Comparison of ex vivo placenta perfusion and in vitro BeWo b30 cell models for assessing transfer of developmental and reproductive toxic compounds.

There is an increasing interest in the prediction of exposure for risk assessment, as next generation risk assessment (NGRA) encompasses an exposure-led approach. Within the field of developmental and reproductive toxicology (DART), data on placental transfer is essential for estimating foetal exposure. However, human-relevant data is often limited or unavailable. Ex vivo human placenta perfusion is considered the gold standard in placental transfer research, but it is hampered by a low success rate, limited availability of tissue, and the inability to allow high throughput data collection. BeWo b30 cells can offer a high-throughput, lower-tier alternative to collect human-relevant placental transfer data. Here, thalidomide, valproic acid, amoxicillin, and antipyrine were tested in both model systems. A comparison matrix was derived to evaluate a set of shared placenta transfer parameter values obtained for each compound in the two systems. Transfer index (TI), relative transfer rate, initial transfer rate, and apparent permeability (Papp) were calculated for both experimental set-ups. The relative transfer rates in BeWo b30 cells and TIs of the placenta perfusions were highly comparable, with only a mean difference factor of 1.1. In addition, for the initial transfer rate and Papp values we found differences between the placenta perfusion and BeWo b30 experiments of an average factor of 4.5 and 2.4, respectively. Which parameter to calculate and extract from experimental data is determined by the underlying scientific question, e.g., whether a qualitative/relative or quantitative/absolute assessment of placental transfer is required. Nevertheless, the Papp values derived from both systems are particularly useful for parameterizing physiological-based kinetic (PBK) models and estimating foetal exposure following maternal external exposure, especially within NGRA.