Hepatocellular neoplasms

Lungarella et al. 1984). In a chronic-duration study in B6C3F, mice where exposure was to commercial hexane (51.5% M-hexanc) for 6 hours/day, 5 days a week for 2 years, a statistically significant treatment-related increase in hepatocellular neoplasms (adenoma and carcinoma) was observed among females exposed at 9,018 ppm (Bio/Dynamics 1995b), but not at 900 or 3,000 ppm. No increases were observed in male mice or in Fischer 344 rats of either sex exposed similarly in a parallel experiment (Bio/Dynamics 1995a). 

Dietary administration of heptachlor (97.6% purity) at 0.65 or 1.3 mg/kg/day for 25 weeks promoted the development of hepatocellular foci and hepatocellular neoplasms in male B6C3F i mice previously initiated with 3.8 mg/kg/day diethyinitrosamine in drinking water for 14 weeks (Williams and Numoto 1984). These results indicate that heptachlor acts as a liver tumor promoter in male mice. 

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). ... 

Male rats dermally administered 300 pi, 5 days/week for 4 weeks had increased relative liver and kidney weights. There was no evidence of carcinogenic activity in male or female rats receiving up to 300pl/day, 5 days/week for 2 years. Equivocal evidence of carcinogenicity was seen in mice receiving up to 30pl/day for 103 weeks based on increased incidences of hepatocellular neoplasms. ... 

In 2-year studies rats were given 0, 25, or 50mg/kg hydroquinone by gavage 5 days/ week whereas doses for mice were 0, 50, or lOOmg/kg on the same schedule. There was evidence of carcinogenicity in male rats as indicated by increased incidences of tubular cell adenomas of the kidney, in female rats as shown by increases in mononuclear cell leukemia, and in female mice based on increases in hepatocellular neoplasms, mainly adenomas. There was no evidence of carcinogenicity in male mice. 

A 2-year gavage study at 250 and 500 mg/ kg demonstrated a dose-related statistically significant excess of tubular cell adenomas and adenocarcinomas of the kidney in male rats, a number of preputial gland tumors in dosed male rats, and a probable increased incidence of hepatocellular neoplasms in high-dose male... 

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. °... 

There was equivocal evidence of carcinogenic activity in male and female mice based on increased incidences of hemangiosarcoma, carcinoma of the intestine (cecum), and hepatocellular neoplasms (females only). There was equivocal evidence of carcinogenic activity of p-nitrotoluene in male rats based on increased incidences of subcutaneous skin neoplasms, and there was some evidence of carcinogenic activity in females based on increased incidences of clitoral gland neoplasms. There was equivocal evidence of carcinogenic activity in male mice based on increased incidences of alveolar/bronchiolar neoplasms, and there was no evidence of carcinogenic activity in female mice exposed to 1250, 2500, or 5000 ppm in the diet. 

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."... 

In male and female rats exposed to 10, 50, 250, or 12 50 ppm vinyl bromide in a lifetime inhalation study, there was a dose-related increase in angiosarcomas of the liver in both sexes. A significant increase in hepatocellular neoplasms was also seen in male rats exposed at 250ppm and in female rats exposed at 10, 50, and 250ppm. The lack of increase in hepatocellular neoplasms in rats at the 12 50 ppm level was probably due to their early mortality and termination at 72 weeks. In limited mice studies, no local tumors were produced by skin application or subcutaneous administration. Vinyl bromide is mutagenic in bacterial assays and Drosophilas It is activated via a P-450-dependent pathway to its epoxide that can covalently bind to DNA. ... 

Cholestatic jaundice, hepatocellular neoplasms, peliosis hepatis, edema with or without congestive heart failure, and suppression of clotting factors II, V, VII, andX have been reported. 

Trichloroethane was tested for carcinogenicity in a two-year study in male and female B6C3F] mice and Osborne-Mendel rats by oral administration and in Sprague-Dawley rats by subcutaneous injection. In the study by oral administration, 1,1,2-trichloroethane produced hepatocellular neoplasms and adrenal phaeochromocytomas in mice of each sex but did not significantly increase the proportion of rats with neoplasms at any site relative to untreated controls. In the study in rats by subcutaneous injection,... 

In a rabbit study, hydroquinone at 150 mg kg day produced minimal developmental alterations in the presence of maternal toxicity. The no-observed-effect level for developmental toxicity was 75mgkg day In rat studies, maternal toxic effects from exposure to hydroquinone included changes in the ovaries, fallopian tubes, and menstrual cycle. Postimplantation mortality was also observed in rat studies. Observed paternal toxic effects from exposure to hydroquinone included changes in the testes, epididymis, sperm duct, prostate, seminal vesicle, Cowper s gland, accessory glands, and male fertility index. Further, exposure to hydroquinone produced skeletal malformations in chickens and ocular and skeletal malformations in rabbits. Hydroquinone can induce renal tubule adenomas, bladder carcinomas, hepatocellular neoplasms, and mononuclear cell leukemia in experimental animals. 

A 2 year drinking water smdy performed in rats and mice showed hepatocellular injury by week 13 and clear evidence of carcinogenic activity in all animals that survived 1 year or longer. Renal tubule neoplasms, mononuclear cell leukemia, hepatocellular neoplasms, and interstitial cell adenoma of the testis were noted. Human... 

Nunez, O., J.D. Hendricks and J.R. Duimstra. Ultrastructure of hepatocellular neoplasms in aflatoxin Bpinitiated rainbow trout. Toxicol. Pathol. 19 11-23, 1991. 

Zatloukal K, Stumptner C, Fuchsbichler A, et al. The keratin cy-toskeleton in liver diseases. The diagnostic value of hepatocyte paraffin antibody 1 in differentiating hepatocellular neoplasms from nonhepatic trrmors a review. J Pathol. 2004 204 367-376. 

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