We propose that gelling kernels those capable of predicting gelation be rejected a priori as unsuitable for modelling systems that do not exhibit physical gelation, since whatever their powers for interpolation of experimental data, they are unsafe for extrapolation from one mode of operation to another, from smaller to larger values of the index of aggregation, or from one feed to another.
Pharmacokinetic data are used in inter- and intraspecies extrapolation and in characterizing the mode of toxic action.
As adults, we may well read loneliness, sadness into these but we don't know if the egocentric child reader reads these partner-less, childless people as extrapolations of themselves, in the mode of grappling with only having one shoe or disappearing cockatoos and so on.
Concerns have been raised about the validity of such extrapolation, in part because accepted modes of action, which do not include direct DNA mutations, would be expected to result in a threshold dose response (Snow et al. 2005).
First, the uncertainty regarding animal-to-human extrapolations can be reduced if a toxicant's mode of action in an animal model is demonstrated to be relevant to humans (Cohen et al. 2004; Meek et al. 2003; Sonich-Mullin et al. 2001).
The U.S. EPA (2005) cancer guidelines state that "The preferred approach [to estimating low-dose risk] is to develop a toxicodynamic model of the agent's mode of action (MOA) and use that model for extrapolation to lower doses".
This not only supports generation of hypotheses about mode of action but also provides knowledge for science-informed extrapolation for high to low dose and from animals to humans (Andersen et al. 2008).
Another way to pose the question is: how will toxicity testing take into consideration the mode of action and relevant measures of tissue dose for risk extrapolations?
Extrapolation to prototype responses requires addition correction to take into account the differences both in structural mode shape and in spanwise correlation of excitation forces between the section model and the prototype.
On the other hand, extrapolation from acute-to-chronic toxicity is associated with uncertainties because some chemicals may show a different mode of action (MoA) under short- and long-term conditions.
