Towards a generic physiologically based kinetic model to predict in vivo uterotrophic responses in rats by reverse dosimetry of in vitro estrogenicity data.

Towards a generic physiologically based kinetic model to predict in vivo uterotrophic responses in rats by reverse dosimetry of in vitro estrogenicity data. Arch Toxicol. 2017 Dec 12;: Authors: Zhang M, van Ravenzwaay B, Fabian E, Rietjens IMCM, Louisse J Abstract Physiologically based kinetic (PBK) modelling-based reverse dosimetry is a promising tool for the prediction of in vivo developmental toxicity using in vitro concentration-response data. In the present study, the potential of this approach to predict the dose-dependent increase of uterus weight in rats upon exposure to estrogenic chemicals was assessed. In vitro concentration-response data of 17β-estradiol (E2) and bisphenol A (BPA) obtained in the MCF-7/BOS proliferation assay, the U2OS ER-CALUX assay and the yeast estrogen screen (YES) assay, were translated into in vivo dose-response data in rat, using a PBK model with a minimum number of in vitro and in silico determined parameter values. To evaluate the predictions made, benchmark dose (BMD) analysis was performed on the predicted dose-response data and the obtained BMDL10 values were compared with BMDL10 values derived from data on the effects of E2 and BPA in the uterotrophic assay reported in the literature. The results show that predicted dose-response data of E2 and BPA matched with the data from in vivo studies when predictions were made based on YES assay data. The YES assay-based predictions of the BMDL10 valu...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research