Cryptorchidism and hypospadias in sons of gardeners and farmers.

Cryptorchidism and hypospadias have been related to prenatal estrogen exposure in animal models. Some chemicals used in farming and gardening have been shown to possess estrogenic and other hormone-disrupting effects. Earlier studies have indicated increased risks of urogenital malformations in the sons of pesticide appliers. In the present study, parental occupation in the farming and gardening industry among 6,177 cases of cryptorchidism, 1,345 cases of hypospadias, and 23,273 controls, born live from 1983 to 1992 in Denmark, was investigated in a register-based case-control study. A significantly increased risk of cryptorchidism but not hypospadias was found in sons of women working in gardening (adjusted odds ratio = 1.67; 95% confidence interval, 1.14-2.47). The risks were not increased in sons of men working in farming or gardening. The increased risk of cryptorchidism among sons of female gardeners could suggest an association with prenatal exposure to occupationally related chemicals.     

Exposure to endocrine disruptors and male urogenital tract malformations [cryptorchidism and hypospadias]

BACKGROUND: It has been proposed that the intrauterine period of child-mother exposure to hormonally active compounds (endocrine disruptors) is of critical importance. OBJECTIVE: We reviewed all Spanish and English-language epidemiological studies published between 1990 and the first trimester of 2006 that studied the possible association between human exposure to chemical compounds and the risk of cryptorchidism and/or hypospadias. METHODS: The MEDLINE (PubMed) database was searched using the following key words: endocrine disruptors, organochlorine pesticides, xenoestrogens, cryptorchidism and hypospadias. Selection of the 16 studies included was based on the following criteria: study design and population, the measures of exposure used, inclusion and exclusion criteria, and the statistical analysis used. RESULTS AND CONCLUSIONS: Although the studies reviewed do not conclusively confirm the association between exposure to endocrine disruptors and the risk of male genital malformation, this association cannot be ruled out. Further in-depth investigation of this association is required. Issues that remain to be resolved are the diagnostic classification to be used and appropriate measurement of exposure to multiple chemical compounds and environmental contaminants that act conjointly through mechanisms similar to endogenous hormones.     

Exposure to endocrine disrupting chemicals and human health: a review of epidemiological studies focused on hypospadias and cryptorchidism

Hypospadias and cryptorchidism are common congenital anomalies. Recently, increases in the prevalence of hypospadias and cryptorchidism have been reported in various countries, including Japan. As male sexual differentiation is critically dependent on normal androgen concentrations, increased exposure to environmental factors affecting androgen homeostasis during fetal life (i.e. EDCs with estrogenic or anti-androgenic effects) may cause hypospadias or cryptorchidism. However, the results from the International Clearinghouse for Birth Defects Monitoring System (ICBDMS), hospital-based studies in each country and population-based studies in Japan are different, because in the present system there are some problems such as the standardization of diagnostic criteria and the difference of the time of diagnosis, we hope to improve the monitoring system method. Previous papers have reported that hypospadias and cryptorchidism were associated with maternal exposure to progesterone, estrogen, diethylstilbestrol (DES) and pesticide. However, there are few studies evaluating the quantity of endocrine disrupting chemicals, using biological samples. In the future, a well-designed epidemiological study is needed to elucidate the relation between endocrine disrupting chemicals and genital development.     

Paternal occupation and anencephaly

It has been suggested that paternal occupational exposures to pesticides and solvents increase the risk of neural tube defects in offspring. With the use of Texas livebirth, fetal death, and linked livebirth-death records, the authors conducted a population-based case-control study among 1981-1986 Texas births to examine the association between paternal occupation and anencephalic births. Fathers employed in occupations associated with solvent exposure were more likely to have offspring with anencephaly (odds ratio (OR) = 2.53), with painters having the highest risk (OR = 3.43). A lesser association was found for fathers employed in occupations involving pesticide exposure (OR = 1.28). Further studies are indicated to clarify these associations.     

Maternal Exposure to a Brominated Flame Retardant and Genitourinary Conditions in Male Offspring

Background

The upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor.

Objective

We investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero.

Methods

In this cohort study of sons born to women accidentally exposed to PBBs during 1973–1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth.

Results

Of 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [≤1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8–5.1]. This risk was increased when we excluded sons born after the exposure but before the mother’s serum PBB measurement (OR = 3.1; 95% CI, 1.0–9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure.

Conclusions

Although cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.     

Parental occupational pesticide exposure and nonsyndromic orofacial clefts

Nonsyndromic orofacial clefts are common birth defects. Reported risks for orofacial clefts associated with parental occupational pesticide exposure are mixed. To examine the role of parental pesticide exposure in orofacial cleft development in offspring, this study compared population-based case-control data for parental occupational exposures to insecticides, herbicides, and fungicides, alone or in combinations, during maternal (1 month before through 3 months after conception) and paternal (3 months before through 3 months after conception) critical exposure periods between orofacial cleft cases and unaffected controls. Multivariable logistic regression was used to estimate odds ratios, adjusted for relevant covariables, and 95% confidence intervals for any (yes, no) and cumulative (none, low [相似文献   

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.     

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。     

Agricultural pesticide use and hypospadias in eastern Arkansas

INTRODUCTION: We assessed the relationship between hypospadias and proximity to agricultural pesticide applications using a GIS-based exposure method. METHODS: We obtained information for 354 cases of hypospadias born between 1998 and 2002 in eastern Arkansas; 727 controls were selected from birth certificates. We classified exposure on pounds of pesticides (estimated by crop type) applied or persisting within 500 m of each subject's home during gestational weeks 6 to 16. We restricted our analyses to 38 pesticides with some evidence of reproductive, developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of pesticide applications using crop phenology and published records. RESULTS: Gestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI), 0.83-0.99], parity (OR = 0.79; 95% CI, 0.65-0.95), and delaying prenatal care until the third trimester (OR = 4.04; 95% CI, 1.46-11.23) were significantly associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05-pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI, 1.01-1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70-0.96) and applications of alachlor (OR = 0.56; 95% CI, 0.35-0.89) and permethrin (OR = 0.37; 95% CI, 0.16-0.86) were negatively associated with hypospadias. CONCLUSIONS: Except for diclofop-methyl, we did not find evidence that estimated exposure to pesticides known to have reproductive, developmental, or endocrine-disrupting effects increases risk of hypospadias. Further research on the potential effects of exposure to diclofop-methyl is recommended.     

A Systematic Review and Meta-analysis of Childhood Leukemia and Parental Occupational Pesticide Exposure

Objectives

We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.

Data sources

Searches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies.

Data extraction

Two authors independently abstracted data and assessed the quality of each study.

Data synthesis

Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3).

Conclusions

Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.     

Risk of hypospadias in relation to maternal occupational exposure to potential endocrine disrupting chemicals

Background: Reported rises in the prevalence of hypospadias and other abnormalities of the male reproductive system may be a result of exposure to endocrine disrupting chemicals. Aims: To analyse the relation between risk of hypospadias and maternal occupation, particularly with regard to exposure to potential endocrine disrupting chemicals (EDCs). Methods: Data (1980–96) from the National Congenital Anomaly System (NCAS) were used to analyse the proportion of all congenital anomaly cases (n = 35 962) which were notified with hypospadias (n = 3471) by occupational codes (348 individual job titles) and by categories of exposure to potential EDCs from a job exposure matrix. Results: Five individual occupations (of 348) showed nominally statistically significant excesses, none of which had possible or probable exposure to potential EDCs. Odds ratios for "possible" or "probable" compared to "unlikely" exposure to potential EDCs did not show statistically significant increases in any of the EDC categories after adjustment for social class of the mother and father, nor was there evidence of an upward trend in risk with likelihood of exposure. In the 1992–96 time period odds ratios were increased for hairdressers (the largest group exposed to potential EDCs) and for probable exposure to phthalates (of which hairdressers form the largest group) before social class adjustment. Conclusions: There was little evidence for a relation between risk of hypospadias and maternal occupation or occupational exposure to potential EDCs, but as the exposure classification was necessarily crude, these findings should be interpreted with caution.     

Maternal diet and the risk of hypospadias and cryptorchidism in the offspring

Male genital tract birth defects have been associated in previous studies with several prenatal exposures to environmental and dietary risk factors. The purpose of this study was to explore the association between hypospadias and cryptorchidism, and the dietary habits of an agricultural population in Italy. A population-based case-control study was conducted in the Sicilian Province of Ragusa. Cases (n = 90) and controls (n = 202) included births for the period 1998-2002. Data on dietary habits of the mothers, as well as health-related social, occupational and environmental exposures prior to and during the index birth, were collected through interviews. Adjusted odds ratios (OR) were calculated by logistic regression after adjustment for confounding variables. Increased ORs were observed for mothers of children with hypospadias who, during pregnancy, frequently consumed fish (OR = 2.33 [95% confidence interval (CI) 1.03, 5.31]) and market-purchased fruit (OR = 5.10 [95% CI 1.31, 19.82]). For cryptorchidism, increased risk was observed in mothers consuming liver (OR = 5.21 [95% CI 1.26, 21.50]), and smoked products (OR = 2.46 [95% CI 1.15, 5.29]). For the two malformations pooled together, increased risk was associated with maternal consumption of liver (OR = 4.38 [95% CI 1.34, 14.26]) and with frequent consumption of wine (OR = 1.98 [95% CI 1.01, 3.86]). This study suggests that some maternal dietary factors may play a role in the development of congenital defects of the male reproductive tract. In particular, our data indicate that further research may be warranted on the endocrine-disrupting effects resulting from the bioaccumulation of contaminants (fish, liver), pesticides (marketed fruit, wine) and/or potentially toxic food components (smoked products, wine, liver).     

Exposure to endocrine disrupting chemicals and children's health: problems in epidemiological studies

Most endocrine disrupting chemicals are characterized by their properties to induce marked phenotypic changes in offspring such as congenital anomalies and neurodevelopmental dysfunctions. Although an increase in the prevalence of hypospadias or cryptorchidism has been reported in various countries, improvement in diagnostic techniques and more attention to the features of the diseases have also been emphasized. Although there have been a few reports that hypospadias or cryptorchidism had been associated with diethylstilbestrol (DES), pesticides and so on, the associations between these diseases and endocrine disrupting chemicals remain unclear. Recently, the association between maternal metabolic polymorphism or paternal smoking during pregnancy and these diseases has been reported. There are also variable clinical features in children's neurobehavioral development, and thyroid and immune functions in relation to exposure to endocrine disrupting chemicals such as polychlorinated biphenyls (PCBs) and dioxins. Only a few Dutch studies have suggested that perinatal exposure to background level of PCB/dioxin confers immunity to allergy development. Genetic susceptibility to environmental endocrine disrupting chemicals may be related to adverse pregnancy outcomes. It is suggested that well-designed epidemiological studies such as prospective cohort studies should be performed to elucidate this association.     

隐睾发生的危险因素研究

目的：研究隐睾发生的危险因素。方法：采用以医院为基础的1：2配比的病例对照研究方法，按统一的调查方法对99例隐睾及198例对照组面对面问卷调查。应用SAS6。12软件对所调查因素进行单因素及多因素logistic回归分析，结果：胎儿隐睾与母亲孕早期感冒伴发热（OR＝9．37，95％CI：2．25－39．09），孕期发生先兆流产（OR＝4．66，95％CI，2．02＝10．74），孕期发生先兆子痫（OR＝16．33，95％CI：1．40－191．20），父亲职业性接触农药（OR＝12．79％CI；2．90－56．43），低出生体重（OR＝5．77，95％CI：1．39－23．98），母亲怀孕年龄＜24（OR＝2．89，95％CI：1．29－4．06）呈正相关。结论：母亲孕早期感冒伴发热，孕期发生先兆流产及先兆子痫，父亲职业性接触农药，低出体重，母亲怀孕年龄＜24岁是隐睾发病的主要危险因素。     

Effect of parents' occupational exposures on risk of stillbirth, preterm delivery, and small-for-gestational-age infants

Epidemiologic research on the effects of parental occupational exposures on fetal development has been limited. The National Natality and Fetal Mortality surveys obtained applicable data on probability samples of live births and fetal deaths which occurred in the US in 1980 among married women. Analyses were conducted for case groups of stillbirths (2,096 mothers, 3,170 fathers), preterm deliveries (less than 37 weeks completed gestation) (363 mothers, 552 fathers), and small-for-gestational-age infants (218 mothers, 371 fathers) compared with controls. Occupational exposures were defined by industry of employment and by imputed exposures based on a job-exposure linkage system. For stillbirth, maternal work in the rubber, plastics, and synthetics industry (odds ratio (OR) = 1.8, 95% confidence interval (Cl) 0.8-4.0) and lead exposure (OR = 1.6, 95% Cl 0.8-3.1), and paternal employment in the textile industry (OR = 1.9, 95% Cl 1.2-2.9), had the largest odds ratios. Preterm birth was most strongly associated with maternal lead exposure (OR = 2.3, 95% Cl 0.7-7.0), corroborating previous findings. Twofold increased risk of preterm delivery was found with paternal employment in the glass, clay, and stone; textile; and mining industries. Paternal exposures to x-rays and polyvinyl alcohol were associated with 1.5-fold increase in risk. The occupation of the mother was not associated with delivery of a small-for-gestational-age infant, in contrast to paternal employment in the art (OR = 2.6, 95% Cl 1.2-5.6) and textile industries (OR = 2.5, 95% Cl 1.3-4.7). Several toxic agents were associated with risk elevation of 1.3 or greater for fathers, most notably benzene (OR = 1.5, 95% Cl 1.1-2.3). In spite of limitations in the exposure data, the size of the exposed populations, and possible confounding, the results in this study encourage further evaluation of the effects of maternal exposure to lead and possibly solvents, as well as paternal exposure in the textile industry and to x-rays and benzene.     

Occupational categories at risk for Parkinson's disease

BACKGROUND: The etiology of Parkinson's disease (PD) is considered to have a strong environmental component, but relatively few studies have investigated the potential association between occupation and the disease. METHODS: In a population-based case-control study, we collected comprehensive occupational histories from all study participants, 144 case and 464 control subjects. RESULTS: Chi-square analysis revealed that working in an agricultural occupation increased estimated PD risk (OR = 1.74; 95% CI = 0.85, 3.60). In contrast, a history of ever working in a service occupation was negatively associated with PD risk (OR = 0.69; 95% CI = 0.47, 1.00). Risk estimates were close to one for specific service occupations. Adjusted odds ratios for all non-service occupational and industrial categories were similar, and working in a service occupation was the only significant inverse predictor of PD risk. CONCLUSIONS: Future investigations focusing on lifestyle factors and environmental exposures within the agricultural and service occupational categories are warranted.     

Paternal occupational exposures and childhood cancer

The objective of the study described here was to test the hypothesis that paternal occupational exposure near conception increases the risk of cancer in the offspring. We conducted a cohort study based on a population of 235,635 children born shortly after two different censuses in Sweden. The children were followed from birth to 14 years, and cases of cancer were identified in the Swedish Cancer Registry. Occupational hygienists assessed the probability of exposure to different agents in each combination of the father's industry and occupation as reported in the censuses. We also analyzed individual job titles. We compared the cancer incidence among children of exposed fathers to that among children of unexposed fathers using Cox proportional hazards modeling. The main findings were an increased risk of nervous system tumors related to paternal occupational exposure to pesticides [relative risk (RR) = 2.36; 95% confidence interval (CI), 1.27-4.39] and work as a painter (RR = 3.65; 95% CI, 1.71-7.80), and an increased risk of leukemia related to wood work by fathers (RR = 2.18; 95% CI, 1.26-3.78). We found no associations between childhood leukemia and paternal exposure to pesticides or paint. Our results support previous findings of an increased risk of childhood brain tumors and leukemia associated with certain paternal occupational exposures. Some findings in previous studies were not confirmed in this study.     

Pregnancy outcome among offspring of airline pilots and cabin attendants

OBJECTIVES: This study assessed the occurrence of perinatal death, low birthweight, preterm birth, and birth defects (total, major, neural tube defects, total cleft, cleft palate, hypospadias, and Down syndrome) in the offspring of airline pilots and cabin attendants. METHODS: A cohort of offspring of airline pilots and cabin attendants was established and characterized in terms of parental exposure to cosmic radiation the year before birth or ever. Pregnancy outcome was derived from the Medical Birth Register of Norway. The reference group comprised offspring of parents without occupational exposure to cosmic radiation. RESULTS: No deviant risks were observed for the offspring of male pilots, either for the year preceding birth (N=2,111) or ever (N=2,356). Specific birth outcomes were fewer for the pilots than for the referents (N=1,621,186), except for Down syndrome, which was more frequent [odds ratio (OR) 1.41, 95% confidence interval (95% CI) 0.53-3.76]. For exposure the year preceding birth (N=2,512), the risk of low birthweight was lower for the female cabin attendants than for the referents (adjusted OR 0.83, 95% CI 0.69-1.00), while Down syndrome was more frequent (OR 1.44, 95% CI 0.60-3.47). For exposure ever (N=3346), the risk of low birthweight was lower (OR 0.82, 95% CI 0.70-0.96) for the cabin attendants, while hypospadias (OR 1.18, 95% CI 0.61-3.04) and Down syndrome (OR 1.79, 95% CI 0.03-3.45) were more frequent CONCLUSIONS: In general, offspring of air pilots and cabin attendants do not seem to be at increased risk of adverse pregnancy outcome.     

Paternal occupational exposure to radiofrequency electromagnetic fields and risk of adverse pregnancy outcome

Background: During the last decades, public concern that radiofrequency radiation (RFR) may be related to adverse reproductive outcomes has been emerging. Our objective was to assess associations between paternal occupational exposure to RFR and adverse pregnancy outcomes including birth defects using population-based data from Norway. Methods: Data on reproductive outcomes derived from the Medical Birth Registry of Norway were linked with data on paternal occupation derived from the general population censuses. An expert panel categorized occupations according to exposure. Using logistic regression, we analyzed 24 categories of birth defects as well as other adverse outcomes. Results: In the offspring of fathers most likely to have been exposed, increased risk was observed for preterm birth (odds ratio (OR): 1.08, 95% confidence interval (CI): 1.03, 1.15). In this group we also observed a decreased risk of cleft lip (OR: 0.63, 95% CI: 0.41, 0.97). In the medium exposed group, we observed increased risk for a category of ‚other defects’ (OR: 2.40, 95% CI: 1.22, 4.70), and a decreased risk for a category of ‚other syndromes’ (OR: 0.75, 95% CI: 0.56, 0.99) and upper gastrointestinal defects (OR: 0.61, 95% CI: 0.40, 0.93). Conclusion: The study is partly reassuring for occupationally exposed fathers.These two authors share first authorship     

Environmental determinants of Parkinson's disease

Increasing toxicologic and epidemiologic evidence suggests that pesticides and other environmental exposures are associated with idiopathic Parkinson's disease. Using a case-control study, the authors examined the impact of farming, pesticide use, rural residence, and well water use (including critical periods of childhood exposure) on the risk of Parkinson's disease. After adjustment for confounding, > or = 40 years of well-water exposure (compared to no well water use) was associated with an increased risk of Parkinson's disease (OR = 7.1; 95% CI: 2.3-22.1). The authors found an increased risk of Parkinson's disease (OR = 2.1; 95% Cl: 0.7-6.4) for well water use during the first 20 years of life (compared with <20 years of exposure) and saw some suggestion of an exposure-response relationship with increasing childhood exposure. Farming and pesticide use (occupational or residential) was not associated with Parkinson's disease but exposure assessment limitations warrant further investigation.