Tier-testing strategies

In the summary of the aforementioned report, the authors recommend, as did earlier reviewers of this subject, the development and evaluation of a tiered testing strategy for neurotoxicity. The further development of in vitro models for establishing mechanisms of neurotoxicity should be part of this strategy. Full consideration should also be given to advances in the omics and other technological fields. 

Gad, S.C. (1989b). A tier testing strategy incorporating in vitro testing methods for pharmaceutical safety assessment. Flumane Innovations and Alternatives in Animal Experimentation 3 75-79. 

Gad, S.C. (1989). A Tier Testing Strategy Incorporating In Vitro Testing Methods for Pharmaceutical Safety Assessment. Humane Innovations Alternatives Anim. Exp. 3 75-79. 

Gad, S.C. (1992). Industrial application for in vitro toxicity testing methods A tier testing strategy for product safety assessment. In In Vitro Toxicity Testing (Frazier, J., Ed.). Marcel Dekker, New York, pp. 253-279. 

E. Incorporation of the Classification Models into a Tiered Testing Strategy... 

B. Comments of the Design of Tiered Testing Strategies References... 

QSARs, PMs based on physicochemical data, and PMs based on in vitro data can all be used to make predictions on a categorical scale. Such CMs are often developed and evaluated on the basis that they will be applied as stand-alone alternatives to animal experiments, but in practice they are more likely to be used in the context of a tiered testing strategy. 

The development of a tiered testing strategy for predicting a particular kind of toxic potential, skin corrosion, based on the sequential use of a QSAR a PM based on physicochemical (pH) data and a PM based on in vitro data obtained with the EPISKIN test, a particular type of human skin model... 

A method for evaluation of the tiered testing strategy in terms of its predictive capacity and its ability to reduce and refine the use of laboratory animals... 

Figure 18.2 A tiered testing strategy for skin corrosion based on the OECD approach to hazard classification.

Table 18.7 Data Set of 51 Chemicals Used to Evaluate a Tiered Testing Strategy for Skin Corrosion... 

This is an area of significant advancement for industrial chemical notification and registration where several in vitro techniques have been legislated in favor of animal tests in certain scenarios or take their place in tier-testing strategies. The European Medicines Evaluation Agency (EMEA) has also taken a positive stand on the replacement of animal studies by in vitro methods. 

Botham PA (2004) Acute systemic toxicity - Prospects for tiered testing strategies. Toxicology In Vitro 18 227-230. 

The European Centre for Validation of Alternative Methods (ECVAM) and other organizations have developed and/or recommended tiered testing approaches and strategies to assess eye and skin corrosion and irritation potential. These tiered approaches use in vitro methods and other nonanimal approaches, for example, structure-activity relationship (SAR) models. A tiered testing strategy is now... 

It is generally accepted that, in the foreseeable future, no single in vitro eye irritation test will be able to replace the in vivo Draize eye test to predict across the full range of irritation for different chemical classes. However, strategic combinations of several alternative test methods within (tiered) testing strategies may be able to replace the Draize eye test. 

The qualification procedure proposed in this chapter follows a two-tier test strategy that enables quick decisions during a material qualification program. The first set of tests is easy to perform and focuses on key properties that should be evaluated when testing a new laminate material. Failure to pass any of them will likely result in rejection of a material for manufacturing. If multiple materials are being evaluated, the first tests will allow the easy elimination of the least probable candidates. 

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