Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case records of and histopathologic findings in 57 dogs with nonangiogenic and nonlymphomatous splenic sarcomas were reviewed. Splenic neoplasms in these dogs included leiomyosarcoma, fibrosarcoma, undifferentiated sarcoma, liposarcoma, osteosarcoma, chondrosarcoma, myxosarcoma, rhabdomyosarcoma, and fibrous histiocytoma. The clinical signs associated with splenic sarcoma included anorexia or decreased appetite, abdominal distention, polydipsia, lethargy, vomiting, weight loss, and weakness. An abdominal mass was detected in 86% of the dogs by use of abdominal palpation (63%), and/or abdominal radiography (74%). The diagnosis was based on histopathologic findings in the spleen. Abdominal exploratory surgery was performed on 43 of the 57 dogs. Twenty-seven dogs were treated by splenectomy, and 16 were euthanatized at the time of surgery because of widespread metastatic lesions. Of the 14 dogs on which surgery was not performed, 11 were euthanatized on the basis of results of preoperative diagnostic tests, and the remaining 3 dogs had splenic neoplasms that were incidental findings at necropsy. Of the 27 surgically treated dogs, 5 died in the immediate postoperative period, 12 died or were euthanatized within 1 year after splenectomy, and only 5 dogs survived greater than or equal to 1 year. Three dogs were lost to follow-up evaluation, and 2 were still alive 6 and 7 months after surgery. The median survival time of the 22 dogs for which survival was known was 2.5 months. The median survival time for 11 dogs with no obvious metastasis at the time of splenectomy was 9 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonangiogenic and nonlymphomatous sarcomas of the canine spleen: 57 cases (1975-1987). 255 65

Twenty previously treated patients with advanced bone sarcomas received thrice weekly im 50 X 10(6) IU/m2 doses of human alfa-interferon (interferon alfa-2a, recombinant; Roche). Seventeen patients had metastatic osteosarcomas and one each had fibrosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma. Two patients with osteosarcoma and the one with malignant fibrous histiocytoma experienced objective partial tumor regression for 1, 3, and 2 months, respectively. Fever, anorexia, myalgia, fatigue, lethargy, and moderate myelosuppression were observed commonly, and some patients developed mild nausea, vomiting, and diarrhea. No patient withdrew because of toxicity and no dose reductions were necessary except adjustments for changes in body surface area secondary to weight loss.
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PMID:Phase II study of recombinant alfa-2a interferon in patients with advanced bone sarcomas. 303 15

To determine the clinical presentation and manifestations of Paget's disease of the bone in patients older than 60 years, we reviewed the cases of 56 patients attending a bone clinic. Pain was the presenting symptom in 34 cases. It was attributed to the disease process in 21 cases, to osteoarthritis in 11, to trigeminal neuralgia in 1, and to osteosarcoma in 1. Other clinical manifestations included deformities (15 cases), diminished mobility and unsteady gait (9), hearing impairment (7), lethargy (4), diminished vision (3), cognitive deficit (3), sense of warmth in limbs (2), ill-fitting dentures (1), and fracture (1). We concluded that in patients older than 60 years, Paget's disease of the bone may present itself in a variety of ways, some of which may be mistakenly attributed to the "aging process" or some other disease. Furthermore, in this age group, osteoarthritis is responsible for the pain experienced by about one third of symptomatic patients.
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PMID:Clinical presentation of Paget's disease of the bone in older patients. 821 23

N,N-Dimethylaniline is used as a chemical intermediate in the synthesis of dyestuffs. Toxicology and carcinogenesis studies were conducted by administering N,N-dimethylaniline (greater than 98% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 2 weeks, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse lymphoma cells, and Chinese hamster ovary (CHO) cells. Two-Week and Thirteen-Week Studies: In the 2-week studies, doses were 94-1,500 mg/kg; deaths of rats and mice were observed in groups given doses of 750 or 1,500 mg/kg. The final mean body weights of male rats that received 375 or 750 mg/kg were 15% or 47% lower than that of vehicle controls; final mean body weights of other groups of rats and mice were similar to those of vehicle controls. Compound-related clinical signs observed included cyanosis in rats and lethargy and tremors in rats and mice. Splenomegaly occurred in nearly all dosed groups of rats and mice, and the incidences were dose related. In the 13-week studies, doses were 32-500 mg/kg; no compound-related deaths occurred. The final mean body weights of male rats that received 250 or 500 mg/kg were 15% or 27% lower than that of vehicle controls. The final mean body weights of all groups of dosed female rats and male and female mice were within 12% of those of vehicle controls. Compound-related clinical signs included lethargy in rats and mice and cyanosis in rats. Splenomegaly was observed in all dosed groups of rats and mice; the severity was dose related. Compound-related extramedullary hematopoiesis and hemosiderosis occurred in the kidney or testis of dosed rats and liver and spleen of dosed rats and mice. Two-year studies were conducted by administering 0, 3, or 30 mg/kg N,N-dimethylaniline in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 rats of each sex. The lower dose was selected to be one-tenth the higher dose to increase the likelihood that one dose would cause only a minimal nonneoplastic response. Groups of 50 mice of each sex were administered 0, 15, or 30 mg/kg on the same schedule. Body Weight and Survival in the Two-Year Studies: Mean body weights of vehicle control and dosed rats and mice were similar throughout the studies. Survival rates of all respective groups were similar after 2 years, except for the lowered survival of vehicle control female rats (vehicle control, 21/50; low dose 32/50; high dose, 36/50). This may reflect the large number (24/50) of vehicle control female rats killed when observed to be in a moribund state. Final survival for other groups was as follows: male rats--29/50; 32/50; 28/50; male mice-- 34/50; 30/50; 34/50; female mice--35/50; 39/50; 33/50. Nonneoplastic and Neoplastic Effects in the Two-Year Studies: In these 2-year studies, the spleen was the expected site of chemical-related effects. Fatty metamorphosis and fibrosis in the spleen of high dose male rats were increased (fatty metamorphosis: vehicle control, 0/49; low dose, 1/49; high dose, 10/50; fibrosis: 5/49; 2/49; 22/50). Splenic hemosiderosis and hematopoiesis were present at an incidence greater than 85% in all groups of rats; however, the severity of the lesions was greater in dosed groups than in vehicle controls. Sarcomas of the spleen were seen in 3/50 high dose male rats, and an osteosarcoma was seen in another high dose male rat. One additional high dose male rat had a sarcoma of the thymus. Splenic sarcomas are uncommon in corn oil vehicle control male F344/N rats (NTP historical incidence 3/2,081, 0.1%), and thus, these neoplasms in high dose male rats (4/50, 8%) were considered to be chemically related. Lower incidences of mononuclear cell leukemia (which apparently originates in the spleen) were seen in dosed male and female rats than in vehicle controls (male: 13/50; 4/50; 3/50; female: 11/50; 7/50; 0/50). The incidence of squamous cell papillomas of the forestomach in high dose female mice was marginally greater than that in vehicle controls (2/50; 2/50; 8/50). No malignant forestomacin vehicle controls (2/50; 2/50; 8/50). No malignant forestomach neoplasms were observed. Genetic Toxicology: N,N-Dimethylaniline was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of exogenous metabolic activation. In the mouse lymphoma assay, N,N-dimethylaniline produced a positive response with and without metabolic activation. In CHO cells, N,N-dimethylaniline induced both sister chromatid exchanges (SCEs) and chromosomal aberrations in the presence of exogenous metabolic activation. Without activation, an increase in chromosomal aberrations was observed, but no increase in SCEs occurred. Conclusions: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity of N,N-dimethylaniline for male F344/N rats, as indicated by the increased incidences of sarcomas or osteosarcomas(combined) of the spleen. There was no evidence of carcinogenic activity of N,N-dimethylaniline for female F344/N rats given 3 or 30 mg/kg body weight by gavage for 2 years. There was no evidence of carcinogenic activity of N,N-dimethylaniline for male B6C3F1 mice given 15 or 30 mg/kg body weight by gavage for 2 years. There was equivocal evidence of carcinogenic activity of N,N-dimethylaniline for female B6C3F1 mice, as indicated by an increased incidence of squamous cell papillomas of the forestomach. Both rats and mice could have tolerated doses higher than those used in these studies. There were decreased incidences of mononuclear cell leukemia in dosed male and high dose female rats. Compound-related splenic fibrosis, hemosiderosis, and fatty metamorphosis were increased in male rats. Synonyms: dimethylaminobenzene; N,N-dimethylbenzeneamine; dimethylaniline; dimethylphenylamine; N,N-dimethylphenylamine
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PMID:Toxicology and Carcinogenesis Studies of N,N-Dimethylaniline (CAS No. 121-69-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1269 81

2-Amino-5-nitrophenol is used as a colorant in semipermanent hair dyes and in the manufacture of C.I. Solvent Red 8, an azo dye for synthetic resins, lacquers, and wood stains. 2-Amino-5-nitrophenol was nominated for toxicology and carcinogenesis studies by the National Cancer Institute because of widespread human exposure associated with its use in hair dyes. Toxicology and carcinogenesis studies were conducted by administering 2-amino-5-nitrophenol (98% pure) by gavage in corn oil 5 days per week to groups of F344/N rats and B6C3F1 mice of each sex in 16-day, 13-week, and 2-year studies. In the 2-year studies, male and female rats were given doses of 0, 100, or 200 mg/kg and male and female mice were given doses of 0, 400, or 800 mg/kg. Sixteen-Day and Thirteen-Week Studies: During the 16-day studies, F344/N rats of each sex received 0, 156, 313, 625, 1,250, or 2,500 mg/kg 2-amino-5-nitrophenol by gavage in corn oil vehicle. One of the five males that received 2,500 mg/kg, 1/5 females that received 1,250 mg/kg, and 2/5 females that received 313 mg/kg died before the end of the studies. Final mean body weights of rats that received 1,250 or 2,500 mg/kg were 11% and 30% lower than that of vehicle controls for males and 9% and 13% lower for females. B6C3F1 mice of each sex received doses of 0, 313, 625, 1,250, 2,500, or 5,000 mg/kg 2-amino-5-nitrophenol. Two of five males and 5/5 females that received 5,000 mg/kg, 3/5 males and 3/5 females that received 2,500 mg/kg, 3/5 females that received 1,250 mg/kg, 1/5 females that received 625 mg/kg, and 2/5 male vehicle controls died before the end of the studies. Final mean body weights of chemically exposed mice were not different from those of the vehicle controls. Rats that received 625, 1,250, or 2,500 mg/kg and male mice that received 5,000 mg/kg had loose stools. In 13-week studies, F344/N rats and B6C3F1 mice of both sexes received 0, 100, 200, 400, 800, or 1,600 mg/kg 2-amino-5-nitrophenol by gavage in corn oil. Five of 10 male and 2/10 female rats that received 1,600 mg/kg, 1/10 male and 3/10 female rats that received 800 mg/kg, and 1/10 male rats that received 400 mg/kg died before the end of the studies. Final mean body weights of males that received 400, 800, or 1,600 mg/kg were 10%, 25%, and 43% lower than that of vehicle controls. The final mean body weight of females that received 1,600 mg/kg was 16% lower that of vehicle controls. Four of 10 male and 3/10 female mice that received 1,600 mg/kg died before the end of the 13-week studies. The final mean body weight of male mice that received 1,600 mg/kg was 11% lower than that of vehicle controls; male and female mice that received 1,600 mg/kg appeared lethargic. During the 13-week studies, acute/chronic perivasculitis of vessels of the cecum and colon was observed in rats that received 400, 800, or 1,600 mg/kg and in mice that received 1,600 mg/kg. Body Weight and Survival in the Two-Year Studies: Mean body weights of rats receiving 200 mg/kg were 5%-10% lower than those of vehicle controls after week 33 for males and 4%-5% lower than those of vehicle controls after week 93 for females. Survival of male rats was significantly lower than that of vehicle controls after week 99 for the 100 mg/kg dose group and after week 75 for the 200 mg/kg dose group (final survival: vehicle control, 33/50; 100 mg/kg group, 16/50; 200 mg/kg group, 4/50). Survival of female rats was comparable to that of vehicle controls (30/50; 32/50; 29/50). Loose or poorly formed stools were observed for male rats and occasionally for females that received 200 mg/kg. Mean body weights of mice that received 800 mg/kg were 8%-11% lower than those of vehicle controls between weeks 29 and 74 for males and 8%-13% lower than those of vehicle controls after week 69 for females; mean body weights of mice that received 400 mg/kg were greater than those of vehicle controls after week 69 for males and 5%-9% lower than those of vehicle controls after week 69 for females. Survival of mice that received 800 mg/kg was significantly reduced compared with that of ose of vehicle controls after week 69 for females. Survival of mice that received 800 mg/kg was significantly reduced compared with that of vehicle controls after week 20 for males and week 22 for females and was not considered adequate to evaluate a carcinogenic response (final survival--male: vehicle control, 31/50; 400 mg/kg group, 36/50; 800 mg/kg group, 12/50; female: 37/50; 36/50; 10/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Pigmentation was present at increased incidences in all groups of chemically exposed animals and was characterized by varying amounts of an orange, granular pigment present in the fibrous connective tissue of the lamina propria, in the submucosa, and around vessels in the submucosa of the cecum and colon. Pigmentation of the rectum was observed at increased incidences in male rats that received 100 mg/kg, male and female rats that received 200 mg/kg, and both groups of chemically exposed mice. No pigmentation was found in the intestines of vehicle control rats or mice. Associated with pigmentation was an increased incidence of acute/chronic inflammation in the cecum and colon of all groups chemically exposed rats and mice; this inflammation was similar to that observed in the 13-week studies but was of greater severity. Acute/chronic inflammation was also present in the rectum of male rats that received 100 mg/kg, male and female rats that received 200 mg/kg, and male mice that received 800 mg/kg. The incidence of pancreatic acinar cell adenomas was significantly increased (P≤0.002) in male rats that received 100 mg/kg 2-amino-5-nitrophenol (vehicle control, 1/50; 100 mg/kg, 10/50; 200 mg/kg, 3/49); the increase was considered to be associated with chemical exposure. The reduced survival of male rats that received 200 mg/kg markedly reduced the sensitivity of this group for detecting the presence of neoplasms. The incidences of adenomas or carcinomas (combined) of the preputial or clitoral glands were marginally increased in male or female rats that received 200 mg/kg 2-amino-5-nitrophenol (preputial gland: 3/50; 2/50; 5/50; clitoral gland: 3/50; 3/50; 7/50). Neoplasms found in the intestinal tract of 3/50 male rats that received 100 mg/kg (one leiomyoma of the small intestine, one adenocarcinoma of the jejunum, one leiomyoma of the cecum), 2/50 male rats that received 200 mg/kg (one lipoma and one osteosarcoma of the cecum), and 1/50 female rats that received 200 mg/kg (one leiomyoma of the cecum) were not considered to be the result of chemical exposure. No compound-related neoplasms were found in mice exposed to 2-amino-5-nitrophenol in the 2-year studies. Genetic Toxicology: 2-Amino-5-nitrophenol was mutagenic in Salmonella typhimurium strains TA98, TA100, and TA1537 when tested in a preincubation protocol with and without exogenous metabolic activation, and it exhibited equivocal mutagenic activity in strain TA1535 in the presence of induced liver S9. 2-Amino-5-nitrophenol induced forward mutations in mouse L5178Y lymphoma cells in the absence of metabolic activation; it was not tested with S9. An increase in chromosomal aberrations and sister chromatid exchanges was observed in cultured Chinese hamster ovary (CHO) cells following incubation with 2-amino-5-nitrophenol both in the presence and absence of exogenous metabolic activation. Data Audit: The data, documents, and pathology materials from the 2-year studies of 2-amino-5-nitrophenol were audited at the NTP Archives. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Conclusions: Under the conditions of these 2-year gavage studies, there was some evidence of carcinogenic activity for male F344/N rats that received 100 mg/kg 2-amino-5-nitrophenol, as shown by the increased incidence of acinar cell adenomas of the pancreas. Reduced survival of male F344/N rats that received 200 mg/kg decreased the sensitivity of this group for detecting a carcinogenic response. There was no evidence of carcinogenic activity for female rats that received 100 or 200 mg/kg per day. Marginally increased incidences of preputial or clitoral gland adenomas or carcinomas (combined) occurred in male and female F344/N rats administered 200 mg/kg 2-amino-5-nitrophenol. There was no evidence of carcinogenic activity for B6C3F1 mice that received 400 mg/kg 2-amino-5-nitrophenol; reduced survival of B6C3F1 mice that received 800 mg/kg caused this group to be considered inadequate for detecting a carcinogenic response.
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PMID:NTP Toxicology and Carcinogenesis Studies of 2-Amino-5-Nitrophenol (CAS No. 121-88-0) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1273 2

Seventeen client-owned dogs diagnosed with spirocercosis-associated esophageal sarcomas were retrospectively reviewed. The most common clinical signs noticed were vomiting and/or regurgitation (94%), lethargy and depression (59%), pyrexia and anorexia (41% each). Leukocytosis (82%) and microcytic hypochromic anemia (30%) were the most common hematological abnormalities. Caudal thoracic masses were demonstrated on survey radiographs of 13/15 of the dogs and thoracic spondylitis was detected in 12/15 dogs. Spirocerca lupi eggs were detected in 2/8 patients and worms were demonstrated on 1/11 at necropsy. Ten cases underwent surgical attempt to remove the tumors. In six of them partial esophagectomy (PE) was performed and all of them survived the immediate postoperative hospitalization. Five of the cases that underwent PE also received chemotherapy after surgery (doxorubicin (Adriamycin, Upjohn)) with an average survival time of 267 days. The histopathological results of the esophageal tumors were osteosarcoma (9), fibrosarcoma (5) and undifferentiated sarcoma (1). In areas endemic to spirocercosis, regurgitation or vomiting in dogs and microcytic hypochromic anemia and neutrophilia warrant ruling out esophageal sarcomas. Proper surgical treatment could prolong the dogs' lifespan for months, and improve their quality of life.
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PMID:Spirocercosis-associated esophageal sarcomas in dogs. A retrospective study of 17 cases (1997-2003). 1474 80

A seven-and-a-half-year-old dog presented with anorexia, lethargy and haematurla. A 1.8 kg abdominal mass was excised and determined to be a primary renal osteosarcoma. Haematuria was observed five months after surgery and the tumour was radiographically determined to have recurred locally. The dog was euthanased 12 days later due to refractory pain and anorexia. Although osteosarcomas are expected to develop distant metastases, this dog was euthanased due to clinical evidence of local tumour recurrence. Haematuria was an indication both of initial tumour development and later recurrence.
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PMID:Renal osteosarcoma in a dog. 1560 Feb 74

A 10-year-old spayed female Boxer-mix was presented with a history of several weeks of soft stools, straining to defecate, inappetance, and lethargy and several days of hematochezia, melena, and dyschezia. Physical examination findings included mild tachycardia and tense cranial abdomen. CBC results indicated moderate mature neutrophilia. Ultrasonographic examination of the abdomen revealed a large mass with complex echogenicity in the cranial abdomen, likely associated with the intestines. Cytologic examination of a fine-needle aspirate revealed a population of round, stellate, and spindle-shaped cells arranged individually and in aggregates with occasional cells embedded in an eosinophilic extracellular matrix. The cytologic interpretation was malignant mesenchymal neoplasm with osteosarcoma being the primary differential. Surgical exploration of the abdomen revealed a 10-cm-diameter mass located at the intestinal mesenteric root. The mass occluded blood flow to portions of the gastrointestinal tract. The dog was euthanized due to the nonresectable nature of the tumor. Histopathologic examination revealed an expansile poorly demarcated mesenchymal neoplasm composed predominantly of spindloid and pyriform cells, occasionally embedded in a matrix compatible with osteoid. The diagnosis was extraskeletal osteosarcoma of the intestinal mesenteric root, only rarely reported in dogs.
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PMID:Primary mesenteric root osteosarcoma in a dog. 2064 59

Several essential oils contain pulegone and are used for flavoring foods, drinks, and dental products, as fragrance agents, and in herbal medicines. Pulegone was nominated for study by the National Institute of Environmental Health Sciences based on the potential for human exposure and the absence of carcinogenicity data. Male and female F344/N rats and B6C3F1 mice received pulegone (approximately 96% pure) by gavage for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were administered 0, 37.5, 75, 150, 300, or 600 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 16 days. All male rats and nearly all female rats in the 300 and 600 mg/kg groups died prior to the end of the study. All moribund sacrifices and early deaths were attributed to liver toxicity. Mean body weight gains of males administered 37.5 or 150 mg/kg were significantly less than that of the vehicle controls. Clinical findings in 300 and 600 mg/kg rats included nasal/eye discharge, thinness, lethargy, and ruffled fur. Liver and kidney weights of dosed groups of females were generally significantly greater than those of the vehicle control group. The incidences of necrosis and cytoplasmic vacuolization of the liver in 300 and 600 mg/kg males and females were significantly greater than those in the vehicle control groups. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were administered 0, 18.75, 37.5, 75, 150, or 300 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 16 days. Four females and one male in the 300 mg/kg groups died by study day 5. All early deaths were attributed to liver toxicity. Mean body weights of the dosed groups were similar to those of the vehicle controls. Clinical findings were observed only in 300 mg/kg mice and included thinness, lethargy, and ruffled fur. Liver weights of 300 mg/kg males were significantly greater than those of the vehicle controls. The incidences of cytoplasmic vacuolization and diffuse fatty change in 300 mg/kg females and necrosis in 300 mg/kg males were significantly greater than those in the vehicle controls. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 9.375, 18.75, 37.5, 75, or 150 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. All rats survived until the end of the study except for one female in the 150 mg/kg group that died on day 9. Mean body weights of 75 and 150 mg/kg males and 150 mg/kg females were significantly less than those of the vehicle controls. At the end of the study, there was a small dose-related decrease in the erythron, evidenced by decreases in the hematocrit and hemoglobin values and the erythrocyte counts. An apparent erythroid response to the decreased erythron was evidenced by increased reticulocyte counts. Reduced and oxidized glutathione levels were generally increased in 75 and 150 mg/kg males and in 37.5 mg/kg or greater females. Absolute and relative liver weights of 75 and 150 mg/kg females and relative liver weights of males administered 18.75 mg/kg or greater were significantly greater than those of the vehicle controls. The absolute kidney weight of 150 mg/kg females and the relative kidney weights of all dosed groups, except 9.375 mg/kg males, were significantly greater than those of the vehicle controls. Absolute and relative thymus weights of 150 mg/kg males and females and the absolute thymus weight of 75 mg/kg males were significantly less than those of the vehicle controls. In the kidney, there was hyaline glomerulopathy in 75 mg/kg males and 150 mg/kg males and females. The incidence of renal tubule protein casts was significantly increased in the 150 mg/kg females. In the liver, incidences of bile duct hyperplasia and hepatocyte hypertrophy in 75 and 150 mg/kg males and 150 mg/kg females, hepatocyte focal necrosis in 150 mg/kg males, and oval cell hyperplasia and periportal fibrosis in 150 mg/kg males and females were increased. Incidences of bone marrow hyperplasia in 37.5 mg/kg males and 75 and 150 mg/kg males and females, heart mineralization in 150 mg/kg males, glandular stomach mineralization in 75 and 150 mg/kg females, and cellular histiocytic infiltration in the lung and ovarian cyst in 150 mg/kg females were significantly increased. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 9.375, 18.75, 37.5, 75, or 150 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. All mice survived to the end of the study. Mean body weights of dosed mice were similar to those of the vehicle controls. Reduced and oxidized glutathione levels were generally greater than vehicle control levels in 150 mg/kg males and in 75 and 150 mg/kg females. Liver weights of 150 mg/kg males and 75 and 150 mg/kg females were significantly greater than those of the vehicle controls. No histopathologic lesions were observed that could be attributed to the administration of pulegone. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were administered 0, 18.75 (males only), 37.5, 75, or 150 (females only) mg pulegone/kg body weight in corn oil by gavage, 5 days per week for up to 104 weeks. Due to excessive morbidity and mortality, 75 mg/kg males and 150 mg/kg females were not administered pulegone after week 60 (stop-exposure); these groups were administered the corn oil vehicle until the end of the study. Survival of 37.5 mg/kg males was significantly less than that of the vehicle controls; only two 75 mg/kg stop-exposure males survived, and no 150 mg/kg stop-exposure females survived to the end of the study. Compared to those of the vehicle controls, mean body weights were less in 75 mg/kg stop-exposure males after week 13 and in 75 mg/kg and 150 mg/kg stop-exposure females after weeks 21 and 9, respectively. Clinical findings included thinness, lethargy, and ruffled fur in the 75 mg/kg stop-exposure males and 150 mg/kg stop-exposure females. The incidences of urinary bladder papilloma and of papilloma or carcinoma (combined) were significantly increased in 150 mg/kg stop-exposure females. In the kidney, incidences of hyaline glomerulopathy were significantly increased in 37.5 mg/kg and 75 mg/kg stop-exposure males and in all dosed groups of females. The severity of chronic progressive nephropathy was increased in 37.5 mg/kg and 75 mg/kg stop-exposure males and in 75 mg/kg and 150 mg/kg stop-exposure females; the incidences of nephropathy were significantly increased in 75 mg/kg and 150 mg/kg stop-exposure females. The incidence of renal cyst was significantly increased in 75 mg/kg stop-exposure males. In the liver, incidences of diffuse hepatocyte cellular alteration were significantly increased in 37.5 mg/kg and 75 mg/kg stop-exposure males and 75 mg/kg and 150 mg/kg stop-exposure females. There were significant increases in the incidences of other liver lesions including fatty change, bile duct cyst, hepatocyte necrosis, oval cell hyperplasia, bile duct hyperplasia, and portal fibrosis. In the nose, 37.5 mg/kg and 75 mg/kg stop-exposure males and all dosed groups of females had significantly increased incidences of olfactory epithelium degeneration. All dosed groups of females had significantly increased incidences of respiratory metaplasia of the olfactory epithelium and nasal inflammation. In the forestomach, incidences of inflammation and ulcer were significantly increased in 37.5 mg/kg and 75 mg/kg stop-exposure males, and incidences of epithelial hyperplasia and perforation were increased in 75 mg/kg stop-exposure males. In the glandular stomach, the incidence of inflammation was significantly increased in 75 mg/kg stop-exposure males. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered 0, 37.5, 75, or 150 mg pulegone/kg body weight in corn oil by gavage, 5 days per week for 105 weeks. Survival of all dosed groups was similar to that of the vehicle controls. Mean body weights of 150 mg/kg males and females were less than those of the vehicle controls after weeks 25 and 33, respectively. The incidences of multiple hepatocellular adenoma were significantly increased in all dosed groups of males, and the incidences of hepatocellular adenoma (includes multiple) and hepatoblastoma (includes multiple) were significantly increased in the 75 mg/kg males. The combined incidences of hepatocellular adenoma, hepatocellular carcinoma, or hepatoblastoma occurred with positive trends and were significantly increased in 75 mg/kg males and 150 mg/kg females. The incidence of hepatocellular adenoma was significantly increased in 150 mg/kg females. The incidences of several nonneoplastic liver lesions were significantly increased, primarily in the 75 and 150 mg/kg groups. These nonneoplastic lesions included clear cell, eosinophilic, and mixed cell foci; focal fatty change; centrilobular hepatocyte hypertrophy; intravascular hepatocyte; necrosis; pigmentation; bile duct cyst and hyperplasia; and oval cell hyperplasia. In the kidney, incidences of hyaline glomerulopathy were significantly increased in all dosed groups of males and 75 and 150 mg/kg females. The incidence of mineralization was significantly increased in 150 mg/kg females, and the incidence of nephropathy in 150 mg/kg females and severity of nephropathy in 150 mg/kg males were increased. Incidences of congestion of the glomerulus were increased in 150 mg/kg males and females. The incidence of osteoma or osteosarcoma (combined) in all organs of 75 mg/kg females exceeded the historical control ranges. One 150 mg/kg male and one 75 mg/kg female had nasal osteoma; no nasal osteomas have been observed in historical control mice. (ABSTRACT TRUNCATED)
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PMID:Toxicology and carcinogenesis studies of pulegone (CAS No. 89-82-7) in F344/N rats and B6C3F1 mice (gavage studies). 2192 62

A four-year-old neutered male nutria (Myocastor coypus) was presented for a one-day history of lethargy and anorexia. A right-sided facial swelling and loose right mandibular fourth molar that exuded caseous exudate from the root were noted; however, the animal continued to decline despite removal of the affected tooth and antibiotic and anti-inflammatory therapy. Radiographs showed a lytic proliferative bony lesion on the right mandible that appeared to expand in size over the course of a week. Due to its declining clinical condition and poor response to therapy, the animal was euthanized. Necropsy revealed an invasive bony neoplasm of the right mandible, histologically consistent with an osteosarcoma, that was invading the mandible and dental arcade, likely contributing to tooth root infection and osteomyelitis. Endocardiosis of the tricuspid valve was incidentally found as well with early cardiac remodeling of the right ventricle. This is the first report of an osteosarcoma and endocardiosis in a nutria.
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PMID:Mandibular osteosarcoma in a nutria (Myocastor coypus). 2531 53


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