Four-step method proposed to test chemicals’ Parkinson’s risk
Data suggest strong association between disease risk, toxin exposure
A team led by scientists in the Netherlands is proposing a new screening strategy to test whether pesticides or other chemicals might increase the risk of Parkinson’s disease.
“We are still largely in the dark about the safety of these substances. The current admission criteria for pesticides provide insufficient insight into the risk of Parkinson’s and other brain diseases,” Bas Bloem, MD, PhD, co-author of the study and professor at Radboud University Medical Center, said in a press release. “We now propose a clear plan of action to properly assess safety.”
The team made their case in npj Parkinson’s Disease, in the paper “Towards improved screening of toxins for Parkinson’s risk.”
While the causes of Parkinson’s disease remain incompletely understood, a substantial body of data indicates, at least in some cases, exposure to toxic chemicals may cause it. In their paper, the scientists reviewed data from epidemiological studies and laboratory experiments that show certain chemicals like rotenone and paraquat can increase Parkinson’s risk in people and induce Parkinson’s-like disease in animal models.
“Epidemiological, animal, neuropathological data strongly suggest that there are associations between PD [Parkinson’s disease] risk and exposure to toxins, specifically rotenone, paraquat, organochlorine compounds, and metals,” the researchers wrote.
Assessing chemicals’ Parkinson’s risk
The data show some chemicals can cause Parkinson’s, but new chemicals entering marketplaces don’t have to be checked for the risk of it. The researchers called this especially concerning because “over the past half century, tens of thousands of chemicals have become commercially available and are now widely being used worldwide.”
To address this, the scientists proposed a four-step process to screen chemicals for potential Parkinson’s risk. The process could be applied to existing compounds as well as future chemicals entering markets, they said.
“[A] multi-tier approach including in silico [in computers], in vitro [in dishes], single organism models and in vivo rodent experiments is required,” wrote the scientists, who said the first step is computer-based analyses of compounds for signs of potential toxicity, which can be done rapidly and cheaply.
The next step is in vitro tests of cells and chemicals in dishes, followed by tests in invertebrate laboratory models like fruit flies or nematode worms, or in zebrafish. These models don’t live as long as common lab animals like mice so experiments in them can generate results faster, said the scientists, who noted time is of the essence.
“Because toxins in humans display their [Parkinson’s] risk after a relatively long period of exposure, it will take years for us to identify the risk and it will take even longer for legislative actions banning or regulating these highly pervasive neurotoxic substances,” wrote the scientists, who said the advantage of models like fish and flies “is that they are well suited for high-throughput testing.”
The fourth step would be studies in mammals, such as mice or rats. Mammal studies are required to confirm whether substances can cause Parkinson’s-like toxicity, but saving these tests as the final tier means fewer animals would be needed.
“Unfortunately, research on rats and mice is necessary to definitively determine the safety of a substance,” said Judith Homberg, a researcher at Radboudumc and the study’s co-author.
By using the four-step process with computer and lab bench tests first, “we test the pesticides very thoroughly, without needing a large number of laboratory animals,” Homberg said.
The researchers have started discussions with regulators and industry leaders, and hope to begin implementing the screening methods with an initial focus on pesticides. More than 1,000 pesticide chemicals are registered in the U.S., they said.
‘This test is just a first step to systematically and effectively screen pesticides. The aim is to subsequently implement this as a routine screening for other toxic substances in the environment,” said Ling Shan, PhD, study co-author at the Netherlands Institute for Neuroscience. “The next step is to conduct the experiments, in which we have to collaborate with national partners.”
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