Uncertainty in toxicological risk assessment for non-carcinogenic health effects.
Uncertainty in risk assessment results from the lack of knowledge on toxicity to the target population for a substance. Currently used deterministic risk assessment methods yield human limit values or margins of safety (MOS) without quantitative measurements of uncertainty. Qualitative and quantitative uncertainty analysis would enable risk managers to better judge the consequences of different management options. This article discusses sources of uncertainty and possibilities for quantification of uncertainty associated with different steps in the risk assessment of non-carcinogenic health effects. Knowledge gaps causing uncertainty in risk assessment are overcome by extrapolation. Distribution functions for extrapolation factors are based on empirical data and provide information about the extent of uncertainty introduced by these factors. Whereas deterministic methods can account only qualitatively for uncertainty of the resulting human limit value, probabilistic risk assessment methods are able to quantify several aspects of uncertainty. However, there is only limited experience with these methods in practice. Their acceptance and future application will depend on the establishment of evidence based distribution functions, flexibility and practicability of the methods, and the unambiguity of the results.
Kalberlah
Fritz
F
Research and Advisory Institute on Hazardous Substances (FoBiG), Werderring 16, D-79098 Freiburg, Germany. fritz.kalberlah@fobig.de
Schneider
Klaus
K
Schuhmacher-Wolz
Ulrike
U
D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D006262:Health; D006801:Humans; D015233:Models, Statistical; D004364:Pharmaceutical Preparations; D018570:Risk Assessment / Q000379:methods* / Q000706:statistics & numerical data; D013045:Species Specificity; D035501:Uncertainty
D004364:Pharmaceutical Preparations