Confidence in the Database Summary and Recommendations

In the hazard assessment, it is important to evaluate the toxicological database with regard to its adequacy, i.e., the overall confidence regarding the quality, completeness, and consistency of the database should be considered. 

Major aspects for the evaluation of the quality of the data supporting the NOAEL or LOAEL are essential deviations from test guidelines that are not properly substantiated, number of animals used, number of dose levels tested, and adequacy of the examined endpoints. 

Regarding consistency of the database, conflicting results between studies are an indication of a lower confidence in the database, whereas consistency of results from different studies, consistency of animal and human data, and reliable mechanistic data are indicative of a high-confidence database. 

The question of an extra assessment factor in the hazard and risk assessment for chemicals of concern for children is specifically addressed in Section 5.2.1.13. The U.S. Food Quality Protection Act (FQPA) (US-EPA 1996) directed the US-EPA to apply an extra safety factor of 10 in assessing the risks of pesticides to infants and children. The US-EPA (2002) noted the overlap of areas covered by the FQPA factor and those addressed by the traditional UFs, and it was concluded that an additional UF (children-specific) is not needed in the setting of reference values because the currently available UFs (interspecies, intraspecies, LQAEL-to-NOAEL, subchronic-to-chronic, and database-deficiency) were considered sufficient to account for uncertainties in the database from which the reference values are derived. Renwick et al. (2000) concluded that the available data did not provide a scientific rationale for an additional 10-fold UF for infants and children and pointed out that when adequate reproduction, multigeneration, or developmental studies are conducted, there will be no need for an additional 10-fold factor. 

In conclusion, the uncertainty related to the confidence in the database should be taken into account by the use of an assessment factor. Since the quality, completeness, and/or consistency of different databases vary, the assessment factor will also vary and can only be assigned on the basis of expert judgment, preferably made transparent through the application of a set of criteria. In any case, the size of the factor should be considered in terms of other information in the database. The default value should be 1 in case of a high-confidence database, and a factor of 10 would be appropriate where major deficiencies in the data exist, e.g., a lack of chronic and reproductive toxicity studies when setting a tolerable intake. 

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