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Goodbye to the bioassay.

Jay I Goodman1

  • 1Department of Pharmacology and Toxicology , Michigan State University , East Lansing , MI 48824 , USA . Email: goodman3@msu.edu ; Tel: +1-517-353-9346.

Toxicology Research
|August 10, 2018
PubMed
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The standard two-year rodent bioassay for cancer risk lacks scientific validity. New approaches, focusing on dose-response and mechanism of action, offer a more rational way to assess human carcinogen potential.

Area of Science:

  • Toxicology
  • Carcinogenesis
  • Risk Assessment

Background:

  • The traditional two-year rodent bioassay is widely used for evaluating potential human carcinogens.
  • This method relies on two key assumptions: rodent carcinogens are human carcinogens, and high-dose results predict low-dose effects.
  • These assumptions lack a strong scientific foundation.

Purpose of the Study:

  • To critically evaluate the scientific validity of the standard two-year rodent bioassay.
  • To highlight the limitations and flawed assumptions of the rodent bioassay.
  • To advocate for alternative approaches in carcinogen identification and risk assessment.

Main Methods:

  • Reevaluation of National Toxicology Program (NTP) bioassay data.
  • Analysis of the impact of varying rodent group sizes on bioassay outcomes.

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  • Review of existing proposals for alternative methods, including decision trees incorporating dose-response and mechanism of action (MOA).
  • Main Results:

    • The rodent bioassay's core assumptions are scientifically inaccurate.
    • Increasing rodent group size in bioassays dramatically increases the number of positive results, suggesting the method can induce carcinogenicity.
    • Virtually all tested chemicals can be made into rodent carcinogens under bioassay conditions.

    Conclusions:

    • The two-year rodent bioassay is not a scientifically sound method for identifying human carcinogens or informing risk assessment.
    • Alternative approaches, such as decision trees emphasizing dose-response and MOA, provide a rational basis for evaluating cancer risk.
    • A shift towards more scientifically robust methods is necessary for accurate human health risk assessment.