Qualitative read-across

In qualitative read-across the potential of a chemical to exhibit a property is inferred from the established potential of one or more analogues. The analogue approach could simply be regarded as the use of SAR. The process involves (1) the identification of a chemical substructure that is common to two substances (which are considered to be analogues) and (2) the assumption that the presence (or absence) of a property/activity for a substance can be inferred from the presence (or absence) of the same property/activity for the analogous substance. 

Predictions based on structure-activity relationships (SARs), including qualitative and quantitative mathematical models, and the use of read-across data from related chemicals. 

In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, through the use of alternative methods, for example, in vitro methods or qualitative or quantitative structure-activity relationship models or from information from structurally related substances (grouping or read-across). 

In the read-across or analogue approach, endpoint information for one chemical is used to make a prediction of the endpoint for another chemical, which is considered to be similar in some way. In principle, read-across can be used to assess physicochemical properties, environmental fate, and (eco)toxicity effects, and it may be performed in a qualitative or quantitative manner. A one-to-one read-across is an ad hoc comparison based on the similarity between two chemicals. Read-across carried out between three or more chemicals can lead to the formulation of generalizations about the group, and eventually to establish that a common substructure can be associated with a SAR. Although the distinction between SAR and read-across may appear vague, the term SAR usually refers to an approach that has been subjected to some degree of statistical validation, and thus to a more formalized approach than read-across. 

This information may derive from laboratory testing. Alternatively, toxicologists may predict hazards from a structure-activity relationship (SAR), which is "the relationship of the molecular structure of a chemical with a physicochemical property, environmental fate attribute, and/or specific effect on human health or an environmental species. These correlations may be qualitative (simple SAR) or quantitative (quantitative SAR, or QSAR)" [79, p. 1]. Both "read across" from the behavior of one chemical to that of a similar chemical and the practice of assessing chemicals by categories are forms of SAR [80,81]. 

Though in principle the steady-state solution of Eq. 20-50 together with the mentioned boundary conditions can be derived by well-known techniques (see Chapter 22), we will spare the reader the derivation. Instead, we prefer to discuss the qualitative aspects of the concentration of species A and D across the stagnant film. In order to make it easier to read Fig. 20.12, we draw the concentrations of A and D as if the equilibrium constant Kr of Eq. 12-17 and the Henry s law constant of compound A were 1. Thus, [A] and [D] at equilibrium are equal, and [A] does not show a concentration jump at the air-water interface. Note that the following... 

One major goal for conducting metabolism-related studies in both nonclinical and human subjects is to make sure that the metabolites detected in human circulation show exposure in the toxicology species. Therefore, metabolism studies are conducted both in humans and in the toxicology species used in the long-term safety studies. Prior to IND filing, in the absence of in vivo human data, in vitro systems like human liver microsomes and hepatocytes are heavily relied on to get an early read on the potential human metabolites. These studies along with in vitro and in vivo animal studies provide a qualitative comparison of metabolism across species. 

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