Tumors carcinogen statistics

D-Phenothrin (I) Not likely to be carcinogenic to humans. Rat liver tumors occurred only at excessively toxic doses (limit dose) and mouse hepatocellular adenomas, which are common, did not achieve statistical significance (p < 0.01). Additionally, acceptable mutagenicity studies were negative for mutagenic potential [97] No tumorigenicity was observed [11]. 

Irrespective of the specific protocols used, all carcinogenicity studies end with a statistical comparison of tumor proportions between treated and control groups. This analysis is necessary because the control incidence of most tumor types is rarely zero. In the unlikely case that a type of tumor is found in treated animals but not in concurrent or appropriate historical controls, it is reasonable to conclude that the tumor is drug-related without statistical analysis. 

A method proposed by Schweder and Spjotvoll (1982) is based on a plot of the cumulative distribution of observed p values. Farrar and Crump (1988) have published a statistical procedure designed not only to control the probability of false positive findings, but also to combine the probabilities of a carcinogenic effect across tumor sites, sexes, and species. 

There are three generally accepted criteria for a positive result in a carcinogenicity study. The first two are derived directly from the results of the statistical analysis (1) a statistically significant increase in the incidence of a common tumor and (2) a statistically significant reduction in the time-to-tumor development. The third criterion is the occurrence of very rare tumors, that is, those not normally seen in control animals, even if the incidence is not statistically significant. 

Dinse, G.E. (1985). Estimating Tumor Prevalence, Lethality and Mortality, Presented at the Symposium on Long-Term Animal Carcinogenicity Studies A Statistical Perspective, March 4-6, 1985, Bethesda. 

We shall begin with a little history, and then move to a discussion of cancer statistics and the causes of cancer, and then provide some background on cancer biology and the mechanisms of tumor development. Some of the general characteristics of chemical carcinogens will also be covered. The methods for identifying chemical carcinogens are the subject of Chapter 6. How their risks are estimated is left to later chapters. 

Formaldehyde has been shown to be carcinogenic in two strains of rats, resulting in squamous cell cancers of the nasal cavity after repeated inhalation of about 14 ppm. In one study, 51 of 117 male and 42 of 115 female Fischer 344 rats developed this tumor, but no nasal tumors were seen at 0 or 2 ppm. No other neoplasm was increased significantly. In a similar study of mice, this nasal tumor occurred in two male mice at 14.3 ppm. None of the excesses was statistically significant except for the high-exposure rats. °... 

Chronic oral exposure of rats and mice to MDA and its dihydrochloride is carcinogenic. Treatment-related increases in the incidences of thyroid follicular cell adenomas and hepatocellular neoplasms were observed in mice after chronic ingestion of MDA in drinking water. In rats, increases in the incidences of thyroid follicular cell carcinoma and hepatic nodules were observed in males and thyroid follicular cell ademonas occurred in females. Although not statistically significant, certain uncommon tumors such as bile duct adenomas, papillomas of the urinary bladder, and granulosa cell tumors of the ovary also were reported. These tumors are of low incidence in historical controls. In another report, MDA acted as a promoter of thyroid tumors in rats. °... 

---