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Risk assessment methodology: maximum tolerated dose and two-stage carcinogenesis models
1Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey 08855.
Toxicologic Pathology
|March 1, 1994
Summary
The National Academy of Sciences committee suggests retaining the maximum tolerated dose (MTD) in cancer bioassays but recommends using lower doses and mechanistic studies. This approach aims to improve risk assessment for environmental chemicals.
Area of Science:
- Toxicology
- Environmental Health
- Carcinogenesis Research
Background:
- The Committee on Risk Assessment Methodology reviewed current practices for cancer risk assessment.
- Key issues included the use of maximum tolerated dose (MTD) and two-stage carcinogenesis models.
Purpose of the Study:
- To evaluate if current risk assessment methodologies need revision based on MTD and two-stage models.
- To determine if existing data support changes in regulatory agency practices.
Main Methods:
- Committee deliberations on the utility of MTD in bioassays.
- Consideration of two-stage carcinogenesis models for risk assessment.
- Analysis of data requirements for advanced modeling.
Main Results:
- Majority favored retaining MTD but recommended using lower doses and mechanistic studies for better extrapolation.
- Minority suggested preliminary studies to define a human-relevant high dose for bioassays.
- Two-stage models offer insights but require extensive toxicological data.
Conclusions:
- Enhanced understanding of chemical mechanisms is crucial for advancing risk assessment methodology.
- Integrating mechanistic studies and lower doses can improve extrapolation to environmental concentrations.
- Current data limitations impact the broad application of complex models like two-stage carcinogenesis.