The author tried to review and summarize low-dose effects of endocrine disrupting chemicals (EDCs) through an extensive literature survey of toxicological studies with bisphenol A (BPA), taking BPA as an example for which many studies were published. Data on low-dose effects with BPA, especially on neurobehavioral effects after fetal or early postnatal exposures, suggested that there would be new aspects to be considered. Specific mention for future tasks was made. Firstly, toxicity tests should be designed with more elaboration to ensure a sufficient number of animals with careful handling of litters to allow adequate statistical analysis and appropriate selection of dosages to obtain insight in dose-response relationship. Secondly, precise measurement of plasma levels in both humans and rodents and construction of relevant physiologically-based pharmacokinetic models would help obtain quantitative estimates of intake and target-organ exposure relationship. Thirdly, biological backgrounds, particularly differences and similarities in endocrinological, neurological and immunological aspects among species, should be revisited. Fourthly, mechanistic deliberations on the possibilities of epigenetic mechanism and examinations of putative neurobehavioral effects or a presumptive link of miscarriage with BPA exposures are requested. Finally, general public concerns must be addressed in a thoughtful way so that a simple precautionary approach is not pursued, but uncertainties of the new toxicological aspects should be carefully explained. Further researches and internationally concerted efforts on elucidating risk of low-dose effects by integrating knowledge will contribute to setting new directions in toxicology and improving chemical risk assessments.
2008 The Japanese Society of Toxicology