Renal neoplasms

There may be similar incidences of tumors in aging people, but the real prevalence of tumors in human populations is uncertain. In the United States, where autopsies are uncommon, over one-third reveal previously undiagnosed cancers when they are conducted (Silverberg, 1984). A single type of neoplasm, renal adenoma, is present in 15-20% of all adult kidneys (Holm-Nielson and Olsen,... 

The uses of the copper chelator ammonium tetrathiomolybdate have been reviewed apart firom Wilson s disease, they include fibrotic diseases, idiopathic pulmonary fibrosis, primary biliary cirrhosis, neoplasms (renal and prostate carcinoma, mesothelioma), macular degeneration, and Alzheimer s disease [36 ]. In most of these indications experience with the use of ammonium tetrathiomolybdate is still limited. 

Neoplasm (e.g., renal cell carcinoma and Wilms tumor)... 

NTP determined that there was clear evidence of carcinogenicity in male rats based on the increased incidence of renal neoplasms and no evidence of carcinogenic activity in female rats (NTP 1989). The EPA classified hexachloroethane as a possible human carcinogen (Group C). The slope factor calculated by EPA is 1.4xl0 2 (mg/kg/day) 1 for both the oral and inhalation routes of exposure (IRIS 1995). IARC has determined that hexachloroethane is not classifiable as to human carcinogenicity (Group 3). 

In 2-year dermal studies there was no evidence of carcinogenicity in rats but there was clear evidence of carcinogenicity in mice based on increased incidences of liver neoplasms in males and females and increased incidences of renal tubule neoplasms in males. It has also been noted that in the presence of N-nitrosating agents, DEA may give rise to 7VN-nitrosodiethanolamine, a known animal carcinogen. The lARC has determined that there is limited evidence for the carcinogenicity of diethanolamine in experimental animals and inadequate evidence in humans. ... 

In chronic inhalation studies rats and mice were exposed to 0, 75, 250, or 750ppm 6 hours/day, 5 days/week for 104 weeks. Eor male rats exposed at 750 ppm survival was decreased, and the incidence of renal tubule neoplasms and testicular adenomas was increased. The findings from an extended evaluation of the kidneys showed a significant increase in the incidences of renal tubule adenoma and hyperplasia in high-dose males and females. In high-dose mice there were increased incidences of alveolar/bronchiolar neoplasms in males, whereas females had... 

Large gavage doses, approximately 500 and lOOOmg/kg per day for 78 weeks, caused a statistically significant increase in the incidence of hepatocellular carcinomas in mice. Inhalation exposure by rats to 200 or 400 ppm for 2 years caused an increased incidence of mononuclear cell leukemia a dose-related trend for a rare renal tubular neoplasm was observed in males. ... 

In 2-year inhalation studies (0, 200, 600 or 1800 ppm) there was some evidence of carcinogenicity in male rats based on increased incidences of renal tubule adenoma or carcinoma and clear evidence of carcinogenicity in female mice based on increased incidences of hepatocellular neoplasms."... 

Studies in rats reported renal tubular adenomas and adenocarcinomas in male and female animals at doses of 20 mg/kg/day (Kociba et al. 1977a). Metastasis to the lungs was observed. Combined incidences of renal tubular neoplasms in males (9/39, 23%) and in females (6/40, 15%) increased (p <0.05) over controls (males-1/90, females-0/90, 0%). The tumor incidence was not increased in the 0.2 and 2 mg/kg/day dose groups but there were some indications of hyperplasia in animals exposed to 2 m /kg/day. The EPA (1990f) evaluated these data and calculated a human potency factor of 7.8x10 (mg/kg/day) (qi ), representing 95% upper confidence limit of extra lifetime human risk. Based on this value, cancer risk levels of 10, 10, and 10 correspond to exposures of 0.001, 0.0001, 0.00001 mg/kg/day. 

A group of 60 female Wistar rats, 15 weeks of age, received two subcutaneous injections of 120 mg/kg bw 1,2-dimethylhydrazine (calculated as base) at 10-day intervals. Twenty-three animals were killed 30 weeks after the first injection. Thirteen of 23 animals exhibited tumours of the colon and one a tumour of the small intestine. Twenty-one (91%) of 23 rats developed renal tumours in 10 rats, they were bilateral and in six rats, there was more than one tumour per affected kidney. All neoplasms were diagnosed as mesenchymal kidney tumours (Sunter Senior, 1983). 

---