Adjustment for Differences in Body Size Exposure Route

4 Adjustment for Differences in Body Size Exposure Route 

In practice, this means that no adjustment for difference in body size is needed for a NOAEC obtained for systemic effects in an inhalation toxicity study (van Genderen 1988, Feron et al. 1990, Vermeire et al. 1999, KEMI 2003). For example, a NOAEC of 50 mg/m observed for laboratory animals is also the equivalent human NOAEC (note that so far species-specific sensitivity has not been taken into account). 

As mentioned in Section 5.3.2.3, extrapolation using allometric scaling based on metabolic rate assumes that the parent compound is the toxic agent and that the detoxification is related to the metabolic rate and thus controls the tissue level. This is relevant for oral exposure only. With regard to inhalation of substances, which act systemically, the lower detoxification (metabolic) rate in larger animals is balanced by a lower uptake (lower respiratory rate) and thus no scaling factor is needed (ECETOC 2003). 

For substances with local effects on the respiratory tract, no general approach for interspecies scaling can be given. Anatomical and physiological differences in the airways between experimental animals and humans contribute to interspecies differences in local effects observed between animals and humans, see Section 4.7.8. It should be noted, however, that for local effects the determining factor for effects to occur in the respiratory tract is generally the concentration of the chemical in the air rather than the total dose and thus allometric scaling is not relevant. 

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S.3.2.4 Adjustment for Differences in Body Size Exposure Route... 

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