The association between oil spill cleanup-related total hydrocarbon exposure and diabetes.

BACKGROUND: Although evidence suggests relationships between some crude oil components and glycemic dysregulation, no studies have examined oil spill-related chemical exposures in relation to type 2 diabetes mellitus (DM) risk. This study examined the relationship between total hydrocarbon (THC) exposure among workers involved in the 2010 Deepwater Horizon (DWH) oil spill and risk of DM up to 6 years afterward. METHODS: Participants comprised 2660 oil-spill cleanup or response workers in the prospective GuLF Study who completed a clinical exam and had no self-reported DM diagnosis prior to the spill. Maximum THC exposure was estimated with a job-exposure matrix based on interview data and personal measurements taken during cleanup operations. We defined incident DM by self-reported physician diagnosis of DM, antidiabetic medication use, or a measured hemoglobin A1c value ≥ 6.5%. We used log binomial regression to estimate risk ratios (RRs) for DM across ordinal categories of THC exposure. The fully adjusted model controlled for age, sex, race/ethnicity, education, employment status, and health insurance status. We also stratified on clinical body mass index categories. RESULTS: We observed an exposure-response relationship between maximum daily ordinal THC exposure level and incident DM, especially among overweight participants. RRs among overweight participants were 0.99 (95% CI: 0.37, 2.69), 1.46 (95% CI: 0.54, 3.92), and 2.11 (95% CI: 0.78, 5.74) for exposure categories 0.30-0.99 ppm, 1.00-2.99 ppm, and ≥3.00 ppm, respectively (ptrend = 0.03). CONCLUSION: We observed suggestively increasing DM risk with increasing THC exposure level among overweight participants, but not among normal weight or obese participants.

Pesticide use and risk of systemic autoimmune diseases in the Agricultural Health Study.

BACKGROUND: Systemic lupus erythematosus (SLE) risk has been associated with pesticide use, but evidence on specific pesticides or other agricultural exposures is lacking. We investigated history of pesticide use and risk of SLE and a related disease, Sjögren's syndrome (SS), in the Agricultural Health Study. METHODS: The study sample (N = 54,419, 52% male, enrolled in 1993-1997) included licensed pesticide applicators from North Carolina and Iowa and spouses who completed any of the follow-up questionnaires (1999-2003, 2005-2010, 2013-2015). Self-reported cases were confirmed by medical records or medication use (total: 107 incident SLE or SS, 79% female). We examined ever use of 31 pesticides and farm tasks and exposures reported at enrollment in association with SLE/SS, using Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), with age as the timescale and adjusting for gender, state, and correlated pesticides. RESULTS: In older participants (>62 years), SLE/SS was associated with ever use of the herbicide metribuzin (HR 5.33; 95%CI 2.19, 12.96) and applying pesticides 20+ days per year (2.97; 1.20, 7.33). Inverse associations were seen for petroleum oil/distillates (0.39; 0.18, 0.87) and the insecticide carbaryl (0.56; 0.36, 0.87). SLE/SS was inversely associated with having a childhood farm residence (0.59; 0.39, 0.91), but was not associated with other farm tasks/exposures (except welding, HR 2.65; 95%CI 0.96, 7.35). CONCLUSIONS: These findings suggest that some agricultural pesticides may be associated with higher or lower risk of SLE/SS. However, the overall risk associated with farming appears complex, involving other factors and childhood exposures.

A prospective study of type 2 diabetes, metformin use, and risk of breast cancer.

BACKGROUND: Type 2 diabetes (T2D) has been associated with increased breast cancer risk, but commonly prescribed antidiabetic medications such as metformin may reduce risk. Few studies have investigated T2D and medications together in relation to breast cancer. PATIENTS AND METHODS: Data came from 44 541 Sister Study participants aged 35 to 74 years at enrollment (2003-2009) who satisfied eligibility criteria, followed through 15 September 2017. Information on time-varying, self-reported, physician-diagnosed, prevalent and incident T2D, use of antidiabetic medications, and covariates was obtained from baseline and follow-up questionnaires. Incident breast cancers were confirmed with medical records. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. RESULTS: During follow-up (median, 8.6 years), 2678 breast cancers were diagnosed at least 1 year after enrollment. There were 3227 women (7.2%) with prevalent and 2389 (5.3%) with incident T2D, among whom 61% (n = 3386) were ever treated with metformin. There was no overall association between T2D and breast cancer risk (HR 0.99; 95% CI, 0.87-1.13). However, T2D was associated with increased risk of triple-negative breast cancer (HR 1.40; 95% CI, 0.90-2.16). Compared with not having T2D, T2D with metformin use was not associated with overall breast cancer risk (HR 0.98; 95% CI, 0.83-1.15), but it was associated with decreased risk of estrogen receptor (ER)-positive breast cancer (HR 0.86; 95% CI 0.70-1.05) and increased risk of ER-negative (HR 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR 1.74; 95% CI, 1.06-2.83). The inverse association with ER-positive cancer was stronger for longer duration (≥10 year) metformin use (HR 0.62; 95% CI, 0.38-1.01; P for trend = 0.09). Results were supported by sensitivity analyses. CONCLUSION: Our findings suggest that associations between T2D and breast cancer may differ by hormone receptor status and that associations between T2D and ER-positive breast cancer may be reduced by long-term metformin use.

Maternal age at birth and daughters' subsequent childlessness.

STUDY QUESTION: Does maternal age at a daughter's birth predict her subsequent probability of lifelong childlessness? SUMMARY ANSWER: In this study population, women born to older mothers were more likely to be childless. WHAT IS KNOWN ALREADY: Although maternal age at childbearing is increasing in many countries, there is limited evidence on whether being born to older parents may influence offspring fertility. STUDY DESIGN SIZE AND DURATION: This analysis included 43 135 women from the US-based Sister Study, a cohort study of 50 884 sisters of women with breast cancer recruited between 2003 and 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants had no breast cancer at baseline. Women were included in the analytic sample if they were born between 1930 and 1964 and were at least 44 years old at enrolment. Median age when reproductive history was last ascertained was 63.8 years. We estimated relative risks (RR) and 95% CI of lifelong childlessness as a function of maternal age at birth, using multivariable log-binomial models, including total number of siblings, birth order, socioeconomic indicators of the family of origin, race and birth cohort. We examined the association in different subgroups and in a sibling-matched analysis including 802 sister pairs discordant for childlessness. MAIN RESULTS AND ROLE OF CHANCE: Compared with women born to 20-24-year-old mothers, those born to mothers aged 25-29, 30-34 and ≥35 years were more likely to be childless [RR (95% CI): 1.21 (1.14-1.29), 1.30 (1.22-1.39) and 1.40 (1.31-1.50), respectively]. The association was consistent in strata defined by birth cohort, number of siblings, birth order, and participant's educational level, as well as within sister pairs. Overall, we found weak evidence for an independent contribution of paternal age at birth to the daughter's probability of childlessness. LIMITATIONS REASONS FOR CAUTION: All participants had at least one sister, and all information was self-reported. We had no knowledge of whether childlessness was intentional and found only a modest association between maternal age at birth and self-reported indicators of infertility. Still, the association with childlessness was highly consistent. WIDER IMPLICATIONS OF THE FINDING: Given the widespread tendency to delay childbearing, evaluating the influence of maternal age at birth on offspring fertility is a public health priority. STUDY FUNDING/COMPETING INTERESTS: This research was supported in part by the Intramural Research Programme of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005). The authors report no conflict of interest.

An epigenome-wide study of body mass index and DNA methylation in blood using participants from the Sister Study cohort.

BACKGROUND/OBJECTIVES: The relationship between obesity and chronic disease risk is well-established; the underlying biological mechanisms driving this risk increase may include obesity-related epigenetic modifications. To explore this hypothesis, we conducted a genome-wide analysis of DNA methylation and body mass index (BMI) using data from a subset of women in the Sister Study. SUBJECTS/METHODS: The Sister Study is a cohort of 50 884 US women who had a sister with breast cancer but were free of breast cancer themselves at enrollment. Study participants completed examinations which included measurements of height and weight, and provided blood samples. Blood DNA methylation data generated with the Illumina Infinium HumanMethylation27 BeadChip array covering 27,589 CpG sites was available for 871 women from a prior study of breast cancer and DNA methylation. To identify differentially methylated CpG sites associated with BMI, we analyzed this methylation data using robust linear regression with adjustment for age and case status. For those CpGs passing the false discovery rate significance level, we examined the association in a replication set comprised of a non-overlapping group of 187 women from the Sister Study who had DNA methylation data generated using the Infinium HumanMethylation450 BeadChip array. Analysis of this expanded 450 K array identified additional BMI-associated sites which were investigated with targeted pyrosequencing. RESULTS: Four CpG sites reached genome-wide significance (false discovery rate (FDR) q<0.05) in the discovery set and associations for all four were significant at strict Bonferroni correction in the replication set. An additional 23 sites passed FDR in the replication set and five were replicated by pyrosequencing in the discovery set. Several of the genes identified including ANGPT4, RORC, SOCS3, FSD2, XYLT1, ABCG1, STK39, ASB2 and CRHR2 have been linked to obesity and obesity-related chronic diseases. CONCLUSIONS: Our findings support the hypothesis that obesity-related epigenetic differences are detectable in blood and may be related to risk of chronic disease.

Prevalence and predictors of hospital prealerting in acute stroke: a mixed methods study.

BACKGROUND: Thrombolysis can significantly reduce the burden of stroke but the time window for safe and effective treatment is short. In patients travelling to hospital via ambulance, the sending of a 'prealert' message can significantly improve the timeliness of treatment. OBJECTIVE: Examine the prevalence of hospital prealerting, the extent to which prealert protocols are followed and what factors influence emergency medical services (EMS) staff's decision to send a prealert. METHODS: Cohort study of patients admitted to two acute stroke units in West Midlands (UK) hospitals using linked data from hospital and EMS records. A logistic regression model examined the association between prealert eligibility and whether a prealert message was sent. In semistructured interviews, EMS staff were asked about their experiences of patients with suspected stroke. RESULTS: Of the 539 patients eligible for this study, 271 (51%) were recruited. Of these, only 79 (29%) were eligible for prealerting according to criteria set out in local protocols but 143 (53%) were prealerted. Increasing number of Face, Arm, Speech Test symptoms (1 symptom, OR 6.14, 95% CI 2.06 to 18.30, p=0.001; 2 symptoms, OR 31.36, 95% CI 9.91 to 99.24, p<0.001; 3 symptoms, OR 75.84, 95% CI 24.68 to 233.03, p<0.001) and EMS contact within 5 h of symptom onset (OR 2.99, 95% CI 1.37 to 6.50 p=0.006) were key predictors of prealerting but eligibility for prealert as a whole was not (OR 1.92, 95% CI 0.85 to 4.34 p=0.12). In qualitative interviews, EMS staff displayed varying understanding of prealert protocols and described frustration when their interpretation of the prealert criteria was not shared by ED staff. CONCLUSIONS: Up to half of the patients presenting with suspected stroke in this study were prealerted by EMS staff, regardless of eligibility, resulting in disagreements with ED staff during handover. Aligning the expectations of EMS and ED staff, perhaps through simplified prealert protocols, could be considered to facilitate more appropriate use of hospital prealerting in acute stroke.

Thrombolytics in VAD management - A single-center experience.

BACKGROUND: With continued increase in the use of mechanical circulatory support, the incidence of device thrombus remains a challenge. This study is a retrospective analysis of data at a single center to assess the safety and efficacy of thrombolytic use in durable mechanical assist devices. METHODS: Data was analyzed retrospectively from 154 patients who underwent left ventricular assist device (LVAD) implantation from 1/1/2005 to 6/30/2014. The HMII device was implanted in 131 patients while 23 received the HVAD. LVAD thrombus was diagnosed when lactate dehydrogenase levels exceeded 1000 units/l accompanied by clinical signs of hemolysis and heart failure, echocardiographic data and surges in pump power. TPA (tissue plasminogen activator) protocol consisted of a 5 mg intravenous bolus followed by 3 mg/h infusion in normal saline for 10 h. If symptoms persisted another cycle of TPA at 1 mg/h was continued up to 48 h. RESULTS: The TPA group had a 70% success rate. Success was defined as complete resolution of hemolysis and clinical symptoms with no requirement for LVAD exchange at 30 days. 95% survival was noted at 30 days and 90% were free of a hemorrhagic stroke in the TPA group. The rates of hemorrhagic strokes in the TPA group and the control group were not different (OR = 0.92). CONCLUSION: The TPA protocol described here was successful consistently. Though this study is limited by its size and retrospective nature it leads the way for larger studies to generate more robust comparisons between different types of mechanical assist devices as well as the tailored use of thrombolytics in this patient population.

Investing in prospective cohorts for etiologic study of occupational exposures.

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures.

Tubal ligation in relation to menopausal symptoms and breast cancer risk.

BACKGROUND: Local inflammation after tubal ligation may affect ovarian function and breast cancer risk. METHODS: We analysed tubal ligation, menopausal characteristics, and breast cancer risk in the Sister Study cohort (N=50,884 women). RESULTS: Tubal ligation was associated with hot flashes (hazard ratio (HR) 1.09; 95% confidence interval (CI): 1.06-1.12) but not menopausal age (HR 0.99; 95% CI: 0.96-1.02). Tubal ligation did not have an impact on breast cancer overall (HR 0.95; 95% CI: 0.85-1.06), but had a suggested inverse relation with oestrogen receptor+/progesterone receptor+ invasive tumours (HR 0.84; 95% CI: 0.70-1.01), possibly because of subsequent hysterectomy/bilateral oophorectomy. CONCLUSION: Tubal ligation does not influence overall breast cancer risk.

Employment and work schedule are related to telomere length in women.

OBJECTIVES: To examine the association of employment and work schedule with shorter DNA telomeres, a marker of cellular ageing and disease risk factor, and consider whether differences were related to health, behaviours and sociodemographic factors, or varied by stress levels or menopausal status. METHODS: This cross-sectional analysis of 608 women aged 35-74 in the Sister Study examined determinants of relative telomere length (rTL) measured by quantitative PCR in leucocyte DNA. Age-adjusted regression models estimated base pair (bp) rTL differences for current and lifetime schedule characteristics (ie, part-time, full-time or overtime hours; multiple jobs; irregular hours; shiftwork; work at night). Covariates included race, smoking, perceived stress, sleep, physical activity, health and menopausal status, education, marital status, live births, children under 18, measured body mass index and urinary stress hormones. RESULTS: Compared with non-employed women with moderate or substantial past work histories (n=190), those currently working full-time (n=247; median 40 h/week) had a shorter rTL, an age-adjusted difference of -329 bp (95% CI -110 to -548). Longer-duration full-time work was also associated with shorter rTL (age-adjusted difference of -472 bp, 95% CI -786 to -158 for 20+ vs 1-5 years). Findings were not explained by health and demographic covariates. However, rTL differences for working at least full-time were greater in women with higher stress and epinephrine levels. CONCLUSIONS: Current and long-term full-time work were associated with shorter rTL, with differences of similar magnitude to smoking and history of heart disease or diabetes. Longitudinal data with specific stress measures are needed to further evaluate the impact of work schedule on rTL.

Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study.

OBJECTIVES: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Príbram region, Czech Republic. METHODS: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. RESULTS: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. CONCLUSIONS: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out.

Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test.

BACKGROUND: The U.S. EPA revised the Reproduction and Fertility Effects Test Guideline (OPPTS 870.3800/OECD 416) in 1998, adding numerous endpoints in an effort to incorporate new methodologies, improve the sensitivity for detecting reproductive toxicants, and more efficiently utilize study animals. Many of these new endpoints have not been used in regulatory reproductive toxicology studies prior to their inclusion in the test guidelines; thus, the Health and Environmental Sciences Institute (HESI) of the International Life Sciences Institute (ILSI) initiated the Reproductive Endpoints Project to examine the utility of these new endpoints. METHODS: This report provides a retrospective analysis of 43 multi-generation studies (16 in Wistar rats, 27 in Sprague-Dawley rats) conducted according to the latest version of the test guidelines. It focuses on vehicle (negative) control values (means and ranges) for the various endpoints to examine inter-laboratory variability. RESULTS: Based on the compiled data, the most variable endpoints across laboratories and their associated coefficients of variation (CV) for each generation were: percent abnormal sperm (166-205%), testicular spermatid concentration (126-147%), postimplantation loss (97-104%), primordial follicle counts (69%, only measured in P2 females), and epididymal sperm concentration (52-57%). Absolute and relative prostate and thymus weights, weanling uterine weights, and anogenital distance had CVs of 25-50%. Sources of variability included procedural differences between laboratories, inherent biological variability, and/or small sample sizes for some endpoints. CONCLUSIONS: These inter-laboratory control data provide a means for laboratories to review their performance on reproductive toxicity measures, and provide perspective for interpreting their own control data and data from treated animals.

Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study.

Although specific pesticides have been associated with wheeze in farmers, little is known about pesticides and asthma. Data from 19,704 male farmers in the Agricultural Health Study were used to evaluate lifetime use of 48 pesticides and prevalent adult-onset asthma, defined as doctor-diagnosed asthma after the age of 20 yrs. Asthma cases were categorised as allergic (n = 127) and nonallergic (n = 314) based on their history of eczema or hay fever. Polytomous logistic regression, controlling for age, state, smoking and body mass, was used to assess pesticide associations. High pesticide exposure events were associated with a doubling of both allergic and nonallergic asthma. For ever-use, 12 individual pesticides were associated with allergic asthma and four with nonallergic asthma. For allergic asthma, coumaphos (OR 2.34; 95% CI 1.49-3.70), heptachlor (OR 2.01; 95% CI 1.30-3.11), parathion (OR 2.05; 95% CI 1.21-3.46), 80/20 mix (carbon tetrachloride/carbon disulfide) (OR 2.15; 95% CI 1.23-3.76) and ethylene dibromide (OR 2.07; 95% CI 1.02-4.20) all showed ORs of >2.0 and significant exposure-response trends. For nonallergic asthma, DDT (dichlorodiphenyltrichloroethane) showed the strongest association (OR 1.41; 95% CI 1.09-1.84), but with little evidence of increasing asthma with increasing use. Current animal handling and farm activities did not confound these results. There was little evidence that allergy alone was driving these associations. In conclusion, pesticides may be an overlooked contributor to asthma risk among farmers.

Rhinitis associated with pesticide exposure among commercial pesticide applicators in the Agricultural Health Study.

OBJECTIVES: Rhinitis is common, but the risk factors are not well described. To investigate the association between current rhinitis and pesticide use, we used data from 2245 Iowa commercial pesticide applicators in the Agricultural Health Study. METHODS: Using logistic regression models adjusted for age, education and growing up on a farm, we evaluated the association between current rhinitis and 34 pesticides used in the past year. RESULTS: 74% of commercial pesticide applicators reported at least one episode of rhinitis in the past year (current rhinitis). Five pesticides used in the past year were significantly positively associated with current rhinitis: the herbicides 2,4-D, glyphosate and petroleum oil, the insecticide diazinon and the fungicide benomyl. The association for 2,4-D and glyphosate was limited to individuals who used both in the past year (OR 1.42, 95% CI 1.14 to 1.77). Both petroleum oil and diazinon showed consistent evidence of an association with rhinitis, based on both current use and exposure-response models. We saw no evidence of confounding by common agricultural rhinitis triggers such as handling grain or hay. CONCLUSIONS: Exposure to pesticides may increase the risk of rhinitis.

Incident diabetes and pesticide exposure among licensed pesticide applicators: Agricultural Health Study, 1993-2003.

Exposure to certain environmental toxicants may be associated with increased risk of developing diabetes. The authors' aim was to investigate the relation between lifetime exposure to specific agricultural pesticides and diabetes incidence among pesticide applicators. The study included 33,457 licensed applicators, predominantly non-Hispanic White males, enrolled in the Agricultural Health Study. Incident diabetes was self-reported in a 5-year follow-up interview (1999-2003), giving 1,176 diabetics and 30,611 nondiabetics for analysis. Lifetime exposure to pesticides and covariate information were reported by participants at enrollment (1993-1997). Using logistic regression, the authors considered two primary measures of pesticide exposure: ever use and cumulative lifetime days of use. They found seven specific pesticides (aldrin, chlordane, heptachlor, dichlorvos, trichlorfon, alachlor, and cyanazine) for which the odds of diabetes incidence increased with both ever use and cumulative days of use. Applicators who had used the organochlorine insecticides aldrin, chlordane, and heptachlor more than 100 lifetime days had 51%, 63%, and 94% increased odds of diabetes, respectively. The observed association of organochlorine and organophosphate insecticides with diabetes is consistent with results from previous human and animal studies. Long-term exposure from handling certain pesticides, in particular, organochlorine and organophosphate insecticides, may be associated with increased risk of diabetes.

Neurologic symptoms in licensed pesticide applicators in the Agricultural Health Study.

Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate pesticide levels. We analysed cross-sectional data from 18 782 Caucasian, male, licensed pesticide applicators, enrolled in the Agricultural Health Study from 1993 to 1997. Applicators provided information on lifetime pesticide use, and 23 neurologic symptoms typically associated with pesticide intoxication. Increased risk of experiencing >/=10 symptoms during the year before enrollment was associated with cumulative pesticide use, personally mixing or applying pesticides, pesticide-related medical care, diagnosed pesticide poisoning, and events involving high personal pesticide exposure. Greatest risk was associated with use of organophosphate and organochlorine insecticides. Results were similar after stratification by pesticide use during the year before enrollment, or exclusion of applicators with a history of pesticide poisoning, or high-exposure events. Use of pesticide application methods likely to involve high personal exposure was associated with greater risk. Groups of symptoms reflecting several neurologic domains, including affect, cognition, autonomic and motor function, and vision, were also associated with pesticide exposure. These results suggest that neurologic symptoms are associated with cumulative exposure to moderate levels of organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.

High pesticide exposure events among farmers and spouses enrolled in the Agricultural Health Study.

We completed a nested case-control analysis of factors associated with reporting a high pesticide exposure event (HPEE) by pesticide applicators and spouses during the five years since enrollment in the Agricultural Health Study (AHS). Cases and controls were identified from the 16,415 private pesticide applicators and 14,045 spouses with completed five-year follow-up interviews as of October 2000. Among the applicators, 306 cases with at least one HPEE in the five years since enrollment and 612 controls, randomly selected from those without a reported HPEE, were identified for analysis. Among the spouses, 63 cases were identified and 126 controls were selected. Risk for a new HPEE was increased among applicators reporting at enrollment ever having an HPEE with an odds ratio (OR) of 3.8 (95% CI: 2.7, 5.3). Compared to applicators who applied pesticides fewer than 5 days per year, the ORs ranged from 1.4 (95% CI: 0.9, 2.2) for 6 to 10 days per year to 2.2 (95% CI: 1.4, 3.6) for more than 20 application days per year. The incidence of HPEE among Iowa applicators was much greater (8.8/1000 applicators) than among North Carolina applicators (2.0/1000). Spouses reported fewer HPEEs compared to applicators (2/1000 spouses). Overall, the observed risk factors for new HPEEs among applicators are similar to risk factors observed in previous cross-sectional analyses of HPEE history. Further, only 13% of applicators and 22% of spouses with symptoms resulting from HPEE sought medical care, suggesting that pesticide poisoning surveillance data may seriously underreport the frequency of such events.

Fertility and exposure to solvents among families in the Agricultural Health Study.

BACKGROUND: Several studies have reported associations between solvent exposure and reduced female fertility, but the evidence is inconclusive for male fertility. OBJECTIVES: To investigate the impact of solvent exposure on subfertility among families of male licensed pesticide applicators in the Agricultural Health Study cohort. METHODS: The couples enrolled between 1993 and 1997. Cross-sectional questionnaire information on work tasks was used to assess exposure to solvents. The data were limited to couples (wife aged less than 40 years) with an attempt at pregnancy in the last four years (n = 2112). RESULTS: Twenty eight per cent of the couples were defined as subfertile (not conceiving a pregnancy after at least 12 months of unprotected intercourse, regardless of whether or not a pregnancy ultimately occurred). Adjusted subfertility odds ratios (OR) for exposure to solvents were calculated with logistic regression. Female (OR 1.42, 95% CI 1.15 to 1.75) and male exposure to solvents (OR 1.21 (95% CI 0.93 to 1.57) for monthly exposure and 1.40 (95% CI 0.97 to 2.03) for daily or weekly exposure) were associated with subfertility. In farming, spouses may share or exchange jobs. To account for potential dual exposure, variables for parental exposure (either parent exposed or both parents exposed) were also defined. Both were strongly associated with subfertility (OR 1.62 (95% CI 1.20 to 2.17) and OR 2.10 (95% CI 1.22 to 3.60), respectively). CONCLUSIONS: Solvents may impair fertility of either gender, though the evidence for female effects is stronger than for male effects.

Disease and injury among participants in the Agricultural Health Study.

The Agricultural Health Study (www.aghealth.org) is a cohort of 89,658 pesticide applicators and their spouses from Iowa and North Carolina assembled between 1993 and 1997 to evaluate riskfactorsfor disease in ruralfarm populations. This prospective study is just now reaching sufficient maturity for analysis of many disease endpoints. Nonetheless, several analyses have already provided interesting and important leads regarding disease patterns in agricultural populations and etiologic clues for the general population. Compared to the mortality experience of the general population in the two states (adjusted for race, gender, age and calendar time), the cohort experienced a very low mortality rate overall and for many specific causes and a low rate of overall cancer incidence. A few cancers, however, appear elevated, including multiple myeloma and cancers of the lip, gallbladder, ovary, prostate, and thyroid, but numbers are small for many cancers. A study of prostate cancer found associations with exposure to several pesticides, particularly among individuals with a family history of prostate cancer. Links to pesticides and other agricultural factors have been found for injuries, retinal degeneration, and respiratory wheeze. Methodological studies have determined that information collected by interview is unbiased and reliable. A third round of interviews scheduled to begin in 2005 will collect additional information on agricultural exposures and health outcomes. The study can provide data to address many health issues in the agricultural community. The study investigators welcome collaboration with interested scientists.