An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population

The toxicity of pesticides on human reproduction is largely unknown--particularly how mixtures of pesticide products might affect fetal toxicity. The Ontario Farm Family Health Study collected data by questionnaire on the identity and timing of pesticide use on the farm, lifestyle factors, and a complete reproductive history from the farm operator and eligible couples living on the farm. A total of 2,110 women provided information on 3,936 pregnancies, including 395 spontaneous abortions. To explore critical windows of exposure and target sites for toxicity, we examined exposures separately for preconception (3 months before and up to month of conception) and postconception (first trimester) windows and for early (< 12 weeks) and late (12-19 weeks) spontaneous abortions. We observed moderate increases in risk of early abortions for preconception exposures to phenoxy acetic acid herbicides [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.1-2.1], triazines (OR = 1.4; 95% CI, 1.0-2.0), and any herbicide (OR = 1.4; 95% CI, 1.1-1.9). For late abortions, preconception exposure to glyphosate (OR = 1.7; 95% CI, 1.0-2.9), thiocarbamates (OR = 1.8; 95% CI, 1.1-3.0), and the miscellaneous class of pesticides (OR = 1.5; 95% CI, 1.0-2.4) was associated with elevated risks. Postconception exposures were generally associated with late spontaneous abortions. Older maternal age (> 34 years of age) was the strongest risk factor for spontaneous abortions, and we observed several interactions between pesticides in the older age group using Classification and Regression Tree analysis. This study shows that timing of exposure and restricting analyses to more homogeneous endpoints are important in characterizing the reproductive toxicity of pesticides.     

Household exposure to pesticides and risk of childhood hematopoietic malignancies: The ESCALE study (SFCE)

OBJECTIVES: We investigated the role of household exposure to pesticides in the etiology of childhood hematopoietic malignancies. METHODS: The national registry-based case-control study ESCALE (Etude sur les cancers de l'enfant) was carried out in France over the period 2003-2004. Population controls were frequency matched with the cases on age and sex. Maternal household use of pesticides during pregnancy and paternal use during pregnancy or childhood were reported by the mothers in a structured telephone questionnaire. Insecticides (used at home, on pets, or for garden crops), herbicides, and fungicides were distinguished. We estimated odds ratios (ORs) using unconditional regression models closely adjusting for age, sex, degree of urbanization, and type of housing (flat or house). RESULTS: We included a total of 764 cases of acute leukemia (AL), 130 of Hodgkin lymphoma (HL), 166 of non-Hodgkin lymphoma (NHL), and 1,681 controls. Insecticide use during pregnancy was significantly associated with childhood AL [OR = 2.1; 95% confidence interval (CI), 1.7-2.5], both lymphoblastic and myeloblastic, NHL (OR = 1.8; 95% CI, 1.3-2.6), mainly for Burkitt lymphoma (OR = 2.7; 95% CI, 1.6-4.5), and mixed-cell HL (OR = 4.1; 95% CI, 1.4-11.8), but not nodular sclerosis HL (OR = 1.1; 95% CI, 0.6-1.9). Paternal household use of pesticides was also related to AL (OR = 1.5; 95% CI, 1.2-1.8) and NHL (OR = 1.7; 95% CI, 1.2-2.6); but for AL the relationships did not remain after adjustment for maternal pesticide use during pregnancy. CONCLUSION: The study findings strengthen the hypothesis that domestic use of pesticides may play a role in the etiology of childhood hematopoietic malignancies. The consistency of the findings with those of previous studies on AL raises the question of the advisability of preventing pesticide use by pregnant women.     

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.     

Pesticide/Environmental Exposures and Parkinson's Disease in East Texas

ABSTRACT

Epidemiological evidence suggests that pesticides and other environmental exposures may have a role in the etiology of idiopathic Parkinson's disease (PD). However, there is little human data on risk associated with specific pesticide products, including organic pesticides such as rotenone with PD. Using a case-control design, this study examined self-reports of exposure to pesticide products, organic pesticides such as rotenone, and other occupational and environmental exposures on the risk of PD in an East Texas population. The findings demonstrated significantly increased risk of PD with use of organic pesticides such as rotenone in the past year in gardening (OR = 10.9; 95% CI = 2.5–48.0) and any rotenone use in the past (OR = 10.0; 95% CI = 2.9–34.3). Use of chlorpyrifos products (OR = 2.0; 95% CI = 1.02–3.8), past work in an electronics plant (OR = 5.1; 95% CI = 1.1–23.6), and exposure to fluorides (OR = 3.3; 95% CI = 1.03–10.3) were also associated with significantly increased risk. A trend of increased PD risk was observed with work history in paper/lumber mill (OR = 6.35; 95% CI = 0.7–51.8), exposure to cadmium (OR = 5.3; 95% CI = 0.6–44.9), exposure to paraquat (OR = 3.5; 95% CI = 0.4–31.6), and insecticide applications to farm animals/animal areas and agricultural processes (OR = 4.4; 95% CI = 0.5–38.1). Cigarette smoking, alcohol use, and fish intake were associated with reduced risk. In summary, this study demonstrates an increased risk of PD associated with organic pesticides such as rotenone and certain other pesticides and environmental exposures in this population.     

尿道下裂危险因素的病例对照研究

目的 探讨尿道下裂病因。方法 采用以医院为基础的1:2配比的病例对照研究方法,以统一的调查表及调查方式对107倒尿道下裂及214例对照进行面对面问卷调查,应用SAS 6.12软件对所有调查因素进行单因素及多因素logistic回归分析。结果 胎儿尿道下裂的发生与母亲孕前自然流产史(OR=3.87,95％CI:1.60～9.39)、孕期发生先兆流产(OR=3.57,95％CI:1.31～9.64)、孕早期感冒伴发热(OR=7.63,95％CI:2.50～23.24)、孕中期用抗感染和/或解热止痛药(OR=16.46,95％CI;3.46～78.21)、父亲职业性接触农药(OR=3.70,95％CI:1.49～9.16)及胎儿低出生体重(OR=12.62,95％CI:2.97～53.67)呈正相关,与母亲孕早期增加蛋白质类营养(OR=0.33,95％CI:O.15～0.74)呈负相关。结论 母亲孕前自然流产史、孕期发生先兆流产、孕早期感冒伴发热、孕中期用抗感染和/或解热止痛药、父亲职业性接触农药、胎儿低出生体重等可能增加胎儿发生尿道下裂的危险,而母亲孕早期增加蛋白质类营养可能降低胎儿发生尿道下裂的危险。     

Gliomas and farm pesticide exposure in men: the upper midwest health study

The National Institute for Occupational Safety and Health evaluated farm pesticide exposure and glioma risk in a study that included 457 glioma cases and 648 population-based controls, all adult men (18-80 yr old) and nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. Multiple logistic regressions were used to control for farm residence, age, age group, education, and exposure to other pesticides. No associations were found between glioma and 12 specific pesticides. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) and found reduced glioma risk for insecticides (OR = 0.53, CI = 0.37-0.77), fumigants (OR = 0.57, CI = 0.34-0.95), and organochlorines (OR = 0.66, CI = 0.47-0.94). In analyses excluding proxy respondents (47% of cases) most CIs included 1.0. No positive association of farm pesticide exposure and glioma was found. Other farm exposures may explain the excess brain cancer risk seen in previous studies.     

Pesticides and respiratory symptoms among farmers

OBJECTIVE: Despite the intensive use of pesticides in agriculture there are few studies assessing the risk of respiratory conditions from this exposure. The study aimed at quantifying the prevalence of respiratory symptoms among farmers and evaluating its relationship with occupational use of pesticides and the prevalence of respiratory symptoms. METHODS: A cross-sectional study was conducted among 1,379 farmers from two municipalities of Southern Brazil in 1996. Frequency and type of chemical exposure and pesticide poisoning were recorded for both sexes. All subjects aged 15 years or older with at least 15 weekly hours of agricultural activity were interviewed. An adapted questionnaire developed by the American Thoracic Society was used for the assessment of respiratory symptoms. Multivariate logistic regression analysis was carried out. RESULTS: More than half (55%) of interviewees were male. The prevalence of asthma symptoms was 12% and chronic respiratory disease symptoms was 22%. Higher odds ratios for both asthma (OR=1.51; 95% CI: 1.07-2.14) and chronic respiratory disease (OR=1.34; 95% CI 1.00-1.81) symptoms were found in women. Logistic regression analysis identified associations between many forms of exposure to pesticides and increased respiratory symptoms. Occurrence of pesticide poisoning was associated with higher prevalence of asthma symptoms (OR=1.54; 95% CI: 1.04-2.58) and chronic respiratory disease symptoms (OR=1.57; 95% CI: 1.08-2.28). CONCLUSIONS: In spite of causality limitations, the study results provide evidence that farming exposure to pesticides is associated with higher prevalence of respiratory symptoms, especially when the exposure is above two days per month.     

Pesticide use and chronic bronchitis among farmers in the Agricultural Health Study

BACKGROUND: Farmers have increased risk for chronic bronchitis. Few investigators have considered pesticides. METHODS: We evaluated pesticides as risk factors for chronic bronchitis using the Agricultural Health Study enrollment data on lifetime pesticide use and history of doctor-diagnosed chronic bronchitis from 20,908 private pesticide applicators, primarily farmers. RESULTS: A total of 654 farmers (3%) reported chronic bronchitis diagnosed after age 19. After adjustment for correlated pesticides as well as confounders, 11 pesticides were significantly associated with chronic bronchitis. Heptachlor use had the highest odds ratio (OR=1.50, 95% Confidence Interval (CI)=1.19, 1.89). Increased prevalence for chronic bronchitis was also seen for individuals who had a history of a high pesticide exposure event (OR=1.85, 95% CI=1.51, 2.25) and for those who also applied pesticides in off-farm jobs (OR=1.40, 95% CI=1.04, 1.88). Co-morbid asthma and current farm activities did not explain these results. CONCLUSIONS: These results provide preliminary evidence that pesticide use may increase chronic bronchitis prevalence.     

Agricultural pesticide use and childhood cancer in California

BACKGROUND: Household pesticide use has been associated with higher risk for several childhood malignancies, but few studies have evaluated risks associated with residential proximity to agricultural pesticide use. We conducted a population-based case-control study of early childhood cancer (age 0-4 years) among California children born between 1990 and 1997 and mother's residential proximity to agricultural applications of pesticides at the time of the child's birth. METHODS: Included in the study were 2189 case children and 4335 controls matched for birth date and sex. We estimated the in utero exposure potential from specific chemicals and chemical groups used in the 9 months before birth within a half mile of the maternal residence. We computed odds ratios (ORs) using conditional logistic regression. RESULTS: No striking patterns emerged. There were modestly elevated ORs for leukemias associated with probable and possible carcinogen use, and with nearby agricultural applications of organochlorines and organophosphates during pregnancy. Two commonly used pesticides were associated with higher leukemia risk when comparing the highest and lowest categories: metam sodium (OR=2.05; 95% confidence interval=1.01-4.17) and dicofol (1.83; 1.05-3.22). CONCLUSIONS: The few elevated risk associations in this study are consistent with chance, given the large number of comparisons, but they may deserve more careful consideration. Future studies that integrate specific temporal and spatial exposure potential for targeted pesticides will be important in further evaluating risks associated with childhood cancer.     

Cancer risk and parental pesticide application in children of Agricultural Health Study participants

Parental exposure to pesticides may contribute to childhood cancer risk. Through the Agricultural Health Study, a prospective study of pesticide applicators in Iowa and North Carolina, we examined childhood cancer risk and associations with parental pesticide application. Identifying information for 17,357 children of Iowa pesticide applicators was provided by parents via questionnaires (1993-1997) and matched against the Iowa Cancer Registry. Fifty incident childhood cancers were identified (1975-1998). Risk of all childhood cancers combined was increased [standardized incidence ratio (SIR) = 1.36; 95% confidence interval (CI), 1.03-1.79]. Risk of all lymphomas combined was also increased (SIR = 2.18; 95% CI, 1.13-4.19), as was risk of Hodgkin's lymphoma (SIR = 2.56; 95% CI, 1.06-6.14). We used logistic regression to explore associations between self-reported parental pesticide application practices and childhood cancer risk. No association was detected between frequency of parental pesticide application and childhood cancer risk. An increased risk of cancer was detected among children whose fathers did not use chemically resistant gloves [odds ratio (OR) = 1.98; 95% CI, 1.05-3.76] compared with children whose fathers used gloves. Of 16 specific pesticides used by fathers prenatally, ORs were increased for aldrin (OR = 2.66), dichlorvos (OR = 2.06), and ethyl dipropylthiocarbamate (OR = 1.91). However, these results were based on small numbers and not supported by prior biologic evidence. Identification of excess lymphoma risk suggests that farm exposures including pesticides may play a role in the etiology of childhood lymphoma.     

Residential pesticide exposure and neuroblastoma

Neuroblastoma is the most common neoplasm in children under 1 year of age. We examined the relation between residential exposure to pesticides and neuroblastoma, using data from a case-control study of risk factors for neuroblastoma. Incident cases of neuroblastoma (N = 538) were identified through the Pediatric Oncology Group and the Children's Cancer Group. One age-matched control was identified for each case by random digit dialing. Telephone interviews with each parent collected information on residential exposure to pesticides. Pesticide use in both the home and garden were modestly associated with neuroblastoma [odds ratio (OR) = 1.6 (95% confidence interval [95% CI] = 1.0-2.3, and OR = 1.7 (95% CI = 0.9-2.1), respectively]. Compared with infants [OR = 1.0 (95% CI = 0.6-2.0)], stronger associations were found for garden pesticides in children diagnosed after 1 year of age [OR = 2.2 (95% CI = 1.3-3.6)], which suggests that pesticides may act through a mechanism more common for neuroblastomas in older children. There was no evidence of differential pesticide effects in subgroups of neuroblastoma defined by MYCN oncogene amplification or tumor stage.     

Occupation, pesticide exposure and risk of multiple myeloma

OBJECTIVES: This population-based case-control study examined the relationship between occupation, living or working on a farm, pesticide exposure, and the risk of multiple myeloma. METHODS: The study included 573 persons newly diagnosed with myeloma and 2131 controls. Information was obtained on sociodemographic factors, occupational history, and history of living and working on a farm. Occupational and industrial titles were coded by standardized classification systems. A job-exposure matrix was developed for occupational pesticide exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. RESULTS: Farmers and farm workers had odds ratios of 1.9 (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An odds ratio of 1.7 (95% CI 1.0-2.7) was observed for sheep farm residents or workers, whereas no increased risks were found for cattle, beef, pig, or chicken farm residents or workers. A modestly increased risk was observed for pesticides (OR 1.3, 95% CI 0.9-1.8). Significantly increased risks were found for pharmacists, dieticians and therapists (OR 6.1, 95% CI 1.7-22.5), service occupations (OR 1.3, 95% CI 1.02-1.7), roofers (OR 3.3, 95% CI 1.1-9.8), precision printing occupations (OR 10.1, 95% CI 1.03-99.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8), and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). CONCLUSIONS: A modest increased risk of multiple myeloma is suggested for occupational pesticide exposure. The increased risk for sheep farm residents or workers indicates that certain animal viruses may be involved in myeloma risk.     

Spontaneous abortion and maternal work in greenhouses

BACKGROUND: A positive association between maternal occupational exposure to pesticide and spontaneous abortion has been reported in some studies. Work in greenhouses may imply exposure of pregnant women to pesticides continuously and at elevated level. METHODS: A total of 717 women working in greenhouses provided information on 973 pregnancies, including 110 spontaneous abortions. These pregnancies were classified as exposed or not exposed according to maternal occupation, re-entry activities and application of pesticides in greenhouses during at least 1 month in the first trimester of pregnancy. The ORs for spontaneous abortion were estimated through a generalised estimate equations model for all orders of pregnancy together, and through a logistic regression model limited to first pregnancies. RESULTS: Increased risks of spontaneous abortion were found for maternal re-entry activities within 24 hr after pesticides were applied (all orders of pregnancy: OR 3.2, 95% CI 1.3-7.7; first pregnancies: OR 3.8, 95% CI 1.0-13.9) and for those who applied pesticides (all orders of pregnancy: OR 2.6, 95% CI 1.0-6.6; first pregnancies: OR 3.7, 95% CI 0.7-20,6) CONCLUSIONS: The observed results support the hypothesis of an association between maternal work in greenhouses and spontaneous abortion. The main limitations of the study are lack of information on the specific chemicals used and the small number of pregnancies heavily exposed to pesticides.     

Mortality of mental disorders in relation to potential pesticide exposure

Some studies have suggested a role of pesticide exposure in the development of neurobehavioral disorders. This case-control study examined the association between mortality from mental disorders and occupational exposure to pesticides. The study population consisted of 7756 deaths and 330,452 eligible controls identified from US death certificate files for the years 1988 through 1992. Exposure assignment was based on job title reported on the death certificates. Employment in jobs potentially involving pesticide exposure was weakly associated with the risk of death from mental disorders (odds ratio [OR] = 1.46; 95% confidence interval (95% CI) = 1.33-1.60). This association was stronger among women (OR = 2.65; 95% CI = 1.89-3.71), in particular for deaths from neurotic disorders (OR = 4.32; 95% CI = 2.44-7.64). These results must be interpreted with caution, however, because the impact of social and work-related factors other than pesticide exposure is not known.     

Parental occupational exposure to pesticides and childhood germ-cell tumors

In a recently completed US case-control study (Children's Oncology Group, 1993-2001) with 253 cases and 394 controls, the authors investigated the association between parental occupational exposure to pesticides and risk of childhood germ-cell tumors. Information on occupational pesticide exposure was collected using job-specific module questionnaires and assessed by an experienced industrial hygienist. Odds ratios for childhood germ-cell tumors associated with maternal exposures before pregnancy, during pregnancy, and after the birth of the index child were 1.0 (95% confidence interval (CI): 0.8, 1.4), 1.1 (95% CI: 0.7, 1.6), and 1.3 (95% CI: 0.9, 1.8), respectively. Paternal exposures before pregnancy, during pregnancy, and after the birth of the index child were not related to germ-cell tumors (odds ratios (ORs) were 0.9 (95% CI: 0.7, 1.2), 0.8 (95% CI: 0.5, 1.2), and 0.8 (95% CI: 0.5, 1.3), respectively). When both parents had ever been occupationally exposed to pesticides before the index pregnancy, the odds ratio was 0.8 (95% CI: 0.4, 1.3). Subgroup analyses showed a positive association between maternal exposure to herbicides during the postnatal period and risk of germ-cell tumors in girls (OR = 2.3, 95% CI: 1.0, 5.2) and an inverse association between paternal exposure to pesticides during the index pregnancy and germ-cell tumors in boys (OR = 0.2, 95% CI: 0.1, 1.0). This study did not provide strong evidence supporting a relation between parental pesticide exposure in the workplace and risk of germ-cell tumors among offspring.     

Rheumatoid arthritis among women in the Agricultural Health Study: risk associated with farming activities and exposures

PURPOSE: Farming has been associated with increased risk of rheumatoid arthritis (RA) in some studies, but specific causes have not been identified. We studied risk factors for RA in the Agricultural Health Study, a cohort of over 57,000 licensed pesticide applicators and their spouses. METHODS: We used a nested case-control design, limited to female participants. Physician-confirmed cases (n = 135) were matched to five controls each (n = 675) by birth date. We used logistic regression, adjusting for birth date and state to examine associations, as estimated by odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Risk of RA was not associated with mixing or applying pesticides overall or with any pesticide class, nor did it vary by number of days or years of use. Certain pesticides were associated with small nonsignificantly increased risks, including lindane (OR = 1.8, 95% CI: 0.6-5.0). RA risk was associated with welding (OR = 2.1, 95% CI: 0.8-5.4), albeit imprecisely, but not with solvents or sunlight. CONCLUSIONS: We did not identify any strong risk factors for RA. Because of the severe disability associated with this relatively common disease, further investigation into causes is warranted both in the Agricultural Health Study and elsewhere.     

Maternal and gestational risk factors for hypospadias

BACKGROUND: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. OBJECTIVES: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. METHODS: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. RESULTS: A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) = 4.6; 95% confidence interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) > or = 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6; 95% CI, 1.2-5.7) compared with boys born to mothers with a normal weight (BMI = 20-24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2-2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6; 95% CI, 1.1-53). CONCLUSIONS: A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.     

A population-based case-control study of farming and breast cancer in North Carolina

We examined the role of farming and pesticide exposure among 862 cases and 790 controls in a population-based, case-control study of breast cancer conducted in North Carolina between 1993 and 1996. We obtained exposure information through personal interview. Increasing duration of farming was inversely associated with breast cancer risk; odds ratios (95% confidence intervals) were 1.2 (0.8-1.7), 0.8 (0.5-1.2), 0.7 (0.5-1.1), and 0.6 (0.4-0.9) for 1-10, 11-17, 18-23, and >23 years of farming, respectively, relative to nonfarmers. Inverse associations persisted when farming was restricted to calendar time periods of 2,2-bis(p-chlorophenyl)- 1,1,1-trichloroethane (DDT) use or to farming at ages 9-16. Among women who farmed, odds ratios (ORs) were elevated for those who reported being present in fields during or shortly after pesticide application (OR = 1.8, 95% CI = 1.1-2.8) and for those who reported not using protective clothing while applying pesticides (OR = 2.0; 95% CI = 1.0-4.3), but not among those who reported using protective clothing (OR = 0.8; 95% CI = 0.4-1.8). We conclude that residence or work on farms may be associated with a reduced risk of breast cancer. Nevertheless, our results suggest a possible increased risk of breast cancer among a subgroup of farming women who were most likely to be exposed to pesticides.     

Parental occupational exposure to pesticides and the risk of childhood leukemia in Costa Rica

OBJECTIVES: Parental exposure to pesticides and the risk of leukemia in offspring were examined in a population-based case-control study in Costa Rica. METHODS: All cases of childhood leukemia (N=334), in 1995-2000, were identified at the Cancer Registry and the Children's Hospital. Population controls (N=579) were drawn from the National Birth Registry. Interviews of parents were conducted using conventional and icon-based calendar forms. An exposure model was constructed for 25 pesticides in five time periods. RESULTS: Mothers' exposures to any pesticides during the year before conception and during the first and second trimesters were associated with the risk [odds ratio (OR) 2.4, 95% confidence interval (95% CI) 1.0-5.9; OR 22, 95% CI 2.8-171.5; OR 4.5, 95% CI 1.4-14.7, respectively] and during anytime (OR 2.2, 95% CI 1.0-4.8). An association was found for fathers' exposures to any pesticides during the second trimester (OR 1.5, 95% CI 1.0-2.3). An increased risk with respect to organophosphates was found for mothers during the first trimester (OR 3.5, 95% CI 1.0-12.2) and for fathers during the year before conception and the first trimester (OR 1.5, 95% CI 1.0-2.2 and OR 1.6, 95% CI 1.0-2.6, respectively), and benzimidazoles during the first, second, and third trimesters of pregnancy (OR 2.2, 95% CI 1.0-4.4; OR 2.2, 95% CI 1.0-5.0; OR 2.2, 95% CI 1.0-5.2, respectively). There was a suggestion of an exposure-response gradient for fathers as regards picloram, benomyl, and paraquat. Age at diagnosis was positively associated with fathers' exposures and inversely associated with mothers' exposures. CONCLUSIONS: The results suggest that parental exposure to certain pesticides may increase the risk of leukemia in offspring.