Inter-species extrapolation

Hazard doses, or points of departure, are commonly only determined for animals, not for humans. In order to derive hazard characterisations for humans, the animal hazard doses need to be converted to toxicologically equivalent doses for humans. This extrapolation is usually expressed as a multiplication factor, and traditionally a factor of 10 is used (which is roughly obtained from the product of a factor of 3.2 for toxicokinetic variability and a factor 3.2 for toxicodynamic variability).

The following methods are available within MCRA:

  1. No inter-species extrapolation: Assume that for all available points of departure, the animal hazard dose is equal to the human hazard dose. Effectively, this is equivalent to using a conversion factor of 1.

  2. Default distribution: Use a conversion factor drawn from a default, substance and species independent lognormal uncertainty distribution specified (as model settings) by a geometric mean (GM) and geometric standard deviation (GSD). In the nominal run, the nominal value of this distribution (i.e., the geometric mean) is used as a conversion factor. In the uncertainty analysis loop, provided that inter-species extrapolation uncertainty is included in the uncertainty analysis, a single factor is drawn from the lognormal distribution.

  3. Substance/species specific distributions: Use conversion factors drawn from substance/species specific lognormal uncertainty distributions specified (as data) by a geometric mean (GM) and geometric standard deviation (GSD). In the nominal run, a factor equal to the geometric mean is used for all combinations of substance and species. In the uncertainty analysis loop, provided that inter-species extrapolation uncertainty is included in the uncertainty analysis, a uncertainty factor is drawn from the lognormal distribution with \(\mu = 0\) and \(\sigma^2 = 1\), which is used to obtain correlated draws for all available inter-species conversion factor distributions. If the distribution parameters are missing for a specific substance/species, then the default distribution is used as a fallback.