Potency, carcinogenic defined

Cancer risk assessment involves a quantitative estimate of the carcinogenic activity of a carcinogen. For genotoxic carcinogens, this estimate is derived from the cancer potency of the carcinogen. Cancer potency is defined as the slope of the dose-response curve for induction of tumors, and is a function of the dose and the magnitude of response, measured as a slope. The endpoint is the cancer incidence or frequency of occurrence of cancer (tumor induction) in... 

With tso as an index of carcinogenicity, an interspecies relative potency (IRP) can be defined, e.g.,... 

In order to express the carcinogenic response or potency, a dose descriptor is used, for example the Tumorigenic Dose (TD). The TD is often set at a defined incidence, for example 5%, the TD5, defined as the dose (or concentration) associated with a 5% incidence of mmors. The dose descriptor can serve as the basis for development of an Exposure/Potency Index (EPl), which is the estimated daily human exposure divided by the TD. A calculated EPl of 10 for the TD5 represents a one million-fold difference between the human exposure and that at the lower end of the dose-response curve, on which the estimate of potency is based. 

Along these same lines, further work would be helpful in defining other fiber characteristics that are important determinants of carcinogenicity. It is suspected, for example, that amphiboles, such as crocidolite and tremolite asbestos, are more likely to cause mesothelioma than chrysotile, but it is not certain if this is attributable to differences in fiber length alone or to differences in chemical properties (e g., fiber morphometry, iron content, durability in biological fluids and tissues). Consequently, additional animal studies of the relative carcinogenic potency of airborne asbestos fibers of different types (e.g., chrysotile versus amphibole asbestos), carefully matched with regard to fiber size distribution, may be valuable. 

Crouch and Wilson (1979) quantitatively compared the results of NCI bioassays of approximately 70 chemicals in rats (Osbome-Mendel and Fisher 344) and mice (B6C3F1), using a carcinogenic potency defined as the parameter )3 in a one-hit dose-response model ... 

This information affords a bird s eye view of the overall landscape. Once the intrinsic capacity to cause injury to a specific target organ or system has been characterized, some measure of the potency of the substance is essential, preferably in the form of dose-response data in appropriate test systems. Thus the potential for neurotoxicity, myelotoxicity, mutagenicity or carcinogenicity is spelled out in terms of a specific bracket within the range of 10 of possible potency. Naturally this definition applies only to a given set of experimental circumstances particular species, strain, sex and age of animals derived from a particular stock at a particular source, housed under particular defined conditions, and given a diet of specified composition. 

A slope factor (SF is used to quantify the cancer potency of a chemical. An SF defines the rate at which effects increase with dose. The higher the SF, the more potent the cancer effects of the chemical. An SF assumes that there is no dose that is associated with no risk. Any amount of the chemical has the potential to cause cancer, but the chance of this occurring might be so small as to be unmeasurable. This assumes that there is no threshold dose below which cancer does not occur (chapter 7). We know this is true for some chemicals, and is likely not true for others. In general, this assumption ensures that we will not underestimate the potency of a potentially carcinogenic chemical to humans. These SF values are typically based on a conservative estimate of the cancer potency in test animals, and therefore include a safety margin in their derivation (see chapter 7). 

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