Surrogate approach

The scope of the toxicity studies when surrogate molecules have been used includes pharmacology studies, subchronic and chronic studies, reproductive toxicity studies, immunotoxicity studies, and even carcinogenicity studies. Short-term assays like safety pharmacology studies are too short for there to be an antisense effect, so we have not used the surrogate approach in these assays. However, when safety pharmacology endpoints are included in subchronic or chronic studies, surrogates are assessed. 

S. (2008) A hydrogen bond surrogate approach for stabilization of short peptide sequences in helical conformation. Acc Chem. Res. 41, 1289-1300. 

Hydrogen-bond surrogate approach Activation of apoptosis by inhibition of Bcl-xL/Bak interaction Metabolically stable peptides [88]... 

The hydrogen bond surrogate approach offers two attractive features. (1) As discussed above, this approach provides peptide stabilization with strict preservation of the helix surfaces. (2) The inherent generality of this approach potentially allows access to several protein secondary structures from a single short peptide. A peptide strand can adopt a variety of secondary structures (a-helices, 310-helices, ji-helices, and (3-sheets) within the context of proteins. The HBS approach has been shown to stabilize the difficult 7i-helix conformation in a short peptide, highlighting the versatility of this approach [130]. 

A. Patgiri, A. L. Jochim and P. S. Arora, A Hydrogen Bond Surrogate Approach for Stabilization of Short Peptide Sequences in a-Helical Conformation , Acc. Chem. Res., 2008, 41, 1289. 

A common solution to the availability problem is the surrogate approach, i.e. if the record of data is too small or no data are available at all, it is attempted to establish a surrogate sample of recorded data larger than the real one of interest. Thus, the record of accidents at nuclear power plants, with no significant entries and a relatively limited exposure, is expanded by use of the record for conventional power plants. Differences are modified subjectively in various ways, depending on the expertise of the system analyst. 

A common use of the surrogate approach is the application of nationwide accident statistics, on a mileage base, to inferences of the probabilities of accidents occurring on particular routes for which no adequate data exist. However, this neglects the presumably significant differences in the physical, environmental, and behavioral characteristics of some specific routes from nationwide average values of these conditions. 

PAH potencies are used to determine quantitative health risks posed by PAH exposure. The risks posed by a mixture of PAHs are based on an assumption of additivity of the individual risks posed by the PAHs. The IPCS monogram on PAHs (IPCS, 1998) describes three approaches used to calculate PAH potencies 1) toxicity equivalence factors approach is based on expressing of individual potencies relative to benzo(a)pyrene, 2) comparative potency approach, which does not identify or quantify the individual compounds but determines the potency of the mixture of compounds and 3) benzo(a)pyrene surrogate approach assumes that benzo(a)pyrene is an indicator of all the PAHs. 

Most field environments are dynamic. There are therefore continuous changes in the input and in the metabolites that are being produced. Interpretation of chemical analyses may therefore be equivocal, and metabolites may be removed at different rates. One approach has been to use surrogate contaminants, for example, ( /Z)-chlorofluoroethene for chloro-ethene, in which only the E isomer is dechlorinated (Ennis et al. 2005). 

It is advisable, then, in a tiered approach to concentrate first on crops and activities (scenarios) that are considered to be relevant with respect to the expected level of exposure and to exclude those not relevant. Second, whether or not the toxicological properties of the product may lead to general restrictions on re-entry should be investigated. If both the likelihood of reentry and the hazard due to the toxicity of the compound cannot generally be neglected, a risk assessment over several steps should be carried out. The assessment may be based on surrogate data and "worst-case" assumptions at first and then refined, if necessary. One possible approach to a tiered evaluation procedure is presented in Figure 1. 

Mainly, the available models have been developed based on the fugacity approach, which use the fugacity as surrogate of concentration, for the compilation and solution of mass-balance equations involved in the description of chemicals fate. However, a new... 

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