724 VOLUME 111 | NUMBER 5 | May 2003 • Environmental Health Perspectives Environmental Medicine | Article Health Impacts of Pesticide Exposure in a Cohort of Outdoor Workers John Beard, 1,2 Tim Sladden, 1 Geoffrey Morgan, 1 Geoffrey Berry, 3 Lyndon Brooks, 1 and Anthony McMichael 4 1 Southern Cross Institute of Health Research, Southern Cross University, Lismore, New South Wales, Australia; 2 Northern Rivers University Department of Rural Health, University of Sydney, Lismore, New South Wales, Australia; 3 School of Biostatistics, University of Sydney, Lismore, New South Wales, Australia; 4 National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australian Capital Territory, Australia The widespread use of synthetic chemicals after the Second World War has revolution- ized agricultural practice. Initial studies of the possible health effects of these substances on humans were small and reassuring (Cameron and Burgess 1945; Hayes and Durham 1956). During the 1960s, however, it became evident that persistent pesticides were having an adverse impact on ecologic communities (Ramade 1987; Ratcliffe 1970). This led to a number of more extensive epidemiologic investigations exploring the possible impact of these exposures on human health [International Agency for Research on Cancer (IARC) 1991; Pearce and Reif 1990). These studies faced numerous methodologic problems common to environmental epidemiology, and even today, our understanding of the relationship between pesticides and human health is lim- ited (Blondell 1990). In this paper we describe a historical cohort study undertaken to examine the health outcomes of a group of agricultural workers with high occupational pesticide exposures. The main group investigated in this study comprised all identifiable field staff employed by the New South Wales (NSW), Australia, Board of Tick Control between 1935 and 1995. The board constructed and operated over 1,600 cattle dips in a tick quarantine zone on the east coast of Australia, and over 3,000 staff worked on the program during the study period. Subjects interviewed during the course of the study report extremely high and recur- rent exposures to the insecticides used in the dips. This is supported by limited evidence from an occupational monitoring program. Methods Identification of cohort. One of the method- ologic challenges encountered by occupa- tional cohort studies is the “healthy worker effect,” characterized by a tendency for rela- tively healthy individuals to be more likely to gain employment and remain employed (Breslow and Day 1987). This may poten- tially bias studies toward finding lower mor- tality rates in an occupational cohort when compared with the general community and thus mask true increases in mortality. To deal with this problem, our study was designed to allow comparison of the exposed group with two reference populations: the Australian population as a whole, and a control group of outdoor workers drawn from a similar socioe- conomic background but not occupationally exposed to insecticides. The study population comprised a dynamic cohort divided into exposed and control sub- cohorts. To facilitate matching with death registries, the cohort was restricted to male workers with known dates of birth. The exposed subcohort was made up of all male staff identified by a search of NSW government records as having worked as field officers or laboratory staff for the NSW Board of Tick Control at any time since 1935. A total of 1,999 subjects met these criteria. The control subcohort was made up of all male staff identified by local governments from the same region as having worked as out- door field officers at any time since 1935. A small group of office staff who had worked for the Board of Tick Control were also included in this group. A total of 1,984 subjects met these criteria. Subjects were followed from 1 January 1935, or their subsequent entry to the study, until their death, loss to follow-up, or study completion on 1 January 1996. Ascertainment of vital status. Vital status was ascertained by matching the cohort with national death registers and health insurance records. This matching was generally under- taken using probabilistic record linkage. Australian citizens are required to register with the Australian Health Insurance Commission to receive a universal health care rebate (Medicare). Medicare commenced operation in October 1983, and the cohort was matched with commission records for registration at any time after this date. Subjects with current Medicare registration were considered alive. The cohort was also matched with the Australian National Deaths Index (operating from 1980) and with the NSW and Queensland Deaths Registers for 1945–1979. Survey of surviving cohort members. We also attempted to locate all cohort members who were thought to still be alive. Possible contact addresses were found for a total of 1,533 subjects, who were sent a questionnaire by mail. Questions focused on factors that might potentially confound the broader study, such as smoking or alcohol consumption, pes- ticide exposure history, a validated neuropsy- chologic score, and a range of nonfatal outcomes that may potentially be related to pesticide exposure. Address correspondence to J. Beard, Northern Rivers University Department of Rural Health, University of Sydney, PO Box 498, Lismore, NSW, Australia, 2480. Telephone: 61 2 66202602. Fax: 61 2 66222151. E-mail: JBEAR@nrhs.health.nsw.gov.au We acknowledge the significant contributions of J. Atkins, M. Dowling, M. Leedow, and R. Maximilian to the success of this study. The authors declare they have no conflict of interest. Received 15 July 2002; accepted 2 October 2002. We compared mortality of 1,999 outdoor staff working as part of an insecticide application pro- gram during 1935–1996 with that of 1,984 outdoor workers not occupationally exposed to insec- ticides, and with the Australian population. Surviving subjects also completed a morbidity questionnaire. Mortality was significantly higher in both exposed and control subjects compared with the Australian population. The major cause was mortality from smoking-related diseases. Mortality was also significantly increased in exposed subjects for a number of conditions that do not appear to be the result of smoking patterns. Compared with the general Australian popula- tion, mortality over the total study period was increased for asthma [standardized mortality ratio (SMR) = 3.45; 95% confidence interval (CI), 1.39–7.10] and for diabetes (SMR = 3.57; 95% CI, 1.16–8.32 for subjects working < 5 years). Mortality from pancreatic cancer was more frequent in subjects exposed to 1,1,1-trichloro-2,2-bis( p- chlorophenyl)ethane (SMR = 5.27; 95% CI, 1.09–15.40 for subjects working < 3 years). Compared with the control population, mortality from leukemia was increased in subjects working with more modern chemicals (standardized inci- dence ratio = 20.90; 95% CI, 1.54–284.41 for myeloid leukemia in the highest exposure group). There was also an increase in self-reported chronic illness and asthma, and lower neuropsychologic functioning scores among surviving exposed subjects when compared with controls. Diabetes was reported more commonly by subjects reporting occupational use of herbicides. These findings lend weight to other studies suggesting an association between adverse health effects and exposure to pesticides. Key words: asthma, cohort study, DDT, diabetes, leukemia, neoplasms, pancreatic cancer, pesticides. Environ Health Perspect 111:724–730 (2003). doi:10.1289/ehp.5885 available via http://dx.doi.org/ [Online 30 October 2002]