 95% confidence interval (CI): −337.3, 3.7] and FEV1/FVC (−1.7, 95% CI: −3.6, 0.2). We also saw nonsignificant reductions in FVC (high vs. referent: −120.9, 95% CI: −319.4, 77.6; p-trend=0.36). Similar associations were seen for average daily maximum PM2.5 exposure. Inverse associations were also observed in analyses stratified by smoking and time from exposure to spirometry and when we restricted to workers without prespill lung disease. Conclusions: Among oil spill workers, exposure to PM2.5 specifically from controlled burning of oil/gas was associated with significantly lower FEV1 and FEV1/FVC when compared with workers not involved in burning. https://doi.org/10.1289/EHP8930

ObjectivesPyrethroid insecticides have been linked with multiple health outcomes. One study reported an association with increased all-cause and cardiovascular mortality. Given the widespread use of pyrethroids, these findings warrant confirmation. We explored associations of permethrin/pyrethroid use with overall and cause-specific mortality among 50 665 licensed pesticide applicators in the Agricultural Health Study.MethodsAt enrolment (1993–1997), participants self-reported information on permethrin/pyrethroid use. Information on causes of death came from linkage with death registries through 2016. We used Cox proportional hazards models to estimate HRs and 95% CIs with adjustment for potential confounders.ResultsOver an average 21 years of follow-up, 19.6% (9,955) of the cohort died. We found no clear evidence that ever-use of permethrin/pyrethroid was associated with elevated overall mortality or with mortality from most causes examined. There was suggestive evidence, based on a small number of deaths among those exposed, for elevated pyrethroid-associated mortality from some neurological, respiratory and genitourinary diseases in the overall sample and from lung cancer among never-smokers.ConclusionAlthough based on mortality, which is also affected by survival, rather than incidence, these findings are biologically plausible, and future investigations in other populations may be warranted.

Following publication of the original article [1], the authors reported an error in the unit of the average emission metric (AEI). The AEI was incorrectly reported as nanograms (ng) toxic equivalency quotient (TEQ)/year in the abstract, methods, discussion, and Table 1. The correct unit is grams (g) TEQ/year. The authors apologize for this error.

The NIEHS GuLF STUDY is an epidemiologic study of the health of workers who participated in the 2010 Deepwater Horizon oil spill response and clean-up effort. Even with a large database of approximately 28 000 personal samples that were analyzed for total hydrocarbons (THCs) and other oil-related chemicals, resulting in nearly 160 000 full-shift personal measurements, there were still exposure scenarios where the number of measurements was too limited to rigorously assess exposures. Also available were over 26 million volatile organic compounds (VOCs) area air measurements of approximately 1-min duration, collected from direct-reading instruments on 38 large vessels generally located near the leaking well. This paper presents a strategy for converting the VOC database into hourly average air concentrations by vessel as the first step of a larger process designed to use these data to supplement full-shift THC personal exposure measurements. We applied a Bayesian method to account for measurements with values below the analytic instrument’s limit of detection while processing the large database into average instrument-hour concentrations and then hourly concentrations across instruments on each day of measurement on each of the vessels. To illustrate this process, we present results on the drilling rig ship, the Discoverer Enterprise. The methods reduced the 26 million measurements to 21 900 hourly averages, which later contributed to the development of additional full-shift THC observations. The approach used here can be applied by occupational health professionals with large datasets of direct-reading instruments to better understand workplace exposures.

OBJECTIVES: Some epidemiological studies have suggested positive associations between glyphosate use and non-Hodgkin lymphoma (NHL), but evidence is inconsistent and few studies could evaluate histological sub-types. Here, associations between glyphosate use and NHL incidence overall and by histological sub-type were evaluated in a pooled analysis of case–control studies. METHODS: The analysis included 1690 NHL cases [647 diffuse large B-cell lymphoma (DLBCL), 468 follicular lymphoma (FL), 171 small lymphocytic lymphoma (SLL), and 404 other sub-types] and 5131 controls. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for NHL overall and sub-types with self-reported ever/never, duration, frequency, and lifetime-days of glyphosate use. RESULTS: Subjects who ever used glyphosate had an excess of NHL overall (OR 1.43, 95% CI 1.11–1.83). After adjustment for other pesticides, the OR for NHL overall with "ever use" was 1.13 (95% CI 0.84–1.51), with a statistically significant association for handling glyphosate >2 days/year (OR 1.73, 95% CI 1.02–2.94, P-trend=0.2). In pesticide-adjusted sub-type analyses, the ordinal measure of lifetime-days was statistically significant (P=0.03) for SLL, and associations were elevated, but not statistically significant, for ever years or days/year of use. Handling glyphosate >2 days/year had an excess of DLBCL (OR 2.14, 95% CI 1.07–4.28; P-trend=0.2). However, as with the other sub-types, consistent patterns of association across different metrics were not observed. CONCLUSIONS: There was some limited evidence of an association between glyphosate use and NHL in this pooled analysis. Suggestive associations, especially for SLL, deserve additional attention.

Research conducted in the wake of a disaster can provide information to help mitigate health consequences, support future recovery efforts, and improve resilience. However, a number of barriers have prevented time-sensitive research responses following previous disasters. Furthermore, large-scale disasters present their own special challenges due to the number of people exposed to disaster conditions, the number of groups engaged in disaster response, and the logistical challenges of rapidly planning and implementing a large study. In this case study, we illustrate the challenges in planning and conducting a large-scale post-disaster research study by drawing on our experience in establishing the Gulf Long-term Follow-up (GuLF) Study following the 2010 Deepwater Horizon disaster. We describe considerations in identifying at-risk populations and appropriate comparison groups, garnering support for the study from different stakeholders, obtaining timely scientific and ethics review, measuring and characterizing complex exposures, and addressing evolving community health concerns and unmet medical needs. We also describe the NIH Disaster Research Response (DR2) Program, which provides a suite of resources, including data collection tools, research protocols, institutional review board guidance, and training materials to enable the development and implementation of time-critical studies following disasters and public health emergencies. In describing our experiences related to the GuLF Study and the ongoing efforts through the NIH DR2 Program, we aim to help improve the timeliness, quality, and value of future disaster-related data collection and research studies.

Tens of thousands of individuals performed oil spill response and clean-up (OSRC) activities following the ‘Deepwater Horizon’ oil drilling rig explosion in 2010. Many were exposed to oil residues and dispersants. The US National Institute of Environmental Health Sciences assembled a cohort of nearly 33 000 workers to investigate potential adverse health effects of oil spill exposures. Estimates of dermal and inhalation exposure are required for those individuals. Ambient breathing-zone measurements taken at the time of the spill were used to estimate inhalation exposures for participants in the GuLF STUDY (Gulf Long-term Follow-up Study), but no dermal measurements were collected. Consequently, a modelling approach was used to estimate dermal exposures. We sought to modify DREAM (DeRmal Exposure Assessment Method) to optimize the model for assessing exposure to various oil spill-related substances and to incorporate advances in dermal exposure research. Each DREAM parameter was reviewed in the context of literature published since 2000 and modified where appropriate. To reflect the environment in which the OSRC work took place, the model treatment of evaporation was expanded to include vapour pressure and wind speed, and the effect of seawater on exposure was added. The modified model is called GuLF DREAM and exposure is estimated in GuLF DREAM units (GDU). An external validation to assess the performance of the model for oils, tars, and fuels was conducted using available published dermal wipe measurements of heavy fuel oil (HFO) and dermal hand wash measurements of asphalt. Overall, measured exposures had moderate correlations with GDU estimates (r = 0.59) with specific correlations of −0.48 for HFO and 0.68 for asphalt. The GuLF DREAM model described in this article has been used to generate dermal exposure estimates for the GuLF STUDY. Many of the updates made were generic, so the updated model may be useful for other dermal exposure scenarios.

Background: Epidemiologic studies suggest an increased risk of leukemia among individuals occupationally exposed to some organochlorine (OC) compounds. Associations between serum OC pesticide and polychlorinated biphenyl (PCB) levels and risk of acute myeloid leukemia (AML), the most common subtype of acute leukemia in adult populations, have not been evaluated prospectively in the general population. Objective: We evaluated the risk of AML in relation to pre-diagnostic serum levels of OC pesticides and PCBs in a case-control study nested within the Janus Serum Bank Cohort. Methods: Janus is a large population-based cohort containing biologic samples collected beginning in the early 1970s from ~318,000 individuals in Norway. Serum levels of 11 OC pesticides or their metabolites and 34 PCB congeners were measured in 56 AML cases and 288 controls. Conditional logistic regression was conducted to evaluate associations between lipid-adjusted serum OC levels and risk of AML. Results: Higher serum levels of total chlordane/heptachlor metabolites were associated with AML risk (3rd vs. 1st tertile odds ratio (OR) = 2.26, 95% confidence interval (CI) = 0.91–5.63; ptrend = 0.11). Significant exposure-response associations were observed for levels of heptachlor epoxide (3rd vs. 1st tertile OR = 2.85, 95% CI = 1.05–7.73; ptrend = 0.02) and dieldrin (3rd vs. 1st tertile OR = 2.71, 95% CI = 1.07–6.83; ptrend = 0.03). No significant exposure-response associations with AML risk were observed for total DDT or individual isomers and derivatives. Higher serum levels of p,p′-DDT showed a non-significant increase in risk, but the exposure-response became attenuated when co-adjusting for heptachlor epoxide or dieldrin levels. Serum PCB levels were not significantly associated with AML risk. Conclusions: Our data suggest that higher serum levels of dieldrin and metabolites derived from chlordane/heptachlor are associated with risk of AML in the general Norwegian population, based on samples collected on average ~17 years before diagnosis. Further research in populations with historically high or recent exposure to DDT is warranted to assess the association with AML risk with body burden of specific DDT isomers and derivatives. Keywords: Acute myeloid leukemia, Organochlorines, Pesticides, Polychlorinated biphenyls

We extended the mortality follow-up of a cohort of 25,460 workers employed at 8 acrylonitrile (AN)-producing facilities in the United States by 21 years. Using 8,124 deaths and 1,023,922 person-years of follow-up, we evaluated the relationship between occupational AN exposure and death. Standardized mortality ratios (SMRs) based on deaths through December 31, 2011, were calculated. Work histories and monitoring data were used to develop quantitative estimates of AN exposure. Hazard ratios were estimated by Cox proportional hazards regression. All-cause mortality and death from total cancer were less than expected compared with the US population. We observed an excess of death due to mesothelioma (SMR = 2.24, 95% confidence interval (CI): 1.39, 3.42); no other SMRs were elevated overall. Cox regression analyses revealed an elevated risk of lung and bronchial cancer (n = 808 deaths; for >12.1 ppm-year vs. unexposed, hazard ratio (HR) = 1.43, 95% CI: 1.13, 1.81; P for trend = 0.05), lagged 10 years, that was robust in sensitivity analyses adjusted for smoking and co-exposures including asbestos. Death resulting from bladder cancer (for >2.56 ppm vs. unexposed, lagged 10-year HR = 2.96, 95% CI: 1.38, 6.34; P for trend = 0.02) and pneumonitis (for >3.12 ppm-year vs. unexposed, HR = 4.73, 95% CI: 1.42, 15.76; P for trend = 0.007) was also associated with AN exposure. We provide additional evidence of an association between AN exposure and lung cancer, as well as possible increased risk for death due to bladder cancer and pneumonitis.

PURPOSE: To evaluate cancer incidence in the Agricultural Health Study (AHS), a cohort of private pesticide applicators, their spouses, and commercial applicators, based on 12,420 cancers, adding 5,989 cancers and nine years of follow-up since last evaluation. METHODS: We calculated age, year, sex, and race-adjusted standardized incidence ratios (SIR) and 95% confidence intervals (CI) for cancer sites in the AHS relative to the general population. RESULTS: Overall AHS cancer incidence was lower than the general population (SIR(private)=0.91, CI:0.89–0.93; SIR(spouse)=0.89, CI:0.86–0.92; SIR(commercial)=0.83, CI:0.76–0.92), with notable deficits across applicators and spouses for oral cavity, pancreas, and lung cancers. Cancer excesses included prostate cancer, lip cancer, certain B-cell lymphomas (e.g multiple myeloma), acute myeloid leukemia (AML), thyroid cancer, testicular cancer, and peritoneal cancer. The lung cancer deficit was strongest among applicators reporting potential exposure to endotoxin at study enrollment (tasks such as raising animals and handling stored grain). CONCLUSIONS: Although an overall deficit in cancer was observed, there were notable exceptions, including newly-observed excesses for AML, thyroid, testicular, and peritoneal cancers. Furthermore, endotoxin exposure may, in part, account for observed lung cancer incidence deficits. Cancer incidence patterns in the AHS suggest farm exposures’ relevance to cancer etiology.

The Deepwater Horizon oil spill response and clean-up (OSRC) involved over 9000 large and small vessels deployed in waters of the Gulf of Mexico across four states (Alabama, Florida, Louisiana, and Mississippi). For the GuLF STUDY, we developed exposure estimates of oil-related components for many work groups to capture a wide range of OSRC operations on these vessels, such as supporting the four rig vessels charged with stopping the spill at the wellhead; skimming oil; in situ burning of oil; absorbing and containing oil by boom; and environmental monitoring. Work groups were developed by: (i) vessel activity; (ii) location (area of the Gulf or state); and (iii) time period. Using Bayesian methods, we computed exposure estimates for these groups for: total hydrocarbons measured as total petroleum hydrocarbons (THC), benzene, toluene, ethylbenzene, xylene, and n-hexane (BTEX-H). Estimates of the arithmetic means for THC ranged from 0.10 ppm [95% credible interval (CI) 0.04, 0.38 ppm] in time periods 2 and 3 (16 July–30 September 2010) to 15.06 ppm (95% CI 10.74, 22.41 ppm) in time period 1a (22 April–15 May 2010). BTEX-H estimates were substantially lower (in the parts per billion range). Exposure levels generally fell over time and differed statistically by activity, location, and time for some groups. These exposure estimates have been used to develop job–exposure matrices for the GuLF STUDY.

ObjectivesPesticide exposure may impair human olfaction, but empirical evidence is limited. We examined associations between occupational use of 50 specific pesticides and olfactory impairment, both self-reported, among 20 409 participants in the Agricultural Health Study, a prospective cohort of pesticide applicators (mostly farmers, 97% male).MethodsWe used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between pesticide use at enrolment (1993–1997) and olfactory impairment reported two decades later (2013–2016), adjusting for baseline covariates.ResultsAbout 10% of participants reported olfactory impairment. The overall cumulative days of any pesticide use at enrolment were associated with a higher odds of reporting olfactory impairment (OR (highest vs lowest quartile): 1.17 (95% CI: 1.02 to 1.34), p-trend = 0.003). In the analyses of 50 specific pesticides, ever-use of 20 pesticides showed modest associations with olfactory impairment, with ORs ranging from 1.11 to 1.33. Of these, higher lifetime days of use of 12 pesticides were associated with higher odds of olfactory impairment compared with never use (p-trend ≤ 0.05), including two organochlorine insecticides (dichlorodiphenyltrichloroethane and lindane), two organophosphate insecticides (diazinon and malathion), permethrin, the fungicide captan and six herbicides (glyphosate, petroleum distillates, 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid and metribuzin), although many of these did not exhibit clear, monotonic exposure-response patterns.ConclusionOverall, we found relatively broad associations between pesticides and olfactory impairment, involving many individual pesticides and covering several chemical classes, suggesting that pesticides could affect olfaction through multiple pathways. Future epidemiological studies with objective measurement of olfaction are required to confirm these findings.

Background Extensive literature suggests an association between general pesticide use and Parkinson's disease (PD). However, with few exceptions, little is known about associations between specific pesticides and PD. Objective We evaluated use of pesticides and incident PD in 38,274 pesticide applicators and 27,836 of their spouses in the Agricultural Health Study cohort followed over 20 years. Methods We used self-reported information on ever-use of 50 specific pesticides as of enrollment for both applicators and spouses, and considered intensity-weighted lifetime days (IWLD) reported at enrollment and through the first 5-year follow-up among applicators. We estimated covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression. We also examined heterogeneity in associations by history of head injury and chemical resistant glove use. Results A total of 373 applicators and 118 spouses self-reported incident doctor-diagnosed PD. Ever-use of the insecticide terbufos (HR:1.31, 95%CI:1.02–1.68) and the herbicides trifluralin (HR:1.29, 95%CI: 0.99–1.70) and 2,4,5-T (HR:1.57, 95%CI:1.21–2.04) was associated with elevated PD risk. On the other hand, diazinon (HR:0.73, 95%CI: 0.58–0.94) and 2,4,5-TP (HR:0.39, 95%CI:0.25–0.62) were associated with reduced risk. We observed heterogeneity in ever-use associations by head injury and chemical-resistant glove use for some pesticides, with higher risk among those who reported a history of head injury, or who did not use gloves. PD risk was also elevated for applicators in the highest category of IWLD for dichlorvos, permethrin (animal use), and benomyl. Conclusions We found evidence of increased PD risk for some pesticides. Our results also suggest higher susceptibility for pesticide-associated PD among individuals with head injury as well as protection with use of chemical resistant gloves, although further research is needed to understand the impact of head injury. Research on current and newer pesticides, including mechanisms relevant to PD, is important given widespread pesticide use.

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 RRIWD Tertile 3=2.92 (95% CI: 1.65, 5.17; ptrend=0.001)], with similar risk estimates for lagged exposure [20-y lag RRIWD Tertile 3=3.37 (95% CI: 1.83, 6.22; ptrend=0.001)]. In 20-y lagged analyses, we also found exposure–response associations with chlorpyrifos [RRIWD Quartile 4=1.68 (95% CI: 1.05, 2.70; ptrend=0.01)], chlordane [RRIWD Tertile 3=2.06 (95% CI: 1.10, 3.87; ptrend=0.02)], atrazine [RRIWD Quartile 4=1.43 (95% CI: 1.00, 2.03; ptrend=0.02)], cyanazine [RRIWD Quartile 4=1.61 (95% CI: 1.03, 2.50; ptrend=0.02)], and paraquat [RRIWD>Median=1.95 (95% CI: 1.03, 3.70; ptrend=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

Background Although occupational exposure to animals has been associated with lymphohematopoietic malignancies, to our knowledge no studies have evaluated adult cancer risks associated with living near intensive animal agriculture. Methods We linked participants in the prospective Agricultural Health Study to permitted animal feeding operations in Iowa. We created metrics reflecting the intensity of animal exposures within 2 and 5 km of participants' residences, enumerating both total and inverse distance-weighted animal units (AUs), standardized by animal size and manure production. We estimated risk of lymphohematopoietic malignancies and subtypes [hazard ratio (HR), 95% confidence interval (95% CI)], adjusting for demographic and farming-related factors, including occupational pesticide exposure. We stratified associations by animal type and animal-related work activities. Results We observed 519 cases (1993-2015) among 32,635 pesticide applicators and 211 cases among 19,743 spouses. Among applicators, no associations were evident within 2 km, but risk of any lymphohematopoietic cancer was elevated across quintiles of weighted AUs within 5 km. Risk of non-Hodgkin lymphoma (NHL) was elevated for the second (HR = 1.5; 95% CI, 1.1, 2.1), third (HR = 1.6; 95% CI, 1.1, 2.2), and fourth (HR = 1.7; 95% CI, 1.3, 2.4) highest quintiles of weighted AUs within 5 km (Ptrend = 0.52) and increased with dairy cattle AUs (Ptrend = 0.04). We found positive trends for leukemia and some NHL subtypes with increasing numbers of both beef and dairy cattle. Risks did not vary by animal-related work (Pinteraction = 0.61). Associations were similar using the total exposure metric and inconsistent among spouses. Conclusion Residential proximity to intensive animal agriculture was positively associated with risk of NHL and leukemia, even after consideration of occupational animal and pesticide exposures.

Background Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men in developed countries; however, little is known about modifiable risk factors. Some studies have implicated organochlorine and organophosphate insecticides as risk factors (particularly the organodithioate class) and risk of clinically significant PCa subtypes. However, few studies have evaluated other pesticides. We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators in North Carolina and Iowa, to extend our previous work and evaluate 39 additional pesticides and aggressive PCa. Methods We used Cox proportional hazards models, with age as the time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ever use of individual pesticides and 883 cases of aggressive PCa (distant stage, poorly differentiated grade, Gleason score ≥ 7, or fatal prostate cancer) diagnosed between 1993 and 2015. All models adjusted for birth year, state, family history of PCa, race, and smoking status. We conducted exposure-response analyses for pesticides with reported lifetime years of use. Results There was an increased aggressive PCa risk among ever users of the organodithioate insecticide dimethoate (n = 54 exposed cases, HR = 1.37, 95% CI = 1.04, 1.80) compared to never users. We observed an inverse association between aggressive PCa and the herbicide triclopyr (n = 35 exposed cases, HR = 0.68, 95% CI = 0.48, 0.95), with the strongest inverse association for those reporting durations of use above the median (≥ 4 years; n = 13 exposed cases, HR=0.44, 95% CI=0.26, 0.77). Conclusion Few additional pesticides were associated with prostate cancer risk after evaluation of extended data from this large cohort of private pesticide applicators.

Purpose With observational epidemiologic studies, there is often concern that an unmeasured variable might confound an observed association. Investigators can assess the impact from such unmeasured variables on an observed relative risk (RR) by utilizing externally sourced information and applying an indirect adjustment procedure, for example, the “Axelson adjustment.” Although simple and easy to use, this approach applies to exposure and confounder variables that are binary. Other approaches eschew specific values and provide only bounds on the potential bias. Methods For both multiplicative and additive RR models, we present formulae for indirect adjustment of observed RRs for unmeasured potential confounding variables when there are multiple categories. In addition, we suggest an alternative strategy to identify the characteristics that the confounder must have to explain fully the observed association. Results and Conclusions We provide examples involving studies of pediatric computer tomography scanning and leukemia and nuclear radiation workers and smoking to demonstrate that with externally sourced information, an investigator can assess whether confounding from unmeasured factors is likely to occur.

Residents of agricultural areas experience pesticide exposures from sources other than direct agricultural work. We developed a quantitative, active ingredient-specific algorithm for cumulative (adult, married lifetime) non-occupational pesticide exposure intensity for spouses of farmers who applied pesticides in the Agricultural Health Study (AHS). The algorithm addressed three exposure pathways: take-home, agricultural drift, and residential pesticide use. Pathway-specific equations combined (i) weights derived from previous meta-analyses of published pesticide exposure data and (ii) information from the questionnaire on frequency and duration of pesticide use by applicators, home proximity to treated fields, residential pesticide usage (e.g., termite treatments), and spouse's off-farm employment (proxy for time at home). The residential use equation also incorporated a published probability matrix that documented the likelihood active ingredients were used in home pest treatment products. We illustrate use of these equations by calculating exposure intensities for the insecticide chlorpyrifos and herbicide atrazine for 19,959 spouses. Non-zero estimates for ≥1 pathway were found for 78% and 77% of spouses for chlorpyrifos and atrazine, respectively. Variability in exposed spouses' intensity estimates was observed for both pesticides, with 75th to 25th percentile ratios ranging from 7.1 to 7.3 for take-home, 6.5 to 8.5 for drift, 2.4 to 2.8 for residential use, and 3.8 to 7.0 for the summed pathways. Take-home and drift estimates were highly correlated (≥0.98), but were not correlated with residential use (0.01‒0.02). This algorithm represents an important advancement in quantifying non-occupational pesticide relative exposure differences and will facilitate improved etiologic analyses in the AHS spouses. The algorithm could be adapted to studies with similar information.

Background Much of the marked increase in incidence of non-Hodgkin lymphoma (NHL) over the past few decades remains unexplained. Organochlorines, including organochlorine pesticides (OCPs), have been implicated as possible contributors to the increase, but the evidence is inconsistent. Objectives To investigate the relation between pre-diagnostic levels of OCPs and risk of NHL in a case-control study nested within the population-based Janus Serum Bank Cohort in Norway. Methods Prediagnostic concentrations of 11 OCPs or OCP metabolites were measured in baseline blood samples collected between 1972 and 1978 from 190 cases and 190 controls matched on sex, county, age at blood draw, and date of blood draw. We conducted conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for each quartile of lipid-corrected OCP/metabolite relative to the lowest quartile. Results We observed non-significantly elevated ORs across quartiles of β-hexachlorocyclohexane compared to the lowest quartile (OR range: 1.40–1.82) although with no apparent monotonic exposure-response relationship. We also found an inverse association between risk of NHL and o,p'-DDT (OR for Q4 vs. Q1 = 0.44, 95% CI: 0.19, 1.01; p-trend = 0.05). In analyses stratified by age at blood collection and duration of follow-up, several other analytes, primarily chlordane-related compounds, showed inverse associations among younger participants or those with longer follow-up time between blood draw and NHL diagnosis. Conclusions We found only limited evidence of positive association between selected OCPs and development of NHL.

Background The herbicide alachlor has been widely used in US agriculture since its introduction in 1969. Experimental animal studies show that alachlor causes tumors in vivo; however, few epidemiologic studies have examined associations with human cancer risk. We evaluated alachlor use and cancer incidence in the Agricultural Health Study, updating an earlier analysis that suggested associations with lymphohematopoietic cancers with an additional 540 142 person-years of follow-up and 5113 cancer cases. Methods Pesticide applicators in Iowa and North Carolina reported lifetime alachlor use at enrollment (1993-1997) and follow-up (1999-2005). Exposure was characterized by cumulative intensity-weighted days. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using Poisson regression for incident cancers from enrollment through 2012(NC)/2013(IA). Models adjusted for age, tobacco, alcohol, and other pesticides. All statistical tests are two-sided. Results Among 49 685 applicators, 25 640 (51.6%) used alachlor, with 3534 alachlor-exposed cancers. The relative risks of laryngeal cancer (nexposed = 34) increased in the second (RR = 4.68, 95% CI = 1.95 to 11.23), third (RR = 6.04, 95% CI = 2.44 to 14.99), and fourth quartiles (RR = 7.10, 95% CI = 2.58 to 19.53) of intensity-weighted days of use compared with no use (Ptrend = .001). Risk of myeloid leukemia was elevated, though not statistically significantly so, in the fourth quartile of intensity-weighted days of use (RR = 1.82, 95% CI = 0.85 to 3.87, Ptrend = .17). Conclusions We observed a strong positive association with use of alachlor and laryngeal cancer and a weaker association with myeloid leukemia. The strength and robustness of the association with laryngeal cancer suggests that long-term occupational exposure to alachlor may be a risk factor for laryngeal cancer. This first report requires confirmation.