In vitro

and in silico test strategy for estimation of developmental neurotoxicity

During pregnancy, some environmental chemicals are transferred to the developing foetus from maternal exposure. Some of these chemicals such as acrylamide and methylmercury, have been implicated to induce neurodevelopmental effects (e.g. autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), intellectual disabilities) in children later in life. A number of data have since been generated from cell-based studies investigating this. However, the translation of these cell base studies, to human relevant exposure pathways, and doses still remains a challenge. We thus propose the application of adverse outcome pathways (AOPs) to give systematic organization of events from molecular to individual (population) level, in the developing foetal nervous system. We also introduce, knowledge of chemical adsorption, distribution, metabolism, excretion, clearance

in target tissues

, to extrapolate the cell base toxic concentrations to human oral doses. This will be done using maternal-foetus physiology-based toxicokinetic (PBTK) models. The generated information will be of great use in chemical risk assessment during pregnancy, and would be relevant to regulatory bodies in setting chemical safety standard levels.