Kidney renal tumors, rats

The carcinogenic potential of hexachloroethane has not been evaluated following chronic inhalation or dermal exposure. Hexachloroethane increased the incidence of renal tumors in male rats (NTP 1989) following chronic oral exposure. However, these tumors were associated with renal hyaline droplets and, thus, are unique to male rats. Although kidney damage was present in female rats after lifetime exposures to 80 and 160 ppm hexachloroethane, there was no increase in renal tumors. Liver lesions and liver tumors were found in mice following long-term oral exposure (NTP 1977). 

In studies conducted using animals, evidence of carcinogenicity from 1,4-dichlorobenzene exposure is based on 2-year oral studies in mice and rats. 1,4-Dichlorobenzene was administered by gavage to male rats at doses of 150 mg/kg/day and 300 mg/kg/day, and to female rats and mice of both sexes at doses of 300 mg/kg/day and 600 mg/kg/day. There was a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidneys of male rats. There were no tubular cell tumors in dosed or vehicle-control female rats. There was a marginal increase in the incidence of mononuclear cell leukemia in dosed male rats compared with either vehicle controls or historical controls (NTP 1987). Based on the finding of renal tumors in this study, 1,4-dichlorobenzene was found to be carcinogenic in male rats. 

Further analysis of the results of the NTP (1987) bioassay has raised certain questions as to the relevance of the observed renal tumors in male rats and hepatic tumors in mice to the potential carcinogenicity of 1,4-dichlorobenzene in humans. The observation that kidney tumors are induced in male but not female rats in response to exposure to chemicals in addition to 1,4-dichlorobenzene has been the focus of recent... 

DMN is clearly carcinogenic, producing tumors in a number of animal species at relatively low doses. Swiss mice fed a diet containing 0.005% DMN for 1 week developed tumors of the kidney and lung. Hamsters fed a diet containing 0.0025% for 11 weeks developed liver tumors. A consistent observation after oral administration of DMN in rats has been that long-term treatment with doses compatible with a favorable survival rate leads to liver tumors, whereas short-term treatment with high doses produces renal tumors. ... 

At 2 years, adrenal medulla tumors occurred with positive trends in male rats, and the incidences in the 550 and 1100mgm groups were significantly increased. Also, a slightly increased incidence of renal adenomas occurred in the 1100mgm group. Non-neoplastic lesions related to Stoddard Solvent exposure occurred in the kidney of male rats. 

Although chronic exposure to MeHg increased the incidence of renal tumors in male mice in some studies, that effect was observed only at doses that were toxic to the kidneys and is thought to be secondary to cell damage and repair. Exposure to MeHg did not increase tumor rates in female mice or in rats of either sex. 

Streptozotocin Nicotinamide Rat Kidney Renal cell tumor 4. = Rakieten, 1971 ... 

Nicotinamide Rat Kidney Renal tubular cell tumor t Rosenberg, 1985 ... 

Male Sprague-Dawley rats were administered lead acetate equivalent to 37 mg lead/kg/day in their drinking water for 76 weeks as part of a study to determine interactions between sodium nitrite, ethyl urea, and lead. There were no kidney tumors in the 10 control rats. Renal tubular carcinomas were found in 13 (81%) of the 16 treated rats. Three of these tumors were detected at 72 weeks and the remaining were found at terminal necropsy (Roller et al. 1985). 

The lead-induced nephropathy observed in humans and rodents shows a comparable early pathology (Goyer 1993). However, in rodents, proximal tubular cell injury induced by lead can progress to adenocarcinomas of the kidney (see Section 2.2.3.8). The observation of lead-induced kidney tumors in rats may not be relevant to humans. Conclusive evidence for lead-induced renal cancers (or any other type of cancer) in humans is lacking, even in populations in which chronic lead nephropathy is evident. 

Based on a combination of available human case studies and experiments with laboratory animals, the major public health concerns associated with exposure to 1,4-dichlorobenzene are effects on the liver, kidneys, and blood. Some immunological, dermatological, and neurological effects have also been reported in exposed humans. There is information from animal studies which raises the question of whether 1,4-dichlorobenzene can cross the placenta and elicit structural effects on the developing fetus. Data from a study conducted in rats using the intraperitoneal route have demonstrated sperm abnormalities. Cancer of the liver as a result of lifetime exposure to 1,4-dichlorobenzene has been shown in mice, and renal cancer has been reported in male rats. However, recent studies related to the mechanism of renal carcinogenesis in rats suggest that these tumors may not be expected to occur in exposed humans. Issues relevant to children are explicitly discussed in Section 2.6, Children s Susceptibility, and Section 5.6, Exposures of Children. 

Chronic oral smdies in mice and rats show clear evidence that bromodichloromethane is carcinogenic. Male mice administered 50 mg/ kg/day by gavage 5 days/week for 2 years had an increased incidence of renal carcinoma hepatic tumors were observed in female mice similarly dosed with 75 or 150 mg/kg/day. Tumors of the large intestine (intestinal carcinoma) occurred in rats at incidences of 13/50 and 45/50 in males exposed to 50 or lOOmg/ kg/day, 5 days/week for 2 years, respectively 12 of 47 females were affected at the higher dose. Kidney tumors were observed in both male and female rats exposed to 100 mg/kg/day,... 

The principal effects of carbon tetrachloride in humans are on the liver, the kidneys and the central nervous system. These effects are apparent following either oral or inhalation exposure, and limited data indicate they can occur after dermal exposure as well. All of the effects seen in humans except renal injury are demonstrable at roughly comparable exposure levels in animals, although there are some variations in susceptibility between species that are likely to be related to differences in metabolism. No studies were located regarding reproductive and developmental effects in humans after exposure to carbon tetrachloride. In rats, carbon tetrachloride was not shown to adversely affect reproduction or development. Studies with both mice and rats suggest that sufficiently high doses of carbon tetrachloride may increase the risk of liver tumors in exposed humans. 

Antitoxic effect. Sesame oil, adiministered to male Wistar rats, ameliorated hepatic and renal damage in a dose-dependent manner and increased survival in lipopolysaccha-ride-treated rats. It decreased lipid peroxide concentration in serum but not in liver and kidney. Serum nitrite production was unaffected by sesame oil ingestion, and the activity of xanthine oxidase was reduced in the lipopolysaccharide-challenged rats k Anti-tumor activity. Water extract of the dried seed, administered intragastrically to mice at a dose of 50 mg/animal daily for 5 days, was active on CA-Ehrlich-ascites, 18% increase in life-span. Intraperitoneal administration was active on Dalton s lyphoma and CA-Ehrlich-ascites, 19 and 39% increase in life-span, respectively ". Seed oil, administered to rats intraperito-neally with 1,2,5,6-dibenzanthracene or re-tene, was active on sarcoma ". 

In the chronic gavage study by NTP (1986), dosed male rats had increased incidences of renal tubular cell hyperplasia, epithelial cell hyperplasia of the renal pelvis, and tubular mineralization. The male rats also had increased incidences of renal tubular cell tumors. The hyperplasia of the tubular cells, therefore, may represent a preneoplastic response (see discussion of cancer below). These proliferative kidney lesions were not observed in male or female mice or in female rats. The mechanism for the induction of proliferative kidney lesions may also be related to a2p-globulin-induced nephropathy (see discussion of cancer below), again raising the question of the relevance of the proliferative kidney lesions in male rats to humans. This issue is presently the subject of scientific investigation. 

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