Publication List English

2017/07/29
New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae.

2017/03/09
Potential protective function of the sterol regulatory element binding factor 1-fatty acid desaturase 12 axis in early-stage age-related macular degeneration

2016/07/11
Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish

2016/06/14
Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy

2016/06/07
Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension

tComparative study of the zebrafish embryonic toxicity test and mouse embryonic stem cell test to screen developmental toxicity of human pharmaceutical drugs

                     
2016/03/18

Fundamental Toxicological Sciences
Vol. 3 No. 2 March 26, 2016 p.79-87
Atsuto Inoue, Yuhei Nishimura, Norihito Matsumoto, Noriko Umemoto , Yasuhito Shimada, Toru Maruyama, Kana Kayasuga, Motohiko Morihara, Jun Katagi, Tsutomu Shiroya, Yasushi Hirota, Soonih Kim , Toshio Tanaka

Abstracts
According to International Conference on Harmonization guidelines, each drug in development for administration to women of child-bearing potential must be tested for possible developmental toxicities using at least two species (a rodent and non-rodent). With the high cost and slow pace of embryonic-fetal toxicity testing in mammals, both the zebrafish embryonic toxicity test (ZET) and mouse embryonic stem cell test (mEST) have been shown to be useful to assess developmental toxicity of various chemical compounds, including human pharmaceutical drugs, in a high-throughput manner. However, comparative study of the sensitivity and specificity of these methods using the same set of human pharmaceutical drugs is scarce. In this study, we assessed developmental toxicity tests of 39 chemical compounds, including human pharmaceutical drugs, in both the ZET and mEST. The accuracy, sensitivity, and specificity of the ZET were 69%, 59%, and 82%, respectively. The accuracy, sensitivity, and specificity of the mEST were 64%, 50%, and 82%, respectively. As a result, both the ZET and mEST showed acceptable accuracies compared with rat embryo-fetal toxicity study and Food and Drug Administration pregnancy categories. By comparing the results between the ZET and mEST, we identified different types of true positives and true negatives. Thus, complementary tests using both the ZET and mEST may better predict the developmental toxicity of human pharmaceuticals.

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Fundamental Toxicological Sciences