Tier-testing development

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. 

As was the case with tier testing, developmental immunotoxicology has been driven by expert workshops to reach consensus on the most important issues three workshops were held in 2001 [79-81], and another in 2003 [82], These workshops contributed to the development of a proposed testing framework to detect developmental immunotoxicity, which is described in detail in chapter 21. 

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... 

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... 

Guidance for testing compounds for immunotoxicity is relatively few. The earliest guidelines were developed for pesticides in 1996 by US EPA (OPPTS 880.3550 followed by 880.3800 and 870.7800). The studies were taken from the National Toxicology Program (NTP) tier-testing approach. They typically request tests in rodents and most immunotoxicology is done in vivo [12]. 

M Aikman, L Augsburger, I Berry et al. Collaborative development of two-tiered dissolution testing for gelatin capsules and gelatin-coated tablets using enzyme-containing media. Pharmacop Forum 24(5) 7045-7050, 1998. 

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. 

Tier 2 PRA process involved developing environmental exposure data and chronic toxicity data distributions for individual POPs. The mean concentrations of POPs in local marine water measured at various locations were used as exposure data in the construction of the exposure distribution. The chronic toxicity data distribution was established based on published international acute toxicity data (LC50, EC50) on a variety of aquatic organisms tested in many jurisdictions, drawn primarily from the USEPA ECOTOX database (2002) (available at http //www.epa.gov/ ecotox). If the upper 5th centile of the measured chemical exposure data distribution did not exceed the lower 5th centile of its estimated chronic toxicity distribution, the potential ecological risk posed by the chemical was judged to be tolerable (Hall and Giddings, 2000). 

WASTOXHAS was developed for assessing leaching hazardous impact of wastes in laboratory and field situations. It is a part of a tiered approach (Fig. 1). It assumes that classical batch leaching tests (see for example Sahuquillo et al., 2003), followed by application of relevant bioassays, have been initially undertaken for i) deciding to continue ecotoxic hazard assessment and ii) selecting adequate and sensitive bioassays. It can be eventually followed by a more complex and elaborate hazard assessment scheme based on microcosms or mesocosms. ... 

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