Extrapolation factors quantification

In a report on a research project quantification of extrapolation factors (Kalberlah and Schneider 1998), it is noted that extrapolation factors are intended to replace lack of knowledge by a plausible assumption, and that instimtions with responsibihty for establishing the mles must decide which level of statistical certainty, e.g., applicable for 50% or for 90% of a representative selection of substances, is desired for the selection of a standard value. It is furthermore noted that extrapolation factors are required for (1) time extrapolation, e.g., from a subchronic to a chronic duration of exposure (2) extrapolation from the LOAEL to the NAEL (3) interspecies extrapolation, i.e., from experimental animals to humans and (4) intraspecies extrapolation, i.e., from groups of persons with average sensitivity to groups of persons characterized by special sensitivity. In addition to these extrapolations, route-to-route extrapolation, e.g., oral-to-inhalation or dermal-to-oral must also be discussed. 

Kalberlah and Schneider (1998) have analyzed the information on the quantification of extrapolation factors. They noted that in interspecies extrapolation, two variables must be differentiated The systematic differences between different species, and the variability in the sensitivity of the species. Systematic differences can, e.g., be recorded by means of allometric approaches, scaling (Section 5.3.2). The reasons for the variability in sensitivity may be due to both toxicokinetic and toxicodynamic characteristics of a species. 

Source Modified fi om Kalberlah, F. and Schneider, K., Quantification of extrapolation factors. Final report of the research project No. 11606113 of the Federal Environmental Agency, Bremeihaven, 1998. 

A more recent Dutch report (Vermeire et al. 2001) provides a practical guide for the application of probabilistic distributions of default assessment factors in human health risk assessments, and it is stated that the proposed distributions will be applied in risk assessments of new and existing substances and biocides prepared at RIVM (the National Institute of Public Health and the Environment) and TNO. The report concentrated on the quantification of default distributions of the assessment factors related to interspecies extrapolation (animal-to-human), intraspecies extrapolation (human-to-human), and exposure duration extrapolation. 

Using Eqs. (24) and (25) on properly corrected experimental data. should allow the true Auger peak areas to be determined. However, the method is not yet well established and it suffers from the disadvantage that data must be acquired over a very wide spectral range before the extrapolations can be done accurately. An advantage is that, after normalization, the sensitivity factors required for use in Eq. (21) should be exactly equal to the theoretical values, thereby reducing a source of uncertainty in quantification. 

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