Carcinogens characterization

In the first step of the evaluation, the available data are evaluated to determine the likelihood that the agent is a human carcinogen. The evidence is characterized separately for human studies and animal studies as sufficient. 

Second Generation Second generation SERMs were developed with the objective of obtaining ER-targeted pharmaceuticals that lacked the utero-trophic and carcinogenic effects of tamoxifen. The most well characterized second generation SERM is... 

Hepatic peroxisome proliferation, characterized by liver enlargement due to hyperplasia and hypertrophy, has been proposed as a basis for differences in species susceptibility to trichloroethylene carcinogenicity. Peroxisomes are membrane-bound organelles which contain enzymes generally involved in lipid metabolism. 

The pyrrolizidines and indolizidines are a group of alkaloids that are characterized by the presence of the basic azabicyclo[3.3.0]octane and azabicyclo[4.3.0]nonane frameworks, respectively. These alkaloids exhibit remarkably diverse types of biological activity and have been reported to act as antitumor, hypotensive, anti-inflammatory, carcinogenic, or hepatoxic agents. Various pyrrolizidines and indolizidines have been prepared by 1,3-dipolar cycloaddition.115 Synthesis of these is described in the section 8.2 discussing cycloaddition. 

The well characterized reactions of carcinogens such as benzols] pyrene and aflatoxin B with DNA (39-50) suggested to us that an analysis of the kinds of mutations these agents induced could shed light on the contribution of specific DNA lesions to mutagenesis. 

Fabacher, D.L., J.M. Besser, C.J. Schmitt, J.C. Harshbarger, P.H. Peterman, and J.A. Lebo. 1991. Contaminated sediments from tributaries of the Great Lakes chemical characterization and carcinogenic effects in medaka (Oryzias latipes). Arch. Environ. Contam. Toxicol. 20 17-34. 

Category C (possible human carcinogen) was evidenced by a dose-related increase in the incidence of leiomyosarcomas in the urinary bladder, a significant dose-related trend for combined hepatocellular adenomas and carcinomas in males, and a significantly higher incidence of combined lung adenomas and carcinomas in females. For the purpose of risk characterization, the RfD approach should be used for quantification of human cancer risk. The chronic exposure analysis revealed <100% RfD, and it is assumed that the chronic dietary endpoint is protective for cancer dietary exposure [64]. 

Metofluthrin (I) The committee determined that the new data were sufficient to support a mitogenic mode of action for the development of liver tumors in rats exposed to metofluthrin in the carcinogenicity study. The report summarized mode of action study data that characterized effects such as increased P450 enzyme levels, increased smooth endoplasmic reticulum, hepatocellular hypertrophy, hepatocellular proliferation, and inhibition of intracellular communication, which were described as steps leading to tumor development via a nongenotoxic mechanism (i.e., mitogenicity). Some of these studies used sodium phenobarbital as a positive control,... 

Cancer is a condition characterized by the uncontrolled replication and growth of the body s own cells (somatic cells). Carcinogenic agents may be categorized as follows ... 

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