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Dose-response relationship in multistage carcinogenesis: promoters
K T Kitchin1, J L Brown, R W Setzer
1Genetic Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Environmental Health Perspectives
|January 1, 1994
Summary
This study analyzed dose-response curves for chemical carcinogens in rats and mice, revealing varying concavity. Understanding these relationships is crucial for developing accurate cancer risk assessment models.
Area of Science:
- Toxicology
- Carcinogenesis Research
- Risk Assessment
Background:
- Multistage carcinogenesis involves multiple steps influenced by various factors.
- Chemical promoters play a significant role in accelerating cancer development.
- Accurate dose-response data is essential for quantitative risk assessment.
Purpose of the Study:
- To analyze published dose-response curves of chemical promoters in rodent models.
- To evaluate the concavity of these dose-response relationships.
- To identify research needs for biologically based cancer risk assessment models.
Main Methods:
- Selected published dose-response studies meeting criteria for long study times, multiple doses, and low doses.
- Included studies on rat liver promoters (phenobarbital, TCDD, clophen A-50, HCH isomers, chloroform) and mouse skin promoters (TPA, anthralin, chrysarobin, BHTOOH).
- Dose-response relationships were analyzed based on moles, percentage of effective dose, or percentage of LD50, and curve concavity was determined.
Main Results:
- Analyzed 12 rat liver studies and 10 mouse skin studies with a wide range of chemical doses and exposure durations.
- Dose-response data for various promoters like TCDD, phenobarbital, and TPA were evaluated.
- The degree of concavity for each dose-response curve was quantified.
Conclusions:
- Dose-response curves for chemical promoters exhibit varying degrees of concavity.
- Critique of available data highlights the need for further research.
- Findings inform the development of more accurate, biologically based cancer risk assessment models.