Assessment factors—Applications in health risk assessment of chemicals

We review the scientific basis for default assessment factors used in risk assessment of nongenotoxic chemicals including the use of chemical- and pathways specific assessment factors, and extrapolation approaches relevant to species differences, age and gender. One main conclusion is that the conventionally used default factor of 100 does not cover all inter-species and inter-individual differences. We suggest that a species-specific default factor based on allometric scaling should be used for inter-species extrapolation (basal metabolic rate). Regarding toxicodynamic and remaining toxicokinetic differences we suggest that a percentile from a probabilistic distribution is chosen to derive the assessment factor. Based on the scarce information concerning the human-to-human variability it is more difficult to suggest a specific assessment factor. However, extra emphasis should be put on sensitive populations such as neonates and genetically sensitive subgroups, and also fetuses and children which may be particularly vulnerable during development and maturation. Factors that also need to be allowed for are possible gender differences in sensitivity, deficiencies in the databases, nature of the effect, duration of exposure, and route-to-route extrapolation. Since assessment factors are used to compensate for lack of knowledge we feel that it is prudent to adopt a “conservative” approach, erring on the side of protectiveness.