Cancer risk factors, carcinogens

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... 

Verified inhalation and oral slope factors were unavailable from U.S. EPA for dimethylhydrazine. A cancer assessment based upon the carcinogenic potential (withdrawn cancer slope factors) of dimethylhydrazine revealed that AEGL values for a theoretical excess lifetime 10 4 carcinogenic risk exceeded the AEGL-2 values that were based on noncancer endpoints. Because the risk for dimethylhydrazine exposure was estimated from nonverified sources and because AEGLs are applicable to rare events or single once-in-a-lifetime expo... 

Cigarette smoking is responsible for about 80% of lung cancer cases. Other risk factors include exposure to respiratory carcinogens (e.g., asbestos, benzene), genetic risk factors, and history of other lung diseases (e.g., tuberculosis, pulmonary fibrosis). 

Most chemical carcinogens have been identified from epidemiological studies, for which incidence of cancer is linked to a particular occupation or lifestyle (Table 21.6). Such studies are enormously beneficial, because identification of a risk factor can lead to changes in behaviour which decrease the incidence of cancer. This is illustrated by a quotation from Roy Porter s book. Greatest Benefit to Mankind (1999) ... 

In order to account for differences in metabolic rates between experimental animals and humans, a surface area to body weight correction (Section 5.3.2.2) is sometimes applied to quantitative estimates of cancer risk derived by low-dose extrapolation. The WHO stated that incorporation of this factor increases the risk by approximately one order of magnitude, depending on the species upon which the estimate is based, and increases the risk estimated on the basis of studies in mice relative to that in rats. The WHO considered incorporation of this factor to be overly conservative, particularly in view of the fact that linear extrapolation more likely overestimates risk at low doses. Therefore, the guideline values for carcinogens were developed on the basis of quantitative estimates of risk that were not corrected for the ratio of surface area to body weight. 

For carcinogens, the risk is expressed in terms of increased risk of developing a cancer (e.g., 1 in 106). This is calculated from the cancer slope factor and the 70-year average daily intake in mg/kg/day. 

Siematycki, J., ed. (1991) Risk Factors for Cancer in the Workplace, Boca Raton, FL, CRC Press Simmon, V.F. (1979) In vitro assays for recombinogenic activity of chemical carcinogens and related compounds with Saccharomyces cerevisiae D3. J. natl Cancer Inst., 62,... 

An increased incidence of cancer of the paranasal sinuses was observed in workers at factories where isopropanol was manufactured by the strong-acid process. The risk for laryngeal cancer may also have been elevated in these workers. It is unclear whether the cancer risk was due to the presence of diisopropyl sulfate, which is an intermediate in the process, to isopropyl oils, which are formed as by-products, or to other factors, such as sulfuric acid. Epidemiological data concerning the manufacture of isopropanol by the weak-acid process are insufficient for an evaluation of carcinogenicity (lARC, 1987). 

Based on the evidence reviewed above, EPA has concluded that BCME is a known human carcinogen (EPA Group A). Employing the data of Kuschner et al. (1975), EPA (1988) has calculated an upper bound cancer potency factor (q ) of 220 (mg/kg/day)1. Assuming that a 70-kg adult inhales 20 m3/day, the concentrations of BCME associated with upper bound human risk levels of 10 4, 10 5, 10 6 and 10"7 are 3.4 x 10"7, 3.4 x 10"8, 3.4 x 10 9 and 3.4 x 10 10 ppm, respectively. These values, and doses which have been observed to cause cancer, are plotted in Figure 2-1. 

Cancer slope factors are upper bounds, approximating a 95% confidence limit, on the increased cancer risk posed by a lifetime exposure to a carcinogen (EPA 2006). 

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