Alpha-terpineol induced developmental toxicity in Wistar rats: Embryotoxic, teratogenic, and targeted gene expression...

Alpha-terpineol (α-terpineol), a ubiquitous monoterpenoid alcohol found in numerous essential oils, is widely employed in cosmetics, perfumes, and aromatic therapies. Despite its extensive application, concerns regarding its potential reproductive and developmental toxicity remain inadequately characterized, particularly concerning specific teratogenic effects and underlying molecular mechanisms. This study presents novel findings, demonstrating that α-terpineol exposure during the critical organogenesis period significantly induces developmental toxicity in Wistar rat fetuses. α-terpineol was administered at the doses of 0, 75, 150, and 300 mg/kg with a dose volume of 5 mL/kg. We report dose-dependent embryotoxic and teratogenic effects, including reduced fetal weight and a spectrum of severe skeletal malformations such as anophthalmia, club foot, micrognathia, phocomelia, and irregularities in the vertebral column, ribs, and limb bones. Crucially, our comprehensive gene expression analysis revealed statistically significant alterations in the expression patterns of HOXD13 and GDF11, two pivotal genes essential for skeletal patterning and limb development. The observed downregulation of these genes suggests a potential molecular association into α-terpineol-induced teratogenesis. These findings underscore the significant developmental risks associated with α-terpineol exposure during pregnancy and provides insights into potential molecular changes underlying its teratogenic potential, warranting further investigation into human health implications and the establishment of safe exposure limits for this widely used compound.