Molecular-based screening assays using new technologies such as High-Throughput Screening (HTS) and High-Content Screening (HCS), developed initially for use in the pharmaceutical industry, enable a cost-effective approach for prioritisation and hazard identification of large numbers of chemicals in a short period of time.
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, these newly emerging science and technologies provide tools for improving the understanding of mechanisms of toxicity, reducing uncertainty in grouping of chemicals, and providing alternative methods for screening chemicals. In the future they could be used for hazard identification and characterisation.
OECD assists internation collaborative efforts on Molecular Screening and Toxicogenomics, with the aim of defining needs and possibilities for their application in a regulatory context.
(1) Molecular Screening Project
The current OECD work in this field focuses on the Molecular Screening Project started in 2007 and led by the US. For the details of this project, see here.
(2) 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.
The work initially started in close cooperation with the International Programme on Chemical Safety (IPCS) on Toxicogenomics. 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.
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.
In 2007, OECD started the “Molecular Screening for Characterizing Individual Chemicals and Chemical Categories Project” (Molecular Screening Project). This 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.
The project is led by the United States and supervised by extended Advisory Group on Molecular Screening and 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 member countries and research institutions.
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Subgroup |
Objective(s) |
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Chemical Nomination |
To identify national priorities and chemicals for HTS evaluation in phase 2 of the US ToxCast and other similar research programmes. To characterize and categorise chemicals for further investigation of screening by in vitro assays. |
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Databases |
To coordinate collation and integration of various national databases on in vivo animal toxicity test results that can be used in the development and validation of HTS approaches. |
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Specific Passways, mechanisms, effects |
Thyroid Signalling |
To identify current HTS approaches for elucidation of each pathway/mechanism/effect. To compare results with existing in vivo findings. To establish research needs for such assessments. |
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PPAR-Alpha Associated Pathways |
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Cancer Epigenetics |
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Sensitisation/Immunotoxicity |
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Developental and Reproductive Effects |
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Developmental Neurotoxicity |
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Comparative Toxicology |
To accommodate molecular screening and toxicogenomics across various animal models. |
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The US EPA 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.
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