Chemicals tier-testing

Whatever the specific need or application, the use of a tier testing scheme can significantly reduce, and in some cases eliminate, the use of animals. An example of a decision-making tree and its applications in ocular testing is provided in Figure 17.3. First, all available data about a test material (or related compounds), including chemical characteristics, historical data, other known toxicity, and the like, are collected. Analysis of these data could provide a strong indication of irritation potential, in which case the material would be labeled a presumed positive and... 

The European Union has adopted a tiered testing approach for new chemicals. This approach requires stepwise increases in detailed testing and evaluation when known factors (such as tonnage) warrant such increased testing. For those compounds that are produced at less than 1 tonne per annum and for which there are no structural or other alerts, no formal additional testing is required. As tonnage increases,... 

The data development effort planned by the EPA has the potential to add significantly to the database on endocrine disruption. The use of standardized laboratory protocols and careful evaluation procedures will maximize the value of the results. In addition to providing data relevant to the regulation of the chemicals being tested, the data will also be useful for understanding the relationship between the relatively simple endpoints examined in some of the Tier I screens (such as receptor binding) and the development of more toxicologically relevant apical endpoints noted in the Tier II tests. 

Single species tests and tests using bioassay batteries are called lower-tier tests.19 But in order to carry out a more stringent examination of the complex interactions between potentially toxic chemical compounds and organisms inhabiting specific ecosystems, experiments are sometimes carried out in microcosms and mesocosms the literature describes these as higher-tier tests.19... 

There are a number of other good short-term systems, some of which have been extensively tested. If the tier tests lead to inconsistent, ambiguous, or doubtful results, it may be desirable to use other short-term tests these may resolve the doubts without the necessity for mouse tests. Another reason for using supplementary tests is that the primary tests may be inappropriate for a particular chemical for example, one may not want to test insecticides in Drosophila. 

Chemical Tier I Tests Tier II Test Supplemar itary Tests ... 

Another observation from Table 9-3 is the sensitivity of the sister chromatid exchange (SCE) test and its general agreement with the tier tests. Every tested chemical that produced positive results in the tier system... 

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. 

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. 

Dean JH, Padarathsingh ML, JerreUs TR. Assessment of immunobiological effects induced by chemicals, dmgs and food additives. I.Tier testing and screening approach. Dmg Chem Toxicol 1979 2(l-2) 5-17. 

Induced models are often used to the study the pathogenesis of, and therapeutic venues for relevant autoimmune diseases. Some of these models, in particular EAE and AA models, have also been proposed as means to evaluate the immunomodulatory effects of chemicals on established autoimmune diseases in the Tiered Approach of immunotoxicity testing. 

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