Rethinking Irgarol toxicity: a unified framework linking environmental fate, bioactivity, and human exposure

Irgarol, originally aimed as antifouling biocide for marine environments, has become a contaminant of emerging concern due to its environmental persistence and widespread dissemination. The prevailing approach to assessment has centered on environmental prevalence and immediate toxicological repercussions, with insufficient attention paid to the dynamic mechanisms that dictate biological effects across ecological and human domains. We introduce a novel Exposure-Transformation-Response (ETR) framework, which advances the concept that Irgarol toxicity is a function of environmental persistence, biotic and abiotic transformation pathways, ecosystem transfer dynamics, and organism-specific biological responses, in addition to environmental concentrations. Through a synthesis of evidence spanning environmental chemistry, ecotoxicology, endocrine disruption research, and exposure science, we delineate the capacity of transformation products to manifest independent toxicological characteristics and illustrate how chronic, low-dose exposures can induce novel biological effects at various trophic levels. Our analysis extends to the potential for ecological disruptions to propagate through aquatic food webs, thereby contributing to previously unacknowledged human exposure pathways. The ETR framework augments existing fate-and-effects paradigms by moving towards systems toxicology, thereby providing mechanistic foundation for predictive risk assessment, pioneering sustainable antifouling solutions, and enabling next-generation regulatory strategies that address chemical persistence, transformation, and biological vulnerability within integrated environmental systems.