Modeling and Risk Assessment of Carcinogenic Dose-Response

  • Ajit K. Thakur
Part of the NATO ASI Series book series (NSSA, volume 145)

Abstract

Before a pharmaceutical or agricultural compound is put in the consumer market, it is customary to evaluate its safety for humans. In many cases the safety is evaluated in terms of the compound’s carcinogenic potential. The experiments for this purpose are generally performed on rodents, specifically, rats and mice. Generally the human equivalent of life-span in rodents is taken as 2 years. Since there may be sex-specific changes taking place in humans, these studies are performed on both sexes. The end points of such chronic toxicityoncogenicity studies are multiple. The dose levels at which the compound is administered should ideally cover a “NOEL” (no-observable-effectlevel) and an “MTD” (maximum tolerable dose). At the “NOEL”, the animals in the study should not show any biologically meaningful effect, and at “MTD” it should provide some indication of homeostatic imbalance. Furthermore, there is a concurrent negative or vehicle control group in the study for providing valid comparisons of treatment effect. Traditionally the design of such a study includes randomly selected equal number of animals per group per sex in some selected strains of rats and mice and between three to five dosed groups along with the control (three treatment groups and a control is the common practice now-a-days as accepted by most regulatory agencies).

Keywords

Toxicity Dioxide Adenoma Toxicology Dieldrin 

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Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Ajit K. Thakur
    • 1
  1. 1.Biostatistics DepartmentHazleton Laboratories America, Inc.ViennaUSA

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