- Biochemical pathway
- chemical exposure
- chemical risk assessment
- gene expression
- Modes of action
- Omics data
- omics technologies
- Risk assessment
WR 25 : Workshop on ‘Omics and Risk Assessment Science | 3 October 2013
Workshop Report no.25. ‘Omics and risk assessment science 25-26 February 2013, Málaga
SCIENCE NEWS FLASH
ECETOC reports on February 2013 workshop addressing ‘omics
Omics is a general term used in biological sciences describing molecular techniques. For example, genomics is the study of the DNA in an organism, the study of proteins is proteomics, metabolites is metabolomics and RNA transcripts is transcriptomics.
There has been growing interest in the use of ‘omics data for risk assessment of chemicals. In particular how the combined analysis of transcriptomics, proteomics and metabolomics can be used to understand how chemicals can induce toxic effects. The aim of this workshop, that attracted scientists from industry, regulatory agencies and academia (several European and North American Universities) was to review progress on the application of ‘omics technologies to chemical safety and assess their potential impact on the risk assessment of chemical substances.
Using several worked examples and case studies the participants of the workshop concluded that ‘omics data are particularly valuable for understanding modes of action (MoA)*. By studying exposure-associated differential gene expression patterns it is becoming possible to examine each key event in the pathway leading from an early molecular event in a cell to an adverse outcome, such as liver disease in an individual. Analysis of the most sensitive pathway for transcriptomics allows for a reasonable approximation of the NO(A)EL of an individual compound.
Progress is gaining pace and ‘omics tools are being used to identify biomarkers and guide study design towards shorter more targeted studies with the potential to reduce the numbers of animal studies currently required to assess chemical safety. While more work remains to be done before it is possible to predict adversity from ‘omics data, the workshop report provides guidance on further standardisation of ‘omics study protocols and how to obtain a better understanding of the association of differentially expressed genes with MoA. The information and ideas developed at the workshop adds to the knowledge base that will ultimately result in improvements in human and environmental risk assessment.
A description and the findings of the Workshop and can be found in ECETOC Workshop Report No.25: ‘Omics and Risk Assessment Science. 25-26 February 2013, Málaga
The previous ‘Omics workshop reports are also available:
Workshop Report No.19: ‘Omics in (Eco)toxicology: Case Studies and Risk Assessment 22-23 February 2010, Málaga (Published June 2010)http://bit.ly/ecetoc-wr19
Workshop Report No.11: The Application of ‘Omics in Toxicology and Ecotoxicology: Case Studies and Risk Assessment 6-7 December 2007, Malaga (Published July 2008) http://bit.ly/ecetoc-wr11
*Further information on Mode of Action (MOA) is found in the following ECETOC reports:
Workshop Report No.26: Mode of Action: Recent Developments, Regulatory Applications and Future Work. 21-22 February 2013, Vienna (Published June 2013)http://bit.ly/ecetoc-wr26
2011 Article: Carmichael N, Bausen M, Boobis AR, Cohen SM, Embry M, Fruijtier-Pölloth C, Greim H, Lewis R, Bette Meek ME, Mellor H, Vickers C, Doe J. 2011. Using mode of action information to improve regulatory decision-making: An ECETOC/ILSI RF/HESI workshop overview. Critical Reviews in Toxicology 41(3):175-86 Doi:10.3109/10408444.2010.541225
TR102 Intelligent Testing Strategies in Ecotoxicology: Mode of Action Approach for Specifically Acting Chemicals (December 2007) http://bit.ly/ecetoc-tr102
There have been two previous ECETOC workshops in 2007 and 2010 on ‘The Application of ‘Omics Technologies in Toxicology and Ecotoxicology: Case Studies and Risk Assessment’. The results were published in ECETOC Workshop Reports 11 and 19 respectively. Their main recommendations were:
1. Conduct studies in a more standardised form using reference chemicals.
2. Obtain a common and agreed definition of what constitutes a toxicologically relevant biochemical pathway.
3. Study the toxicity dose- and time-dependent transition on relevant biochemical pathways from normal variability through adaptive response, to adverse effect.
These recommendations seem to have been applied when using these ‘omics technologies, but there is still some uncertainty in defining reliable toxicological effect pathways with validated key molecular events (expression of genes/ proteins) that regulate the responses.
The aim of the 2013 workshop was to review the progress made since the 2010 workshop on the application of ‘omics technologies to chemical safety and assess the potential impact of these new technologies on the risk assessment of chemical substances.
In particular the workshop addressed the following points:
1. Case studies of the application of ‘omics data for risk assessment and regulatory (eco)toxicology.
2. Guidance to help to increase the intrinsic value of ‘omics data and stimulate its use in (eco)toxicology.
3. Impact of ‘omics sciences on the risk assessment process.
4. Can ‘omics data contribute to the elucidation of (1) life stage / subpopulation sensitivity, (2) low-dose effects and (3) the effects of mixtures?
Over a dozen case studies were presented from industry, regulatory agencies and academia (several European and North American Universities). In turn, four parallel syndicates groups discussed the following topics:
1. Assessing the opportunities for ‘omics to help improve (eco)toxicology.
2. Identifying what key data/knowledge is missing that would help improve (eco)toxicology.
3. Considering the main challenges for using ‘omics in risk assessment in general.
4. Considering the specific challenges for using ‘omics in human risk assessment.
One of the main conclusions of this workshop was that ‘omics data are particularly valuable for understanding modes of action via exposure-associated differential gene expression patterns and that such data are now being used to improve the quality of the risk assessment process. Moreover, ‘omics data are now also used for early recognition adverse outcome pathways from which mode of action may be inferred. There was general agreement that molecular ‘omics information should ideally be connected to the outcome of apical studies (phenotypic anchoring). Analysis of the most sensitive pathway for transcriptomics (at several pointsin time) allowed for a reasonable approximation of the NO(A)EL of the individual compounds studied. Bioinformatics was identified as a key area where efforts are needed since a great deal of data are being generated and require expert assembly and interpretation.
There are a number of opportunities for the use of ‘omics data for risk assessment of chemicals. The combined analysis of transcriptomics, proteomics and metabolomics should provide a better understanding of underlying mechanisms. Using ‘omics technologies in in vitro studies is an attractive way to investigate, and hopefully predict adverse outcome pathways. Combining such information with ‘omics data derived from current in vivo studies in which the whole organism response to a toxicant is better represented, should help to validate the in vitroapproach.
Progress is gaining pace and ‘omics tools are being used to identify biomarkers and guide study design towards shorter more targeted studies. However, predicting adversity from ‘omics data remains an important issue for the use of such data in the risk assessment process. A number of solutions have been discussed in this and previous workshops, e.g. use of Bradford Hill criteria, biological plausibility of associations, phenotypic anchoring, pathway / pattern development. The WHO IPCS MoA/ Human Relevance Framework can be used in a weight of evidence approach to confirm MoA where the outcome is already known or to predict potential apical effects based on evidence of ‘key events’ (molecular and physiological changes) being triggered in an adverse outcome pathway (AOP).
Overall, it was concluded that with more standardisation in study protocols studies and a better understanding of the association of differentially expressed genes with modes of action the relevance of animal (or in vitro) data for human and environmental risk assessment will be improved by the inclusion of data obtained with ‘omics technologies.