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Background
Toxicogenomics is defined as a study of the response of a genome to hazardous substances, using “omics” technologies such as genomic-scale mRNA expression (transcriptomics), cell and tissue-wide protein expression (proteomics), and metabolite profiling (metabolomics), in combination with bioinformatic methods and conventional toxicology.
In relation to chemical hazard/risk assessment, this emerging science could provide tools for:
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Improving the understanding of mechanisms of toxicity;
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Identifying biomarkers of toxicity and exposure;
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Reducing uncertainty in grouping of chemicals for assessments, (Q)SARs, inter-species extrapolation, effects on susceptible populations, etc.; and
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Providing alternative methods for chemical screening, hazard identification and characterisation.
Molecular-based screening assays using new technologies such as High-Throughput Screening (HTS) and High-Content Screening (HCS) developed in the pharmaceutical industry could also contribute to these aspects, especially by providing a cost-effective approach for prioritization or hazard identification of large numbers of chemicals in a short period of time.
Current Status of the Work by OECD
The OECD works in close cooperation with the International Programme on Chemical Safety (IPCS) on following three working areas.
1. Molecular screening for characterizing individual chemicals and chemical categories
2. New Biomarkers
3. Survey on the available omics tools
The IPCS focuses its work on new biomarkers by exploring the science and evidence basis for toxicogenomics, and the OECD is responsible to the other two items, focusing more on defining the needs and possibilities for the application of toxicogenomics in a regulatory context. Works by both programmes are being coordinated closely and will feed into each other.
Molecular Screening Project
In 2007, the OECD started the “Molecular Screening for Characterizing Individual Chemicals and Chemical Categories Project” (Molecular Screening Project). The project evaluates a number of selected chemicals in a series of molecular screening in vitro assays (High Throughput Screening (HTS)) with the aim of establishing a strategy for rationally and economically prioritizing chemicals for further evaluation based on molecular properties and categories linked to potential toxicity.
The project is led by the United States and supervised by joint OECD/IPCS Advisory Group on Toxicogenomics. In late 2008 several subgroups related to specific pathways, mechanisms and effects as well as nomination of target chemicals and database development were set up under a cooperation between the US and other members.
Survey on the Available Omics Tools
In the preparation for the OECD/IPCS Workshop on Toxicogenomics in Kyoto in November 2004 (see below), the OECD Secretariat conducted a survey on existing toxicogenomic tools in OECD member countries.
Since the survey, there has been accelerating development in the toxicogenomic field. In view of this situation, the OECD/IPCS Advisory Group on Toxicogenomics agreed to follow-up current approaches in toxicogenomics in member countries. The result of the follow-up survey led by Japan was published in January 2009.
Report of the Second Survey on Available Omics Tools
OECD/IPCS Workshops
In order to develop a strategy concerning the future application of toxicogenomics in regulatory assessment of chemical safety, the OECD, along with the IPCS, organized twin workshops.
The first workshop on human health aspects was held in November 2003 in Berlin, with the IPCS in the lead. The OECD took a lead of the second workshop held in October 2004 in Kyoto, Japan which focuses on eco-toxicological aspects.
Summary Report of the Berlin Workshop
Report of the Kyoto Workshop
Member Countries’ Activities on Toxicogenomics and Molecular Screening
For the future application of toxicogenomics and Molecular Screening Technologies in regulatory assessment of chemical safety, various novel efforts are implemented or planned among member countries.
For instance, the U.S. Environmental Protection Agency (EPA) published the white paper titled “Potential Implications of Genomics for Regulatory and Risk Assessment Applications at EPA” in December 2004. This paper was issued to present exemplary applications and resultant implications of the use of genomics technologies in EPA practice.
The US Genomics White paper
The US EPA also started the ToxCast™ Program in 2007, which forms the core activity of the OECD Molecular Screening Project above. Using data from high throughput screening (HTS) bioassays, the program is building computational models to forecast the potential human toxicity of chemicals.
The US ToxCast™ Program
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