|
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:
-
Improving the understanding of mechanisms of toxicity;
-
Identifying biomarkers of toxicity and exposure;
-
Reducing uncertainty in grouping of chemicals for assessments, (Q)SARs, inter-species extrapolation, effects on susceptible populations, etc.; and
-
Providing alternative methods for chemical screening, hazard identification and characterisation.
OECD/IPCS Workshops
In February 2002, the OECD member countries decided that exploratory workshops should be held to develop a strategy concerning the future application of toxicogenomics in regulatory assessment of chemical safety. The OECD agreed, along with the International Programme on Chemical Safety (IPCS), to hold twin workshops. The first workshop, focusing on human health aspects, was held on 17-19 November 2003 in Berlin, with the IPCS in the lead. This workshop recommended the following:
-
Further global collaboration should be undertaken to develop case-studies involving chemicals with known modes-of-action and available toxicogenomic data. Associated knowledge bases should be established, e.g. by identifying sentinel genes or gene clusters involved in toxicological responses and investigating sources of human toxicology data including the potential of existing “bio-banks”;
-
In the area of hazard identification, possibilities for the design and execution of research to add toxicogenomic endpoints to existing test guideline protocols should be investigated; and
-
For risk assessment, support should be given for the development of improved biomarkers of exposure and protocols for their validation and continuing to develop a scientific understanding of factors associated with increased susceptibility to chemical risks.
Summary Report of the Berlin Workshop
The second of these twin Workshops, focusing on environmental aspects was held on 13-15 October 2004 in Kyoto, Japan, with the OECD in the lead. Key recommendations from the Kyoto Workshop were:
-
Concerted efforts are required to conduct comprehensive (eco)toxicogenomic studies to differentiate compensatory and adaptive responses from adverse toxicological outcomes;
-
Concerted efforts are required to determine which “omics” technological platforms hold the most promise for studying diverse taxa and for cross-taxa comparisons, and to improve and develop platforms for use across species and taxa;
-
Quality assurance and quality control of all sequencing data and the individual “omics” techniques need to be coupled to good data management and good annotation. All sequencing data and clones should be publicly available;
-
A strategic plan is required to realise the transfer of genomic-based techniques from fundamental research to a potential regulatory use; and
-
An OECD/IPCS Expert Group to implement these recommendations and coordinate future actions should be established. Responsibilities of such a group would include the development of an OECD initial policy for the evaluation and use of “omics” data for regulatory purposes.
Report of the Kyoto Workshop
The two Workshops reviewed the current state of the science in the light of regulatory needs for new chemical assessment methods. It was recognised that there is no fundamental difference between the use of genomic methods for studying human health and environmental effects. It has been further noted that one of the greatest opportunities that toxicogenomic methods may provide is bridging the human health and environmental hazard/risk assessments.
Implementing the Recommendations from Workshops
In order to follow up with the recommendations detailed above, the OECD continues to maintain close cooperation with the IPCS. As part of the ongoing work, the IPCS can focus its work on further exploring the science and evidence basis for toxicogenomics, linking with existing work on biomarkers, modes-of-action and ethical considerations, and the OECD can focus 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.
Member Countries’ Activities on Toxicogenomics
For the future application of toxicogenomics 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.
US Genomics White Paper
USEPA Website
|
