Liver Tumors in Mice and Rats

Mirex has caused liver tumors in mice and rats and must be considered a potential human carcinogen (Waters et al. 1977 NAS 1978). Long-term feeding of 50 and 100 mg mirex/kg ration to rats of both sexes was associated with liver lesions that included neoplastic nodules and hepatocellular carcinomas neither sign was found in controls (Ulland et al. 1977). 

Mild irritant acute oral toxicity in animals very low oral LD50 value (rats) 7000 mg/kg carcinogenic to animals oral administration caused blood and liver tumors in mice and rats carcinogenicity animal limited evidence, no evidence in humans. 

Mirex has caused liver tumors in mice and rats and must be considered a potential human carcinogen. Long-term feeding of 50.0 and... 

Trichloroethylene exhibited evidence of carcinogenicity in laboratory animals. Oral administration produced liver tumors, while inhalation caused lung and blood tumors in mice and rats. 

The best evidence that MC causes cancer is from laboratory studies in which rats, mice and hamsters inhaled MC 6 hours per day, 5 days per week for 2 years. MC exposure produced lung and liver tumors in mice and mammary tumors in rats. No carcinogenic effects of MC were found in hamsters. 

Cancer. No studies have been conducted in human populations to determine whether mirex or chlordecone causes cancer. However, studies in mice and rats have demonstrated the ability of mirex to cause liver tumors (Innes et al. 1969 NTP 1990 Ulland et al. 1977a), pheochromocytomas (NTP 1990), and rare renal tumors (NTP 1990). A study in mice and rats also showed the ability of chlordecone to increase liver tumors (NC11976). As indicated above, available data on the genotoxicity of mirex and chlordecone indicate that these chemicals do not cause cancer by a mutagenic mechanism but rather by tumor promotion. Both mirex and chlordecone are considered by the DHHS to be substances that may reasonably be anticipated to be carcinogens and by IARC to be possible human carcinogens. EPA has not classified mirex or chlordecone as to their carcinogenicity. 

All PCB mixmres adequately tested in mice and rats have shown carcinogenic activity. For example, of 20 rats fed Aroclor 1242 at 100 ppm in the diet for 24 months, 11 developed liver tumors, of which 3 were hepatomas. A significant incidence of hepatocellular neoplasms was found in female rats but not males in another smdy of Arochlor 1242 in the diet. Evidence from bioassays suggests that the less highly chlorinated PCBs (e.g., Aroclor 1242) have less carcinogenic potential than the more highly chlorinated mixtures (e.g., Aroclor 1254). ... 

Cancer. 2,3-Benzofuran is carcinogenic to rats and mice (NTP 1989). Chronic oral exposure increased the incidence of kidney tumors in female rats, and increased the incidence of lung, forestomach, and liver tumors in male and female mice (NTP 1989). These findings indicate that chronic exposure to... 

Effects in offspring of rats exposed to 0.5 mg/kg/day FireMaster FF-1 for 60 days before breeding until 8 weeks postpartum (4 weeks postweaning) and observed for up to the following 2 years included vacuolization and altered foci in the liver (Chhabra et al. 1993 NTP 1992). Pups of mice that were similarly perinatally exposed to 1.5 mg/kg/day FireMaster FF-1 developed liver cytomegaly and altered foci (Chhabra et al. 1993 NTP 1992). As discussed in Section 3.2.2.8 (Carcinogenic Effects), these mice also developed hepatocellular adenoma and carcinoma combined perinatal and adult exposme induced higher incidences of liver tumors in mice than adult exposure alone (Chhabra et al. 1993 NTP 1992). 

The toxicity of eugenol was tested in mice and rats by oral administration of a diet containing a high dose of eugenol. There was a significant increase in the incidence of liver tumors in female mice. The incidence increase in males was significant only for those receiving lower doses. There was no increase incidence of tumors observed in rats. 

A number of the chemicals administered were found to induce cancer in rats and mice. Some chemicals, particularly agricultural products, were negative in the rat models but induced liver tumors in mice. With either type of response, a chemical that induced cancer in any test was labeled a carcinogen, and by extrapolation was considered to be a human cancer risk without questioning its relevance or the imderlying mechanism. 

Results of chronic MTBE exposure studies are the most widely available of all studies on the ether-like fuel oxygenates (MTBE, ETBE, TAME, DIPE). Evidence from animal bioassays demonstrates that long-term, high-level exposures to MTBE by either ingestion or inhalation cause cancer in rodents. Inhalation exposure to MTBE produced an increased incidence of renal and testicular tumors in male rats and liver tumors in mice. Oral administration of MTBE produced an increased incidence of lymphomas and leukemias in female rats and testicular tumors in male rats. Chronic exposure to ethanol also produces cancers (e.g., esophageal) in laboratory animals. 

There is sufficient evidence of carcinogenicity in animals. Repeated dietary administration has produced liver cell tumors in mice and bile duct and liver tumors in rats. Cirrhosis has also been observed in both rats and mice. Thioacetamide is a developmental toxin. 

RDX can cause seizures (a problem of the nervous system) in humans and animals when large amounts are inhaled or eaten. We do not know the effects of long-term, low-level exposure on the nervous system. No other significant health effects have been seen in humans. Rats and mice have had decreased body weights and slight liver and kidney damage from eating RDX for 3 months or more. We do not know if RDX causes cancer in people, but it did cause liver tumors in mice. We do... 

Low incidences of renal tubular cell adenomas or adenocarcinomas (1/49, 3/49,4/50) occurred in male rats (NTP 1986). Although the incidence of these tumors was not statistieally signifieant, the fact that there was any increase was itself significant because these tumors are considered uncommon in untreated male rats. In mice of both sexes exposed to 100 or 200 ppm, there were significantly increased incidences of hepatocellular neoplasms (Table 2-2). Study limitations include numerous instances of rats and mice loose from their cages within the exposure chambers, with the potential for aberrations in exposure and animal identification, as well as a very high incidence of mononuclear cell leukemia in control rats, and liver tumors in mice. 

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