27
Jan
Widely Used Insecticide in Food Production Triggers Neurological Effects Linked to Parkinson’s Disease
(Beyond Pesticides, January 27, 2026) A three-part study published in Molecular Neurodegeneration draws a connection between Parkinson’s disease (PD) and the organophosphate chlorpyrifos. “Since chlorpyrifos (CPF) exposure has been implicated as a risk factor for PD, we investigated its association to incident PD and if this association is biologically plausible using human, rodent, and zebrafish (ZF) studies,” the researchers state. Together, the three experiments “strongly implicate exposure to CPF as a risk factor for developing PD,” as the authors find that exposure, even at very low concentrations, causes selective toxicity to dopaminergic neurons that are critical for functions of movement, cognition, emotion, and more.
The results reveal that in humans, long-term residential exposure is associated with more than a 2.5-fold increased risk of developing PD, while exposure in mice causes “motor impairment, dopaminergic neuron loss, microglial activation, and an increase in pathological α-synuclein (α-syn) [proteins primarily found in the brain].” The researchers continue, “Using ZF, we found that CPF-induced dopaminergic neuron loss was at least partially due to autophagy dysfunction and synuclein accumulation, as knocking down LC3 [a protein chain] recapitulated the dopaminergic neuron loss.” These three studies highlight the association of CPF with increased risks for developing PD, as “relevant exposures in animal models establish biological plausibility.”
Study Importance and Background
According to the Parkinson’s Foundation, PD affects more than 1.1 million people in the U.S., with nearly 90,000 people newly diagnosed each year. Parkinson’s disease is a neurodegenerative disorder with slowly progressive symptoms of motor dysfunction and cognitive decline. There is a wide body of science connecting pesticide exposure to Parkinson’s, as seen in Beyond Pesticides’ Pesticide-Induced Diseases Database (PIDD) and through Daily News coverage. However, as the current study authors explain, it is difficult to prove the causal relationship between PD and pesticides in current research.
“Several studies have investigated the role of environmental toxicants in the development of PD, but there are challenges in determining whether an association is causal,” the researchers note. They continue: “PD develops over decades, and exposure assessment should cover the time before pathology starts. Once a toxicant has been associated with altered risk, further studies are necessary to determine if the disease pathology can be recapitulated by relevant exposures in animal models and the mechanisms by which they act (i.e., biological plausibility).” This is the basis for the present study, incorporating CPF exposure and observed effects in humans, mice, and fish.
As the study references, the etiology (cause) of PD is complex, involving the interaction of both genetic and environmental factors. “The primary pathological hallmarks of PD are the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), the development of fibrillar cytoplasmic inclusions, also known as Lewy bodies and Lewy neuritis, and inflammation,” the authors say. To help unravel the role of environmental contaminants such as CPF in PD, it is crucial to understand the mechanisms of toxicity and if any disease associations are causative.
Chlorpyrifos is a broad-spectrum organophosphate pesticide with a long history of adverse and environmental effects that is extensively used in agriculture. As highlighted in previous Daily News, CPF has been a threat to human and ecological health for decades, originally as a general-use pesticide for homes, gardens, and agriculture, and then restricted to most nonresidential uses in 2000. Currently, the chemical’s permitted uses include food and feed crops, golf courses, as a nonstructural wood treatment, and adult mosquito control for public health (insect-borne diseases) uses only.
According to health and environmental advocates, there is a checkered past of U.S. Environmental Protection Agency (EPA) failure to adequately protect human and environmental health from chlorpyrifos, which is linked to endocrine disruption, reproductive effects, neurotoxicity, brain, kidney, and liver damage, and birth and developmental effects. (See PIDD for studies on each of these effects.) In addition to the adverse human health effects, chlorpyrifos is also known to be toxic to birds, bees, fish, and other aquatic organisms and is detectable in groundwater.
In the late 1970’s and 1980’s, chlorpyrifos was acclaimed as the exciting new alternative to organochlorines, like the insecticide chlordane, because it was hailed by EPA and the chemical industry as a chemical that was less persistent and subject to degradation in the environment. (See additional commentary on chlorpyrifos’ history here.) Beyond Pesticides characterizes the chemical and the family of organophosphates to which it belongs as one of the best examples of the ongoing modern-day pesticide treadmill, with continuous substitution of hazardous chemicals proclaimed to be safe by industry, users, and regulators only to over time result in serious and complex adverse effects to health and the environment.
Study Methodology and Results
In the current study, the researchers incorporate data from a large community-based case-control study in humans, as well as experiments with mice and zebrafish, exposed to CPF. The human model shows that long-term residential exposure to CPF increases PD risk by more than 2.5-fold while the study in mice, “using a novel inhalation method that recapitulates human exposures,” reveals impaired motor behavior, loss of DA neurons, increased pathological α-syn, and inflammation and study in zebrafish identifies CPF as “toxic to neurons by disrupting autophagic flux and was dependent on γ1-synuclein (γ1-syn), the closest functional homologue to human α-syn.”
Human Populations
To assess CPF and PD associations in humans, the authors use data from the Parkinson’s Environment and Genes (PEG) study that includes 829 PD patients and 824 controls in central California. The PEG study, conducted in three agricultural counties, is a population-based case-control study that the current research references to estimate ambient exposure due to living or working near agricultural CPF application by using pesticide use report (PUR) pesticide application data. This results in 12,904 annual records for residential and 8,968 for occupational site CPF exposure.
The findings show long-term exposure to CPF is associated with an up to 174% increased risk of developing PD. The researchers also report: “We estimated ambient exposure to CPF due to living or working near agricultural facilities applying CPF over a 30-plus year period. We observed positive associations between CPF and PD with exposure estimated at residential and workplace addresses and over different exposure time windows. The strongest association was with the longest duration of exposure at the workplace…Importantly, CPF exposures that occurred 10–20 years prior to disease onset were more strongly associated with PD than the 10-year period before PD onset.”
Mice
In the rodent experiment, sixteen 26-week-old male mice were exposed to aerosolized CPF, while another 16 were used as controls. The mice were exposed five days per week, for six hours each day, for a total of 11 weeks to CPF. Behavioral testing was conducted prior to exposure to establish a baseline and again three days after the final CPF exposure. This included a rotarod test, wire hang test, and open field test. (See additional details in the study’s methodology section here.)
The authors further explain, saying: “Most human pesticide exposure is through inhalation, which escapes the 1st pass circulation to the liver with oral ingestion and therefore reduces its metabolism. To model human exposures, mice were exposed to aerosolized CPF or ethanol vehicle in closed chambers five days a week for 11 weeks… CPF-exposed mice deteriorated more than controls in both rotarod, and wire hang tests.”
CPF exposure in the mice also “resulted in a 26% loss of tyrosine hydroxylase (TH) positive dopaminergic neurons in the SN [substantia nigra, midbrain structure] compared to control mice.” Also of note, the microglia in the CPF-exposed mice are more rounded, which is a change in shape that occurs as a response to stimuli such as environmental toxicants and infections. “These morphological changes are consistent with activated microglia similar to those seen in PD brains,” the researchers note.
Zebrafish
To determine the mechanism of CPF neurotoxicity, the third part of the study utilizes transgenic zebrafish. The authors find that CPF-exposed zebrafish swim slower, which is a pattern consistent with dopaminergic neuron loss. Following exposure, the number of aminergic neurons (nerve cells that release neurotransmitters) within the zebrafish are significantly reduced, with increased apoptosis (cell death) in regions of the brain. Morphological changes of the microglia, similar to those seen in the mice, also occurred in the zebrafish, as well as reduced autophagic flux that contributes to dopaminergic neuron loss.
The authors discuss the strength of their findings: “There are some weaknesses to the ZF model. They are developing at the time of exposure, whereas PD is a disease of the aged.” However, they continue in noting: “We do not think this invalidates our results since younger animals generally are more resistant to toxicants relative to older animals, suggesting that we may be underestimating CPF toxicity, not overestimating it. Since the primary purpose of using the ZF was to determine the mechanism of toxicity, we believe this weakness does not alter the validity of our findings.”
The Organic Solution
In the current study, the adverse effects documented in mice and zebrafish models following exposure to human-relevant concentrations of chlorpyrifos not only aids in explaining the mechanisms of toxicity of CPF but provides biological plausibility in the causal link between chlorpyrifos and Parkinson’s disease. The human PEG study in California further supports these findings, highlighting the disproportionate risks of PD in agricultural areas and with occupational exposure.
Pesticides are a critical environmental justice issue. Although pesticide exposure is widespread, these toxic chemicals cause a range of adverse health effects, with disproportionate harm to people of color communities. While pesticide exposure adversely affects the health of all men, women, and children, there are racial disparities due to occupations and living in fenceline communities near chemical production and farmland—all creating elevated risk for people of color. The Centers for Disease Control and Prevention (CDC) finds that over 90% of U.S. citizens carry a detectable mixture of pesticides in their bodies. However, pesticide exposure patterns tend to cause elevated rates of racial and socioeconomic health disparities and disorders. (See Daily News here for more information.)
While a shift away from toxic pesticide use is imperative because of studies like this one on PD, immediate action is needed for those at highest risk, including farmers, farmworkers, and their families, particularly children, as well as communities living near chemical-intensive agricultural areas or chemical manufacturers. Join Beyond Pesticides in our mission of eliminating all petrochemical pesticides and fertilizers that disproportionately impact vulnerable communities and threaten the health of all. The holistic solution that lies in organic practices protects human health, as well as wildlife, overall biodiversity, and the ecosystems in which all life depends.
Take action today: Tell members of Congress to ensure that, with the termination of environmental justice programs at EPA, they must uphold the right of those at the highest risk of harm to sue manufacturers responsible for their failure to warn about their products’ hazards. For other opportunities, please see our Action of the Week archive and sign up page for our weekly newsletters!
All unattributed positions and opinions in this piece are those of Beyond Pesticides.
Source:
Hasan, K. et al. (2025) The pesticide chlorpyrifos increases the risk of Parkinson’s disease, Molecular Neurodegeneration. Available at: https://link.springer.com/article/10.1186/s13024-025-00915-z.
