[Toxicogenomics in hazard assessment of chemicals]. / Toksykogenomika w ocenie zagrozen substancji chemicznych.

Recent changes in the European legislation of chemicals suggest an urgent need for introduction of novel, alternative methods for testing chemical substances. Such possibility is offered by toxicogenomics--a scientific discipline combining knowledge from the field of toxicology, i.e., a science investigating the properties of toxic agents and the negative effects these agents exert on health and environment, with genomics, i.e., a science investigating the structure and function of genomes. New research strategies within the field of toxicology (transcriptomics, proteomics, metabolomics) offer conditions to assess the hazards associated with the effects of chemicals with both established and suspected toxic potentials.

Meeting report: Validation of toxicogenomics-based test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use.

This is the report of the first workshop "Validation of Toxicogenomics-Based Test Systems" held 11-12 December 2003 in Ispra, Italy. The workshop was hosted by the European Centre for the Validation of Alternative Methods (ECVAM) and organized jointly by ECVAM, the U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and the National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM). The primary aim of the workshop was for participants to discuss and define principles applicable to the validation of toxicogenomics platforms as well as validation of specific toxicologic test methods that incorporate toxicogenomics technologies. The workshop was viewed as an opportunity for initiating a dialogue between technologic experts, regulators, and the principal validation bodies and for identifying those factors to which the validation process would be applicable. It was felt that to do so now, as the technology is evolving and associated challenges are identified, would be a basis for the future validation of the technology when it reaches the appropriate stage. Because of the complexity of the issue, different aspects of the validation of toxicogenomics-based test methods were covered. The three focus areas include a) biologic validation of toxicogenomics-based test methods for regulatory decision making, b) technical and bioinformatics aspects related to validation, and c) validation issues as they relate to regulatory acceptance and use of toxicogenomics-based test methods. In this report we summarize the discussions and describe in detail the recommendations for future direction and priorities.

The toxicological application of transcriptomics and epigenomics in zebrafish and other teleosts.

Zebrafish (Danio rerio) is one of a number of teleost fish species frequently employed in toxicology. Toxico-genomics determines global transcriptomic responses to chemical exposures and can predict their effects. It has been applied successfully within aquatic toxicology to assist in chemical testing, determination of mechanisms and environmental monitoring. Moreover, the related field of toxico-epigenomics, that determines chemical-induced changes in DNA methylation, histone modifications and micro-RNA expression, is emerging as a valuable contribution to understanding mechanisms of both adaptive and adverse responses. Zebrafish has proven a useful and convenient model species for both transcriptomic and epigenetic toxicological studies. Despite zebrafish's dominance in other areas of fish biology, alternative fish species are used extensively in toxico-genomics. The main reason for this is that environmental monitoring generally focuses on species native to the region of interest. We are starting to see advances in the integration of high-throughput screening, omics techniques and bioinformatics together with more traditional indicator endpoints that are relevant to regulators. Integration of such approaches with high-throughput testing of zebrafish embryos, leading to the discovery of adverse outcome pathways, promises to make a major contribution to ensuring the safety of chemicals in the environment.

The fragility of omics risk and benefit perceptions.

How do individuals judge the risks and benefits of toxicogenomics, an emerging field of research which is completely unfamiliar to them? The hypothesis is that individuals' perceptions of the risks and benefits of toxicogenomics are fragile and can by influenced by different issues and context framings as a technology. The researchers expected that the effects on risk and benefit judgements would differ between lay individuals and experts in toxicogenomics. A 2×2×2 experiment that encompassed three factors was conducted. The first factor, issue framing incorporated the field of application for the technology (therapy vs. diagnosis setting). The second factor, context framing included organisations and institutions that would profit from the technology (companies vs. regulatory agencies) and the third factor encompasses the quality of individuals' level of knowledge, for example lay vs. expert knowledge. Research results suggest the differential power of framing effects. It seems that the clues provided by context frames - but not by issue frames - are able to influence the ways in which lay people and experts process information. The findings are interpreted in the line of the fuzzy trace theory that predicts reliance on fuzzy gist representations formed by stereotypes on a wide range of judgement problem including risk and benefit perceptions.

Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring: hurdles, achievements, and future outlook.

BACKGROUND: In this commentary we present the findings from an international consortium on fish toxicogenomics sponsored by the U.K. Natural Environment Research Council (Fish Toxicogenomics-Moving into Regulation and Monitoring, held 21-23 April 2008 at the Pacific Environmental Science Centre, Vancouver, BC, Canada). OBJECTIVES: The consortium from government agencies, academia, and industry addressed three topics: progress in ecotoxicogenomics, regulatory perspectives on roadblocks for practical implementation of toxicogenomics into risk assessment, and dealing with variability in data sets. DISCUSSION: Participants noted that examples of successful application of omic technologies have been identified, but critical studies are needed to relate molecular changes to ecological adverse outcome. Participants made recommendations for the management of technical and biological variation. They also stressed the need for enhanced interdisciplinary training and communication as well as considerable investment into the generation and curation of appropriate reference omic data. CONCLUSIONS: The participants concluded that, although there are hurdles to pass on the road to regulatory acceptance, omics technologies are already useful for elucidating modes of action of toxicants and can contribute to the risk assessment process as part of a weight-of-evidence approach.