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Since the 1980s, epidemiological studies have linked occupational pesticide exposure to several different medical conditions, chief among them cancers, neurological diseases, and reproductive disorders. These studies have likewise highlighted the long-term health effects that may result from exposure to even low doses of pesticides during critical periods of development (e.g., in utero or early childhood).
In light of these concerns, the DGS (Direction générale de la santé; French General Health Directorate) requested that INSERM conduct a review of the scientific literature regarding the health risks associated with pesticides in the following contexts: (1) occupational exposure, particularly within the agricultural sector, and (2) early-life exposure (i.e., in the fetus and young children). INSERM accordingly sought the expertise of a multidisciplinary team composed of environmental/occupational epidemiologists and biologists specializing in cellular or molecular toxicology.
These experts examined international scientific publications from the past thirty years. Based on their analysis of the data presented in these articles, a positive correlation appears to exist between occupational exposure to pesticides and specific medical conditions among adults. These conditions include Parkinson’s disease, prostate cancer, and certain cancers of the blood (non-Hodgkin’s lymphoma, multiple myeloma). In addition, prenatal, perinatal, and early-childhood pesticide exposure appear to pose a distinct risk to the developing child.
The word pesticide has two Latin roots: pestis (“plague”) and caedere (“to kill”). As its derivation suggests, the term comprises an extensive and highly disparate array of substances serving to eradicate, control, or repel living organisms (insects, vertebrates, worms, plants, mushrooms, bacteria).
The number and variety of available pesticides is enormous: 1000 active ingredients have been placed on the market to date, and 309 phytopharmaceuticals are currently authorized for use in France. The products differ based on their target organism, mechanism of action, chemical classification (organophosphates, organochlorines, carbamates, pyrethroids, triazines, and so forth), and/or persistence in the environment.
Pesticides consist of an active ingredient combined with adjuvants; nearly 10000 different commercial formulations are available, both liquid and solid (e.g., pellets, powders). Some have an environmental persistence of just a few hours or days, while others remain in active form for several years; in each instance, the pesticide is ultimately transformed or degraded into a number of metabolites. In the case of organochlorines and certain other compounds, the pesticides not only persist in the environment for years but have also been detected in the food chain.
Among scientists, “pesticide” denotes the full array of pesticide active ingredients; however, regulatory agencies may define the term differently.
How Are Pesticides Used?
In France, limited quantitative data are available regarding specific applications of pesticides. Agriculture accounts for the majority (90%) of use by weight, but pesticides play a role in other occupational sectors as well, including road, garden, and park maintenance; the industrial sector (e.g., manufacture and treatment of wood products); and human and veterinary health initiatives, such as vector (e.g., mosquito) or rodent control. In addition, pesticides have important household applications – for instance, in plant and animal control, disinsectization, and maintenance of gardens and woods.
By weight, fungicides constitute nearly half the pesticides used in France. 80% of pesticides (again, by weight) are involved in treatment of small-grain cereals, maize, and rapeseed, as well as in viticulture. The active ingredient in the most commercially successful pesticides is either sulfur or glyphosate.
Pesticides are omnipresent in the environment. They can be found in the air (in the form of “pesticide dust”) both in and out of doors, as well as in water (groundwater and surface and inshore waters), soil, and foodstuffs (including some sources of drinking water).
In an occupational context, exposure occurs most frequently (approximately 80%) via dermal contact, though in certain instances (fumigation; use of the pesticide in a confined space), the product may also be inhaled. Exposure may occur in a variety of circumstances: during the handling, preparation, or application of the pesticide; cleaning of treated areas; and violation of the restricted entry interval (i.e., engaging in unsanctioned tasks in a freshly-treated area). For the population at large, exposure is believed to occur chiefly via dietary intake (“oral exposure”).
INSERM’s collective appraisal concentrated on eight types of cancers: four cancers of the blood, prostate and testicular cancer, brain tumors, and melanomas. Prior meta-analyses had already flagged the potential ties between most of these cancers and pesticide exposure, but had not attempted to determine the links between specific active ingredients and the cancers in question.
Prostate Cancer
According to the data presented in the literature, agricultural workers, workers in pesticide production plants, and rural populations all exhibit an increased risk of prostate cancer. This risk varies from 12% to 28%, depending on the population in question. A handful of specific active ingredients have been implicated in this increased prostate cancer risk, including chlordecone (linked to elevated risk within the general population) and carbofuran, coumaphos, fonofos, and permethrin (all of which are associated with elevated risk among the occupationally exposed). All five are currently banned from use; it should be noted that some are associated with an increased risk of cancer only among agricultural workers with a family history of the disease.
Cancers of the Blood
Based on the data presented in the literature, workers who have been occupationally exposed to pesticides exhibit an increased risk of non-Hodgkin’s lymphoma and multiple myeloma. This correlation applies to workers in both the agricultural and non-agricultural sectors. Organophosphate pesticides and certain organochlorines (lindane, DDT) are thought to be responsible for this increased risk. An increased risk of leukemia also ought not to be ruled out, though the data here are less conclusive.
As regards the other cancers of interest, comprehensive analysis of the literature was hampered by (1) the low incidence of testicular cancer, brain tumors, and Hodgkin’s disease, and (2) the presence of significant confounding variables – for instance, the agricultural community experiences considerable exposure to the sun’s ultraviolet rays; such exposure is a recognized risk factor for melanoma.
The collective appraisal focused on three neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis) as well as on cognitive impairments that may predict or accompany certain neurodegenerative conditions.
Parkinson’s Disease
An increased risk of Parkinson’s disease has been observed among individuals occupationally exposed to pesticides. Researchers have shown, for instance, that exposure to insecticides and herbicides is linked to development of Parkinson’s; a similar association with fungicides has not been established as yet, but it is important to recognize that far fewer studies are available.
The data regarding other neurodegenerative diseases are more ambiguous, as epitomized by the literature on Alzheimer’s disease: cohort studies point unanimously to an increased risk of the disease while case-control studies are substantially less conclusive. Due to the paucity of pertinent studies, it is not possible to determine whether a similar correlation exists for amyotrophic lateral sclerosis.
In addition, several reviews and a recent meta-analysis have concluded that occupational exposure to pesticides, particularly organophosphates, has deleterious effects on cognitive function. These effects are presumably most pronounced in individuals with a history of acute pesticide poisoning.
Researchers have published a number of epidemiological studies suggesting that prenatal exposure to pesticides has short- and medium-term impacts on child development.
Prenatal Exposure: Consequences of Occupational Exposure Among Pregnant Women
The literature suggests that pregnant women occupationally exposed to pesticides experience a significant increase in the risk of fetal death (miscarriage) and that their children are more likely to display birth defects. Other studies have noted that children exposed during key periods of development are also more likely to suffer impairment of fine motor skills, visual acuity, or short-term memory. Lastly, recent meta-analyses have demonstrated that such children experience a significantly increased risk of leukemia and brain tumors.
Prenatal Exposure: Consequences of Residential Exposure Among Pregnant Women [those living near pesticide treatment zones/those using pesticides for household purposes]
Several case-control and cohort studies have indicated that the children of women living near agricultural zones or exposed to pesticides in household settings are at greater risk of birth defects (cardiac and neural tube malformations; hypospadias).
Studies have also reported that such children exhibit low birthweight, neurodevelopmental deficits, and a significantly increased risk of leukemia.
Specific pesticides (particularly dibromochloropropane), now no longer in use, have been unequivocally linked to reduced male fertility. Whether pesticides currently in use produce similar effects remains unclear.
The relationship between pesticides and female infertility is poorly understood and warrants further study.
As discussed above, the literature has identified medical conditions potentially linked to exposure to certain pesticides, but the precise cellular and molecular mechanisms at play have yet to be determined. However, the available information regarding various pesticides’ mechanisms of action do largely correspond with the epidemiological data. For instance, a key property of many pesticides appears to be their ability to cause oxidative stress in cells; such stress has likewise been implicated in Parkinson’s disease. Similarly, some pesticides damage DNA, perturb certain signaling pathways (potentially resulting in dysregulation of cell proliferation/cell death), or alter immune responses; such mechanisms likely underpin pesticide-associated health effects.
Communities today are generally exposed on a permanent basis to low doses of multiple pesticides, along with the many other chemical substances that contaminate the modern environment. This exposure to combinations of pesticides and other substances may present distinct health risks, but these are as yet difficult to predict. As such, the impact of combined and/or long-term, low-dose exposure remains a key question within the domains of toxicological research and pesticide risk assessment.
Experts stress that the phrase “the evidence is inconclusive” does not necessarily indicate the total absence of risk.
If the scientific community now recognizes the definite health risks associated with certain pesticides, this simply reflects the extensive research that has been carried out on the products in question (particularly in the United States); many other active ingredients may pose similar threats but simply have not been subjected to the necessary epidemiological studies.
The report strongly recommends that current data regarding direct or indirect occupational exposure to pesticides, as well as corresponding information from previous years, be examined more closely.
In addition, the recommendations point out the importance of studying exposure during “critical periods” (during development, for instance), both among those who are occupationally exposed to pesticides and within the population at large.
Multi- and transdisciplinary research initiatives also merit support, as these would facilitate swifter identification of the potential dangers and risks associated with exposure to the active ingredients in pesticides.
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