Subdivision of Uncertainty Factors to Allow for Toxicokinetics and Toxicodynamics

Tenfold uncertainty factors have been used in risk assessment for about 40 years to allow for species differences and inter-individual variability. Each factor has to allow for toxicokinetic and toxicodynamic differences. Subdividing the 10-fold factors into kinetic and dynamic defaults, which when multiplied give a product of 10, offers a number of advantages. A major advantage is that chemical-specific data can be introduced to replace one or more of the default subfactors, hence contributing to a chemical-related overall factor. Subdivision of the 10-fold factors also facilitates analysis of the appropriateness of the overall 10-fold defaults, and the development of a more refined approach to the use of uncertainty factors.

[1]  Sandra J. S. Baird,et al.  Noncancer Risk Assessment: A Probabilistic Alternative to Current Practice , 1996 .

[2]  A G Renwick,et al.  Safety factors and establishment of acceptable daily intakes. , 1991, Food additives and contaminants.

[3]  A G Renwick,et al.  Inter-ethnic differences in xenobiotic metabolism. , 1996, Environmental toxicology and pharmacology.

[4]  A I Nikiforov,et al.  A new approach to deriving community exposure guidelines from "no-observed-adverse-effect levels". , 1990, Regulatory toxicology and pharmacology : RTP.

[5]  M L Dourson,et al.  Regulatory history and experimental support of uncertainty (safety) factors. , 1983, Regulatory toxicology and pharmacology : RTP.

[6]  G Vettorazzi,et al.  Advances in the safety evaluation of food additives. A conceptual and historical overview of the Acceptable Daily Intake (ADI) and Acceptable Daily Intake 'not specified'. , 1987, Food additives and contaminants.

[7]  A G Renwick,et al.  Toxicokinetics in infants and children in relation to the ADI and TDI. , 1998, Food additives and contaminants.

[8]  D Hattis,et al.  Human variability in susceptibility to toxic chemicals--a preliminary analysis of pharmacokinetic data from normal volunteers. , 1987, Risk analysis : an official publication of the Society for Risk Analysis.

[9]  R Kroes,et al.  Workshop on the scientific evaluation of the safety factor for the acceptable daily intake (ADI): editorial summary. , 1993, Food additives and contaminants.

[10]  A. Renwick Incidence and severity in relation to magnitude of intake above the ADI or TDI: use of critical effect data. , 1999, Regulatory toxicology and pharmacology : RTP.

[11]  O. G. Fitzhugh,et al.  100-Fold margin of safety , 1954 .

[12]  Bruce D. Naumann,et al.  Scientific basis for uncertainty factors used to establish occupational exposure limits for pharmaceutical active ingredients , 1995 .

[13]  E J Calabrese,et al.  Uncertainty factors and interindividual variation. , 1985, Regulatory toxicology and pharmacology : RTP.

[14]  David R. Williams,et al.  What Is Safe? The Risks of Living in a Nuclear Age , 1998 .

[15]  A. Renwick Data-derived safety factors for the evaluation of food additives and environmental contaminants. , 1993, Food additives and contaminants.

[16]  A. Renwick Duration of intake above the ADI/TDI in relation to toxicodynamics and toxicokinetics. , 1999, Regulatory toxicology and pharmacology : RTP.

[17]  F. Lu,et al.  Acceptable daily intake: inception, evolution, and application. , 1988, Regulatory toxicology and pharmacology : RTP.

[18]  A G Renwick The use of an additional safety or uncertainty factor for nature of toxicity in the estimation of acceptable daily intake and tolerable daily intake values. , 1995, Regulatory toxicology and pharmacology : RTP.