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New streamlined approaches that use fewer resources and animals are needed for the safety assessment of chemicals. Data gathering should be streamlined to fit regulatory need and the specific properties of the chemicals being assessed. Toward this goal, the Organization for Economic Cooperation and Development (OECD) has introduced the concept of integrated approaches to testing and assessment (IATA) to inform hazard or risk assessment. An IATA is designed to address a specific question, and may include exposure or regulatory considerations, depending on the context. IATA can be informed by mechanistic information about the chemical and related biology. OECD’s of Adverse Outcome Pathways (AOPs) framework is designed to gather biological information related to adverse outcomes of regulatory significance. An AOP is the collected chemical and biological information about a particular biological pathway. The OECD has developed guidance for building and assessing AOPs, and is coordinating development of the AOP Knowledge-base (AOP-KB) for collecting and using this information. The AOP-KB also accepts information about the perturbations of these pathways caused by chemical exposure – information can be used to design prediction models. AOPs can form the logical basis for the integration of information and the design of integrated testing strategies (ITS), within the context of an (IATA), to more effectively and efficiently inform hazard or risk determination.

We have been developing a carcinogenicity prediction system based on gene expression profiles focusing on omics technology to enable mechanism-based evaluations of toxicity to reduce the numbers of animals and toxicological endpoints required by animal studies. Here, we report the development of a mechanism-based evaluation system focused on chemically induced hepato- and nephrotoxicity or hepatic and renal carcinogenicity using a gene expression analysis with a DNA microarray. As a case study, the mode-of-action (MoA)/adverse outcome pathway (AOP) was constructed from the gene expression profiles and histopathological findings of carbon tetrachloride and cisplatin for hepatotoxicity and nephrotoxicity, respectively. Consequently, we developed an advanced toxicity evaluation system for hepato- and nephrotoxicity or hepatic and renal carcinogenicity based on the toxicity mechanisms. We also developed a new prediction system named “CARCINOscreen” for evaluating the carcinogenic potentials of chemicals using the gene expression profiles of liver and kidney tissues from rats after a 28-day repeated administration. The prediction system could predict the carcinogenicity potential of a training chemical set including carcinogens and non-carcinogens with an accuracy of more than 90%. The marker genes established in this study are promising for the development of new effective in vitro testing methods in the future.

Development of an organism is accompanied by rapid and complex changes within a relatively short period, and embryotoxic chemicals administered to a mother during pregnancy can result in persistent lesions, general growth retardation, or delayed organ growth. toxicity tests are useful for evaluating the safety or hazards of small quantities of chemicals. Since cell death and inhibition of differentiation in mouse embryonic stem cells (ESCs) can occur within different concentration ranges of compounds, depending on the toxic potency of the compound, these cell properties can be used as guides for classifying the embryotoxicity of a compound. The use of multiple endpoints, such as assessing the inhibition of viability in ESCs (ICESC) and 3T3 cells (IC3T3), and reduction in embryoid body (EB) area (IDEB), has the advantage of providing a detailed baseline for the classification of a compound’s toxicity level and for establishing a prediction model that utilizes those endpoints. The EB area-based toxicity test (EBT) is an animal-free, novel drug screening system that can be useful in evaluating of various embryotoxic chemicals within a short time.

The use of mammalian models for toxicological risk assessment of chemicals has been a widespread practice for well over 50 years. This has remained controversial in view of the species differences. Further, the advances in molecular biology techniques have revolutionized the toxicological risk assessment scenario by creating demand for rapid, less expensive and highly relevant methods to risk-evaluate chemical substances quickly. In order to take advantage of these advances the US EPA funded the National Research Council to develop a strategy and vision for toxicity testing in 21 century (Tox21). Tox21 envisions a paradigm shift in toxicity testing and proposes the use of emerging technologies based on non-animal methods for better understanding of chemical-environment interaction, and also emphasizes the adoption of animals belonging to lower levels of taxonomic hierarchy, which are less sentient, in toxicity testing. Adoption of this shift would perhaps benefit translation of the REACH Legislation, which otherwise greatly relies on animal experiments for chemical risk assessment. We aimed at establishing , a simple organism belonging to Phylum Cnidaria, as a model organism for toxicity testing of environmental chemicals. Besides, offers advantages such as easy to culture, reproduces fast, cost-effective and highly sensitivity to inorganic pollutants. Moreover, the whole genome sequence of hydra revealed that most of the genes are conserved in which sense it offers advantage over even in the most routinely used other invertebrate model organisms. We standardized several assay methods which formed the nucleus of several publications. Herein we show that can be used as a viable bio-indicator for early warning of aquatic pollutants.

The Lush Prize is now in its fifth year and awards a total of 52,000,000 JPY (approx.) annually to initiatives working to end the use of animals in toxicology testing. There are six categories of award: Science; Training; Young Researcher; Lobbying and Public Awareness. The sixth category is the Lush Black Box Prize which offers, in any one year, a further 38,000,000 JPY (approx.) for a key breakthrough in human toxicology. Many initiatives are directed at the ‘3Rs’: reduction, refinement, and replacement of the use of animals. The Lush Prize seeks only to support projects working on the genuine replacement of animal tests and is the largest reward in its field [].

In 2016, the Prize is very pleased to announce the launch of its Young Researcher Asia awards, to welcome young scientists from across Asia, up to 35 years old at time of application, who wish to pursue a career in animal-free toxicology. Applicants complete a nomination explaining their research proposals, including how they would use a bursary of approx. 1,400,000 JPY. To date in 2016, a total of 37,800,000 JPY has been awarded to nineteen international young researchers for 21st century human-relevant toxicology projects.

The Lush Prize continues to welcome nominations from across the Asia region, not only for Young Researcher awards, but all other prize categories. This report aims to provide an overview of the Prize, the categories of award available, achievements to date and further background information.