New Study Links Fungicides to Parkinson’s Disease

(Beyond Pesticides, December 1, 2008)

A new study by researchers at the University of California Los Angeles finds chronic exposure to commonly used dithiocarbamate fungicides, such as ziram, contribute to the development of Parkinson’s disease. According to the study, Ziram Causes Dopaminergic Cell Damage by Inhibiting E1 Ligase of the Proteasome, published in the Journal of Biological Chemistry, researchers screened several pesticides for their ability to interfere with the ubiquitin-proteasome system (UPS). Impaired UPS activity is reported in Parkinson’s disease patients’ brains. The researchers then focused on dithiocarbamate fungicides because they were found to be one of the most potent UPS inhibitors and are commonly used.

The researchers discovered the mechanisms by which the UPS is impaired, showing that ziram and structurally related dithiocarbamates inhibit E1 ligase (a protein activating enzyme). Ziram is also found to increase alpha-synuclein (a protein expressed in the central nervous system) levels and selectively damages dopaminergic neurons in vitro. The study also cites unpublished data from a population-based study in central California that is determining pesticide exposure using state application registry, finding that individuals living within 500 meters of where ziram is applied are at three times the increased risk of developing Parkinson’s compared to those with lower exposure.

The second most common neurodegenerative disease affecting more than one million people in the U.S., Parkinson’s occurs when nerve cells in the substantia nigra region of the brain are damaged or destroyed and can no longer produce dopamine, a nerve-signaling molecule that helps control muscle movement. Individuals exposed to chemicals that have a particular affinity for the substantia nigra region of the brain are at risk for developing the disease.

This study builds on the existing body of evidence of animal data and epidemiological studies that links exposure to pesticides, as well as gene-pesticide interactions, to Parkinson’s. Published case-control studies show a statistically significant association and elevated odds-ratio (that determine the elevated disease rate above the norm of 1.0) for the disease and exposure to pesticides. A Harvard School of Public Health study of more than 140,000 adults found that those exposed to long-term, low levels of pesticides had a 70 percent higher incidence of Parkinson’s. Rural residency, well water consumption, and farming are all correlated with an increased incidence of developing Parkinson’s. A study published in the Journal of the American Medical Association finds a 70 percent increased risk of developing Parkinson’s for individuals that use pesticides in their home and a 50 percent increased risk for garden insecticides.

The United Nation’s World Health Organization report on children’s heightened vulnerability to chemical exposures at different periods of their growth and development states that “neurotoxic insults during development that result in no observable phenotype at birth or during childhood could manifest later in life as earlier onset of neurodegenerative diseases such as [PD].” Several studies show that exposure in utero, post-natal or in childhood affect the substantia nigra causing direct damage or increasing the susceptibility to additional exposures and neurodegenerative damage in adulthood. In addition, a number of genes are linked to Parkinson’s as they interact with toxic chemicals in such a way that they may not cause the disease directly, but cause subtle changes in the genes that can make individuals more or less likely to develop the disease later in life.

Although implicating specific pesticides is difficult in epidemiological studies, toxicological lab studies have been better apt to identifying specific pesticides linked to Parkinson’s. These studies have identified the mechanisms by which pesticides lead to Parkinson’s, such as protein aggregation (alpha-synuclein), effects on the striatal dopminergic system and altered dopamine levels, mitochondrial dysfunction and oxidative stress.

This new UCLA study builds on existing data that shows that exposure to dithiocarbamates are linked to Parkinson’s disease. For example, Wang et al. found that ziram shows inhibitory effects on proteasome activities at low concentrations. Other dithiocarbamates, such as the fungicides mancozeb and maneb and the herbicide diethyldithiocarbamate, are implicated as well in published studies.

Besides being a neurotoxin, ziram is listed by the U.S. EPA as a likely human carcinogen, and is linked to reproductive effects and is a suspected endocrine disruptor. Ziram is mainly used on agriculture (mostly on almonds, peaches, nectarines, pears and grapes) but is also used on ornamentals and in landscape management. Ziram can be found in dog and cat repellents and microbiocides. Earlier this year, EPA was seeking public comments on a proposed list of 104 possible drinking water contaminants, one of which is ziram, that are currently unregulated and are known or anticipated to occur in public water systems and may require regulation (See Daily News Blog.)

Lea Brooks, assistant director of communications, stated in an article in The Fresno Bee highlighting the study that “The California Department of Pesticide Regulation has placed a high priority on assessing the risk of ziram.”

Take Action: Now let’s hold them accountable. Let the U.S. EPA Administrator and Deputy Administrator know that they have a duty to alert the public to the scientific findings that link pesticides with Parkinson’s. Urge these U.S. EPA officials to initiate an urgent and expedited review of pesticides’ link to Parkinon’s. Also let your elected members of Congress know how you feel. In addition, learn how you can protect your family, community and environment from the effects of pesticide sin food and water, at home, on lawns, parks and gardens, in schools, hospitals and other public buildings through resources available from Beyond Pesticides.

For more information on pesticides’ link to Parkinson’s disease, see Beyond Pesticides report Pesticides Trigger Parkinson’s Disease.