The in vivo developmental toxicity of diethylstilbestrol (DES) in rat evaluated by an alternative testing strategy.

The in vivo developmental toxicity of diethylstilbestrol (DES) in rat evaluated by an alternative testing strategy. Arch Toxicol. 2019 May 22;: Authors: Adam AHB, Zhang M, de Haan LHJ, van Ravenzwaay B, Louisse J, Rietjens IMCM Abstract In the present study, we evaluated an alternative testing strategy to quantitatively predict the in vivo developmental toxicity of the synthetic hormone diethylstilbestrol (DES). To this end, a physiologically based kinetic (PBK) model was defined that was subsequently used to translate concentration-response data for the in vitro developmental toxicity of DES, obtained in the ES-D3 cell differentiation assay, into predicted in vivo dose-response data for developmental toxicity. The previous studies showed that the PBK model-facilitated reverse dosimetry approach is a useful approach to quantitatively predict the developmental toxicity of several developmental toxins. The results obtained in the present study show that the PBK model adequately predicted DES blood concentrations in rats. Further studies revealed that DES tested positive in the ES-D3 differentiation assay and that DES-induced inhibition of the ES-D3 cell differentiation could be counteracted by the estrogen receptor alpha (ERα) antagonist fulvestrant, indicating that the in vitro ES-D3 cell differentiation assay was able to mimic the role of ERα reported in the mode of action underlying the developmental toxicity of DES in vivo. In sp...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research