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


Zhang X(1), Peng Y(1), Wu C(2).
Author information:
(1)Department of Animal and Food Sciences, University of Delaware, Newark, DE, 19716, USA.
(2)Department of Animal and Food Sciences, University of Delaware, Newark, DE, 19716, USA. Electronic address: [Email]


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 10-6 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 10-12 to 10-7 M (1.5 × 10-4 to 15 μg/L) by the MCF-7 cell proliferation assay, mutagenicity at 10-12 to 10-6 M (1.5 × 10-4 to 150 μg/L) by the Ames test, and an in silico method for ED. Carvacrol showed mutagenic risks at 10-7, 10-8, and 10-11 M (15, 1.5, and 0.0015 μg/L) while thymol at 10-6 and 10-8 M (150 and 1.5 μg/L). Carvacrol negatively impacted embryonic growth at 50 μg/kg, with weak EA at 10-8 M (1.5 μg/L). Carvacrol but not thymol had weak EA at 10-12 M (1.5 × 10-4 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.