Effects of Environmental Chemicals on the Development of the Central Nervous System: Establishment of Endpoints for the Evaluation of Behavioral Effects in Mice

Chemical substances are an indispensable part of the development of civilization; however, there are many known cases of health hazards induced by exposure to chemicals and their byproducts. In particular, the effects of exposure on the developing cerebral nervous system, even after a single exposure, may have lifelong effects; therefore, careful evaluation is required. In this paper, we provide examples of assessments conducted by our research group regarding the effects of exposure to chemicals in the environment during development, as well as the endpoints at which we were able to assess these effects. This will ultimately deepen our understanding of developmental neurotoxicity. Here, we demonstrate a case of late-onset abnormalities in female behavior and reproductive physiology due to developmental exposure to tris(2,6-dimethylphenyl)phosphate (TDMPP), a phosphorus-based flame retardant that exhibits typical estrogen-like effects. Also, we used IntelliCage, a fully automated behavioral measurement system for group-reared mice, to assess basal activity and adaptation to the social environment. An example of how IntelliCage can be used to assess behavior is dioxins, which are chemicals that are unintentionally produced. We focused on brominated dioxins and reported a case of abnormal exploratory behavior in a novel environment. Currently, there is growing public concern regarding substances and particle bodies that have not been adequately evaluated for use in the developing brain, such as PFAS and micro/nanoplastics. We believe that the establishment of more sophisticated evaluation methods and endpoints, including those introduced here, will continue to be necessary for building a foundation for a safe and secure society.