Chicken embryonic toxicity and potential in vitro estrogenic and mutagenic activity of carvacrol and thymol in low dose/concentration.

Thymol and carvacrol are phenolic isomers with the potential developmental toxicity and endocrine disruptions (ED) at low concentrations. However, few reports estimated their toxicity and ED below 10 M (150 μg/L) (MW of thymol and carvacrol: 150 g/mol). In this study, both chemicals were determined for the developmental toxicity and potential ED at 500 μg/kg and 50 μg/kg using the chicken embryonic assay, potential estrogenic activity (EA) at 10 to 10 M (1.5 × 10 to 15 μg/L) by the MCF-7 cell proliferation assay, mutagenicity at 10 to 10 M (1.5 × 10 to 150 μg/L) by the Ames test, and an in silico method for ED. Carvacrol showed mutagenic risks at 10, 10, and 10 M (15, 1.5, and 0.0015 μg/L) while thymol at 10 and 10 M (150 and 1.5 μg/L). Carvacrol negatively impacted embryonic growth at 50 μg/kg, with weak EA at 10 M (1.5 μg/L). Carvacrol but not thymol had weak EA at 10 M (1.5 × 10 μg/L). Molecular docking to 14 types of hormone-related receptors revealed that carvacrol had higher binding affinities to two estrogen receptors and the mineralocorticoid receptor than those to thymol. Carvacrol and thymol varied in toxicities due to a different location of one phenolic hydroxyl group.