Assessment factors ECETOC approach

The approach of deriving a tolerable intake by dividing the N/LOAEL, or alternatively a BMD for the critical effect(s) by an assessment factor has been described and discussed extensively in the scientihc literature. It is beyond the scope of this book to review all these references. This chapter presents an overview of pubhshed extrapolation methods for the derivation of a tolerable intake based on the assessment factor approach, i.e., limited to address effects with threshold characteristics, and is not meant to be exhaustive. The main focus is on the rationale for and the use of the assessment factors. Pertinent guidance documents and reviews for the issues addressed in this chapter include WHO/IPCS (1994, 1996, 1999), US-EPA (2002, 2004), IGHRC (2003), ECETOC (2003), KEMI (2003), Kalberlah and Schneider (1998), Vermeire et al. (1999), and Nielsen et al. (2005). 

This approach discriminates factors to a large extent in order to distinguish between the single adjustments and to separate best estimates from uncertainty. It should be noted that the ECETOC approach does not mention the establishment of an overall factor and although they mention that all discriminated aspects introduce uncertainties, they do not give guidance on how to account for this. It could also be questioned here whether a nonscientific factor should be discussed in a scientific risk assessment. 

ECETOC (2003) recommended that in the absence of any substance- or species-specific mechanism or PBPK modeling (Section 4.3.6), allometric seating based on metabolic rate (W° ) (caloric requirement approach. Section 5.3.2.3) is considered to provide an appropriate default for an assessment factor for interspecies differences with respect to systemic effects. Allometric scaling was stated as being a tool for estimating interspecies differences of internal exposure or body burden and to provide indirectly information on differences in sensitivity between species. Typical scaling factors for interspecies adjustment were noted as 7 for mouse, 4 for rat, and 2 for dog however. 

ECETOC (2003) recommended that if an appropriate NOAEL is available, then no extrapolation and hence, no assessment factor is necessary. Where it is considered more appropriate to use the LOAEL, a default assessment factor of 3 was recommended however, the factor may need to be adjusted depending on the effects observed at the LOAEL and the slope of the dose-response curve. The BMD could be an alternative approach for defining or confirming a NOAEL depending on the data quality and dose spacing. 

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