Unraveling the exposure pathways and toxicity mechanisms of representative systemic insecticides in amphibians.

Systemic insecticides, comprising neonicotinoids, systemic organophosphates, phenylpyrazoles (fipronil), and anthranilic diamides, now dominate global insecticide use. Their high water solubility and systemic translocation also drive migration into paddy fields, wetlands, and agricultural waterways and persistence in soils and sediments, the habitats amphibians depend on. Permeable skin, gill-dominated respiration, and obligate aquatic larval phases make amphibians especially vulnerable, yet assessments linking field exposure to internal toxicity remain limited. Focusing on these four classes, this review synthesizes 103 peer-reviewed studies (2005-2025) across environmental occurrence, toxicokinetics, sublethal effects, and toxicity mechanisms. Concentrations in amphibian-occupied waters span several orders of magnitude, yet amphibian-specific threshold comparisons are supported for only a subset of compounds; toxicokinetic profiles differ by compound in tissue accumulation, metabolic activation, and elimination. Sublethal evidence consistently documents neurobehavioral impairment, developmental disruption, endocrine interference, and multi-organ histopathology at environmentally relevant concentrations, with non-monotonic dose-response and species- and stage-specific sensitivity recurring throughout. Oxidative stress emerges as a consistently supported mechanistic node across all four classes; calcium dysregulation is proposed as a shared downstream pathway converging from their distinct primary targets, but rests largely on cross-taxon extrapolation. The field's core limitation lies less in study volume than in unverified mechanistic extrapolation and exposure-effect correspondence.