Naturally occurring renal neurofibroma in a laboratory beagle.
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Biomedical subjects
Publications and source records attributed to G M Zwicker.
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Primary neoplasms of the kidneys occurred in 11/682 male (1.6%) and 2/694 female (0.3%) Crl:CDBr strain Sprague-Dawley rats. Eight of 13 neoplasms were of mesenchymal origin and 5 of 13 were epithelial. Five neoplasms were lipoma (3) or liposarcoma (2). Three of 13 were either hemangioma (1) or mesenchymal tumors (2). The epithelial neoplasms were carcinomas. There was no microscopic evidence of metastasis among those neoplasms judged malignant on morphologic criteria. The overall natural incidence in males was nearly double that compiled for this strain while in females the incidence was similar to that reported for other females.
Spontaneous primary epithelial neoplasms of the intestinal tract occurred in 6/682 (0.9%) male and 1/694 (0.1%) female Sprague-Dawley rats. Six of 7 neoplasms were adenocarcinomas, and 1 of 7 was an adenoma. Metastasis to the liver or lung occurred in 3 of the rats with adenocarcinoma. These findings are consistent with those reported for female Sprague-Dawley rats and for males and females of other strains over the past 25 years. The intestinal neoplasm incidence in males exceeded that reported for other Sprague-Dawley males with one exception, reported 30 years ago.
A total of 93 tumors of the epidermis, its appendages, and dermis were observed in 1,433 (717 males, 716 females) rats employed in oncogenicity studies over a 2-yr period. Mammary gland neoplasms will be reported separately. Fifty-seven (61.3%) were epithelial with 49 in males and 8 in females. Keratoacanthoma was the most frequent epithelial neoplasm in males (22) followed by squamous cell carcinoma (11) and papilloma (5). Sebaceous gland neoplasms seen in males (5) included both adenomas (3) and carcinomas (2). In males, there were also 3 trichoepitheliomas, 1 pilomatricoma, 1 basal cell tumor, and 1 malignant melanoma. Of the 8 epithelial neoplasms in females, there were 3 squamous cell carcinomas, 2 keratoacanthomas, and 1 each basal cell tumor, malignant melanoma, and trichoepithelioma. There were 21 mesenchymal neoplasms in males and 15 in females. The most frequent neoplasm was fibroma (7 males, 8 females) followed by lipoma (7 males, 4 females) and fibrosarcoma (4 males, 3 females). One male had a liposarcoma and 2 males each had hemangioma. The total neoplasm incidence of 70/717 (9.8%) in males and 23/716 (3.2%) in females showed that skin neoplasms were 3 time more common in males than in females. Epithelial neoplasms of the skin were 6 times more common in males than in females. Males were more than twice as likely to have epithelial rather than mesenchymal skin neoplasms whereas the reverse was seen in females.
Primary malignant neoplasms of the brain and spinal cord occurred in 20/718 male (2.8%) and in 13/717 female (1.8%) Crl:CD Br strain Sprague-Dawley rats. Of 33 neoplasms, 30 were found in brain while 3 were in the spinal cord. In males and females, the most common brain neoplasm was astrocytoma (13 males, 9 females). Other neoplasms, granular cell tumor (1 male), mixed glioma (2 males, 1 female), reticulosis (1 male, 2 females), and oligodendroglioma (2 males), were especially uncommon. Spinal cord neoplasms included 2 schwannomas (1 male, 1 female) and an astrocytoma (1 male). The overall brain neoplasm incidence was similar for males (2.8%) compared to data compiled for this strain, and there was a 2-fold increase for females (1.8% vs 0.9%) compared to available incidence data.
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This study conducted to evaluate the subchronic toxicity of FYROL 6 [diethyl N,N-bis-(2-hydroxyethyl)aminomethylphosphonate] in rats demonstrated an hepatic effect not commonly reported for related compounds. Sprague-Dawley rats of both sexes were gavaged daily with 0, 10, 100, or 500 mg/kg FYROL 6 in corn oil for 13 wk. No treatment-related mortality and few signs of toxicity were noted during the study. Fyrol 6 did not inhibit plasma, erythrocyte, or brain cholinesterase activities. Treatment-related necropsy and microscopic alterations were restricted to the liver. Increased liver weights, hepatocellular hypertrophy, and eosinophilia of centrilobular hepatocytes were evident in 100-mg/kg females and in both sexes at 500 mg/kg. Morphometric analysis revealed a 40% increase in cross-sectional area of individual hepatocytes in 500-mg/kg males, compared to controls. There was no morphologic evidence of hepatic necrosis or clinical evidence of liver dysfunction. This study demonstrated low toxicity for FYROL 6 and treatment-related changes restricted to the liver suggestive of an adaptive response to FYROL 6.
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MV-678 [1-(8-methoxy-4,8-dimethynonyl)-4-(1-methylethyl)benzene], a recently developed insect growth regulator, increased the hepatic cytochrome P-450-dependent monooxygenase enzymes that metabolize endogenous and exogenous chemicals. In an initial set of experiments, male and female rats received 0, 50, or 800 mg/kg X d of MV-678 by gavage for 3 d, and in a second set of experiments, male rats received 0, 50, or 800 mg/kg X d of MV-678 by gavage for 30 d. A significant increase in both absolute and relative liver weight, microsomal protein content, cytochrome P-450 content, NADPH-cytochrome P-450 reductase activity, and ethylmorphine N-demethylase activity was observed in male and female rats at the high dose level at 3 d. Similar increases were observed in the 800-mg/kg X d males at 30 d. Hepatocellular hypertrophy and proliferation of endoplasmic reticulum observed at both 3 and 30 d correspond to and was consistent with microsomal enzyme induction. Reversibility of both induction and changes in morphology was determined by measuring the same parameters in animals treated for 30 d after a 15- or 30-d recovery period. At 15 d recovery, all biochemical parameters at the high dose level, except relative liver weight and microsomal ethylmorphine N-demethylase activity, had returned to control levels. No significant differences between the control and high dose group animals were noted at 30 d recovery. The hepatocellular changes observed in the high-dose group at 30 d were less apparent at 15 d recovery, and absent at 30 d recovery.
Two insecticide formulations were evaluated for skin irritation using albino rabbits (Stauffland-White strain). While the active ingredient alone produced only mild skin irritation, corn grit formulation produced severe skin irritation. Corn grit from three sources (A, B, and C) was similarly evaluated for skin irritation and at 24 hr, all samples produced erythema and edema of both the abraded and nonabraded test sites. Eschar was observed in 72 hr in about half of the rabbits and persisted through termination on the 7th day. Histologic examination of skin specimens revealed that all three corn grit samples produced epidermatitis. In addition, rabbits exposed to corn grit from two sources (A and B), developed moderate focal to severe diffuse suppurative necrotizing folliculitis and dermatitis. Large tubular branching nonseptate hyphae compatible with the Mucorales species were seen in hair follicle micropustules of rabbits treated with corn grit from sources A and B. Mycologic culture techniques applied to corn grit from each source revealed a potential pathogen in the genus Rhizopus isolated from samples from sources A and C but not B. The skin irritation test involved application of test material covered with gauze to both abraded and nonabraded skin. Rubber damming was placed over the gauze and secured with tape. After 24-hr exposure all bandaging and visible test material were removed. Skin irritation was evaluated immediately after removal and then periodically until termination at 7 days.
Histopathology of the reproductive system of 76 young adult Dutch Belted and 22 young adult or adult male New Zealand White rabbits was conducted as part of fertility studies. Thirty-five (46%) of the Dutch Belted and 11 (50%) of the New Zealand White males had multifocal vesicular gland basal epithelial cell atypia and hyperplasia without metaplasia. The affected cells were taller with pale cytoplasm and a prominent basophilic nucleus longitudinally oriented and increased in number compared to more normal adjacent epithelium. Thirty-one (41%) of the Dutch Belted and 10 (45%) of the New Zealand White males showed one or more nodules of squamous metaplasia in the alveolar epithelial lining or seen occasionally within alveolar walls of the vesicular gland. The prostate was less commonly affected and none of the early cellular atypia or later cornification changes were seen. A few cornified nodules with mitotic figures resembled "carcinoma in situ," but the morphology and available biologic data supported the judgment that the lesion was benign, metaplastic, proliferative, and clinically silent.
One case of interstitial cell tumors in the testicles of a New Zealand White rabbit was reported. The rabbit was 8-10 months old and had bilateral testicular lesions. There was no enlargement of either testicle and the lesions were first seen on the cut surface. Light and electron microscopy revealed that the cellular morphology resembled the features observed for this tumor in rats, dogs, and a few other domestic animals in which reports are available.
Sodium aluminium phosphate [NaAl3H14(PO4)8. 4H2O], a leavening acid, was administered to groups of six male and six female beagle dogs at dietary concentrations of 0, 0.3, 1.0 or 3.0% for 6 months. No adverse treatment-related clinical signs were observed. There were no statistically significant differences in mean body weights between test and control groups at any of the weekly determinations. Weekly mean food consumption values of all male treated groups did not differ significantly from those of the control group at any stage of the study. Statistically significant reductions in food consumption occurred sporadically in all treated groups of female dogs. No significant absolute or relative organ-weight differences were found between any of the treated groups and their respective controls. Haematological, blood chemistry and urinalysis data showed no toxicologically significant trends. Histopathological examination revealed no changes considered to be related to treatment. Thus dietary administration of sodium aluminum phosphate for 6 months at concentrations of 3% or lower caused no significant toxicological effects in beagle dogs.
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In lifespan studies of 2,242 rats of three strains, 32 neoplasms were identified in brain, meninges and pineal gland. They were astrocytoma (16 Wistar, three Sprague-Dawley), ependymoma (four Osborne-Mendel), meningioma (two Osborne-Mendel, one Wistar), pinealoma (two Osborne-Mendel), reticulosis (two Wistar), oligodendroglioma (one Wistar), and gliomatosis (one Wistar).
10 spontaneous tumours were observed. Several had not been previously reported for this species and 1 occurred in the youngest gerbil yet reported to have a spontaneous tumour. 7 of the 10 tumours originated from the female reproductive tract.
To compare the clinical and pathological effects of high and low nicotine cigarette smoke 12 young adult male beagles were separated into four equal groups and exposed to smoke from high (4.6 mg) or low (1.4 mg) nicotine cigarettes, administered in six or 12 cigarettes per day. Two control groups, sham-exposed and nontracheostomized, consisted of three dogs each. The dogs were exposed seven days per week for five months. Tracheobronchitis developed in smoke-exposed dogs; gross lesions were generally confined to the lungs and tracheobronchial lymph nodes. Histopathological changes were found in all smoke-exposed dogs, with slightly more severe or extensive lesions in the dogs exposed to 12 cigarettes per day. The incidence and severity of rhinitis, turbinate basal epithelial cell hyperplasia, and squamous metaplasia were increased among dogs in the high nicotine cigarette groups.
Bacillus piliformis infection (Tyzzer's disease) occurred in two young guinea pigs, causing unthriftiness and diarrhea which resulted in death. There was necrosis and inflammation of the ileum, cecum, and colon. Intestinal epithelial cells contained organisms resembling Bacillus piliformis. Spirochetes were found in the cecum and colon, mainly in crypts. Acute diarrhea occurred in another guinea pig which became cachetic and was killed. Histologically, large numbers of spirochetes were present in the wall of both the cecum and colon, and they were associated with severe necrosis and inflammation. Bacillus pilformis was not found in this animal.