Bifenthrin Under Scrutiny: Revisiting Toxicological Evidence Amid Regulatory Gaps.

Despite growing health concerns, bifenthrin (BF) remains widely used for controlling agricultural and residential pests. However, different perspectives on its toxicological profile and regulatory framework warrant a revisit and update on BF regulation towards a robust risk-safety assessment. Out of 4102 search outputs, only 62 studies on BF disposition and biological effects met screening and eligibility criteria. Our findings demonstrate oral, dermal, and inhalation toxicity of BF. Studies suggest potential effects, including immunotoxic, endocrine, and reproductive effects, but lack multi-level substantiation and modeling approaches amidst risk biases. Emerging evidence of anxiogenic, depression-like, and Parkinsonian-like effects, which implicate monoaminergic, metabolic, and enzymatic pathways, supports the involvement of several molecular culprits beyond voltage-gated channel disruption. Toxicity concerns raised by the Food and Agriculture Organization-World Health Organization (FAO/WHO), the United States Environmental Protection Agency (USEPA), and the European Food Safety Authority (EFSA) inform the establishment of reference doses of 0.01, 0.03, and 0.031 mg/kg per day, respectively. While the USEPA considers the current toxicological and safety benchmarks adequate for approved uses, it identified potential acute risks of concern to pollinators and terrestrial invertebrates, leading to precautionary labeling measures. In contrast, the EFSA has questioned the reliability of toxicological data and recommended lowering maximum residue levels. Regulatory disparities are traceable to variations in the study designs and risk assessments. While emerging data on behavioral and neurochemical changes may warrant a regulatory reevaluation of BF's toxicological data, integrating predictive models and other new approach methodologies, using high-quality designs, may address current regulatory gaps and inconsistencies.