Cancer Animals

Industries that burn wood, gas, oil or coal contribute most of the rest of airborne B(a)P. Studies on animals have shown that contact with BaP and PAH can cause skin cancer, but the effects of breathing or ingesting them are not yet well enough studied to draw a conclusion as to other cancers. Animal tests have shown that exposure to BaP may cause reproduction difficulty. The U.S. government considers BaP a human carcinogen. 

Hawrylewicz, E.J., Zapata, J.J. and Blair, W.H. (1995). Soy and experimental cancer animal studies, J. Nutr., 125, 698S-708S. 

T (with its contaminant TCDD), might increase their risk of adverse health effects, particularly various forms of cancer. Animal studies do not support the notion that 2,4,5-T itself is carcinogenic. Chronic feeding studies in rats did not produce an increased mmor incidence, even at doses of 30mg/l /day, which produced toxic effects. The lARC has determined that there is inadequate evidence for carcinogenicity of 2,4,5-T in animals and that... 

In addition to in vivo studies in models of CML, BMS-354825 has also been studied in models of solid tumors. BMS-354825 was efficacious in head and neck squamous cell carcinoma and non-small cell lung cancer animal models [151]. Based on this activity, BMS-354825 has been advanced into clinical trials for the treatment of solid tumors. 

Chromium and cancer Several studies have shown that chrominm (VI) compounds can increase the risk of lung cancer. Animal studies have also shown an increased risk of cancer. The WHO has determined that chromium (VI) is a human carcinogen. The DHHS has observed that certain chromium (VI) compounds are known to cause cancer in humans. The U.S. EPA has reported that chrominm (VI) in air is a human carcinogen. ... 

Morroquin et al. [44] studied the effect of high-dose IL-2 therapy in the treatment of patients with metastatic melanoma and renal cell cancer. Animal models have shown that successful treatment with IL-2 is dose and schedule dependent. They found that there was a subset of patients who could not tolerate high doses or retreatment due to renal toxicity. Pretreatment factors that were significantly associated with renal toxicity were male sex, diagnosis of renal cancer, previous nephrectomy, and older age. These patients also had higher baseline creatinine. 

Certain chemicals are known to cause skin cancer. Animal studies show that topical applications of substances, such as polynuclear aromatic hydrocarbons, can induce skin cancer. Coal tar, soots, shale oils, and many arsenical compounds can induce skin tumor. 

Hard metal lung disease (Co + tungsten carbide) Occupational lung cancer (animal data)... 

Kawakami, K., Kawakami, M., and Puri, R.K. (2004). Nitric oxide accelerates interleukin-13 cy totoxin-mediated regression in head and neck cancer animal model. Clin. Cancer Res. 70(15), 5264-5270. 

Saccharin. Sacchatin [81-07-2] C H NO S, which is approximately 300 times as sweet as sucrose ia coaceatratioas up to the equivaleat of a 10% sucrose solutioa, has beea used commercially as a nonnutritive sweeteaer siace before 1900, predomiaanfly ia carboaated soft drioks, tabletop sweeteaers, and dietetic foods marketed primarily to diabetics. In 1977, the FDA proposed a ban on sacchatin because of its association with bladder cancer ia laboratory animals. At the time, it was the only commercially available nonnutritive sweetener, and pubflc outcry led to a delay of the ban, which was officially withdrawn ia 1991. Instead, the FDA required that warning labels be placed on all foods that contained the iagredient. Although sacchatin is heat stable, the pubflc debate over its safety, as well as the fact that approximately one-third of the population perceives it to have a bitter aftertaste, has limited its use. 

Other Sweeteners. Two other sweeteners, sucralose and cyclamates, are approved for use outside of the United States. Sucralose, a chlorinated derivative of sucrose which is 500—600 times as sweet as sugar, has received limited approval in Canada, and petitions for its approval are pending in the United States and Europe (71). Cyclamate sweeteners, once available in the United States, but now baimed because they caused bladder cancer in animals, are stiU available in Canada and Europe. Table 7 gives several examples of nonnutritive sweeteners that have been developed. 

A toxic component of braken fern, perhaps either quercetin (105) or ptaquiloside, a glucoside (106), has a mixed history of carcinogenicity. It is sometimes impHcated in an increased incidence of bladder cancer in animals and esophageal cancer in humans. Multiple other dietary components seem to either promote or interfere with its action, and the significance of braken fern in human carcinogenesis remains unproven. 

Urethane [51-79-6] (ethyl carbamate) occurs as a natural by-product in fermented products such as wine, Hquors, yogurt, beer, bread, oHves, cheeses, and soy sauces. Whereas urethane has a known cancer etiology in experimental animals, no such relationship has yet been proven in humans (108,109). Alcohol may act by blocking the metaboHsm of urethane, and thus exert a protective effect in humans consuming alcohoHc beverages (110). 

Epidemiologic studies in Japan indicate an increased risk of stomach cancer owing to consumption of broiled fish and meats (116). In the United States, stomach cancer incidence has steadily declined since the 1940s, whereas consumption of broiled food has increased (108). In addition, the average human intake of PAHs is only 0.002 of that required to produce cancer in half of animals fed. Test results are often contradictory (117) and many components of food, such as vitamin A, unsaturated fatty acids, thiols, nitrites, and even saUva itself, tend to inhibit the mutagenic activity of PAHs (118—120). Therefore, the significance of PAHs in the human diet remains unknown (121,109). 

Formaldehyde is classified as a probable human carcinogen by the International Agency for Research on Cancer (lARC) and as a suspected human carcinogen by the American Conference of Governmental Industrial Hygienists (ACGIH). This is based on limited human evidence and on sufficient evidence in experimental animals (136). Lifetime inhalation studies with rodents have shown nasal cancer at formaldehyde concentrations that overwhelmed cellular defense mechanisms, ie, 6 to 15 ppm. No nasal cancer was seen at 2 ppm or lower levels (137). 

Eadier reports of a link between testicular cancer and DMF exposure have not been corroborated ia a study of 4000 Du Pont employees (34). Very recendy, inhalation studies ia mice and rats have shown no oncogenic effect from DMF (35). The International Agency for Research on Cancer (lARC) has concluded that evidence associating DMF with cancer ia animals is "iaadequate," but has classified DMF as "possibly carciaogenic to humans" (Group 2B) (36). 

In experimental animals and in vitro, DHBs show a variety of biological effects including binding of metaboHtes to various proteins. Clastogenic effects have been observed in vitro and in some in vivo studies with the three compounds. No reproductive effects have been shown by conventional studies with either hydroquinone, catechol, or resorcinol (122). Hydroquinone has been shown to induce nephrotoxicity and kidney tumors at very high doses in some strains of rat (123) catechol induces glandular stomach tumors at very high dose (124). Repeated dermal appHcation of resorcinol did not induce cancer formation (125). 

Molybdenum, recognized as an essential trace element for plants, animals, and most bacteria, is present in a variety of metaHo enzymes (44—46). Indeed, the absence of Mo, and in particular its co-factor, in humans leads to severe debility or early death (47,48). Molybdenum in the diet has been impHcated as having a role in lowering the incidence of dental caries and in the prevention of certain cancers (49,50). To aid the growth of plants. Mo has been used as a fertilizer and as a coating for legume seeds (51,52) (see FERTILIZERS Mineral NUTRIENTS). 

A comprehensive study of the tolerance of laboratory animals to vapors of 2-nitropropane was reported in 1952 (100). In a study pubHshed in 1979, rabbits and rats survived exposure to nitromethane for six months at 750 and 100 ppm, respectively, with no unexpected findings (101). Similarly, no compound-related effects were found for rabbits exposed to 2-nitropropane at 200 ppm or for rabbits or rats exposed at 27 ppm. Liver damage was extensive in male rats exposed at 207 ppm for six months, and hepatocellular carcinomas were observed. Subsequendy, the International Agency for Research on Cancer (lARC) found that there is "sufficient evidence" to conclude that 2-nitropropane causes cancer in rats but that epidemiologic data are inadequate to reinforce the conclusion in humans (102). The National Toxicology Program also concluded that it "may reasonably be anticipated to be a carcinogen" (103). 

Depletion of the Ozone Layer. As a constituent of the atmosphere, ozone forms a protective screen by absorbing radiation of wavelengths between 200 and 300 nm, which can damage DNA and be harmful to life. Consequently, a decrease in the stratospheric ozone concentration results in an increase in the uv radiation reaching the earth s surfaces, thus adversely affecting the climate as well as plant and animal life. Pot example, the incidence of skin cancer is related to the amount of exposure to uv radiation. 

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