Benchmark-Dose Modeling Aligns Molecular Remodeling with Neurofunctional Impairment in Imidaclothiz-Exposed Honey Bees

Abstract

Pollinator risk assessment for emerging neonicotinoids still relies heavily on lethality-oriented apical end points, which may miss the intake region in which sensory or behavioral impairment emerges without overt mortality. We asked whether imidaclothiz (IMT) produces neurofunctional impairment at realized intakes below those associated with reduced survival. Adult worker honey bees (Apis mellifera) were exposed to IMT for 10 days, and realized-intake dosimetry was combined with benchmark-dose (BMD) modeling for survival, electroantennography (EAG), proboscis extension reflex (PER), and untargeted head-tissue metabolomic end points. Across alternative lower-tail summaries, metabolomic BMDs extended below the Day-10 mortality BMD10 (≈0.107 μg bee–1 day–1) and overlapped with the lowest EAG and PER benchmarks. This cross-level alignment supports the interpretation that lower-tail molecular sensitivity summaries and selected neurofunctional benchmarks occupy an intake region that lethality-based end points alone do not resolve. Dose-responsive metabolomic features were tentatively assigned to tryptophan–kynurenine and glycerophospholipid/redox-related pathways; orthogonal protein measurements showed broad concordance with these metabolomic patterns. By placing molecular, neurofunctional, and apical responses on a common realized-intake scale, this cross-level BMD comparison approach supports characterization of sublethal neonicotinoid risk in pollinators.