Alternative methods: a mandate for changing the way industry meets requirements to show drug and pro

来源 :2016(第二届)毒性测试替代方法与转化毒理学(国际)学术研讨会暨有害结局路径(AOP)与风险评估培训会议 | 被引量 : 0次 | 上传用户:applebanana0204
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  Risk assessment required by the cosmetics regulation is defined as the progress of organizing and analyzing information to determine if a chemical might cause harm to exposed person.This especially provides the identification of an adverse effect (depending on potency /dose of the chemical).For obtaining information whether a chemical produces one or more of these adverse effects on human, methods using animals (in vivo testing) were historically used.Since 1959, the principle of "3R", after which alternative methods should completely replace animal tests, has been introduced.One of the most common alternatives was in vitro testing that uses living tissues.As such, there are by now at least 12 non-animal methods (on skin absorption,phototoxicity, skin irritation, eye irritation, mutagenicity, skin corrosion...) that went through validation phase and regulatory acceptance demonstrating the reliability and relevance of the particular approach, method process or assessment.As such for some toxicological endpoints, the fully replacement of animal tests is currently achieved (e.g.skin absorption, phototoxicity, skin irritation/corrosion).With regard to other endpoints, the replacement is at present still not entirely established, but partially succeeded (e.g.eye irritation, genotoxicity).Combining alternative methods (test batteries) are recently being introduced to predict an endpoint (eye irritation).The results can be (statistically) weighted as this will be illustrated.Additionally, integrated testing strategies integrated different types of data (existing in vivo data, in silico, in chemico, in vitro...)into the decision-making are currently established.It is anticipated that (Q(SAR) and molecular and/or cell-based assays will be in a test battery used together to predict the hazard and also its potential (skin sensitization).Only with view to the very complex toxicological mechanisms (e.g.repeated-dose toxicity, toxicokinetics), no alternatives methods are validated today.This can partially be explained by the fact that already the mechanisms themselves are not completely understood by now.But even in this field considerable efforts and progress were made.The advances in technologies (e.g.human-on-chip, bioprinting, human relevance system) and the gain of toxicological knowledge pathways (system biology) appear to make novel approaches feasible for systemic toxicities in a not-so-distant future.Therefore, examples of the range of state-of-the-art non-animal research methods available and their demonstrated benefits are investigated.
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