Bisphenol S and Neurological Health: An Integrated Overview of Neurotoxicity and Underlying Mechanisms

Bisphenol S (BPS), a pervasive contaminant used in consumer and industrial products, has been widely detected in human serum, urine, hair, placenta, and breast milk. Although initially studied mainly as an endocrine disruptor, accumulating evidence indicates that BPS also exerts neurotoxicity by perturbing neuroinflammatory responses, neuroendocrine regulation, and neuronal development. However, its neurotoxic profile and mechanistic basis remain incompletely defined. This review systematically retrieved and synthesized epidemiological, animal, and cellular studies published between 2000 and February 2026 across multiple databases to delineate the neurotoxic features and mechanisms of BPS. Evidence from 14 epidemiological and 76 experimental studies consistently indicates neurotoxic risk. Epidemiological data associate BPS exposure with increased risks of neuropsychiatric outcomes, including attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease (AD), and depression, often with sex-specific patterns. Animal studies show that exposure across life stages induces behavioral impairments, encompassing social deficits, cognitive and emotional disturbances, motor dysfunction, and memory decline. In vitro studies further elucidate molecular underpinnings. Mechanistically, BPS neurotoxicity involves endocrine-axis disruption, neurotransmitter imbalance, oxidative stress, and transcriptional dysregulation and extends to gut-brain axis perturbation, brain region-specific vulnerability, and neural circuit dysfunction. These pathways interact and are modified by toxicokinetics, exposure dose and timing, sex, and species. Future work should integrate longitudinal human cohorts with mechanistic studies to clarify BPS's contribution to neurological disease development and inform regulation. We propose an integrative framework summarizing BPS neurotoxicity and its key modifying factors.