Carcinogens exposure factors

Carcinogen Potency Factor (CPF) A CPF is the slope of the dose-response cun e at very low exposures. The dimensions of a CPF, are expressed as the iin erse of daily dose (mg/kg-day)". ... 

Slope Factor The slope factor is used to estimate an upper-bound lifetime probabilit) of an individual dc cloping cancer as a result of exposure to a particular le cl of a potential carcinogen. Also sec Carcinogen Potency Factor (CPF)... 

It is also clear that apart from exposure to carcinogens, other factors such as the genetic predisposition of the organism exposed may also be important. Thus, patients with the genetic disease xeroderma pigmentosum are more susceptible to skin cancer. It has already been mentioned that the incidence of bladder cancer is significantly higher in those individuals who have the slow acetylator phenotype. 

The carcinogenic risk may be defined as the chronic daily intake dose (as developed in the exposure assessment) multiplied by the carcinogenic slope factor (as selected by the toxicity assessment). The product is the probability of developing cancer during lifetime from exposure to this chemical. 

Exposure studies have been made using mice and rats (257). These experiments have demonstrated species differences in butadiene toxicity and carcinogenicity. Butadiene was found to be a potent carcinogen in the mouse, but only a weak carcinogen in the rat. The interpretations have focused on differences in toxification rates and detoxification metaboHsms as causative factors (257). The metaboHsm is beHeved to proceed through intermediates involving butadiene monoepoxide and butadiene diepoxide (257). A similar mechanism has been proposed for its biodegradation pathway (258). 

For carcinogens, risks are estimated as the incremental probability of an indii idual developing ameer o er a lifetime as a result of exposure to the potential carcinogen. The slope factor (SF) converts estimated daily intakes averaged over a lifetime of exposure directly to incremental risk of an individual developing cancer. 

A = absorption factor, i.e.,the fraction of carcinogen absorbed by the human body ED = exposure duration... 

Although the positive effects of ERT have been well established, it has been shown that the cell proliferative actions of estrogen can increase the incidence of breast cancer in some patients. In addition, duration of exposure to physiological levels of unopposed estrogens is an established risk factor for breast, uterine, and ovarian cancer. In an effort to attain pharmaceutical agents that oppose the carcinogenic... 

Some established cell lines were derived from malignant tissue. Many of these cell lines can form tumors when injected into susceptible animals. Other established cell lines are not Uunorigenic. However, exposure to carcinogens, and irradiation can cause these cells to form tumors in susceptible animals. In addition, transformation can be caused by spontaneous mutations, by growth factors, and by viral (or oncogenic) transformation (Table 6). Malignant transformation is defined as consisting of the series of events that cause normal cells to develop the capacity to form tumors. 

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