1-B-W04-1
生体模倣システム(MPS)開発研究の最新動向と実用化
Current status of the development and social implementation of microphysiological systems (MPS)
〇酒井 康行
Sakai Yasuyuki
東京大・大学院工学系研究科・化学システム工学専攻
Department of Chemical System Engineering, Graduate School of Engineering, University of Tokyo
Through the rapid progress in stem cell technology and in engineering technologies such as microfluidic devices and microfabrication, research and development of a new cultured human tissue/organ model, "micro-physiological system" (MPS), has been active. MPS can realize physiological environment better than conventional two-dimensional static culture. Worldwide, MPS World Summit series had begun toward the establishment the international MPS society, where intimate cooperation among developers, uses and regulation authorities is focused. In Japan, the development of promising devices has progressed mainly through the AMED-MPS project. By fully utilizing these advanced technologies, it will be no longer a dream to realize in vivo-like tissues in vitro. With such academic achievements, it is also important to develop MPS satisfying Context of Use (CoU) in various applications in industries and society. These two progresses should be in parallel toward full utilization of in vitro or non-animal testing. This also meets the demand from the society to realize 3Rs concept in animal experiments. In the mid- to long-term, it is expected to develop into a new methodology for the evaluation of human body responses, in which the response of MPS is analyzed by multi-omics, and the biological response is described and predicted through the construction and extended use of a multi-scale mathematical model.
1-B-W04-2
Computational Toxicology の利用の実際と将来展望
Actual and Future Prospects for the Use of Computational Toxicology
〇小島 肇1
Kojima Hajime1
1国立医薬品食品衛研・安全性予測評価部、2国立医薬品食品衛研・食品添加物部、3(一財)食品薬品安全センター・秦野研究所
1Div. of Risk Assessment, National Institute of Health Sciences, 2Div. of Food Additives, National Institute of Health Sciences, 3Hatano Research Institute (HRI), Food and Drug Safety Center (FDSC)
The Organisation for Economic Co-Operation and Development (OECD) Quantitative Structure-Activity Relationship (QSAR) Toolbox Management Group presented the QSAR model in 2008,and since around 2010, the Center for Computational Toxicology & Exposure (CCTE) of the United States Environmental Protection Agency (US EPA) has been developing and utilizing computational toxicology and reviewing existing chemical substances. In response, the US EPA, the European Chemicals Agency (ECHA), and the European Food Safety Authority (EFSA) have recently expanded the scope of their in silico approaches, such as the threshold of toxicological concern (TTC), QSAR, and read-across, and put them into practical use for risk assessment. However, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the ICH M7: Guidelines for the Evaluation and Management of DNA-Reactive Impurities in Pharmaceuticals for the Reduction of Potential Carcinogenic Risks also promote the use of TTC and QSAR by the government.
In Japan, the Food Safety Commission prepared a draft guidance on the use of QSARs to assess mutagenicity. In the review of chemicals and food additives, read-across predictions are beginning to be carefully applied on a case-by-case basis for substances for which toxicity test data are lacking.
In the future, the use of in silico methods for administrative purposes is expected to expand worldwide. Although animal testing has become difficult for global consensus of 3Rs, the predictability of in vitro testing is limited to approximately 70-80% and may not be more economical than animal testing. The role of in silico methods in safety assessments is expected to increase with time.
1-B-W04-3
生殖発生毒性試験の現状と将来
Reproductive and developmental toxicity study, its present and future
〇秋田 正治
Masaharu Akita
鎌倉女子大学・家政学部・管理栄養学科
Fac. of Family and Consumer Sciences, Dept. of Nutrition and Dietetics, Kamakura Women's Univ.
It has been approximately 30 years since the OECD held the conference on validation of alternatives to experimental animals for its safety evaluation and the administrative acceptance was held in 1996. During this period, OECD has admitted various alternative methods.
There are many future issues. One of them is said to develop alternatives to reproductive and developmental toxicity study. However, this development has been far more troublesome than we expected. In fact, its future direction is still unclear.
As an alternative to the developmental toxicity test, more than 30 ways of testing methods using both the vertebrate and invertebrate have been devised. From about 20 years ago, within the various methods, especially three methods, MM, EST, and WEC have been drawn attention and various data comparing each characteristics exist. As a result of comparing these data, WEC matches most of those three methods with in vivo test data, and recently in EU, WEC has come to attract attention as an alternative to the developmental toxicity test. The fact that WEC is the only method of them that we can confirm the morphological abnormality explains well about (makes us understand) its match with in vivo testing data.
Today, I would like to introduce the characteristics of each testing method as alternatives to the developing toxicity test, and the advantage and disadvantage of WEC especially.
On top of it, I will also introduce the zebrafish and refer to the present situation and the future possibility of the alternatives to reproductive and developmental toxicity study.