Toxicity of Organotin Compounds Present in the Environment to Mammals

Organotin compounds are synthetic organometallic compounds with high lipophilicity, persistence, and slow degradation rates in the environment, which promote bioaccumulation and biomagnification through the food chain. Tributyltin (TBT) is widely used in antifouling paints, wood preservatives, and pesticides. It persists in sediments and enters the human diet via seafood. Exposure has been detected in breast milk and umbilical cord blood. In mammals, organotin compounds demonstrate efficient gastrointestinal absorption, are distributed in lipid-rich organs, that is, the liver, adipose tissue, adrenal glands, and brain, and are primarily excreted via bile and feces. Regarding its mechanism of action, TBT disrupts endocrine and cellular homeostasis through multiple pathways. It disturbs steroid production, acting as an agonist for RXR/PPARγ to promote lipogenesis, impairs mitochondrial function, increases reactive oxygen species, disrupts Ca2+ balance, and induces intrinsic apoptosis. Immunotoxicity and developmental toxicity are issues of concern. The neurotoxic effects include increased blood–brain barrier permeability, localized brain accumulation, glutamate-mediated excitotoxicity, and sustained downregulation of the AMPA subunit GluA2 via NRF-1. This renders neurons Ca2+ permeable and vulnerable to stress. Although TBT is the most studied species, comparative findings for its metabolites, dibutyltin and monobutyltin, remain fragmentary, and chronic and life-stage-specific risks have not been fully elucidated. In this review, I have synthesized the current knowledge on environmental sources, fate, and mammalian toxicity and outlined priority areas for risk assessment.