Same evidence, different methodological choices: how six regulators dealt with paraquat and its links to Parkinson's disease
Same evidence, different methodological choices: how six regulators dealt with paraquat and its links to Parkinson's disease
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Original abstract
Purpose of review: Six regulatory assessments of the association between paraquat exposure and Parkinson’s disease (PD), conducted 2003-2026, drew on a substantially overlapping body of epidemiological, toxicological, and mechanistic evidence yet reached divergent conclusions. This review examines the selection methodologies, inclusion criteria, and evidence-weighting practices that produced these outcomes.Recent findings: The Australian Pesticides and Veterinary Medicines Authority (APVMA, June 2026) found the evidence it assessed did not convincingly demonstrate a causal association and affirmed paraquat registrations under reduced conditions. The US Environmental Protection Agency (EPA, 2019) found limited but insufficient epidemiological evidence for occupational exposure and insufficient evidence for non-occupational exposure, reopening its paraquat assessment in late 2025 following new volatilisation data. The California Department of Pesticide Regulation (DPR, December 2024) reviewed two of the meta-analyses the APVMA excluded and acknowledged moderate to strong associations in the most recent paraquat-specific study, yet determined that the evidence was insufficient to show a direct causal association. Japan’s Food Safety Commission (FSCJ, 2022) adopted the conclusions of the Joint FAO/WHO Meeting on Pesticide Residues (JMPR, 2003), APVMA (2016), and EPA (2019), as its analytical basis. Brazil’s health regulatory agency (ANVISA, 2017) reached a positive causation finding, prohibited paraquat, and identified specific methodological mechanisms producing the divergence from the APVMA’s 2016 toxicology assessment. The European Union revoked paraquat authorisation in 2007 on procedural grounds. Divergent outcomes are attributable to structural characteristics of the selection process: whether meta-analyses are classified as eligible quantitative evidence; whether differential scrutiny is applied to studies reporting positive and null associations; whether the provenance of key negative studies is disclosed and weighted; and whether data is eligible for scrutiny on the basis of use scope. Summary: Regulatory appraisal criteria applied to complex evidence bases can produce directional bias irrespective of assessment intent. The paraquat-PD case illustrates that methodological choice of data preceding any substantive evaluation of study quality influences the outcome of a weight-of-evidence assessment.