Toxicological modeling techniques

In 1966 experimental studies were initiated on the susceptibility of anaesthetized hamsters to decompression insult, attempting to utilize existing pharmacokinetic and toxicological modeling techniques to characterize the role of the inert gas in producing decompression sickness. The hamster model consisted of three discrete elements. First, a mass transfer model had to be developed that would describe the uptake,... 

In the area of predictive toxicology the applicability domain is taken to express the scope and limitations of a model, that is, the range of chemical structures for which the model is considered to be applicable [106]. Although this issue has been fundamental to the use of QSAR (and indeed any predictive technique) since its conception, there remain few reliable methods to define and apply an applicability domain in predictive toxicology. The current status of methods to define the applicability domain for use in (Q)SAR has been assessed recently by Netzeva et al. [106]. 

In the last 30 years, the use of in vitro tools for toxicological studies and evaluation has become relevant and the number of scientific works and techniques has increased day by day. One of the most important advantages of in vitro systems is their ability to serve as model for the central events in the in vivo toxicological process, and a depth evaluation of the intrinsic cellular toxicity can provide useful information for toxicological safety evaluation. 

Griffiths-Johnson, D.A. and Karol, M.H., Validation of a non-invasive technique to assess development of airway hyperreactivity in an animal model of immunologic pulmonary hypersensitivity, Toxicology, 65, 283, 1991. 

A tiered system for mixture extrapolation is proposed. The lowest tier is based on extrapolation using toxicological point-estimate information such as EC50 values. This translates into the use of toxic units, toxic equivalencies, and similar techniques. The use of the entire concentration-response relationships of the separate compounds is recommended for Tier-2, in conjunction with the use of either concentration or response addition as a modeling approach. In Tier-3, a mixed-model approach can be considered, to more specifically address considerations on toxic modes of action. In the latter case, the approach may be extended to allow incorporation of the responses of different ecological receptors (Tier-4). Research needs have been clearly identified in community-level mixture assessments. 

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