Dose-Response Relationships carcinogenic chemicals

Models for determining the dose-response relationship vary based upon the type of toxicological hazard. In the dose-response for chemical carcinogens, it is frequently assumed that no threshold level of exposure (an exposure below which no effects would occur) exists, and, therefore, any level of exposure leads to some finite level of risk. As a practical matter, cancer risks of below one excess cancer per million members of the population exposed (1 x 10 ), when calculated using conservative (risk exaggerating) methods, are considered to represent a reasonable certainty of no harm (Winter and Francis, 1997). 

Risk Index for Mixtures of Hazardous Substances. For the purpose of developing a comprehensive and risk-based hazardous waste classification system, a simple method of calculating the risk posed by mixtures of radionuclides and hazardous chemicals is needed. The method should account for the linear, nonthreshold dose-response relationships for radionuclides and chemical carcinogens (stochastic effects) and the threshold dose-response relationships for noncarcinogenic hazardous chemicals (deterministic effects). 

For any hazardous substance, estimates of the relationship of dose to response in humans are based on either animal or human data. For example, only about 20 of the approximately 300 chemical carcinogens regulated by EPA have dose-response relationships based on human data from epidemiologic studies the remainder are based on animal bioassays. In contrast, the dose-response relationships for radiation are based primarily on the results of human epidemiologic studies. 

Few chemicals identified as carcinogens in laboratory animals are known to cause cancer in humans, and the dose to affected tissues for these chemicals usually is not known well enough to define the dose-response relationship except in a general way. In this respect, the carcinogenic effects of most chemicals in humans are far less well known than are those of ionizing radiation. 

In the evaluation of carcinogenicity of chemicals, data obtained from human and animal studies are analyzed for hazard identification and dose-response relationships. The results are used in combination with exposure assessment and risk characterization for the assessment of cancer risks of the chemicals to humans. 

Dose-response, or toxicity, assessment is the determination of how different levels of exposure to a hazard or pollutant affect the likelihood or severity of health effects. Responses/effects can vary widely since all chemicals and contaminants vary in their capacity to cause adverse effects. The dose-response relationship can be evaluated for either carcinogenic or noncarcinogenic substances. 

Over the past decade there has been a movement to harmonize cancer and noncancer risk assessment (Gaylor 1997 Bogdanffy et al. 2001) based on the premise that cancer and noncancer events share similar pharmacokinetic dependencies and overlapping MOAs and thus have similar dose-response relationships. The benchmark dose approach lends itself to the evaluation of both linear and nonlinear dose-response. In fact, one of the stated purposes of EPA s formalization of the benchmark dose process was to provide a standardized approach to chemical dose-response assessment, regardless of whether the chemical is a carcinogen. 

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