Testicular tumors, animals

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. 

Zinc is not carcinogenic however, testicular tumors were induced by direct injection of zinc chloride into the testes of experimental animals (copper chloride produced the same effect). 

Premenopausal use There is no indication for premenopausal use of raloxifene. Hepatic function impairment Raloxifene was studied, as a single dose, in Child-Pugh class A patients with cirrhosis and serum total bilirubin ranging from 0.6 to 2 mg/dL. Plasma raloxifene concentrations were approximately 2.5 times higher than in controls and correlated with total bilirubin concentrations. Safety and efficacy have not been evaluated further in patients with severe hepatic insufficiency. Carcinogenesis In long term carcinogenicity studies in animals there was an increased incidence of ovarian tumors, testicular interstitial cell tumors, and prostatic adenocarcinomas. 

The vasoconstriction, which is caused by cadmium, may underlie the hypertension observed in experimental animals. Cadmium is also carcinogenic in experimental animals, causing tumors at the site of exposure. Also, Leydig cell tumors occur in the testis of animals after acute doses of cadmium sufficient to cause testicular necrosis. This seems to be an indirect effect due to the reduced level of testosterone in the blood, which follows testicular damage. This causes Leydig cell hyperplasia and tumors to occur. 

The numbers of males with testicular Leydig cell tumors was increased in animals exposed to 5.2 mg/kg/day triphenyltin hydroxide for 104 weeks (16.7% as opposed to 1.7% in the controls). 

In the studies of long-term exposure of rats to both triphenyltin hydroxide and bis(tributyltin)oxide, most of the tumors were found in endocrine glands. In addition to the pituitary adenomas associated with bis(tributyltin)oxide and triphenyltin hydroxide, there was also an increased incidence of pheochromocytomas of the adrenal gland, parathyroid carcinomas and pancreatic adenocarcinomas in animals from at least one sex. Triphenyltin hydroxide was associated with an increased incidence of testicular Leydig cell tumors in male rats at the highest dose. Hepatic tumors were found in male and female mice following 80 weeks of triphenyltin hydroxide administration. 

Accutane is a potent rat and rabbit developmental toxin (teratogen). Testicular atrophy and evidence of lower spermatogenesis was noted in dogs given isotretinoin for 30 weeks at 20 or 60 mg kg day Fischer 344 rats dosed at 8 or 32 mg kg day for over 18 months had a dose-related raised incidence of pheochromocytoma, an adrenal gland tumor. The relevance in man is unknown since this animal develops spontaneous pheochromocytoma at a significant rate. 

Early animal studies demonstrated reduced testicular weights, with testicular atrophy at higher exposure levels. Several studies reported decreased sperm count and infertility with long-term exposure to DBCP. It is an experimental carcinogen, capable of increasing tumor incidence in a variety of tissues. 

Repeated exposures to APFO, the most widely used salt of PFOA, produced liver, kidney, pancreas and testes changes, anemia, and cyanosis. Tests in male rats demonstrated weak tumorigenic activity based on an increased incidence of benign testicular, pancreatic, and liver tumors. Tests in animals demonstrate no developmental toxicity. 

Embryonic exposure to vinclozolin, an antiandrogenic endocrine disruptor, has been shown to promote prostate disease, kidney disease, immune system abnormalities, testicular abnormalities, breast and other tumor development, and a number of blood abnormalities in the F1-F4 generations of laboratory animals. I8,91 The effects observed were noted in the adults of the four ensuing generations that followed the exposure. 

Zinc and its compounds induce testicular sarcomas in birds and rodents when injected directly into the testes however, zinc is not carcinogenic by any other route. Growth of animal tumors is stimulated by zinc, and retarded by zinc deficiency. Under some conditions excess zinc can suppress carcinoma growth, although the mechanisms are imperfectly understood. Organozinc compounds are effective mutagens when presented to susceptible cell populations in an appropriate form the... 

In fact cis-DDP is active against a wide range of tumors in animals (4) and man (5) including several which are particularly resistant to treatment by other techniques such as ovarian and testicular carcinomas. 

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