The State-of-the Art of Environmental Toxicogenomics: Challenges and Perspectives of "Omics" Approaches Directed to Toxicant Mixtures.

The last decade witnessed extraordinary advances in "omics" methods, particularly transcriptomics, proteomics and metabolomics, enabling toxicologists to integrate toxicokinetics and toxicodynamics with mechanistic insights on the mode-of-action of noxious chemicals, single or combined. The toxicology of mixtures is, nonetheless, a most challenging enterprise, especially for environmental toxicologists and ecotoxicologists, who invariably deal with chemical mixtures, many of which contain unknowns. Despite costs and demanding computations, the systems toxicology framework, of which "omics" is a major component, endeavors extracting adverse outcome pathways for complex mixtures. Still, the interplay between the multiple components of gene expression and cell metabolism tends to be overlooked. As an example, the proteome allocates DNA methyltransferases whose altered transcription or loss of function by action of chemicals can have a global impact on gene expression in the cell. On the other hand, chemical insult can produce reactive metabolites and radicals that can intercalate or bind to DNA as well as to enzymes and structural proteins, compromising their activity. These examples illustrate the importance of exploring multiple "omes" and the purpose of "omics" and multi-"omics" for building truly predictive models of hazard and risk. Here we will review the state-of-the-art of toxicogenomics highlighting successes, shortcomings and perspectives for next-generation environmental toxicologists.

[Prospects of systemic radioecology in solving innovative tasks of nuclear power engineering].

A need of systemic radioecological studies in the strategy developed by the atomic industry in Russia in the XXI century has been justified. The priorities in the radioecology of nuclear power engineering of natural safety associated with the development of the radiation-migration equivalence concept, comparative evaluation of innovative nuclear technologies and forecasting methods of various emergencies have been identified. Also described is an algorithm for the integrated solution of these tasks that includes elaboration of methodological approaches, methods and software allowing dose burdens to humans and biota to be estimated. The rationale of using radioecological risks for the analysis of uncertainties in the environmental contamination impacts,at different stages of the existing and innovative nuclear fuel cycles is shown.

Necessity and approach to integrated nanomaterial legislation and governance.

Nanotechnology is one of the most promising technologies to emerge in recent decades. Materials that are specially engineered to have at least one dimension that is no larger than 100 nm are now continuously manufactured and incorporated as critical components of different products that people use daily. While we are taking advantage of nanomaterials (NMs) and nano-products, they may pose a risk to humans and the broader environment. Some types of fibrous NMs such as carbon nanotubes and nano-fibers may present a risk similar to that of asbestos. Some carbon or metal based NMs may threaten the environment due to their bioaccumulative nature within food webs. In order to prevent future adverse effects from products or byproducts of nanotechnology, we suggest an integrated multi-faceted approach which includes an integrated regulation that is based upon life cycle assessment, empirically derived risk assessment. Advanced research that fills the knowledge gap regarding the understanding of NMs in scientific and social norms will be helpful in a full life cycle assessment of NMs. Emphasizing nanotechnology education to the public for an increased understanding and participation associated with media coverage will finally draw governments' attention with an integrated legislation to be instituted. Developing the optimal mix of these tools, including research, public education, media coverage, integrated legislation, will be significant to proactively manage the complexity of nanotechnology and prevent any undesirable effect due to the NMs exposure.

Aggregating data for computational toxicology applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System.

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.

[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.