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Tributyltin chloride is an environmental pollutant that, among other effects, provokes a dysfunction of the oxidative phosphorylation system and has adverse effects on the nervous system. We studied neuronal differentiation of human neuroblastoma cells and neural stem cells in the presence of tributyltin chloride concentrations found in human blood (\u2264\u2009100\u2009nM), and brain development in two\u2010year\u2010old mice after perinatal exposure to tributyltin chloride (\u2264\u20091000\u2009nM). Pregnant mice (8\u20139\u2009weeks old) were exposed to TBTC (0, 100, 500, or 1000\u2009nM) via drinking water throughout gestation and lactation and ended upon weaning of the pups. Genetic\u2010molecular, biochemical and cellular studies were performed on human SH\u2010SY5Y neuroblastoma cells and on neural stem cells differentiating into neurons. In addition to these studies, histological studies of the brain and functional tests were performed in two\u2010year\u2010old mice. A decrease in the oxidative phosphorylation activity, essential for the proper function of the nervous system, affected neuronal differentiation of human neural stem cells and neuroblastoma cells in\u00a0vitro. Exposure to this compound during pregnancy and lactation resulted in a modification of global deoxyribonucleic acid methylation levels in 2\u2010year\u2010old mice. Additionally, various histological changes were detected in the brains of these mice. Therefore, the alteration of brain development with long\u2010term consequences may be one of the manifestations of early exposure to tributyltin.<\/jats:p>","DOI":"10.1002\/tox.70047","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:26:33Z","timestamp":1769606793000},"page":"906-921","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Tributyltin Chloride on Human Neuronal Differentiation and Mice Brain Development"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3217-1424","authenticated-orcid":false,"given":"Ester","family":"L\u00f3pez\u2010Gallardo","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Biolog\u00eda Molecular y Celular Universidad de Zaragoza  Zaragoza Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria (IIS) de Arag\u00f3n  Zaragoza Spain"},{"name":"Centro de Investigaciones 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