Modeling to incorporate defense mechanisms into the estimation of dose responses

Environmental Health Perspectives
R L Sielken, D E Stevenson

Abstract

Several adverse health effects (including cancer and noncancer effects) may be the result of an imbalance between exogenous and endogenous invading substances and defense mechanisms. In these cases the probability of an adverse effect depends on how much the exposure to a substance increases or decreases the number of defenders or their efficiency as well as increasing or decreasing the number of invaders. Rather than using a dose scale such as parts per million or milligram/kilogram/day in these cases, dose-response models can directly incorporate the impact of defense mechanisms by using a dose scale that corresponds to the number of invaders that break through the defenders and become free to do their damage. The number of breakthroughs at a specific age, the cumulative number of breakthroughs by a specific age, or the cumulative number of breakthroughs in a window of time would usually be the appropriate age-dependent dose. Although a lifetime average daily dose level can be used as a surrogate for an age-dependent dose in simplistic dose-response models, the age-dependent dose itself can be used in more biologically based models that include time, reflect the key role of feedback mechanisms, and treat the human body as an ...Continue Reading

References

Apr 1, 1983·Environmental Health Perspectives·H W KunzG Schaude
Apr 1, 1995·Regulatory Toxicology and Pharmacology : RTP·R L SielkenD E Stevenson

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Citations

Nov 11, 1999·Toxicology Letters·D E StevensonJ E Klaunig
Apr 15, 2000·Risk Analysis : an Official Publication of the Society for Risk Analysis·R L SielkenG de Jong
Dec 1, 2004·Environmental Toxicology and Pharmacology·Peter Robinson, Margaret Macdonell
Aug 30, 2000·Human & Experimental Toxicology·D E Stevenson, R L Sielken
Jan 14, 2011·Critical Reviews in Toxicology·Lorenz R RhombergSamuel M Cohen

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