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.

Riesgo ecotoxicológico acuático y terrestre del bioplaguicida catahua, Hura crepitans (Euphorbiaceae) / Ecotoxicological aquatic and terrestrial risk of biopesticide sandbox tree, Hura crepitans (Euphorbiaceae)

Hura crepitans (catahua) Linnaeus (Euphorbiaceae) es una planta nativa de América. El objetivo del presente trabajo fue evaluar el riesgo ecotoxicológico (REA) del bioplaguicida H. crepitans. Se determinaron los valores de toxicidad de la catahua para 42 puntos finales de efecto en 30 especies acuáticas y terrestres. Los valores de toxicidad (CL(E/I)50, NOEC o LOEC) obtenidos para las especies acuáticas y terrestres fueron comparados con la dosis promedio de aplicación de catahua en extracto acuoso para plagas del algodón (30000 mg i.a L-1), observándose que a esta concentración ocasionaría un riesgo en todas las especies acuáticas (100%) y en 16 especies terrestres (88,88%). Con un segundo procedimiento para la determinación del REA, se tomaron los valores de CL50 a 48 h de la larva de Spodoptera frugiperda, plaga en los cultivos de maíz y caña de azúcar, y se contrastó con los niveles de toxicidad para las especies acuáticas y terrestres no destinatarias, observándose riesgo sobre cuatro especies acuáticas (50%) (Daphnia magna, Chironomus calligraphus, Isochrysis galbana y Paracheirodon innesi), y sobre cinco especies terrestres (27,77%) (Apis mellifera, Orius insidiosus, Eisenia foetida, Trichogramma cacoeciae y Chrysoperla asoralis). Las saponinas y los flavonoides son los posibles grupos funcionales de importancia relacionados con la toxicidad de la catahua (AU)

Hura crepitans (catahua) Linnaeus (Euphorbiaceae) is a native plant of America. The aim of this study was to assess the ecotoxicological risk (REA) of the biopesticide H. crepitans. Values of sandbox toxicity for 42 endpoints on 30 aquatic and terrestrial species were determined. The toxicity values (LC(E/I)50, NOEC or LOEC) obtained for aquatic and terrestrial species were compared with the average application rate of sandbox aqueous extract for cotton pests (30000 mg i.a L-1), observed that this concentration would cause a risk to all aquatic species (100%) and 17 terrestrial species (94.44%). With a second method for determining the REA, the LC50 values at 48 h larva Spodoptera frugiperda, pest in corn and sugar cane were taken, and was compared with the levels of toxicity to non-target aquatic and terrestrial species, risk observed upon four aquatic species (50%) (Daphnia magna, Chironomus calligraphus, Isochrysis galbana y Paracheirodon innesi), and six terrestrial species (33.3%) (Apis mellifera, Orius insidiosus, Eisenia foetida, Trichogramma cacoeciae and Chrysoperla asoralis). Saponins and flavonoids are the possible functional groups of importance regarding sandbox toxicity (AU)

[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.

Diferencias del sexo y de la edad en el contenido de metales pesados (Cd, Cu, Pb y Zn) en pelos de lobo ibérico (Canis lupus signatus) del Norte de España / Sex and age differences in heavy metals content (Cd, Cu, Pb and Zn) in hairs of Iberian wolf (Canis lupus signatus) from the North of Spain

Como consumidor situado en la cumbre de las cadenas alimenticias, el lobo ibérico (Canis lupus signatus) puede sufrir fenómenos de bioacumulación de diferentes contaminantes que se encuentran distribuidos en el medio ambiente. Esto permite pensar en su posible empleo para detectar y evaluar los efectos toxicológicos de xenobióticos diversos como los metales pesados en los ecosistemas terrestres, pudiendo por ello llegar a ser considerado como adecuado biomonitor del medio. Sin embargo, debido a su importancia ecológica, los métodos destructivos no son los más adecuados para dicha determinación toxicológica, de modo que las muestras no destructivas cobran gran importancia como herramienta para dicha biomonitorización. En el presente trabajo se ha determinado la influencia del sexo y de la edad en la concentración de Cd, Cu, Pb y Zn en pelo de lobos procedente del noroeste de España. Las muestras de pelo (n = 158) fueron lavadas y tras ser sometidas a una digestión por vía húmeda, las concentraciones de Cd, Cu, Pb y Zn fueron determinadas mediante Voltamperometría de Disolución Anódica. Con respecto a la variable sexo, las concentraciones más altas de todos los metales pesados estudiados se cuantificaron en el pelo de las hembras, coincidiendo con lo observado por otros autores, lo cual puede estar asociado a las diferencias fisiológicas y a los diferentes hábitos nutricionales. No obstante, sólo se observaron diferencias estadísticamente significativas para un nivel de significación 0,05 en el caso del cobre, acumulándose más en las hembras que en los machos. Respecto a la variable edad, no se observó un patrón de acumulación de estos metales bien definido. Las concentraciones de Cd y Zn fueron superiores en los individuos cachorros (< 1 año) mientras que las de Cu y Pb resultaron más altas en los jóvenes (entre 1 y 2 años). En todos los casos, los niveles cuantificados pueden ser considerados indicativos de unas concentraciones relativamente bajas, sin relevancia ecotoxicológica y no constituyendo un factor medioambiental serio que pueda afectar a la supervivencia de la población considerada (AU)

As top consumers in food chains, the Iberian wolves (Canis lupus signatus) might experiment bioaccumulation of contaminants which are distributed in the environment, thus offering opportunities to detect and assess the toxicological effects of xenobiotics like the heavy metals on terrestrial ecosystems and to use this species as an adequate bioindicator within the environmental biomonitoring programs. Notwithstanding, destructive methods are not acceptable for those ecotoxicological purposes, thus rendering non-destructive samples as the most important tools for such biomonitoring. At the present study the sex and age influence on Cd, Cu, Pb and Zn concentration in hair of wolves from NW Spain has been determined. Hair samples (n=158) were washed and after wet digestion, Cd, Cu, Pb and Zn concentrations were measured by Anodic Stripping Voltammetry. With respect to sex, the highest concentrations of all heavy metals were quantified on female's hair, similarly to that observed by other authors, which could be associated to different physiological characteristics and nutritional habits. Nevertheless, statistically differences with a significant level of 0.05 were only observed in the case of the copper, being higher in female than in males. With respect to age, there was not a well-defined accumulation standard of the studied heavy metals. The Cd and Zn concentrations were higher in wolf cubs (< 1 year), meanwhile the Cu and Pb concentrations were higher in the young ones (between 1 and 2 years). In all cases, the quantified metal amounts could be considered as indicative of low contaminations levels, with no ecotoxicological concern, and not constituting a serious environmental factor affecting the survival of the considered populations (AU)

Evaluación ecotoxicológica de dos derivados del Nim en lombriz de tierra y abejas / Ecotoxicological assessment of two Neem derivatives in earthworm and honey bees

La utilización de productos con bajo o nulo impacto en organismos circundantes y el ambiente, constituye parte del nuevo concepto de protección de cultivos. Los productos NeoNim 60 y OleoNim 80, obtenidos del árbol del Nim, están propuestos para su uso como insecticida, nematicida y acaricida. Con el objetivo de realizar la evaluación ecotoxicológica de estos productos, se realizaron los ensayos de toxicidad aguda en lombriz de tierra Eisenia andrei y de toxicidad aguda por contacto en abejas Apis mellifera. Cada ensayo contó con un grupo control y dos tratados. El ensayo en lombrices se realizó durante 14 días utilizando suelo artificial, realizando observaciones clínicas, conteo de animales y estudio del comportamiento de la biomasa. La prueba en abejas se prolongó por 48 horas, realizándose observaciones clínicas y conteo de animales. Se obtuvo un 100% de supervivencia en las lombrices de los grupos tratados, obteniendo en el NeoNim 60 valores de disminución de la biomasa significativamente inferiores al grupo control, mientras que el grupo tratado con OleoNim 80 mostró aumento en la biomasa del inicio al final del ensayo. En el ensayo en abejas, la comparación estadística no mostró diferencias entre grupos en cuanto a la mortalidad. Teniendo en cuenta el conjunto de los resultados obtenidos, se pudo concluir que los derivados del Nim NeoNim 60 y OleoNim 80 no producen efecto tóxico sobre las lombrices de tierra y las abejas (AU)

The use of products with low or null impact in surroundingorganisms and the environment constitutes part of the new concept of crop protection. The products NeoNim 60 and OleoNim 80, obtained from the Neem tree, are proposed for its use as insecticide, nematicide and acaricide. With the objective of perform the ecotoxicological assessment of these products, it were carried out the earthworm acute toxicity and the honey bee acute contact toxicity tests. For each assay two Treated and one Control group were established. The assay in earthworms Eisenia andrei was carried out during 14 days using artificial soil, with daily clinical observations, count of animals and study of the changes of the biomass. The test in honey bees Apis mellifera was prolonged for 48 hours, with daily clinical observations and count of animals. A survival of 100% was obtained in the earthworms of the Treated groups, obtaining in the NeoNim 60 group significative lower values of biomass when compared to the Control, while the group treated with OleoNim 80 showed an increase in the biomass from the beginning to the end of the assay. In the assay in bees, the statistical comparison didn't show differences among groups as for the mortality. Taken into account the obtained results, it could be concluded that the Neem derivatives NeoNim 60 and OleoNim 80 don't produce toxic effect on the earthworms and the honeybees (AU)

[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.