Transformation Products of Neonicotinoids: A Review of Human Exposure, Toxicity, and Health Risks

Transformation products of neonicotinoids (t-NEOs) have gained substantial attention owing to their potential greater environmental persistence and toxicity than their parent compounds (p-NEOs). To date, a systematic review focusing on t-NEOs─particularly their human health risks─remains lacking compared with p-NEOs. This review comprehensively summarizes the current knowledge on the physical properties, transformation patterns, and predicted toxicity of t-NEOs. The Population, Exposure, Comparator, and Outcome (PECO) framework was systematically employed to optimize specificity in exposure assessment, enabling novel characterization of exposure dynamics and risk prioritization. This Perspective aims to develop a conceptual framework for t-NEOs toxicity and propose risk assessment prioritization strategies. The toxic effects of t-NEOs differ substantially from those of p-NEOs, especially following the removal of nitro or cyano groups, with hydroxylation processes potentially elevating mammalian toxicity. The consumption of tap water, drinking water, and foodstuffs is a predominant external exposure pathway for humans, with t-NEOs potentially resulting in higher internal exposure levels than p-NEOs. Furthermore, t-NEOs can infiltrate various human tissues, potentially causing adverse effects, with oxidative stress as the key event in contributing to toxicity outcomes. Critically, t-NEOs pose distinct health risks versus p-NEOs, including unique transplacental transfer ability and potentially enhanced neurotoxicity from the altered binding affinity of nicotinic acetylcholine receptors. Given the evidence presented, a heightened emphasis is warranted on t-NEOs within the framework of the "One-Health" perspective.