S2: New trend on alternative to animal testing in Japan
National Institute of Health Sciences
In Japan, a main organization on the alternative to animal testing is the Japanese Center for the Validation of Alternative Methods (JaCVAM). JaCVAM is hereby established as part of the Biological Safety Research Center (BSRC), the National Institute of Health Sciences (NIHS) in 2005 and the BSRC director serves as head of JaCVAM. JaCVAM was established to promote the use of alternative methods to animal testing in regulatory studies, thereby replacing, reducing, or refining (the 3 Rs) the use of animals wherever possible while meeting the responsibility of the BSRC to ensure the protection of the general public by assessing the safety of chemicals and other materials, as stipulated in the regulations of the NIHS. JaCVAM activities are also beneficial to application and approval for the manufacture and sale of pharmaceutical and other products as well as to revisions to standards for cosmetic products. Under the International Cooperation on Alternative Test Methods (ICATM), JaCVAM contributed to establish nine test guidelines in OECD. Japan has proposed four test methods in the OECD Work plan such as 1) the Reactive Oxygen Species (ROS) assay for in chemico method for identifing the phototoxic potential of chemicals, 2) Hand1-Luc EST (Embryo Stem cell Test) for the developmental screening, 3)Vitrigel-EIT (Eye Irritation Test) and 4) LabCyte Cornea model-EIT. Additionally, JaCVAM is coordinating, along with several other international collaborators, in ongoing validation studies, which include MITA (Multi-ImmunoTox assay) for immunotoxicity, ADRA (Amino acid Derivative Reactivity Assay) for skin sensitization testing, and LbL (Layer by layer) dermal model for skin irritation testing.
On the other hand, Japanese new projects started last year. One is “Human Organ-on-chips” project supported by AMED (Japan Agency for Medical Research and Development). In this project, a few types of models have developed for drug screening by collaborations with pharmaceutical companies and academia, etc. The other one is “Development of AI based next generation safety prediction system using related Big data (AI-SHIPS)” project supported by METI (Ministry of Economy, Trade and Industry). Basic strategy of this project is to develop the prediction system of hepatotoxicity (cytotoxicity, lipid abnormality, cholangiopathy and hypertrophy etc.) and to develop hemo-toxicity and renal-toxicity using the data based on 28-day Repeated Dose Toxicity Test.
For the systemic toxicological endpoints of repeated dose toxicity, carcinogenicity and reproductive toxicity, new test methods are expected to be developed in the future worldwide. I believe Japan will make a significant contribution to these developments in the Japanese projects.