Assessment Factors for Human Health Risk Assessment: A Discussion Paper

Abstract

The general goal of this discussion paper is to contribute toward the further harmonization of human health risk assessment. It first discusses the development of a formal, harmonized set of assessment factors. The status quo with regard to assessment factors is reviewed, that is, the type of factors to be identified, the range of values assigned, as well as the presence or absence of a scientific basis for these values. Options are presented for a set of default values and probabilistic distributions for assessment factors based on the state of the art. Methods of combining default values or probabilistic distributions of assessment factors are also described. Second, the effect parameter, the no-observed-adverse-effect level (NOAEL), is discussed. This NOAEL as selected from the toxicological database may be a poor substitute for the unknown, true no-adverse-effect level (NAEL). New developments are presented with respect to the estimation of the NAEL. The already widely discussed Benchmark Dose concept can be extended to obtain an uncertainty distribution of the Critical Effect Dose (CED). This CED distribution can be combined with estimated uncertainty distributions for assessment factors. In this way the full distribution of the Human Limit Value will be derived and not only a point estimate, whereas information on dose-response relations is taken into account. Finally, a strategy is proposed for implementation of the new developments into human health risk assessments.

Uncertainty and variability in environmental life-cycle assessment

“…The effects assessment is seriously hampered by a lack of relevant data. The inhalatory HLVs used here are in most cases derived by applying route-to-route extrapolation, although this extrapolation procedure is not very reliable (Vermeire et al, 1998). Due to a lack of ecotoxicity data about 50% of the terrestrial PNECs and 100% of the sediment PNECs were based on aquatic PNECs (Huijbregts, 1999a, b).…”

“…The extrapolation constant needed in the statistical extrapolation method of Aldenberg and Slob (1993) and the ecotoxicological assessment factors (Jager et al, 1997) were considered uncertain in the ecotoxicological effects assessment. If necessary, Human Limit Values (HLVs) were derived with help of assessment factors (Health Council of the Netherlands, 1996; USEPA, 1999), in which the interspecies extrapolation factor from animals to humans was considered uncertain (Baird et al, 1996; Health Council of the Netherlands, 1996; Vermeire et al, 1998). Uncertainty in toxicity data was not taken into account, because the potential deviation of the No Observed Effect Concentration (NOEC) or the No Observed Adverse Effect Level (NOAEL) from the true threshold concentration or level cannot be quantified (Slob and Pieters, 1999).…”

Statistical modelling of variability and uncertainty in risk assessment of nanoparticles

“…We used the average body weight values as given by Vermeire et al (1999). The I E F i nt r a accounts for variability that exists within the human population.…”

“…Interspecies differences can be quantified in different ways, such as extrapola- tion based on body weight, caloric demand or surface area (Vermeire et al, 1999). We used caloric demand because it is a "biologically plausible and data-based extrapolation method applicable to a wide range of chemical substances" (Schneider et al, 2004) and is preferred above body weight scaling (Vermeire et al, 1999). In allometric body weight scaling based on caloric demand, the ratio of animal to human dose is equal to the ratio of animal body weight to human body weight raised to the power 0.75 (Vermeire et al, 1999).…”

“…We used caloric demand because it is a "biologically plausible and data-based extrapolation method applicable to a wide range of chemical substances" (Schneider et al, 2004) and is preferred above body weight scaling (Vermeire et al, 1999). In allometric body weight scaling based on caloric demand, the ratio of animal to human dose is equal to the ratio of animal body weight to human body weight raised to the power 0.75 (Vermeire et al, 1999). The E F i nt er based on the test species used, in our case the rat, is obtained as …”