Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study.

BACKGROUND: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. METHODS: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. RESULTS: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs.

Health outcomes among offspring of US Coast Guard responders to the Deepwater Horizon oil spill, 2010-2011.

OBJECTIVE: To evaluate the potential for adverse health outcomes among infants born to US Coast Guard (USCG) responders to the Deepwater Horizon (DWH) oil spill disaster. METHODS: Department of Defense Birth and Infant Health Research programme data identified a cohort of singleton infants born 2010-2011 to USCG personnel in the DWH Oil Spill Coast Guard Cohort study. Infants were included if their military parent ('sponsor') responded to the oil spill during a selected reproductive exposure window (ie, 3 months preconception for male sponsors and periconception through pregnancy for female sponsors), or if their sponsor was a non-responder. χ2 tests and multivariable log-binomial regression were used to compare the demographic and health characteristics of infants born to spill responders and non-responders. RESULTS: Overall, 1974 infants with a male sponsor (n=182 responder, n=1792 non-responder) and 628 infants with a female sponsor (n=35 responder, n=593 non-responder) in the DWH Oil Spill Coast Guard Cohort were identified. Health outcomes were similar among the offspring of male responders and non-responders. The frequency of any poor live birth outcome (ie, low birth weight, preterm birth or birth defect) was higher among infants born to female responders (17.1%, n=6) than non-responders (8.9%, n=53); the maternal age-adjusted association was suggestively elevated (risk ratio 1.93, 95% CI 0.89 to 4.16). CONCLUSION: Infant health outcomes were comparable between the offspring of male USCG oil spill responders and non-responders. Findings were limited by the small number of infants identified, particularly among female responders, and should be interpreted with caution.

Risk of longer-term neurological conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort Study - Five years of follow-up.

BACKGROUND: Long-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill. METHODS: We used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010-2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking. RESULTS: Compared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only. CONCLUSION: In this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions.

Incidence of chronic respiratory conditions among oil spill responders: Five years of follow-up in the Deepwater Horizon Oil Spill Coast Guard Cohort study.

BACKGROUND: Over ten years after the Deepwater Horizon (DWH) oil spill, our understanding of long term respiratory health risks associated with oil spill response exposures is limited. We conducted a prospective analysis in a cohort of U.S. Coast Guard personnel with universal military healthcare. METHODS: For all active duty cohort members (N = 45,193) in the DWH Oil Spill Coast Guard Cohort Study we obtained medical encounter data from October 01, 2007 to September 30, 2015 (i.e., ~2.5 years pre-spill; ~5.5 years post-spill). We used Cox Proportional Hazards regressions to calculate adjusted hazard ratios (aHR), comparing risks for incident respiratory conditions/symptoms (2010-2015) for: responders vs. non-responders; responders reporting crude oil exposure, any inhalation of crude oil vapors, and being in the vicinity of burning crude oil versus responders without those exposures. We also evaluated self-reported crude oil and oil dispersant exposures, combined. Within-responder comparisons were adjusted for age, sex, and smoking. RESULTS: While elevated aHRs for responder/non-responder comparisons were generally weak, within-responder comparisons showed stronger risks with exposure to crude oil. Notably, for responders reporting exposure to crude oil via inhalation, there were elevated risks for allsinusitis (aHR = 1.48; 95%CI, 1.06-2.06), unspecified chronic sinusitis (aHR = 1.55; 95%CI, 1.08-2.22), chronic obstructive pulmonary disease (COPD) and other allied conditions (aHR = 1.43; 95%CI, 1.00-2.06), and dyspnea and respiratory abnormalities (aHR = 1.29; 95%CI, 1.00-1.67); there was a suggestion of elevated risk for diseases classified as asthma and reactive airway diseases (aHR = 1.18; 95%CI, 0.98-1.41), including the specific condition, asthma (aHR = 1.35; 95%CI, 0.80-2.27), the symptom, shortness of breath (aHR = 1.50; 95%CI, 0.89-2.54), and the overall classification of chronic respiratory conditions (aHR = 1.18; 95%CI, 0.98-1.43). Exposure to both crude oil and dispersant was positively associated with elevated risk for shortness of breath (HR = 2.24; 95%CI, 1.09-4.64). CONCLUSIONS: Among active duty Coast Guard personnel, oil spill clean-up exposures were associated with moderately increased risk for longer term respiratory conditions.

A nested case-control study of serum polychlorinated biphenyls and papillary thyroid cancer risk among U.S. military service members.

BACKGROUND AND OBJECTIVES: Although polychlorinated biphenyls (PCBs) were banned decades ago, populations are continuously exposed to PCBs due to their persistence and bioaccumulation/biomagnification in the environment. Results from limited epidemiologic studies linking PCBs to thyroid cancer have been inconclusive. This study aimed to investigate the association between individual PCBs and PCB mixture and papillary thyroid cancer (PTC), the most common thyroid cancer histologic subtype. METHODS: We carried out a nested case-control study including 742 histologically confirmed PTC cases diagnosed in 2000-2013 and 742 individually matched controls among U.S. military service members. Pre-diagnostic serum samples that were collected on average nine years before PTC diagnosis were used to measure PCB congeners by gas chromatography isotope dilution high resolution mass spectrometry (GC/ID-HRMS). Conditional logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression were employed to estimate the association between single PCB congeners as well as their mixture and PTC. RESULTS: Four PCB congeners (PCB-74, PCB-99, PCB-105, PCB-118) had significant associations and dose-response relationships with increased risk of PTC in single congener models. When considering the effects from all measured PCBs and their potential interactions in the BKMR model, PCB-118 showed positive trends of association with PTC. Increased exposure to the PCB congeners as a mixturewas also associated with an increased risk of PTC in the WQS model, with the mixture dominated by PCB-118, followed by PCB-74 and PCB-99. One PCB congener, PCB-187, showed an inverse trend of association with PTC in the mixture analysis. DISCUSSION: This study suggests that exposure to certain PCBs as well as a mixture of PCBs were associated with an increased risk of PTC. The observed association was mainly driven by PCB-118, and to a lesser extent by PCB-74 and PCB-99. The findings warrant further investigation.

Risk factors for acute mental health symptoms and tobacco initiation in Coast Guard Responders to the Deepwater Horizon oil spill.

Acute mental health symptoms experienced during oil spill response work are understudied, especially among nonlocal responders. We assessed potential risk factors for acute mental health symptoms and tobacco initiation among U.S. Coast Guard responders to the 2010 Deepwater Horizon (DWH) oil spill who completed a deployment exit survey. Cross-sectional associations among responder characteristics, deployment-related stressors (deployment duration, timing, crude oil exposure, physical symptoms, injuries), and professional help-seeking for stressors experienced with concurrent depression/anxiety and tobacco initiation were examined. Log-binomial regression was used to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals. Sensitivity analyses excluded responders with a history of mental health conditions using health encounter data from the Military Health System Data Repository. Of the 4,855 responders, 75.5% were deployed from nonlocal/non-Gulf home stations, 5.8% reported concurrent depression and anxiety, and 2.8% reported the initiation of any tobacco product during oil spill response. Self-report of concurrent depression and anxiety was more prevalent among female responders and positively associated with longer deployments, crude oil exposure via inhalation, physical symptoms and injuries, and professional help-seeking during deployment, aPRs = 1.54-6.55. Tobacco initiation was inversely associated with older age and officer rank and positively associated with deployment-related stressors and depression/anxiety during deployment, aPRs = 1.58-4.44. Associations remained robust after excluding responders with a history of mental health- and tobacco-related health encounters up to 3 years before deployment. Depression, anxiety, and tobacco initiation were cross-sectionally associated with oil spill response work experiences among DWH responders, who largely originated outside of the affected community.

A review of the toxicology of oil in vertebrates: what we have learned following the Deepwater Horizon oil spill.

In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.

The deepwater horizon oil spill coast guard cohort study: A cross-sectional study of acute respiratory health symptoms.

INTRODUCTION: Over 8500 United States Coast Guard (USCG) personnel were deployed in response to the Deepwater Horizon (DWH) oil spill; however, human respiratory effects as a result of spill-related exposures are relatively unknown. METHODS: USCG personnel who responded to the DWH oil spill were queried via survey on exposures to crude oil and oil dispersant, and acute respiratory symptoms experienced during deployment. Adjusted log binomial regressions were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI), investigating the associations between oil spill exposures and respiratory symptoms. RESULTS: 4855 USCG personnel completed the survey. More than half (54.6%) and almost one-fourth (22.0%) of responders were exposed to crude oil and oil dispersants, respectively. Coughing was the most prevalent symptom (19.4%), followed by shortness of breath (5.5%), and wheezing (3.6%). Adjusted analyses showed an exposure-response relationship between increasing deployment duration and likelihood of coughing, shortness of breath, and wheezing in the pre-capping period. A similar pattern was observed in the post-capping period for coughing and wheezing. Adjusted analyses revealed increased PRs for coughing (PR=1.92), shortness of breath (PR=2.60), and wheezing (PR=2.68) for any oil exposure. Increasing frequency of inhalation of oil was associated with increased likelihood of all three respiratory symptoms. A similar pattern was observed for contact with oil dispersants for coughing and shortness of breath. The combination of both oil and oil dispersants presented associations that were much greater in magnitude than oil alone for coughing (PR=2.72), shortness of breath (PR=4.65), and wheezing (PR=5.06). CONCLUSIONS: Results from the present study suggested strong relationships between oil and oil dispersant exposures and acute respiratory symptoms among disaster responders. Future prospective studies will be needed to confirm these findings.

Cancer incidence and metolachlor use in the Agricultural Health Study: An update.

Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-1997. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n = 5,701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors.

Endocrine disrupting chemical mixture exposure and risk of papillary thyroid cancer in U.S. military personnel: A nested case-control study.

Single-pollutant methods to evaluate associations between endocrine disrupting chemicals (EDCs) and thyroid cancer risk may not reflect realistic human exposures. Therefore, we evaluated associations between exposure to a mixture of 18 EDCs, including polychlorinated biphenyls (PCBs), brominated flame retardants, and organochlorine pesticides, and risk of papillary thyroid cancer (PTC), the most common thyroid cancer histological subtype. We conducted a nested case-control study among U.S. military servicemembers of 652 histologically-confirmed PTC cases diagnosed between 2000 and 2013 and 652 controls, matched on birth year, sex, race/ethnicity, military component (active duty/reserve), and serum sample timing. We estimated mixture odds ratios (OR), 95% confidence intervals (95% CI), and standard errors (SE) for associations between pre-diagnostic serum EDC mixture concentrations, overall PTC risk, and risk of histological subtypes of PTC (classical, follicular), adjusted for body mass index and military branch, using quantile g-computation. Additionally, we identified relative contributions of individual mixture components to PTC risk, represented by positive and negative weights (w). A one-quartile increase in the serum mixture concentration was associated with a non-statistically significant increase in overall PTC risk (OR = 1.19; 95% CI = 0.91, 1.56; SE = 0.14). Stratified by histological subtype and race (White, Black), a one-quartile increase in the mixture was associated with increased classical PTC risk among those of White race (OR = 1.59; 95% CI = 1.06, 2.40; SE = 0.21), but not of Black race (OR = 0.95; 95% CI = 0.34, 2.68; SE = 0.53). PCBs 180, 199, and 118 had the greatest positive weights driving this association among those of White race (w = 0.312, 0.255, and 0.119, respectively). Findings suggest that exposure to an EDC mixture may be associated with increased classical PTC risk. These findings warrant further investigation in other study populations to better understand PTC risk by histological subtype and race.

Exposure patterns among Coast Guard responders to the Deepwater Horizon Oil Spill: A latent class analysis.

Background: The Deepwater Horizon Oil Spill was an environmental crisis for which multiple groups, including the United States Coast Guard (USCG), provided emergency response services. A cohort of 5,665 USCG oil spill responders completed postdeployment surveys eliciting information on a variety of topics, including oil spill-related exposures and experiences. Our objective was to determine the most common exposure patterns among USCG responders. Methods: We used latent class analysis based on six indicator variables reflecting different aspects of the responders' experiences: exposure to oil, exposure to engine exhaust fumes or carbon monoxide, hand sanitizer use, sunblock use, mosquito bites, and level of anxiety. We validated our interpretation of these latent classes using ancillary variables. Results: The model distinguished four distinct exposure profiles, which we interpreted as "low overall exposure" (prevalence estimate = 0.18), "low crude oil/exhaust and moderate time outdoors/anxiety (prevalence estimate = 0.18), "high crude oil/exhaust and moderate time outdoors/anxiety" (prevalence estimate = 0.25), and "high overall exposure" (prevalence estimate = 0.38). The validation analysis was consistent with our interpretation of the latent classes. Conclusions: The exposure patterns identified in this analysis can help inform future studies of the health impacts of exposure mixtures among USCG oil spill responders.

Acute and longer-term cardiovascular conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort.

INTRODUCTION: In 2010, the U.S. Coast Guard (USCG) led a clean-up response to the Deepwater Horizon (DWH) oil spill. Human studies evaluating acute and longer-term cardiovascular conditions associated with oil spill-related exposures are sparse. Thus, we aimed to investigate prevalent and incident cardiovascular symptoms/conditions in the DHW Oil Spill Coast Guard Cohort. METHODS: Self-reported oil spill exposures and cardiovascular symptoms were ascertained from post-deployment surveys (n = 4,885). For all active-duty cohort members (n = 45,193), prospective cardiovascular outcomes were classified via International Classification of Diseases, 9th Edition from military health encounter records up to 5.5 years post-DWH. We used log-binomial regression to calculate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) in the cross-sectional analyses and Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% CIs for incident cardiovascular diagnoses during 2010-2015 and stratifying by earlier (2010-2012) and later (2013-2015) time periods. RESULTS: Prevalence of chest pain was associated with increasing levels of crude oil exposure via inhalation (aPRhigh vs. none = 2.00, 95% CI = 1.16-3.42, p-trend = 0.03) and direct skin contact (aPRhigh vs. none = 2.72, 95% CI = 1.30-5.16, p-trend = 0.03). Similar associations were observed for sudden heartbeat changes and for being in the vicinity of burning oil exposure. In prospective analyses, responders (vs. non-responders) had an elevated risk for mitral valve disorders during 2013-2015 (aHR = 2.12, 95% CI = 1.15-3.90). Responders reporting ever (vs. never) crude oil inhalation exposure were at increased risk for essential hypertension, particularly benign essential hypertension during 2010-2012 (aHR = 2.00, 95% CI = 1.08-3.69). Responders with crude oil inhalation exposure also had an elevated risk for palpitations during 2013-2015 (aHR = 2.54, 95% CI = 1.36-4.74). Cardiovascular symptoms/conditions aPR and aHR estimates were generally stronger among responders reporting exposure to both crude oil and oil dispersants than among those reporting neither. CONCLUSIONS: In this large study of the DWH oil spill USCG responders, self-reported spill clean-up exposures were associated with acute and longer-term cardiovascular symptoms/conditions.

Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study.

OBJECTIVE: Terbufos is the fourth most commonly used organophosphate insecticide (OP) in the United States. Terbufos has not been demonstrated to be carcinogenic in rodents, although non-arsenical insecticides, including OPs, have been associated with excess cancer in epidemiologic studies. We investigated associations between use of terbufos and the incidence of cancer. METHODS: The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Terbufos intensity-weighted lifetime exposure-days were defined as (lifetime exposure-days) x (exposure intensity score). Cases include all first primary cancers diagnosed between enrollment and December 31, 2005. Hazard ratios (HR) and 95% CI were calculated with Cox proportional hazards models, adjusting for potential confounders. RESULTS: Overall cancer risk was slightly increased among terbufos users [HR 1.21 (1.06-1.37)]. Suggestive associations were observed between terbufos use and cancers of the prostate (HR(highest tertile) = 1.21; 95% CI = 0.99-1.47) and lung (HR(middle tertile) = 1.45; 95% CI = 0.95-2.22) and leukemia (HR(middle tertile) = 2.38; 95% CI = 1.35-4.21) and non-Hodgkin's lymphoma (HR(middle tertile) = 1.94; 95% CI = 1.16-3.22), although the exposure-response gradients were non-monotonic and p for trends were not significant. CONCLUSION: We found suggestive associations between occupational terbufos use and several cancer sites. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.

Effectiveness, suitability, and performance testing of the SKC Deployable Particulate Sampler (DPS) as compared to the currently deployed Airmetrics MiniVol portable air sampler.

Epidemiological studies have linked particulate matter (PM) exposure to morbidity and mortality from cardiovascular and respiratory disease. In order to monitor and assess the potential PM health risk to deployed military personnel, the U.S. Army must field a portable sampler that can accurately sample particles with an aerodynamic diameter less than or equal to a nominal 2.5 mm (PM2.5). In the study described in this article, the SKC Deployable Particulate Sampler (DPS) was compared to the currently deployed Airmetrics MiniVol portable air sampler in the hot, dry environment of Yuma Proving Grounds, Arizona, and the cold, wet environment of Fort Drum, New York. For all measurements taken and averaged, the DPS and the MiniVol did not differ significantly for mean concentration collected; however, the DPS collected 4.0 times more mass than the MiniVol (p < .05). The DPS was shown to be an improvement over the MiniVol when evaluated for measures of effectiveness, suitability, and performance.

Heterocyclic aromatic amine pesticide use and human cancer risk: results from the U.S. Agricultural Health Study.

Imazethapyr, a heterocyclic aromatic amine, is a widely used crop herbicide first registered for use in the United States in 1989. We evaluated cancer incidence among imazethapyr-exposed pesticide applicators enrolled in the Agricultural Health Study (AHS). The AHS is a prospective cohort of 57,311 licensed pesticide applicators in the U.S., enrolled from 1993-1997. Among the 49,398 licensed pesticide applicators eligible for analysis, 20,646 applicators reported use of imazethapyr and 2,907 incident cancers developed through 2004. Imazethapyr exposure was classified by intensity-weighted lifetime exposure days calculated as [years of use x days per year x intensity level]. Poisson regression analysis was used to evaluate the relationship between imazethapyr exposure and cancer incidence. We found significant trends in risk with increasing lifetime exposure for bladder cancer (p for trend 0.01) and colon cancer (p for trend 0.02). Rate ratios (RRs) were increased by 137% for bladder cancer and 78% for colon cancer when the highest exposed were compared to the nonexposed. The excess risk for colon cancer was limited to proximal cancers, (RR = 2.73, 95% confidence intervals 1.42, 5.25, p for trend 0.001). No association was observed for prostate, lung, rectum, kidney, oral, pancreas, lymphohematopoietic cancers or melanoma. These findings provide new evidence that exposure to aromatic amine pesticides may be an overlooked exposure in the etiology of bladder and colon cancer. The use of imazethapyr and other imidazolinone compounds should continue to be evaluated for potential risk to humans.

Environmental Heat Exposure and Heat-Related Symptoms in United States Coast Guard Deepwater Horizon Disaster Responders.

OBJECTIVES: The response to the 2010 Deepwater Horizon oil spill was impacted by heat. We evaluated the association between environmental heat exposure and self-reported heat-related symptoms in US Coast Guard Deepwater Horizon disaster responders. METHODS: Utilizing climate data and postdeployment survey responses from 3648 responders, we assigned heat exposure categories based on both wet bulb globe temperature (WBGT) and heat index (HI) measurements (median, mean, maximum). We calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) via adjusted Poisson regression models with robust error variance to estimate associations with reported heat-related symptoms. We also evaluated the association between use of personal protective equipment (PPE) and heat-related symptoms. RESULTS: Those in the highest WBGT median-based heat exposure category had increased prevalence of heat-related symptoms compared to those in the lowest category (PR=2.22 [95% CI: 1.61, 3.06]), and there was a significant exposure-response trend (P<.001). Results were similar for exposure categories based on WBGT and HI metrics. Analyses stratified by use of PPE found significantly stronger associations between environmental heat exposure and heat-related symptoms in those who did not use PPE (PR=2.23 [95% CI: 1.10, 4.51]) than in those who did (PR=1.64 [95% CI: 1.14, 2.36]). CONCLUSIONS: US Coast Guard Deepwater Horizon disaster responders who experienced higher levels of environmental heat had higher prevalences of heat-related symptoms. These symptoms may impact health, safety, and mission effectiveness. As global climate change increases the frequency of disasters and weather extremes, actions must be taken to prevent heat-related health impacts among disaster responders. (Disaster Med Public Health Preparedness. 2019;13:561-569).

Neurological symptoms associated with oil spill response exposures: Results from the Deepwater Horizon Oil Spill Coast Guard Cohort Study.

INTRODUCTION: The Deepwater Horizon (DWH) oil spill was the largest marine oil spill in U.S. history, involving the response of tens of thousands clean-up workers. Over 8500 United States Coast Guard personnel were deployed in response to the spill. Little is understood about the acute neurological effects of oil spill clean-up-related exposures. Given the large number of people involved in large oil spill clean-ups, study of these effects is warranted. METHODS: We utilized exposure, health, and lifestyle data from a post-deployment survey administered to Coast Guard responders to the DWH oil spill. Crude oil exposure was assessed via self-reported inhalation and skin contact metrics, categorized by frequency of self-reported exposure to crude oil during deployment (never, rarely, sometimes, most/all of the time). Combined exposure to crude oil and oil dispersant was also evaluated. Adjusted log binomial regressions were used to calculate prevalence ratios (PRs) and 95% confidence intervals (CI), investigating the associations between oil spill exposures and neurological symptoms during deployment. Stratified analyses investigated potential effect modification by sex, exhaust fume exposure, personal protective equipment (PPE) use, and deployment duration and timing. RESULTS: Increasing frequency of crude oil exposure via inhalation was associated with increased likelihood of headaches (PRmost/all vs. never = 1.80), lightheadedness (PRmost/all vs. never = 3.36), difficulty concentrating (PRmost/all vs. never = 1.72), numbness/tingling sensation (PRmost/all vs. never = 3.32), blurred vision (PRmost/all vs. never = 2.87), and memory loss/confusion (PRmost/all vs. never = 2.03), with significant tests for trend. Similar results were found for crude oil exposure via skin contact. Exposure to both oil and oil dispersants yielded associations that were appreciably greater in magnitude than for oil alone for all neurological symptoms. Sensitivity analyses excluding responders in the highest environmental heat categories and responders with relevant pre-existing conditions indicated robustness of these results. Stratified analyses indicated possible effect modification by sex, PPE use, and heat exposure. CONCLUSIONS: This study provides evidence of a cross sectional association between crude oil exposures and acute neurological symptoms in a sample of U.S. Coast Guard responders. Additionally, it suggests that exposure to both crude oil and oil dispersant may result in stronger associations and that heat may interact synergistically with oil exposures resulting in more acute neurological symptoms. Future investigations are needed to confirm these findings.

Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit.

BACKGROUND: Persistent organic pollutants (POPs) may influence epigenetic mechanisms; therefore, they could affect chromosomal stability and gene expression. DNA methylation, an epigenetic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide. OBJECTIVE: Our aim in this study was to evaluate the relationship between plasma POPs concentrations and global DNA methylation (percent 5-methylcytosine) in DNA extracted from blood samples from 70 Greenlandic Inuit. Blood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPs. METHODS: We used pyrosequencing to estimate global DNA methylation via Alu and LINE-1 assays of bisulfite-treated DNA. We investigated correlations between plasma POP concentrations and global DNA methylation via correlation coefficients and linear regression analyses. RESULTS: We found inverse correlations between percents methylcytosine and many of the POP concentrations measured. Linear regressions, adjusting for age and cigarette smoking, showed statistically significant inverse linear relationships mainly for the Alu assay for p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; beta = -0.26), p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; beta = -0.38], beta-hexachlorocyclohexane (beta = -0.48), oxychlordane (beta = -0.32), alpha-chlordane (beta = -0.75), mirex (beta = -0.27), sum of polychlorinated biphenyls (beta = -0.56), and sum of all POPs (beta = -0.48). Linear regressions for the LINE-1 assay showed beta estimates of similar magnitudes to those using the Alu assay, however, none was statistically significant. CONCLUSIONS: This is the first study to investigate environmental exposure to POPs and DNA methylation levels in a human population. Global methylation levels were inversely associated with blood plasma levels for several POPs and merit further investigation.

Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study.

BACKGROUND: Chlorothalonil is a broad spectrum, non-systemic fungicide widely used to control diseases affecting over 50 fruit, vegetable, and agricultural crops. Despite its extensive use for over 30 years, little is known about the potential human carcinogenicity associated with the routine application of chlorothalonil. Rodent studies have shown evidence of renal tubular carcinomas and adenomas. We explored cancer incidence with chlorothalonil exposure using data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. METHODS: Licensed private and commercial pesticide applicators were recruited into this study from 1993 to 1997. Detailed information regarding pesticide use was obtained via self-administered questionnaires. Cancer incidence was followed through December 31, 2004. Chlorothalonil exposure was classified by lifetime exposure days and intensity-weighted lifetime exposure days, and then categorized into tertiles. The intensity-weighted lifetime exposure days metric was calculated based on a complex algorithm which includes pesticide application methods among other factors. This may increase or decrease exposure. RESULTS: Of the 47,625 pesticide applicators included in this analysis, 3657 applicators reported using chlorothalonil with a median of 3.5 application days per year. Chlorothalonil was not associated with overall cancer incidence, nor did we find any association with colon, lung, and prostate cancers--the only cancers for which we had sufficient numbers to explore associations. CONCLUSION: We did not find any strong evidence for an association between chlorothalonil and the cancers investigated. Although animal studies have suggested renal cancer may be associated with chlorothalonil, we had insufficient data to evaluate this cancer.

Mortality among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study.

BACKGROUND: Chlorpyrifos is one of the most widely used organophosphate insecticides in the United States. Although the toxicity of chlorpyrifos has been extensively studied in animals, the epidemiologic data are limited. OBJECTIVE: To evaluate whether agricultural chlorpyrifos exposure was associated with mortality, we examined deaths among pesticide applicators in the Agricultural Health Study, a prospective study of licensed pesticide applicators in Iowa and North Carolina. METHODS: A total of 55,071 pesticide applicators were included in this analysis. Detailed pesticide exposure data and other information were obtained from self-administered questionnaires completed at the time of enrollment (1993-1997). Lifetime chlorpyrifos use was divided into tertiles. Poisson regression analysis was used to evaluate the exposure-response relationships between chlorpyrifos use and causes of death after adjustment for potential confounders. RESULTS: A total of 1,851 deaths (588 among chlorpyrifos users) were observed during the study period, 1993-2001. The relative risk (RR) of death from all causes combined among applicators exposed to chlorpyrifos was slightly lower than that for nonexposed applicators (RR = 0.90; 95% confidence interval, 0.81-1.01). For most causes of death analyzed, there was no evidence of an exposure-response relationship. However, the relative risks for mortality from suicide and non-motor-vehicle accidents were increased 2-fold in the highest category of chlorpyrifos exposure days. CONCLUSIONS: Our findings of a possible association between chlorpyrifos use and external causes of death were based on small numbers. However, the findings may reflect a link between chlorpyrifos and depression or other neurobehavioral symptoms that deserves further evaluation.