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Many in vitro developmental toxicity assays have been proposed over several decades. Since the late 1980s, we have made intermittent attempts to introduce in vitro assays as screening tests for developmental toxicity of in-house candidate products. Two cell-based assays which were developed two decades apart were intensively studied. One was an assay of inhibitory effects on mouse ascites tumor cell attachment to a concanavalin A-coated plastic sheet surface (MOT assay), which we studied in the early days of assay development. The other was an assay of inhibitory effects on the differentiation of mouse embryonic stem cell to beating heart cells (EST assay), which we assessed more recently. We evaluated the suitability of the assays for screening in-house candidates. The concordance rates with in vivo developmental toxicity were at the 60% level. The EST assay classified chemicals that inhibited cell proliferation as embryo-toxic. Both assays had a significant false positive rate. The assays were generally considered unsuitable for screening the developmental toxicity of our candidate compounds. Recent test systems adopt advanced technologies. Despite such evolution of materials and methods, the concordance rates of the EST and MOT systems were similar. This may suggest that the fundamental predictivity of in vitro developmental toxicity assays has remained basically unchanged for decades. To improve their predictivity, in vitro developmental toxicity assays should be strictly based on elucidated pathogenetic mechanisms of developmental toxicity.

by sending out questionnaires to 72 Japanese pharmaceutical companies. The survey yielded data for 108 -tive studies in rodents and non-rodents, respectively. As a result of the analysis, 83% of studies in rodents and 80% in non-rodents showed EFD effects in the DRF studies. When focusing on teratogenicity, 91% of studies in rodents and 100% in non-rodents were judged "positive" in the DRF studies when all EFD toxicities were used as markers. When the effects of both the rodent and non-rodent studies were evaluated together, the combination predictive value in the DRF studies was 96% for EFD toxicants and 100% for compounds for which full examinations (external, visceral and skeletal examination) were conducted in both rodent and non-rodent DRF studies. When the results were judged by including or excluding skelethe results of this survey showed that a pair of the DRF studies in the rodents and non-rodents is useful to increase the predictivity of DRF studies. In addition the inclusion of observations such as fetal survival, -tive studies.