Epigenetic toxicity of environmental chemicals upon exposure during development - Bisphenol A and valproic acid may have epigenetic effects.

ABSTRACT

As of 2017, chemical substances registered in Chemical Abstracts Service (CAS) exceed 100 million, which is increasing yearly. The safety of chemical substances is adequately managed by regulations based on scientific information from toxicity tests. However, there are substances reported to have "biological effects" even though they are judged to be nontoxic in conventional toxicity tests. Therefore, it is necessary to consider a new concept on toxicity, "epigenetic toxicity". In this review, we explain about epigenetic toxicity using bisphenol A (BPA) and valproic acid (VPA) as examples. We also discuss the problems associated with the judgment of epigenetic toxicity. Currently, epigenetic changes can only be detected by biochemical methods, which are labor-intensive. Therefore, we are developing reporter mice that can be used to detect epigenetic toxicity during conventional toxicity tests. In addition, we consider that linking epigenomic changes with phenotypic changes is important, because causality is important for toxicity evaluation. Therefore, we are developing an artificial epigenome-editing technology. If we can develop a safety-assessment system by incorporating epigenetic evaluation into toxicity tests, we can increase the safety of both food and environmental chemical substances. The practical application of such a new safety-assessment system will be increasingly important in the future.