Engineered nanomaterials (NM) present tremendous opportunities for industrial growth and development, and hold great promise for the improvement of our lives, in medicine, electronics, and numerous other areas. However, there are considerable gaps in our knowledge concerning the potential hazardous effects of NM on human health and the environment. As risk is a function of the level of exposure to a substance and how hazardous it is, to truly understand risks of adverse effects (e.g. ill health) resulting from exposure to NM we must understand the hazards a material pose. However an increasing challenge facing hazard identification/risk assessment of the ever increasing numbers of NM being introduced into the market is the diversity and complexity of the types of materials with varying physicochemical properties. To understand the hazardous nature of a material, several approaches are commonly employed ranging from reading across from other similar substances which doesn’t require any actual testing to performing test on living creatures. For NM, there is considerable debate surrounding the accuracy of reading across from other materials (e.g. the bulk form) and it is considered that this is not yet appropriate for NM without further study and validation. Therefore gaining accurate knowledge of the hazard status of NMs will require toxicological testing. However the nature of toxicological testing means that it is a compromise as of course the best test system is the target species which in the case of worker or consumer exposure, means humans but for ethical reasons this is not possible in almost all cases. Therefore toxicologists utilise either animal models (which do differ from humans in many important respects) or where this is not possible due to either financial or increasingly due to ethical reasons, use in vitro models such as immortalized cell lines. In his respect, toxicological testing should be seen as a spectrum where the further we get from humans and use increasingly simplified models we require more caveats to the data, increased potential for false positives/ negatives but improved financial/ ethical considerations as well as improved efficiency. In addition, it is much more straightforward using in vitro systems to interrogate mechanisms of toxicity using various techniques, agonists and antagonists of various pathways and effects allowing specific biological and mechanistic pathways to be isolated. In this way it can tell us much about how a particle may cause toxicity for example when specific test systems in target cell lines are used, effects of nanoparticles on the plasma membrane, protein synthesis, cell cycle, as well as on overall cell function can be elucidated. The toxicological effects and cytotoxicity mechanisms of some widely used nanoparticles have been reviewed. Available in vitro systems for studying mechanisms of toxicity such as inflammation, oxidative stress generation, interfering of signaling functions, modulating gene transcription and DNA damaging for potential organ targets, cell lines, as well as biomarker analysis have also been described. Therefore, although there are limitations of in vitro systems, short-term in vitro tests of toxicity can provide a rapid and relatively inexpensive way to assess the potential toxicity of large numbers of untested nanoparticles. The approaches outlined in this document are ways in which we can gain indicative measures of toxicity to feed into risk assessment and to aid this, we use well known and characterised control particles to allow us to benchmark against substances for which inhalation data and exposure limits do exist to generate a more informed opinion.
HANDBOOK OF TOXICOLOGICAL CHARACTERIZATION: Definition of a panel of toxicological tests to assess hazardous properties of engineered nanomaterials
BERGAMASCHI, Enrico;
2012-01-01
Abstract
Engineered nanomaterials (NM) present tremendous opportunities for industrial growth and development, and hold great promise for the improvement of our lives, in medicine, electronics, and numerous other areas. However, there are considerable gaps in our knowledge concerning the potential hazardous effects of NM on human health and the environment. As risk is a function of the level of exposure to a substance and how hazardous it is, to truly understand risks of adverse effects (e.g. ill health) resulting from exposure to NM we must understand the hazards a material pose. However an increasing challenge facing hazard identification/risk assessment of the ever increasing numbers of NM being introduced into the market is the diversity and complexity of the types of materials with varying physicochemical properties. To understand the hazardous nature of a material, several approaches are commonly employed ranging from reading across from other similar substances which doesn’t require any actual testing to performing test on living creatures. For NM, there is considerable debate surrounding the accuracy of reading across from other materials (e.g. the bulk form) and it is considered that this is not yet appropriate for NM without further study and validation. Therefore gaining accurate knowledge of the hazard status of NMs will require toxicological testing. However the nature of toxicological testing means that it is a compromise as of course the best test system is the target species which in the case of worker or consumer exposure, means humans but for ethical reasons this is not possible in almost all cases. Therefore toxicologists utilise either animal models (which do differ from humans in many important respects) or where this is not possible due to either financial or increasingly due to ethical reasons, use in vitro models such as immortalized cell lines. In his respect, toxicological testing should be seen as a spectrum where the further we get from humans and use increasingly simplified models we require more caveats to the data, increased potential for false positives/ negatives but improved financial/ ethical considerations as well as improved efficiency. In addition, it is much more straightforward using in vitro systems to interrogate mechanisms of toxicity using various techniques, agonists and antagonists of various pathways and effects allowing specific biological and mechanistic pathways to be isolated. In this way it can tell us much about how a particle may cause toxicity for example when specific test systems in target cell lines are used, effects of nanoparticles on the plasma membrane, protein synthesis, cell cycle, as well as on overall cell function can be elucidated. The toxicological effects and cytotoxicity mechanisms of some widely used nanoparticles have been reviewed. Available in vitro systems for studying mechanisms of toxicity such as inflammation, oxidative stress generation, interfering of signaling functions, modulating gene transcription and DNA damaging for potential organ targets, cell lines, as well as biomarker analysis have also been described. Therefore, although there are limitations of in vitro systems, short-term in vitro tests of toxicity can provide a rapid and relatively inexpensive way to assess the potential toxicity of large numbers of untested nanoparticles. The approaches outlined in this document are ways in which we can gain indicative measures of toxicity to feed into risk assessment and to aid this, we use well known and characterised control particles to allow us to benchmark against substances for which inhalation data and exposure limits do exist to generate a more informed opinion.
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