This study utilized a large sample size to highlight the relationship between the residential exposure to agricultural pesticides, and the premature mortality associated with PD. Significant associations were found between exposure to glyphosate application and premature mortality associated with PD. Exposure to Paraquat was not significantly associated with premature mortality, but the effect was in the hypothesized direction. The relationship between Atrazine or Diazinon and premature mortality from PD were not statistically significant.
The strong relationship between Glyphosate exposure and premature mortality attributed to (PD) in our study aligns with the results found in multiple studies. Toxicological studies have found glyphosate and glyphosate-based herbicides to negatively affect neural cells, resulting in oxidative damage [18
]. A study conducted on immature rats using Roundup®
, in which glyphosate is the active ingredient, found that exposure to glyphosate resulted in signaling and enzymatic changes, that may lead to affected uptake of hippocampal cells. The cell damage upon exposure was suggestive of a relationship between glyphosate and neurotoxicity [18
Glyphosate exposures can trigger numerous biological effects that may progress before being made apparent in chronic degenerative diseases or other health problems [28
]. Establishing the causal role of glyphosate in such chronic conditions is further complicated by the temporal relationship between pesticide exposure and adverse health outcomes. The effects following glyphosate-based herbicide exposures are not often immediately observed, but rather, they are caused by early-life exposure and they manifest in the later stages of adulthood, which is the perfect case to be made for those growing up and living in rural agricultural areas.
Although this study found exposure to Paraquat to be insignificantly associated with premature PD mortality, the associations were in the hypothesized direction, which is consistent with wider toxicological and epidemiologic literature. Previous studies most often cite Paraquat as a likely environmental neurotoxicant, because of its near identical molecular structure to MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), whose neurotoxicity has been related to idiopathic PD [30
]. A study conducted on rats found a dose-dependent relationship with Paraquat exposure and neuron loss, in which a slightly greater vulnerability was measured in older rats [31
]. Epidemiologic studies have also found that exposure to Paraquat to increase risk of PD [19
Strengths and Limitations
This study is unique in multiple ways, with many innovative strengths and some implicit limitations. First, studies that relate agricultural chemical exposure and PD often implement a temporal model, in which researchers use the participants’ memory to recount the exposure of the study population. These studies are highly subject to recall bias. By analyzing data that is retrieved from PD-related deaths and by employing the advanced spatial methodologies described above, a much more detailed understanding of the individual exposure was developed, obviating the issues of participant recall bias. Further, agricultural chemical exposure assessments are greatly constricted by the historic pesticide records that are made available to researchers by federal institutions. A great deal of quantitative research on pesticide exposure and PD in the United States has been made possible by California’s independent Pesticide Usage Report (PUR), which offers extensive reports of agricultural chemical application in the state of California [8
]. The USDA and USGS provide public records regarding pesticide application, but the highest resolution is provided on a county level, and only the USGS offers a dataset that is aggregated by specific chemical type from 1992 to 2015. While we acknowledge the limitation of using land-use classifications to estimate application, the USDA’s estimates for the crops that likely received specific pesticide application offered a much finer geographic estimation than the USDA’s county records were able to provide. To employ these records at a much greater resolution, highly comprehensive agricultural land-use data were needed, and unfortunately, the USDA has only made this spatial data available for the years of 2008 to 2017.
Although the agricultural chemical exposure analysis employed in this study did not allow for the temporal relationship of the exposure that predates symptoms of PD, historical geographic land-use analyses offered an important justification for why this technique was employed. A study that analyzed land cover change from 1950 to 2000 reported a boom of agricultural expansion in this region, which coincided with the development of irrigated agriculture in the 1950s [32
]. Beside this period of expansion, agricultural land-use in the United States has declined due to a steady increase in agricultural mechanization and efficiency, albeit staying relatively steady in geographic areas such as the Western United States and the Midwest. Thus, there is good reason to believe that current farmland in Washington was highly likely to be farmland since the 1950s. Another consideration that authors considered when formulating these methods was the complexity of human mobility. Furthermore, we had only a single residential address that was associated with each death record, and had no way of knowing how long an individual that was affected by PD resided in the address where they last lived. We understand that this limitation is significant in considering the exposure estimation because an address cannot truly capture the complexities of pesticide exposure. Nonetheless, our choice in using residential records as an estimation for exposure has been shown to be meaningful to other exposure assessments [33
Previous literature has associated early-onset PD with well-water consumption, which is suggestive of exposure from well-water sources. Glyphosate has been found to leach and contaminate groundwater, and its newly recognized half-life in soil and water varies greatly by geographic location. This chemical half-life can range from a few days to a year, and it depends greatly on soil composition, resulting in a highly variable and long-term buildup of glyphosate. The inherent specificity makes for costly testing and monitoring programs [36
]. This site specificity may have been to blame for the insignificant results in our geographic analysis of well exposures. Lastly, the relationship between occupational exposure and premature mortality was statistically insignificant, which was likely due to the occupational classifications given on death certificates. The number of individuals who had died from PD and that were employed in the agricultural industry was only 112, although Washington State has been estimated to employ roughly 18,000 workers in the agricultural industry annually [37
]. This small proportion of agricultural workers may be due to the misclassification of occupation. Over one half of farmers in Washington State are employed part-time in addition to other forms of employment; thus, death certificate employment records may have not fully encompassed this relationship, resulting in a smaller sample size and insignificant relationships [12
While these findings have provided consistent results that align with previous toxicological, biological, and epidemiological findings, further research is required. In order to circumvent negative health outcomes, the following individual measures can be taken. First, the environmental risks of exposure to glyphosate should be made public knowledge, as should the location and timing of application in agricultural communities. As our research suggests, residents should also consider distancing themselves from agricultural cropland when making residential decisions.
Finally, to perform additional research that questions the associations between agricultural chemical exposure and environmental health, institutional commitments to data collection will need to be reconsidered. Pesticide application collection and distribution should look to California’s Pesticide Use Reporting (PUR) collection, to begin collecting more comprehensive information such as date, time, location, field size, crop type, application type, pesticide type, and amount of pesticide applied. National health examination databases such as the United States Center for Disease Control and Prevention’s National Health and Nutrition Examination Survey (US CDC, NHANES) should work to improve the biomonitoring of pesticide accumulation in the tissues and bodily fluids of human populations, considering that pesticide residue can be found in food products, consumable well-water, and soil surfaces alike. Epidemiological studies would benefit greatly from a continuous database of chemical bioaccumulation, because the greatest limitations among studies are those relating to the temporality of pesticide-related illnesses.