Remaining Species-Specific Differences

As mentioned earlier, the interspecies differences can be divided into differences in metabolic size (Section 5.3.2) and remaining species-specific differences. The average sensitivity of humans to the adverse effects of chemicals (after scaling for caloric requirement) is comparable to that of other species (KEMI 2003). However, an extra assessment factor is needed to account for the remaining 

Toxicological Risk Assessments of Chemicals A Practical Guide 

Eor the purpose of assessing the remaining interspecies uncertainty, Vermeire et al. (1999) collected and analyzed data for 184 chemicals tested in different species and via different exposure routes. NOAELs were selected from studies with mice, rats, and dogs exposed to the same chemical via the same exposure route and with the same duration of exposure. Two categories of exposure duration were defined, subacute and (sub)chronic, in order to increase the comparability of the different studies. The definition of these exposure categories is species specific, partly depending on their maximum lifetime. Subacute exposure was defined as 21-50 days for the mouse and rat, and as 28-90 days for the dog (sub)chronic exposure was defined as 90-730 days for the mouse and rat, and as 365-730 days for the dog. The oral NOAELs were adjusted to account for differences in metabolic size, i.e., by the caloric requirement approach (Section 5.3.2.3). 

The results suggest that the distribution of the ratios can be described sufficiently by a lognormal distribution. If the interspecies differences would depend only on the differences in metabohc size. 

Distribution of Parameters Derived from the NOAEL Ratios 

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Another example for species-specific differences in bioavailability of chemical mixtures is the study of Loureiro et al. (2005), where avoidance behavior of earthworms and isopods was studied in 2 soils from the vicinities of an abandoned gold mine. Isopods (Porcellionides pruinosis) turned out to show avoidance behavior, whereas earthworms (Eisenia andrei) did not, suggesting isopods to be more sensitive than earthworms for these soils that contained a mixture of metals. It remains unclear which factors explain this difference, but routes of exposure and bioavailability difference may have played a role. 

In the following text, various studies will be described, which attempt to establish a scientific rationale for the selection of the interspecies assessment factor. Based on these studies, it can be concluded that a species-specific default factor based on differences in caloric requirement (see Table 5.4) should be used for interspecies extrapolation regarding metabolic size. The remaining interspecies differences should preferentially be described probabilistically, or a deterministic default factor of 2.5 could be used for extrapolation of data from rat studies to the human situation. 

Once the radioactivity has built up inside to a substantial level, we may remove the radioisotope from the external solution. The flux of the radioisotope is then from inside the cells to the external solution. In this case, the specific activity for c° equals zero, and cj determines the net flux of the radioisotope. By Equation 3.16, this efflux of the radioisotope of species j differs in magnitude from the initial influx only by having the factor c° replaced by c ezJFEM RT, the quantities in the first two parentheses remaining the same. The ratio of these two passive flux densities —each of which can be separately measured—takes the following relatively simple form ... 

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