Retinal degeneration in licensed pesticide applicators

BACKGROUND: Retinal degeneration is the leading cause of visual impairment in older adults, but little is known about its relationship to neurotoxic exposures. METHODS: The Agricultural Health Study is a cohort study of licensed pesticide applicators from Iowa and North Carolina. We used cross-sectional data from self-administered questionnaires given at enrollment in 1994-1996 to compare pesticide use in 154 applicators who reported retinal degeneration and 17,804 controls. RESULTS: Retinal degeneration was associated with fungicide use (odds ratio = 1.8, 95% confidence interval = 1.3-2.6). This relationship was seen in subgroups defined by state, demographic characteristics, or medical history, as well as in the entire group. Risk increased with cumulative days of fungicide use (P for trend = 0.011) and was greater when application methods involving greater personal exposure were used. Retinal degeneration was also related to use of organochlorine or carbamate insecticides, but these associations were less consistent. Since nearly all applicators used organophosphate insecticides and herbicides, these exposures could not be effectively evaluated. CONCLUSIONS: These results suggest that exposure to some fungicides and insecticides may increase risk of retinal degeneration. Copyright Published 2000 Wiley-Liss, Inc.     

Patterns of pesticide use and their determinants among wives of farmer pesticide applicators in the Agricultural Health Study

Pesticide exposure among farmers' wives is poorly characterized. Using questionnaire data from a cohort study of licensed pesticide applicators and their spouses, we investigated patterns of pesticide use among farmers' wives (n = 31,173). Wives reported a wide range of pesticide use: 36% never used pesticides during their lifetimes, whereas the heaviest pesticide users (10%) reported lifetime use of 3 or more agricultural pesticides plus commonly used residential pesticides. We identified 5 ordinal pesticide-use categories and studied factors associated with each category through polytomous logistic regression. Engaging in field work and household hygiene practices that could increase exposure were associated with pesticide use, and associations appeared to strengthen with increasing pesticide use category. Farm women reporting the heaviest pesticide use could exacerbate their exposure by engaging in practices that could increase pesticide contact.     

Suicide and pesticide use among pesticide applicators and their spouses in the agricultural health study

Background: An association may exist between pesticide exposure and suicide.Objective: We sought to evaluate the existence of an association between pesticide use and suicide using data from the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators and their spouses in Iowa and North Carolina.Methods: Via linkage to state mortality files and the National Death Index, we identified 110 suicides occurring between enrollment in the AHS (from 1993 to 1997) and 31 May 2009, among 81,998 cohort members contributing 1,092,943 person-years of follow-up. The average length of follow-up was 13.3 years. AHS participants provided data on pesticide use and potential confounders via self-administered questionnaires at enrollment. We evaluated several measures of pesticide use: use of any pesticide, ever use of 50 specific pesticides, cumulative lifetime days of use and intensity-adjusted cumulative lifetime days of use of 22 specific pesticides, and ever use of 10 functional and chemical classes of pesticides. We used Cox proportional hazards regression models to estimate adjusted hazard ratios and 95% confidence intervals.Results: After adjusting for age at enrollment, sex, number of children in family, frequency of alcohol consumption during the past 12 months, and smoking status, we found no association between prior pesticide use and suicide in applicators and their spouses. Results were the same for applicators and spouses together or for applicators alone and were consistent across several measures of pesticide use.Conclusions: Our findings do not support an association between moderate pesticide use and suicide.     

Neurologic symptoms in licensed private 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 levels of pesticides. We analyzed cross-sectional data from 18,782 white male licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993-1997. Applicators provided information on lifetime pesticide use and 23 neurologic symptoms typically associated with pesticide intoxication. An indicator of more symptoms (> or = 10 vs. < 10) during the year before enrollment was associated with cumulative lifetime days of insecticide use: odds ratios (95% confidence intervals) were 1.64 (1.36-1.97) for 1-50 days, 1.89 (1.58-2.25) for 51-500 days, and 2.50 (2.00-3.13) for > 500 days, compared with never users. A modest association for fumigants [> 50 days, 1.50 (1.24-1.81)] and weaker relationships for herbicides [> 500 days, 1.32 (0.99-1.75)] and fungicides [> 50 days, 1.23 (1.00-1.50)] were observed. Pesticide use within the year before enrollment was not associated with symptom count. Only associations with insecticides and fumigants persisted when all four pesticide groups were examined simultaneously. Among chemical classes of insecticides, associations were strongest for organophosphates and organochlorines. Associations with cumulative exposure persisted after excluding individuals who had a history of pesticide poisoning or had experienced an event involving high personal pesticide exposure. These results suggest that self-reported neurologic symptoms are associated with cumulative exposure to moderate levels of fumigants and organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.     

A weight-of-evidence review of colorectal cancer in pesticide applicators: the agricultural health study and other epidemiologic studies

Objective

To systematically evaluate epidemiologic studies on pesticides and colon cancer and rectal cancer in agricultural pesticide applicator populations using a transparent “weight-of-evidence” (WOE) methodological approach.

Methods

Twenty-nine (29) publications from the Agricultural Health Study (AHS) and 13 additional epidemiologic studies were identified that reported data for pesticide applicators and/or specific pesticide compounds and colorectal, colon, or rectal cancer. The AHS evaluated pesticide applicators as well as dose–response associations for specific pesticide compounds, whereas the large majority of non-AHS evaluated applicators but did not analyze specific compounds or dose–response trends. This WOE assessment of 153 different pesticide–outcome pairs emphasized several key evidentiary features: existence of statistically significant relative risks, magnitude of observed associations, results from the most reliable exposure assessments, and evidence of convincing dose–response relationships (i.e., those monotonically increasing, with statistically significant trend tests).

Results

Occupation as a pesticide applicator or pesticide application as a farming-related function was not associated with increasing the risk of colon or rectal cancer. Deficits of colon or rectal cancer were observed across most studies of pesticide applicators. After applying the WOE methodology to the epidemiologic studies of specific pesticide compounds and colon or rectal cancer, a number of pesticide–outcome pairs were identified and evaluated further based on positive statistical associations. Of these, only two—aldicarb and colon cancer and imazethapyr and proximal colon cancer—appears to warrant further discussion regarding a possible causal relationship, although the epidemiologic data are limited. For the remainder, a lack of a clear dose–response trend, inconsistencies in associations between exposure metrics and comparison groups, imprecise associations, variable participation rates for analyses of specific compounds, and the reliance upon data from one study (the AHS) limit interpretation regarding risk.

Conclusion

The available epidemiologic evidence does not support a causal relationship between occupation as a pesticide applicator or specific pesticide exposures and colon or rectal cancer.     

Depression and pesticide exposures in female spouses of licensed pesticide applicators in the agricultural health study cohort

OBJECTIVE: This nested case-control study evaluated the association between depression and pesticide exposure among women. METHODS: The study population included 29,074 female spouses of private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Cases were women who had physician-diagnosed depression requiring medication. Lifetime pesticide use was categorized as never mixed/applied pesticides, low exposure (up to 225 days), high exposure (>225 days), and a history of diagnosed pesticide poisoning. RESULTS: After adjustment for state, age, race, off-farm work, alcohol, cigarette smoking, physician visits, and solvent exposure, depression was significantly associated with a history of pesticide poisoning (odds ratio [OR] = 3.26; 95% confidence interval [CI] = 1.72-6.19) but not low (OR = 1.09; CI = 0.91-1.31) or high (OR = 1.09; 95% CI = 0.91-1.31) cumulative pesticide exposure. CONCLUSION: Pesticide poisoning may contribute to risk of depression.     

Cancer incidence among pesticide applicators exposed to cyanazine in the agricultural health study

BACKGROUND: Cyanazine is a common pesticide used frequently in the United States during the 1980s and 1990s. Animal and human studies have suggested that triazines may be carcinogenic, but results have been mixed. We evaluated cancer incidence in cyanazine-exposed pesticide applicators among the 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS). METHODS: We obtained detailed pesticide exposure information from a self-administered questionnaire completed at enrollment (1993-1997). Cancer incidence was followed through January 2002. Over half of cyanazine-exposed applicators had >or=6 years of exposure at enrollment, and approximately 85% had begun using cyanazine before the 1990s. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple cancer sites among cyanazine-exposed applicators. We calculated ptrend values, and all statistical tests were two-sided. Two exposure metrics were used: tertiles of lifetime days of exposure (LD) and intensity-weighted LD. RESULTS: A total of 20,824 cancer-free AHS applicators reported ever using cyanazine at enrollment. Cancer incidence comparisons between applicators with the lowest cyanazine exposure and those with the highest exposure yielded the following for the LD metric: all cancers, RR=0.99 (95% CI, 0.80-1.24); prostate cancer, RR=1.23 (95% CI, 0.87-1.70); all lymphohematopoietic cancers, RR=0.92 (95% CI, 0.50-1.72); non-Hodgkin lymphoma, RR=1.25 (95% CI, 0.47-3.35); lung cancer, RR=0.52 (95% CI, 0.22-1.25). CONCLUSIONS: We did not find any clear, consistent associations between cyanazine exposure and any cancer analyzed. The number of sites was small for certain cancers, limiting any conclusion with regard to ovarian, breast, and some other cancers.     

Cancer incidence among pesticide applicators exposed to dicamba in the agricultural health study

BACKGROUND: Dicamba is an herbicide commonly applied to crops in the United States and abroad. We evaluated cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in North Carolina and Iowa. METHODS: Detailed pesticide exposure information was obtained through a self-administered questionnaire completed from 1993 to 1997. Cancer incidence was followed through 31 December 2002 by linkage to state cancer registries. We used Poisson regression to estimate rate ratios and 95% confidence intervals for cancer subtypes by tertiles of dicamba exposure. Two dicamba exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days (lifetime days x intensity score). RESULTS: A total of 41,969 applicators were included in the analysis, and 22,036 (52.5%) reported ever using dicamba. Exposure was not associated with overall cancer incidence nor were there strong associations with any specific type of cancer. When the reference group comprised low-exposed applicators, we observed a positive trend in risk between lifetime exposure days and lung cancer (p = 0.02), but none of the individual point estimates was significantly elevated. We also observed significant trends of increasing risk for colon cancer for both lifetime exposure days and intensity-weighted lifetime days, although these results are largely due to elevated risk at the highest exposure level. There was no apparent risk for non-Hodgkin lymphoma. CONCLUSIONS: Although associations between exposure and lung and colon cancer were observed, we did not find clear evidence for an association between dicamba exposure and cancer risk.     

Atrazine and cancer incidence among pesticide applicators in the agricultural health study (1994-2007)

Background: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association.Methods: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure.Results: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic.Conclusions: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.     

Neurobehavioral performance among agricultural workers and pesticide applicators: a meta-analytic study

Chronic low level exposure of agricultural workers and applicators to pesticides has been found to be associated with different degrees of decrement in cognitive and psychomotor functions. The goal of this study was to use meta-analysis to (1) identify and quantify neurobehavioral deficits among agricultural workers and pesticide applicators, and (2) analyse the potential confounders or moderators of these neurobehavioral deficits. Seventeen studies, reporting on 21 independent cohort groups, were included in the meta-analysis. These studies involved 16 neuropsychological tests providing 23 different performance measures that constitute the neurobehavioral constructs. All tests and measures of the neurobehavioral functions of attention, visuomotor integration, verbal abstraction and perception constructs showed significant decrements for exposed participants. One out of three tests of memory, two of five tests of sustained attention, and four of eight tests of motor speed constructs also showed significant decrements. Nine out of these 15 effect size distributions demonstrated significant heterogeneity across cohorts. A search for cohort-level variables (eg, agricultural workers vs applicators, duration of exposure, age and percentage of male participants) to explain this heterogeneity was largely unsuccessful. However, for one test, Block Design, the duration of exposure was positively associated with performance decrements. Furthermore, it was also found that performance decrements on this test were smaller for older participants. Increasing the number of studies and using more consistent methodologies in field studies are needed.     

Exacerbation of symptoms in agricultural pesticide applicators with asthma

Purpose

Exacerbation is a critical event in asthma management. We investigated whether exacerbation of symptoms is associated with farming exposures among agricultural pesticide applicators with asthma.

Methods

Participants were pesticide applicators with active asthma (wheezing and breathing problems in past 12 months) who completed enrollment questionnaires for the Agricultural Health Study (AHS). Exacerbation of asthma was defined as having visited a hospital emergency room or doctor for an episode of wheezing or whistling in the past 12 months. Exposures of interest were using 36 specific pesticides in the past 12 months and conducting various agricultural activities. Adjusted odds ratios (ORs) were estimated by logistic regression while controlling for potential confounders.

Results

The 926 AHS adult pesticide applicators with active asthma included 202 (22 %) with exacerbation. Inverse associations with exacerbation were observed for two herbicides [glyphosate, odds ratio (OR) = 0.5, 95 % confidence interval (CI) 0.3, 0.8, and paraquat, OR = 0.3, 95 % CI 0.1, 0.9] and several agricultural activities (repairing engines, grinding metal, driving diesel tractors, and performing veterinary procedures). Only asthma cases with allergies (i.e., doctor-diagnosed hay fever or eczema, 46 %) had positive exacerbation–pesticide associations, with OR = 2.1 (95 % CI 1.1, 4.1) for the herbicide pendimethalin and OR = 10.2 (95 % CI 1.9, 55) for the insecticide aldicarb.

Conclusions

The inverse associations with two pesticides and specific farm activities are consistent with the possibility that asthma cases prone to exacerbation may avoid exposures that trigger symptoms. Although limited by small sample size and a cross-sectional design, our study suggests that use of specific pesticides may contribute to exacerbation of asthma among individuals with allergies.     

A study of pesticide safety and health perceptions among pesticide applicators in Tarrant County, Texas

Pesticide applicators from North Texas participated in a survey that was based on the constructs of the Health Belief Model of Strecher and Rosenstock. The survey assessed the knowledge, beliefs, and self-efficacy of pesticide applicators working for municipalities or in farming/ranching operations in Tarrant County, Texas. It was administered during a continuing-education class on pesticides sponsored by the Texas Agriculture Extension Service in Fort Worth, Texas. Results showed that while knowledge of the use of personal protective equipment was high, knowledge of the risk from dermal exposure was low.     

The agricultural health study: Factors affecting completion and return of self-administered questionnaires in a large prospective cohort study of pesticide applicators

Response rates were examined in a prospective epidemiologic study of individuals, mostly farmers, from Iowa and North Carolina seeking a pesticide applicator license during the period from 1994 through 1996. In the first year of enrollment 16,535 farmers (representing 77% of eligible farmer applicators) enrolled in the study by completing a 17-page questionnaire administered at a pesticide training session; 47% of the enrolled farmers completed and returned a much longer take-home questionnaire. The characteristics of farmers who completed only the enrollment questionnaire were quite similar to those of farmers who also completed and returned the take-home questionnaire. The most notable difference was the increased age of responders. Thus, the study population might have slightly higher cumulative farm exposures and slightly lower current farm exposures than the base population of all farmer applicators. The lack of evidence for substantial selection bias is reassuring for the Agricultural Health Study, and provides a measure of reassurance for other studies depending on the voluntary completion of self-administered questionnaires. Am. J. Ind. Med. 31:233–242, 1997. (This article is a US Government work and, as such, is in the public domain of the United States of America.) © 1997 Wiley-Liss, Inc.     

Pesticide use and breast cancer risk among farmers' wives in the agricultural health study

The authors examined the association between pesticide use and breast cancer incidence among farmers' wives in a large prospective cohort study in Iowa and North Carolina. Participants were 30,454 women with no history of breast cancer prior to cohort enrollment in 1993-1997. Information on pesticide use and other information was obtained by self-administered questionnaire at enrollment from the women and their husbands. Through 2000, 309 incident breast cancer cases were identified via population-based cancer registries. Rate ratios were calculated for individual pesticides using Poisson regression, controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval: 0.74, 1.02) for women who reported ever applying pesticides and 1.05 (95% confidence interval: 0.89, 1.24) for women who reported never applying pesticides. There was some evidence of increased risk associated with use of 2,4,5-trichloro-phenoxypropionic acid (2,4,5-TP) and possibly use of dieldrin, captan, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-TP), but small numbers of cases among those who had personally used the pesticides precluded firm conclusions. The authors found no clear association of breast cancer risk with farm size or washing of clothes worn during pesticide application, but risk was modestly elevated among women whose homes were closest to areas of pesticide application. Further follow-up of this cohort should help clarify the relation between pesticide exposure and breast cancer risk.     

A review of pesticide exposure and cancer incidence in the agricultural health study cohort

We reviewed epidemiologic evidence related to occupational pesticide exposures and cancer incidence in the Agricultural Health Study (AHS) cohort. Studies were identified from the AHS publication list available on a Medline/PubMed database search in March 2009. Findings related to lifetime-days and/or intensity-weighted lifetime-days of pesticide use are the primary focus of this review, because these measures allow for the evaluation of potential exposure-response relationships. Most of the 32 pesticides examined were not strongly associated with cancer incidence in pesticide applicators. Increased rate ratios and positive exposure-response patterns were reported for 12 pesticides currently registered in Canada and/or the United States. Exposure misclassification is also a concern in the AHS and may limit the analysis of exposure-response patterns. Epidemiologic evidence outside the AHS remains limited with respect to most of the observed associations, but animal toxicity data support the biological plausibility of relationships observed six pesticides. Continued follow-up is needed to clarify associations reported to date. In particular, further evaluation of registered pesticides is warranted.     

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.     

An updated algorithm for estimation of pesticide exposure intensity in the agricultural health study

An algorithm developed to estimate pesticide exposure intensity for use in epidemiologic analyses was revised based on data from two exposure monitoring studies. In the first study, we estimated relative exposure intensity based on the results of measurements taken during the application of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (n = 88) and the insecticide chlorpyrifos (n = 17). Modifications to the algorithm weighting factors were based on geometric means (GM) of post-application urine concentrations for applicators grouped by application method and use of chemically-resistant (CR) gloves. Measurement data from a second study were also used to evaluate relative exposure levels associated with airblast as compared to hand spray application methods. Algorithm modifications included an increase in the exposure reduction factor for use of CR gloves from 40% to 60%, an increase in the application method weight for boom spray relative to in-furrow and for air blast relative to hand spray, and a decrease in the weight for mixing relative to the new weights assigned for application methods. The weighting factors for the revised algorithm now incorporate exposure measurements taken on Agricultural Health Study (AHS) participants for the application methods and personal protective equipment (PPE) commonly reported by study participants.