Abstract:
:This chapter explores the concepts, processes, tools and challenges relating to the validation of alternative methods for toxicity and safety testing. In general terms, validation is the process of assessing the appropriateness and usefulness of a tool for its intended purpose. Validation is routinely used in various contexts in science, technology, the manufacturing and services sectors. It serves to assess the fitness-for-purpose of devices, systems, software up to entire methodologies. In the area of toxicity testing, validation plays an indispensable role: "alternative approaches" are increasingly replacing animal models as predictive tools and it needs to be demonstrated that these novel methods are fit for purpose. Alternative approaches include in vitro test methods, non-testing approaches such as predictive computer models up to entire testing and assessment strategies composed of method suites, data sources and decision-aiding tools. Data generated with alternative approaches are ultimately used for decision-making on public health and the protection of the environment. It is therefore essential that the underlying methods and methodologies are thoroughly characterised, assessed and transparently documented through validation studies involving impartial actors. Importantly, validation serves as a filter to ensure that only test methods able to produce data that help to address legislative requirements (e.g. EU's REACH legislation) are accepted as official testing tools and, owing to the globalisation of markets, recognised on international level (e.g. through inclusion in OECD test guidelines). Since validation creates a credible and transparent evidence base on test methods, it provides a quality stamp, supporting companies developing and marketing alternative methods and creating considerable business opportunities. Validation of alternative methods is conducted through scientific studies assessing two key hypotheses, reliability and relevance of the test method for a given purpose. Relevance encapsulates the scientific basis of the test method, its capacity to predict adverse effects in the "target system" (i.e. human health or the environment) as well as its applicability for the intended purpose. In this chapter we focus on the validation of non-animal in vitro alternative testing methods and review the concepts, challenges, processes and tools fundamental to the validation of in vitro methods intended for hazard testing of chemicals. We explore major challenges and peculiarities of validation in this area. Based on the notion that validation per se is a scientific endeavour that needs to adhere to key scientific principles, namely objectivity and appropriate choice of methodology, we examine basic aspects of study design and management, and provide illustrations of statistical approaches to describe predictive performance of validated test methods as well as their reliability.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Griesinger C,Desprez B,Coecke S,Casey W,Zuang Vdoi
10.1007/978-3-319-33826-2_4subject
Has Abstractpub_date
2016-01-01 00:00:00pages
65-132eissn
0065-2598issn
2214-8019journal_volume
856pub_type
杂志文章,评审abstract::The generic tendency of proteins to misassemble into nonfunctional, and sometimes cytotoxic, structures poses a universal problem for all types of cell. This problem is exacerbated by the high total concentration of macromolecules found within most intracellular compartments but it is solved by the actions of molecula...
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更新日期:2010-01-01 00:00:00
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