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Adverse outcome pathways (AOPs) are designed to provide a clear-cut mechanistic representation of critical toxicological effects that propagate over different layers of biological organization from the initial interaction of a chemical with a molecular target to an adverse outcome at the individual or population level. Adverse outcome pathways are currently gaining momentum, especially in view of their many potential applications as pragmatic tools in the fields of human toxicology, ecotoxicology, and risk assessment. A number of guidance documents, issued by the Organization for Economic Cooperation and Development, as well as landmark papers, outlining best practices to develop, assess and use AOPs, have been published in the last few years. The present paper provides a synopsis of the main principles related to the AOP framework for the toxicologist less familiar with this area, followed by two case studies relevant for human toxicology and ecotoxicology. [ABSTRACT FROM AUTHOR]

Unsaturated compounds are known to cause false-positive reactions in the local lymph node assay (LLNA) but not in the guinea pig maximization test. We have tested a panel of substances (succinic acid, undecylenic acid, 1-octyn-3-ol, fumaric acid, maleic acid, linoleic acid, oleic acid, alpha-linolenic acid, squalene, and arachidonic acid) in the loose-fit coculture-based sensitization assay (LCSA) to evaluate whether unspecific activation of dendritic cells is a confounder for sensitization testing in vitro. Eight out of 10 tested substances caused significant up-regulation of CD86 on dendritic cells cocultured with keratinocytes and would have been classified as sensitizers; only succinic acid was tested negative, and squalene had to be excluded from data analysis due to poor solubility in cell culture medium. Based on human data, only undecylenic acid can be considered a true sensitizer. The true sensitizing potential of 1-octyn-3-ol is uncertain. Fumaric acid and its isomer maleic acid are not known as sensitizers, but their esters are contact allergens. A group of 18- to 20-carbon chain unsaturated fatty acids (linoleic acid, oleic acid, alpha-linolenic acid, and arachidonic acid) elicited the strongest reaction in vitro. This is possibly due to the formation of pro-inflammatory lipid mediators in the cell culture causing nonspecific activation of dendritic cells. In conclusion, both the LLNA and the LCSA seem to provide false-positive results for unsaturated fatty acids. The inclusion of T cells in dendritic cell-based in vitro sensitization assays may help to eliminate false-positive results due to nonspecific dendritic cell activation. This would lead to more accurate prediction of sensitizers, which is paramount for consumer health protection and occupational safety. [ABSTRACT FROM AUTHOR]

The advent of new testing systems and 'omics'-technologies has left regulatory toxicology facing one of the biggest challenges for decades. That is the question whether and how these methods can be used for regulatory purposes. The new methods undoubtedly enable regulators to address important open questions of toxicology such as species-specific toxicity, mixture toxicity, low-dose effects, endocrine effects or nanotoxicology, while promising faster and more efficient toxicity testing with the use of less animals. Consequently, the respective assays, methods and testing strategies are subject of several research programs worldwide. On the other hand, the practical application of such tests for regulatory purposes is a matter of ongoing debate. This document summarizes key aspects of this debate in the light of the European 'regulatory status quo', while elucidating new perspectives for regulatory toxicity testing. [ABSTRACT FROM AUTHOR]

Background: Because of expanding presence of nanomaterials, there has been an increase in the exposure of humans to nanoparticles that is why nanotoxicology studies are important. A number of studies on the effects of nanomatrials in in vitro and in vivo systems have been published. Currently cytotoxicity of different nanoparticles is assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on different cell lines to determine cell viability, a tedious and expensive method. The aim of this study was to evaluate the Artemia salina test in comparison with the MTT assay in the assessment of cytotoxicity of nanostructures because the former method is more rapid and convenient and less expensive. Methods: At the first stage, toxicity of different nanoparticles with different concentrations (1.56-400 µg/mL) was measured by means of the brine shrimp lethality test. At the second stage, the effect of nanoparticles on the viability of the L929 cell line was assessed using the MTT assay. Experiments were conducted with each concentration in triplicate. Results: The results obtained from both tests (A salina test and MTT assay) did not have statistically significant differences (P> 0.05). Conclusions: These findings suggest that the A. salina test may expedite toxicity experiments and decrease costs, and therefore, may be considered an alternative to the in vitro cell culture assay. [ABSTRACT FROM AUTHOR]