Carcinogenic testing for

Genotoxic Effects and Carcinogenicity. Tests for damages of the DNA [3.117] and cell transformation caused by crystalline cadmium sulfide were positive [3.118]. Cadmium sulfide also proved to be carcinogenic by intraperitoneal and after intratracheal administration [3.119]. The significance of such animal studies is being controversially discussed by toxicologists. 

SIB Carcinogenicity Testing for Carcinogenicity of Pharmaceuticals CPMP/ICH/299/95 Step 5... 

A description of the standard approaches in carcinogenicity testing for the safety of chemicals is provided. 

Humans concluded that there was sufficient evidence for the carcinogenicity of soluble calcium chromate and several relatively insoluble hexavalent chromium compounds in laboratory animals. Tumors were mainly induced at the administration site. In addition, experimental exposure to Be, Cd, Ni, and Sb has caused lung tumors in rats, while various beryllium compounds produced osteosarcomas in rabbits by implantation or injection (Hayes 1997). Rossman et al. (2001) could show a co-carcinogenic action of arsenic with solar UV radiation on mouse skin. Apparently strain as well as species differences of the susceptibility to the action of metals may cause variable outcome of carcinogenicity tests for example, in mice this is caused by higher metallo-thionein levels (Oberdorster et al. 1994, Waalkes and Rehm 1994). 

In additional EPA studies, subchronic inhalation was evaluated ia the rat for 4 and 13 weeks, respectively, and no adverse effects other than nasal irritation were noted. In the above-mentioned NTP chronic toxicity study ia mice, no chronic toxic effects other than those resulting from bronchial irritation were noted. There was no treatment-related increase ia tumors ia male mice, but female mice had a slight increase in bronchial tumors. Neither species had an increase in cancer. Naphthalene showed no biological activity in other chemical carcinogen tests, indicating Htde cancer risk (44). No incidents of chronic effects have been reported as a result of industrial exposure to naphthalene (28,41). 

Table 3 Hsts the U.S. producers of methylene chloride and their rated yearly capacities. Since the product mix of a typical chloromethanes process is very flexible, production may be adjusted according to the demand for methylene chloride and chloroform. The demand for methylene chloride has taken a broad downturn as a result of the 1985 NTP carcinogenicity tests (Table 4). The 1988 and 1989 demands were 227,000 t and 216,000 t, respectively, with a forecast 1993 demand of 186,000 t. The historical growth rate (1979—1988) was —2.7% pet year. In the future this should decrease even further to —3 to...

From the detailed studies performed either using individual alcohol sulfates and alcohol ether sulfates or formulated products by oral administration and skin contact, no evidence of carcinogen risk was found. Similar conclusions were obtained when these sulfates or formulated products were tested for mutagenic and teratogenic properties. 

S1A Need for Carcinogenicity Studies of Pharmaceuticais S1B Testing for Carcinogenicity of Pharmaceuticals... 

S1 C(R1) Dose Selection for Carcinogenicity Studies of Pharmaceuticals Limit Dose S2A Guidance on Specific Aspects of Regulatory Genotoxicity Tests for Pharmaceuticals S2B Genotoxicity A Standard Battery for Genotoxicity Testing of Pharmaceuticals Toxicokinetics and Pharmacokinetics... 

Named after its inventor, Bruce Ames, the test has become one of the common screening tests for measuring the potential carcinogenic effects of... 

More recently, the fact that many of the chemical agents whieh eause the induetion of prophage are carcinogenic has led to the use of lysogenie baeteria in sereening tests for deteeting potential carcinogens. 

The related unsaturated compounds, N-nitroso-1,2,3,6-tetra-hydropyridine and N-nitroso-1,2,3,4-tetrahydropyridine, have been tested for carcinogenicity and both were potent esophageal carcinogens, as is nitrosopiperidine. However, N-nitroso-1,2,3,6-tetrahydropyridine also produced liver tumors, whereas N-nitro-so-1,2,3,4-tetrahydropyridine also gave tumors of the forestomach and oropharynx. The difference in tumor spectrum between the two unsaturated isomers may be related to differences in metabolism. N-Nitroso-1,2,3,6-tetrahydropyridine isomerized to N-nitro-so-1,2,3,4-tetrahydropyridine in vivo, but the reverse reaction was not observed (49). 

By a strict definition, these electrical and electronic wastes are hazardous. Fluorescent lamps contain mercury, and almost all fluorescents fail the U.S. Environmental Protection Agency (U.S. EPA) toxicity test for hazardous wastes. Fluorescent lamp ballasts manufactured in the mid-1980s contain polychorinated biphenyls (PCBs), a carcinogen most of these ballasts are still in service. Batteries can contain any of a number of hazardous materials, including cadmium (nickel-cadmium... 

Stoner GD, Shimkin MB, Troxell MC, et al. 1976. Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice. Cancer Res 36 1744-1747. 

In spite of the great effort and advances made on in vitro testing, we are still far to have alternative methods robust enough to cover developmental, neurotoxic, reproductive, or carcinogenic potential for the substances evaluated. However the use of some distinct approaches may cover a great part of the potential toxic effects of some environmental pollutants. 

Results from this preliminary study suggest that a combined approach based on alternative methods could be positively applied to chemical screening in order to reduce the number of animal testing for carcinogenicity studies. 

Arni P. 1985. Induction of various genetic effects in the yeast Saccharomyces cerevisiae strain D7. In Ashby J, de Serres FJ, et al., eds. Progress in mutation research, Vol. 5. Evaluation of short-term tests for carcinogens. Amsterdam, The Netherlands Elsevier Science Publishers, 217-224. 

Progress in mutation research. Vol. 5. Evaluation of short-term tests for carcinogens. Amsterdam,... 

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