Can Environmental Toxicants Cause Parkinson’s Disease?

MIAMI—Accumulating evidence suggests that exposure to certain toxicants may increase the risk of Parkinson’s disease, according to an overview presented at the First Pan American Parkinson’s Disease and Movement Disorders Congress. Researchers seek to learn more about these chemicals and to investigate interventions that could reduce the risks that they present.

Synthetic Heroin and Parkinsonism

In 1983, several cases prompted researchers to think about whether toxicants could cause Parkinson’s disease. A 39-year-old man in California presented to an emergency room with visual hallucinations, jerking of limbs, generalized slowing, and difficulty walking. He had no prior medical history, neurologic history, or family history of neurologic disease. At around the same time, a woman and two men from the same area developed young-onset subacute parkinsonism. James Tetrud, MD, and J. William Langston, MD, the neurologists who examined these patients, learned that they were all IV narcotic addicts. Between two and six weeks before presentation, the patients had injected a synthetic heroin that they had obtained from the same supplier. The toxicant in the synthetic heroin that had induced the parkinsonism was identified as 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). All of these patients responded to levodopa.

Herbicides and Insecticides

In 2009, Dr. Tanner and colleagues conducted a case–control study to investigate whether specific occupations or toxicant exposures were associated with parkinsonism. They found that 2,4-Dichlorophenoxyacetic acid (2,4-D) was associated with a greater than twofold increased risk of Parkinson’s disease. This chemical was introduced as an herbicide in 1945 and is found in more than 1,500 products, including Agent Orange, which the US military used as a defoliant in Vietnam. Parkinson’s disease is considered to be service-connected in certain US military veterans who served in Vietnam. Currently, 2,4-D is used on lawns, golf courses, and large farms.

The authors also found that exposure to paraquat, another herbicide, nearly doubled the risk of Parkinson’s disease. In people with a homozygous deletion of GSTT1, a gene that encodes an enzyme important to xenobiotic metabolism, exposure to paraquat increased the risk of Parkinson’s disease 11-fold. In addition, exposure to rotenone, an insecticide and piscicide, increased the risk of Parkinson’s disease by more than two times.

Persistent Organic Pollutants

Exposure to persistent organic pollutants such as polychlorinated biphenyls (PCBs) and organochlorine pesticides can also increase the risk of developing Parkinson’s disease. A study by Becker et al in 2000 found an elevated prevalence of Parkinson’s disease in Greenland that may have resulted from exposure to PCBs.

This research prompted Dr. Tanner and colleagues to conduct a case–control study of Alaska natives. The investigators examined the food, diet, occupation, toxicant exposure, blood, and DNA of 69 people with Parkinson’s disease and 179 controls in the Alaska native health system. They found higher blood levels of hexachlorobenzene and PCBs in people with Parkinson’s disease, compared with healthy controls. The blood levels approximately doubled the risk of Parkinson’s disease.

In the Agricultural Health Study, investigators found a similar association between serum PCB level and risk of Parkinson’s disease. Furthermore, people with a particular variant of the efflux transporter gene, which protects cells from exogenous chemicals, and people who also had high serum PCB levels had as much as a 12-fold increased risk of Parkinson’s disease. When Dr. Tanner and colleagues reexamined the data from the Alaska native population, they found that this gene variant had a similar effect. People with a low-risk genotype did not have a greatly increased risk of Parkinson’s disease, even after high exposure to PCBs.

In the 1980s, Hawaiian pineapple farmers sprayed organochlorine pesticides on plants that later were fed to dairy cows. More recently, the Honolulu Asia Aging Study, a prospective cohort study, suggested that milk consumption was associated with increased risk of parkinsonism. In addition, G. Webster Ross, MD, and colleagues analyzed postmortem data and found that nonsmokers who consumed high amounts of milk had low neuron density. Other research has found that brain organochlorine levels were associated with Lewy pathology.

Solvents

Solvents are another class of chemicals that has been associated with Parkinson’s disease. In a 2008 study of 30 industrial coworkers with Parkinson’s disease, Gash et al found that trichloroethylene, a solvent used in many industrial processes such as dry cleaning, was a risk factor for parkinsonism. In a twin study, Dr. Tanner and colleagues found that chlorinated solvents were associated with an increased risk of Parkinson’s disease.