Assessing the risk of chemical mixtures is an intricate process that should integrate published laboratory data; comparisons with the composition, toxicity, and functionality of similar mixtures; complete analytical characterization of the mixture components; and in silico modeling. Various tiered assessment protocols have been proposed to address this need, and these protocols may be adapted on a case-by-case basis for both mixture-based and component-based evaluations. Emerging technologies have enabled rapid mixture testing in alternative animal models, such as human organotypic cultures and zebrafish. In addition, quantitative modeling that uses systems toxicology approaches can identify exposure-induced cellular and molecular alterations that would not be detected by standard toxicology assays. This review summarizes the approaches to risk assessment of complex chemical mixtures as presented at the Eighth International Congress of the Asian Society of Toxicology, June 2018.
Transcriptomic approaches can give insight into molecular mechanisms underlying chemical toxicity and are increasingly being used as part of toxicological assessments. To aid the interpretation of transcriptomic data, we have developed a systems toxicology method that relies on a computable biological network model. We created the first network model describing cardiotoxicity in zebrafish larvaea valuable emerging model species in testing cardiotoxicity associated with drugs and chemicals. The network is based on scientific literature and represents hierarchical molecular pathways that lead from receptor activation to cardiac pathologies. To test the ability of our approach to detect cardiotoxic outcomes from transcriptomic data, we have selected three publicly available data sets that reported chemically induced heart pathologies in zebrafish larvae for five different chemicals. Network-based analysis detected cardiac perturbations for four out of five chemicals tested, for two of them using transcriptomic data collected up to 3 days before the onset of a visible phenotype. Additionally, we identified distinct molecular pathways that were activated by the different chemicals. The results demonstrate that the proposed integrational method can be used for evaluating the effects of chemicals on the zebrafish cardiac function and, together with observed cardiac apical end points, can provide a comprehensive method for connecting molecular events to organ toxicity. The computable network model is freely available and may be used to generate mechanistic hypotheses and quantifiable perturbation values from any zebrafish transcriptomic data.
One of the main disadvantages of the convective method of drying polymer coatings is their porosity. Porosity during infrared treatment is much less, and the quality of the coatings is significantly higher. However, the analysis of a priori information showed the lack of information about the infrared treatment of polymer coatings during the restoration of the body parts of the equipment. The effect of the infrared treatment regime on the mechanical properties of the F-40S elastomer-based nanocomposite was investigated. The mechanical properties of the elastomeric nanocomposite were assessed by the tensile strength of the films, relative elongation and specific deformation work when breaking the films according to the method of GOST 14236-81, the elastic modulus of the material for tension and compression - according to GOST 9550-81. The optimal mode of infrared processing of the nanocomposite was determined with an active experiment according to the V2 plan. Faulty samples were evaluated according to GOST 9407-84. As a result of regression analysis, a model of the dependence of the specific destruction work of the films of the F-40S elastomer nanocomposite on the infrared treatment mode was obtained. The optimal mode of thermal treatment of the elastomeric nanocomposite is established: 140,00S temperature, time 3.0 hours, at which the material films have the highest specific fracture work of 56.0 MJ/m3. The thermoradiation method, compared to the convective drying method, increases the strength of the nanocomposite films by 1.13 times, from 19.0 to 21.5 MPa. Infrared treatment increases the deformation of samples from 74 to 98%, 1.32 times. The stiffness of the material increased: an increase in the elastic modulus at tension from 158.3 to 161.8 MPa, by 3%, and compression - from 82.7 to 87.2 MPa, by 5.4%. The thermoradiation way, in comparison with a convective way, considerably increases quality of coverings of an elastomeric nanocomposite: the area of the destroyed covering decreases from 20 to 15%, by 1.33 times; concentration of a time in – from 0.67 to 0.54 pieces/cm2, by 1.24 times and the size of a time – from 0.109 to 0.095 mm, for 15%.
The heat resistance of the polymer material for restoring bearing fits is its most important operational property. The thermal stability of nanocomposites when filling elastomers with nanoparticles varies ambiguously and depends on the type of rubber that is the basis of the elastomer. To restore bearing fits, fillers, in addition to copper nanoparticles, use aluminum nanoparticles, as well as carbon nanotubes in nanocomposites. The effect of carbon nanotubes and aluminum nanoparticles on the heat resistance of elastomers was investigated. The change in the deformation-strength properties of the F-40S elastomer and nanocomposites based on it before and after high-temperature aging was experimentally studied. Composition No. 1: F-40S elastomer – 100 mass parts, Taunit carbon nanotubes – 0.1 mass parts. Composition No. 2: F-40S elastomer – 100 mass parts, aluminum nanopowder – 0.075 mass parts. Samples were made in the form of polymer films. Thermal aging of the samples was carried out under conditions of limited oxygen access to air. The heat resistance of the nanocomposite of composition No. 1, in comparison with the F-40S not filled with elastomer, has increased. The aging coefficient of the nanocomposite in strength, in comparison with the unfilled elastomer, increased by 1.2 times, and in terms of deformation, it increased by 1.38 times. The aging coefficient of the nanocomposite composition No. 2 in strength, in comparison with the unfilled elastomer, increased by 1.17 times, and in terms of deformation, it increased by 1.2 times, which confirms the increase in its heat resistance. Experimental studies have established that the Townit-M carbon nanotubes and aluminum powder nanoparticles are inhibitors of the elastomer thermal oxidation process F-40S and therefore increase the heat resistance of nanocomposites based on it.
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