SAN FRANCISCO—French investigators have found an association between Parkinson’s disease and professional pesticides use and suggested that some pesticides are more likely to be associated with the disease than others. Alexis Elbaz, MD, PhD, and colleagues found an overall association between Parkinson’s disease, insecticides, and fungicides. Sulfur and copper exposure were associated with Parkinson’s disease in women, while copper, carbamate fungicides, organochlorine insecticides, and phenoxy herbicides were associated with the disease in men.

“Epidemiologic studies, including the present one, have quite consistently shown an association between Parkinson’s disease and exposure to pesticides,” Dr. Elbaz told Neurology Reviews. “They are not able, however, to elucidate the underlying mechanisms.” Dr. Elbaz, who is affiliated with Inserm (unit 360, Hôpital de la Salpêtrière, Paris), presented his findings at the 56th Annual Meeting of the American Academy of Neurology.

THE SHORTCOMINGS OF CURRENT STUDIES

Although the available toxicologic studies are insufficient to understand how pesticides can be toxic to neurons and to incriminate a specific pesticide, there is already some evidence—for example, the rotenone animal model—to support a link between pesticides and Parkinson’s disease, according to Dr. Elbaz. Most of the studies, though, are based on short-term exposures to pesticides that are not readily comparable with professional, long-term exposures. “It is therefore unclear whether the findings observed in vitro or in vivo would be reproduced using more environmentally relevant levels and sources of exposure,” Dr. Elbaz said. “Further toxicologic research, using other routes and doses of exposure, is needed. In addition, in recent years, our understanding of the pathophysiology of Parkinson’s disease has greatly improved with the identification of the role of the proteasome and oxidative stress, and it is likely that this will help to better understand how exposure to pesticides can be harmful.”

PARKINSON’S DISEASE AND PESTICIDES

Dr. Elbaz and colleagues sought to examine the relationship between Parkinson’s disease and pesticides exposure in a population characterized by a high prevalence of professional pesticides use. The study included participants from a French health insurance system for agricultural workers, the Mutualité Sociale Agricole, which includes farmers, farmworkers, workers in silos, agricultural cooperatives, and seed shops, as well as tertiary sector professionals. A total of 247 patients (age range, 18 to 75) who had requested health coverage for Parkinson’s disease were included as cases and were subsequently examined by a neurologist. In addition, the researchers included 676 control subjects who did not have Parkinson’s disease. A maximum of three controls were matched to each case on age, gender, and region of residency at the time of the study.

Detailed information on pesticide use was obtained using a two-stage, case-by-case exposure assessment procedure by occupational health physicians. Study participants were classified as never users of pesticides, users for gardening purposes exclusively, and professional users of pesticides. For professional users of pesticides, information on types of pesticides used, number of hours and frequency of spraying per year, and number of years of use was obtained. Data were reviewed by a panel of experts, including an agricultural engineer, an epidemiologist, and an occupational health physician blinded to the case or control status.

CASE VERSUS CONTROLS

Information on pesticides use was available for 224 cases (52% men, median age at disease onset, 65) and 557 matched controls. The authors found that—consistent with previous studies—a family history of Parkinson’s disease was more frequent in cases than in controls, while cigarette smoking was less frequent in cases than in controls. Cases had a lower median Mini-Mental State Examination score and a lower education level than did controls. Patients with Parkinson’s disease had more often been farmers and professionally exposed to pesticides than were matched controls; odds ratios associated with both variables increased with the number of years of exposure.

“The frequency of professional pesticide exposure was considerably higher in men than in women,” stated Dr. Elbaz. However, he added, “There was no significant difference in the relationship between Parkinson’s disease and professional pesticides exposure according to sex.” The frequency of professional pesticides exposure was significantly higher in cases than in controls, in both women (15% cases, 8% controls) and men (77% cases, 70% controls); both cases and controls used a wide variety of pesticides that were coded into 53 broad pesticide families.

Univariate analyses (excluding users for gardening) showed that the following pesticides were associated with Parkinson’s disease in women: copper (14% cases, 5% controls), sulfur (12% cases, 4% controls). In men, associations were observed for copper (72% cases, 63% controls), organochlorine insecticides (65% cases, 48% controls), carbamate fungicides (52% cases, 37% controls), and phenoxy herbicides (55% cases, 44% controls). No association was observed between Parkinson’s disease and paraquat (in men: 33% cases, 32% controls), a commonly used herbicide that has a chemical structure similar to that of the neurotoxic MPTP. Adjustment for Mini-Mental State Examination or cigarette smoking did not modify these results, Dr. Elbaz said. “One of the limitations of our findings is that the proportion of subjects with unknown exposure status was important for some pesticides,” he noted.

CAUTIOUS INTERPRETATION OF THE DATA

Dr. Elbaz emphasized that these findings are preliminary and that further analyses are necessary. A link of causality cannot be established based on epidemiologic data, he added. “Further studies, in particular laboratory in vitro and in vivo studies, will be necessary before we can understand the relationship between pesticides and Parkinson’s disease,” he said. “In addition, more epidemiologic data, for instance, data on dose-effect relations, are needed.”

PUTTING PESTICIDES IN PERSPECTIVE

To place his findings in proper perspective, Dr. Elbaz said that there were at least three important points to consider. “First, exposure to pesticides was carefully assessed at the individual level,” he commented. “Farmers who participated in this study were mainly elderly subjects and had been exposed to a large variety of pesticides for many years. Although it is likely that they recalled pesticides that they had frequently used, it is possible that they did not report pesticides that they had rarely used. In addition, for some pesticides, the proportion of subjects with unknown exposure status was important,” Dr. Elbaz elaborated. “Second,” he continued, “some pesticides are very frequently used together, and it is often difficult—if not impossible— to disentangle the effect of each product.” Third, “new pesticides are marketed each year, while others are banned or abandoned; thus, given the age of the participants in our study, some of the pesticides that they used are not used anymore, while they rarely used many of the most recent products,” Dr. Elbaz said.

THE FUTURE OF PESTICIDE USE

Ultimately, Dr. Elbaz believes that his study and similar ones can help lead to a better understanding of the etiology of Parkinson’s disease and to estimate the importance of the effect of different exposures as well as their interaction. “But it is certainly too early to [recommend] the elimination of certain pesticides based on the epidemiologic and toxicologic data currently available,” he said. “Many factors certainly militate in favor of taking precautions while handling or spraying pesticides. Pesticides can have acute health effects, some of them being severe, including death. In addition, there are other fields, [such as] cancer and reproduction, in which adverse effects of long-term exposure to pesticides are being investigated. Education programs addressing the appropriate and safe use of pesticides should certainly be encouraged, in particular in developing countries,” Dr. Elbaz concluded.

NR

—Colby Stong

Suggested Reading
Baldi I, Cantagrel A, Lebailly P, et al. Association between Parkinson’s disease and exposure to pesticides in southwestern France. Neuroepidemiology. 2003;22:305-310.
Elbaz A, Levecque C, Clavel J, et al. CYP2D6 polymorphism, pesticide exposure, and Parkinson’s disease. Ann Neurol. 2004;55:430-434.
Kamel F, Hoppin JA. Association of pesticide exposure with neurologic dysfunction and disease. Environ Health Perspect. 2004;112:950-958.

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