Tiering strategy

Lelievre, D., Justine, P Christiaens, F., Bonaventure, N., Coutet, J., Marrot, L. and Cotovio, J. (2007) The EpiSkin phototoxicity assay (EPA) development of an in vitro tiered strategy using 17 reference chemicals to predict phototoxic potency. Toxicology In Vitro An International Journal Published in Association with BIBRA,... 

The most successful application of structure-based predictive modeling in the future may be to specific endpoints. As described in Chapter 8 the prediction of something as broad as carcinogenicity is very difficult. If one isolates individual effects and endpoints within this category, then more success will ensue. Such an approach is likely to require the development of tiered strategies for toxicity prediction. It will also allow for the integration of test data from other assays, and where possible, human knowledge. 

To develop a tiered approach to hazard classification, it is first necessary to use existing data to develop the CMs that will serve as the individual steps of the tiered strategy. The example presented in this chapter used existing data on skin corrosion, and represents a development of earlier work (Worth et al., 1998). 

Figure 1. Two-tier Strategy for Conversion of Halogenated Aromatic Compounds.

This two-tier strategy makes explicit the intimate connection between interaction theory (the collection of relevant force laws) and the notion of state (cf... 

PAHs pollution levels have been effectively measured through MWPs since 1970s. Biochemical and biological responses have accompanied many of these studies nowadays this tiered strategy is recommended in environmental monitoring and biomarkers are rapidly becoming part of health assessment and management of aquatic ecosystems (Sundt et al. 2011). For the scope of the present review, only marine field studies characterized by detection of PAHs pollution are included. The review is further narrowed to the last decade (see also Table 5.5). 

A proper assessment of the ability of chemicals, or mixtures of chemicals, to act as endocrine disrupters requires a multi-tiered approach which is able to identify mechanisms, give early warning of adverse effects and identify which of these effects is likely to be ecologically relevant. A strategy has been proposed by Depledge and Billinghurst " and is outlined below. 

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. 

Interest has been expressed in the possibility of using biomarker assays as a part of risk assessment for regulatory purposes, and some workers have suggested tiered testing procedures that follow this approach (see, for example, Handy et al. 2003). It is to be hoped that regulatory schemes, such as that of REACH (see European Union 2003), will be sufficiently flexible to incorporate new assays and testing strategies as the science advances. 

Gray, L.E. (1998). Tiered screening and testing strategy for xenoestrogens and antiandrogens. Toxicology Letters 103, 677-680. 

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. 

It is concluded that the TTC concept for systemic toxicity is suitable as a starting point for a tiered testing and risk assessment strategy within REACH. However, it is also underlined that the... 

Another characteristic example of analytical strategy is that followed in the United Kingdom for the analysis of tranquilizers and -blockers (78). A total of 180 samples distributed over a whole year (15 samples per month) should be analyzed within a turnaround time of 28 days from receipt of sample. In that case, the expense of developing a two-tier analytical strategy was not justified by the sample throughput. Thus, the selection was direct application of a multiresidue LC/PDA confirmatory method (80). 

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