Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chemotherapy, which has greatly improved the prognosis of children with malignant diseases, is potentially hepatotoxic. Furthermore, there is a risk for viral hepatitis acquired by blood products. In this study we looked for hepatotoxicity and for chronic viral hepatitis during and after chemotherapy in 50 unselected children with malignant diseases. 29 children had been treated for leukemia or lymphoma, 19 for solid tumors, 2 for histiocytosis. All patients had been treated before 1991 and had received blood products not screened for hepatitis C-antibodies. In 18 girls and 32 boys aged 12.3 years (range 6.7-24.5 years) hepatitis B- and hepatitis C-serology and liver function tests were measured during a routine check-up 3.6 years (range 0.5-11.8 years) after the last chemotherapy. Liver function tests during chemotherapy were reviewed retrospectively. During chemotherapy 86% of children showed increased ALT and AST levels, 10% had levels above 500 U/l. At follow up 16 children (32%) had pathological liver function tests, especially slightly increased AST and ALT, 13 of these 16 patients had chronic hepatitis C. In contrast only 2 of 34 patients with normal liver function tests had a viral hepatitis (p = 0.001). Patients with elevation of AST and ALT above 100 U/l during chemotherapy had significantly more often a viral hepatitis than those with normal or slightly elevated aminotransferases. Our study shows that hepatocellular damage is a frequent complication following chemotherapy. However this progresses to chronic liver disease very rarely unless the patient acquired a viral hepatitis. The prevalence of chronic hepatitis C was very high in our patients. As screening of blood products for hepatitis C-antibodies is routinely performed since 1991 this problem is likely to have decreased.
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PMID:[Chronic liver disease after treatment of malignancies in children]. 1040 9

In the seventh national voluntary cross-sectional survey (in 1999) of Finnish patients with haemophilia A or B, type 3 von Willebrand disease or factor XIII deficiency, a plasma sample was received from 193 patients (67%). The samples were tested for hepatitis B and C, human immunodeficiency virus (HIV) and human T-cell leukaemia virus (HTLV) antibodies. Fifty-one percent of the patients were hepatitis C antibody positive and 34% hepatitis B core antibody positive. None of the patients had antibodies against HIV or HTLV. Eighteen percent of the patients had an elevated alanine aminotransferase activity. Abnormal alanine aminotransferase was significantly associated with hepatitis C seropositivity. No new seroconversions were detected among the haemophiliacs or patients with type 3 von Willebrand disease when compared with the last two surveys in 1993 and 1996, and there was no seroconversion in sole users of solvent/detergent-treated factor products. Currently, 32% of the patients use prophylactic factor treatment as their principal mode of therapy, particularly the younger patients with severe forms of the bleeding diseases.
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PMID:Viral markers and use of factor products among Finnish patients with bleeding disorders. 1113 80

Over 90% of intravenous heroin addicts (IVHAs) carry the hepatitis C virus (HCV). The other hepatitis viruses, A, B, D, and G are relatively unimportant in IVHAs compared to HCV although active hepatitis B may demonstrate a chronic, degenerative course identical to that of HCV. The clinical course of HCV and active hepatitis B may span three or more decades. It is helpful to classify patients as in the active, cirrhosis, or liver failure stages. Only in the active, early stage are the liver enzymes, ALT and AST, likely to be elevated. It is this stage that will most likely respond to antiviral therapy. HCV has so many extra-hepatic manifestations including immune suppression, collagen diseases, and possibly lymphoma and leukemia that the disease is best termed HCV syndrome rather than simple hepatitis.
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PMID:Hepatitis C, B, D, and A: contrasting features and liver function abnormalities in heroin addicts. 1128 27

A debilitated 9-yr-old female red panda (Ailurus fulgens fulgens) with a recent history of corticosteroid administration displayed anorexia, depression, and diarrhea for 2 days. Blood work revealed a moderate nonregenerative anemia, leukocytosis, hypokalemia, hyperbilirubinemia, and mildly elevated alanine aminotransferase and aspartate aminotransferase. Serology was negative for occult heartworm, Toxoplasma gondii, feline leukemia virus, feline infectious peritonitis, feline immunodeficiency virus, and canine distemper virus. Electron microscopy of the feces demonstrated corona-like virus particles. The panda died 3 days after initial presentation. Histologic findings included multifocal, acute, hepatic necrosis and diffuse, necrotizing colitis. Liver and colon lesions contained intracellular, curved, spore-forming, gram-negative, silver-positive rods morphologically consistent with Clostridium piliforme. This panda most likely contracted Tyzzer's disease subsequent to having a compromised immune system after corticosteroid administration and concurrent disease.
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PMID:Tyzzer's disease in a red panda (Ailurus fulgens fulgens). 1142 5

Indium phosphide is used to make semiconductors,injection lasers, solar cells, photodiodes, and light-emittingdiodes. Indium phosphide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure,and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to indium phosphide (greater than 99% pure) by inhalation for 14 weeks or 2 years. The frequency of micronuclei was determined in the peripheral blood of mice exposed to indium phosphide for 14 weeks. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to particulate aerosols of indium phosphide with amass median aerodynamic diameter of approximately 1.2 microm at concentrations of 0, 1, 3, 10, 30, or 100 mg/m3 by inhalation, 6 hours per day, 5 days per week (weeks 1 through 4 and weeks 10 through 14) or 7 days per week (weeks 5 through 9) to accommodate a concurrent teratology study. One male in the 100 mg/m3 group died before the end of the study. Body weight gains of all males and females exposed to 100 mg/m3 were less than those of the chamber controls. As a result of indium phosphide exposure, the lungs of all exposed rats had a gray to black discoloration and were significantly enlarged, weighing 2.7- to 4.4-fold more than those of the chamber controls. Indium phosphide particles were observed throughout the respiratory tract and in the lung-associated lymph nodes. A spectrum of inflammatory and proliferative lesions generally occurred in the lungs of all exposed groups of rats and consisted of alveolar proteinosis, chronic inflammation, interstitial fibrosis, and alveolar epithelial hyperplasia. Pulmonary inflammation was attended by increased leukocyte and neutrophil counts in the blood. The alveolar proteinosis was the principal apparent reason for the increase in lung weights. Indium phosphide caused inflammation at the base of the epiglottis of the larynx and hyperplasia of the bronchial and mediastinal lymph nodes. Exposure to indium phosphide affected the circulating erythroid mass. It induced a microcytic erythrocytosis consistent with bone marrow hyperplasia and hematopoietic cell proliferation of the spleen. Hepatocellular necrosis was suggested by increased serum activities of alanine aminotransferase and sorbitol dehydrogenase in all exposed groups of males and in 10 mg/m3 or greater females and was confirmed microscopically in 100 mg/m3 males and females. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to particulate aerosols of indium phosphide with a mass median aerodynamic diameter of approximately 1.2 microm at concentrations of 0, 1, 3, 10, 30, or 100 mg/m3 by inhalation, 6 hours per day, 5 days per week (weeks 1 through 4 and weeks 10 through 14)or 7 days per week (weeks 5 through 9). Although the effects of indium phosphide exposure were similar in rats and mice, mice were more severely affected in that all males and females in the 100 mg/m3 groups either died or were removed moribund during the study. One male and three females in the 30 mg/m3 group were also removed before the end of the study. In general, body weight gains were significantly less in males and females exposed to 3 mg/m3 or greater compared to those of the chamber controls. Mice exposed to 30 or 100 mg/m3 were lethargic and experienced rapid, shallow breathing. As in rats, lungs were discolored and enlarged 2.6- to 4.1-fold greater than those of chamber controls due to the exposure-induced alveolar proteinosis. Indium phosphide particles were observed in the nose, trachea,larynx, and lymph nodes of some exposed males and females. Alveolar proteinosis, chronic active inflammation,interstitial fibrosis, and alveolar epithelial hyperplasia were observed; these effects were more severe than in rats. Hyperplasia in the bronchial lymph nodes and squamous metaplasia, necrosis, and suppurative inflammation of the larynx were observed in some exposed males and females. Exposure to indium phosphide induced a microcytic erythrocytosis which was consistent with the observed hematopoietic cell proliferation of the spleen.2-YEAR STUDY IN RATS Groups of 60 male and 60 female rats were exposed to particulate aerosols of indium phosphide at concentrations of 0, 0.03, 0.1, or 0.3 mg/m3, 6 hours per day,5 days per week, for 22 weeks (0.1 and 0.3 mg/m3 groups) or 105 weeks (0 and 0.03 mg/m3 groups). Animals in the 0.1 and 0.3 mg/m3 group were maintained on filtered air from exposure termination at week 22 until the end of the studies. Ten males and 10 females per group were evaluated at 3 months. 3-Month Interim Evaluation: Exposure to indium phosphide for 3 months caused a microcytic erythrocytosis and also caused enlarged lungs and lesions in the respiratory tract and lung associated lymph nodes. Although qualitatively similar to those observed in the 14-week studies, these effects were considerably less severe. However, the lesions in the lungs of rats exposed to 0.1 or 0.3 mg/m3 were considered sufficiently severe that exposure was discontinued in these groups, and the groups were allowed to continue unexposed for the remainder of the study. Survival, Body Weights, and Clinical Findings: Exposure to indium phosphide had no effect on survival or body weight gain. During the last 6 months of the study, rats in the 0.03 and 0.3 mg/m3 groups became lethargic and males breathed abnormally. Pathology Findings: At 2 years, exposure to indium phosphide caused increased incidences of alveolar/bronchiolar adenomas and carcinomas in rats. Squamous cell carcinoma of the lung occurred in four male rats exposed to 0.3 mg/m3. As observed in the 14-week study and at the 3-month interim evaluation, a spectrum of inflammatory and proliferative lesions of the lung were observed in all exposed groups of males and females;however, the extent and severity of the lesions were generally greater and included atypical hyperplasia,chronic inflammation, alveolar epithelial hyperplasia and metaplasia, alveolar proteinosis, and interstitial fibrosis. Exposure to indium phosphide also caused increased incidences of benign and malignant pheochromocytomas of the adrenal gland in males and females. Marginal increases in the incidences of mononuclear cell leukemia in males and females, fibroma of the skin in males, and carcinoma of the mammary gland in females may have been related to exposure to indium phosphide. 2-YEAR STUDY IN MICE: Groups of 60 male and 60 female mice were exposed to particulate aerosols of indium phosphide at concentrations of 0, 0.03, 0.1, or 0.3 mg/m3, 6 hours per day,5 days per week, for 21 weeks (0.1 and 0.3 mg/m3 groups) or 105 weeks (0 and 0.03 mg/m3 groups). Animals in the 0.1 and 0.3 mg/m3 groups were maintained on filtered air from exposure termination at week 21 until the end of the studies. Ten males and 10 females per group were evaluated at 3 months. 3-Month Interim Evaluation:Exposure to indium phosphide for 3 months affected the circulating erythroid mass and caused enlarged lungs and lesions in the respiratory tract and lung associated lymph nodes. These effects, although qualitatively similar to those observed in the 14-week studies, were considerably less severe. However, the lesions in the lungs of mice exposed to 0.1 mg/m3 and greater were considered sufficiently severe that exposure was discontinued in these groups and the groups were allowed to continue unexposed for the remainder of the study. Survival and Body Weights: In general, exposure to indium phosphide for 2 years reduced survival and body weight gain in exposed males and females. Pathology Findings:At 2 years, exposure to indium phosphide caused increased incidences of alveolar/bronchiolar carcinomas in males and alveolar/bronchiolar adenomas and carcinomas in females. In addition to the alveolar proteinosis and chronic active inflammation seen at earlier time points, serosa fibrosis and pleural mesothelial hyperplasia were also present. The incidences of hepatocellular neoplasms were also significantly increased in exposed males and females. Exposed groups of males and females had increased incidences of eosinophilic foci of the liver at 2 years. Marginal increases in the incidences of neoplasms of the small intestines in male mice may have been related to exposure to indium phosphide. Exposure to indium phosphide also caused inflammation of the arteries of the heart, primarily the coronary arteries and the proximal aorta, and to a lesser extent the lung-associated lymph nodes in males and in females. TISSUE BURDEN ANALYSES: Deposition and clearance studies of indium following long term exposure of rats and mice to indium phosphide by inhalation were performed. Although there were quantitative differences in lung burden and kinetic parameters for rats and mice, qualitatively they were similar. Deposition of indium in the lungs appeared to follow a zero-order (constant rate) process. Retained lung burdens throughout the studies were proportional to exposure concentration and duration. No differences in elimination rates of indium from the lungs were observed as a function of exposure concentration in either rats or mice. These studies indicated that elimination of indium was quite slow. Mice exhibited clearance half-times of 144 and 163 days for the 0.1 and 0.3 mg/m3 groups, respectively, as compared to 262 and 291 days for rats exposed to the same concentrations. The lung deposition and clearance model was used to estimate the total amount of indium deposited in the lungs of rats and mice after exposure to 0.03 mg/m3 for 2 years or to 0.1 or 0.3 mg/m3 for 21 or 22 weeks, the lung burdens at the end of the 2-year study, and the area under lung burden curves (AUC). For both species, estimates at the end of 2 years indicated that the lung burdens in the continuously exposed 0.03 mg/m3 groups were greater than those in the 0.1 or 0.3 mg/m3 groups. (ABSTRACT TRUNCATED)
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PMID:Toxicology and carcinogenesis studies of indium phosphide (CAS No. 22398-90-7) in F344/N rats and B6C3F1 mice (inhalation studies). 1208 22

In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).
Leukemia 2002 Jul
PMID:Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. 1209 49

Forty-six cats with clinical haemobartonellosis were studied; 75 per cent of the cats of known age were two-and-a-half years old or younger, 50 per cent were intact males and 19.5 per cent were castrated males. The predominant signs of the disease were tachypnoea, lethargy, depression, anorexia, infestation with fleas, pale mucous membranes, icterus, emaciation, dehydration, splenomegaly, anaemia, leucocytosis, increased activities of alanine aminotransferase and aspartate aminotransferase, and azotaemia. Thirty-eight per cent of the cats that were tested for feline leukaemia virus (FeLV) antigen were positive, and 22 per cent of those tested for feline immunodeficiency virus (FIV) antibodies were positive. The prevalence of both FeLV and FIV was much higher than in the general Israeli cat population. The cats infected with both Haemobartonella felis and FeLV had a significantly lower body temperature, were more anaemic and the mean cell volume of their erythrocytes was greater than in the cats with haemobartonellosis alone.
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PMID:Retrospective study of 46 cases of feline haemobartonellosis in Israel and their relationships with FeLV and FIV infections. 1216 25

Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through optical fibers. Gallium arsenide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to gallium arsenide particles (greater than 98% pure; mass median aerodynamic diameter = 0.8 to 1.0 &mgr;m) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed to gallium arsenide for 14 weeks. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of males and females were similar to those of the chamber controls. Compared to chamber controls, the liver and lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased; the thymus weights of all exposed groups of males were decreased. Gallium arsenide particles were visible in the alveolar spaces and, to a lesser extent, within alveolar macrophages of exposed rats. Moderate proteinosis (surfactant mixed with small amounts of fibrin) and minimal histiocytic cellular infiltrate were observed in the alveoli of exposed males and females. Epithelial hyperplasia and squamous metaplasia of the larynx were observed primarily in males exposed to 150 mg/m(3). 16-DAY STUDY IN MICE: Groups of five male and four or five female mice were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. The final mean body weights were similar among exposed and chamber control groups. Compared to chamber controls, the lung weights of males and females exposed to 10 mg/m(3) or greater were increased. Gallium ar senide particles were visible in alveolar spaces and macrophages in some mice exposed to 150 mg/m(3). Moderate proteinosis, mild epithelial hyperplasia, and histiocytic infiltration of the lung were observed in males and females exposed to 10 mg/m(3) or greater. In the larynx, mild squamous metaplasia was seen in mice exposed to 10 mg/m(3) or greater, and mild chronic inflammation occurred in mice exposed to 75 or 150 mg/m(3). 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. All rats survived until the end of the study. The final mean body weight and body weight gain of males exposed to 75 mg/m(3) were significantly less than those of the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in exposed groups of rats. There were also increases in platelet and neutrophil counts, a transient decrease in leukocyte counts, and increases in the serum activities of alanine aminotransferase and sorbitol dehydrogenase. These changes were of greater magnitude in male rats. The lung weights of all exposed groups of rats were increased, while testis, cauda epididymis, and epididymis weights of males exposed to 37 or 75 mg/m(3) were generally less than those of chamber controls. Total spermatid heads and spermatid counts were significantly decreased in males exposed to 75 mg/m(3), while epididymal spermatozoa motility was significantly reduced in males ees exposed to 10 mg/m(3) or greater. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of exposed rats. Minimal to marked proteinosis and minimal histiocytic cellular infiltration of the alveoli were observed in all exposed groups; minimal squamous metaplasia in the larynx and lymphoid cell hyperplasia of the mediastinal lymph node were observed in some males and females exposed to 37 or 75 mg/m(3). Exposure-related increases in the incidences of plasma cell hyperplasia of the mandibular lymph node, testicular atrophy, epididymal hypospermia, bone marrow hyperplasia (males), and hemosiderosis in the liver were observed in the 37 and 75 mg/m(3) groups. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 1, 10, 37, or 75 mg/m(3), 6 hours per day, 5 days per week, for 14 weeks. One female mouse exposed to 75 mg/m(3) died before the end of the study. Final mean body weights and body weight gains of males in the 75 mg/m(3) group were signifi cantly less than the chamber controls. Hematology and clinical chemistry results indicated that exposure to gallium arsenide affected the circulating erythroid mass and induced a microcytic responsive anemia with an erythrocytosis and increased zinc protoporphyrin/heme ratios in male and female mice. There were also increases in platelet and neutrophil counts. Compared to the chamber controls, the lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased. Testis, cauda epididymis, and epididymis weights, total spermatid heads, spermatid counts, and concentration and motility of epididymal spermatozoa were generally decreased. Gallium arsenide particles were visible in alveolar spaces and macrophages in the lungs of mice exposed to 1 mg/m(3) or greater. Mild to marked proteinosis, histiocytic infiltration, and epithelial hyperplasia were observed in the alveoli of males and females exposed to 1 mg/m(3) or greater. Minimal to mild suppurative inflammation and granuloma in the lung and squamous metaplasia in the larynx were present in males and females exposed to 10 mg/m(3) or greater. Min imal hyperplasia was observed in the tracheobronchial lymph node of males exposed to 10 mg/m(3) or greater and females exposed to 37 or 75 mg/m(3). Exposure- related increases in the incidences of testicular atrophy, epididymal hypospermia, hematopoietic cell proliferation of the spleen, and hemosiderosis of the liver and spleen were observed in groups of male and female mice exposed to 10 mg/m(3) or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.01, 0.1, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights: Survival of exposed male and female rats was similar to the chamber controls. Mean body weights of males exposed to 1.0 mg/m(3) were generally less than those of the chamber controls throughout the study; females exposed to 1.0 mg/m(3) had slightly lower mean body weights during the second year. Pathology Findings: Compared to the chamber controls, the incidences of alveolar/bronchiolar neoplasms were significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control ranges. Exposure-related nonneoplastic lesions in the lungs of male and female rats included atypical hyperplasia, alveolar epithelial hyperplasia, chronic active inflammation, proteinosis, and alveolar epithelial metaplasia. In the larynx of males exposed to 1.0 mg/m(3), the incidences of hyperplasia, chronic active inflammation, squamous metaplasia, and hyperplasia of the epiglottis were significantly increased. The incidences of benign pheochromocytoma of the adrenal medulla occurred with a positive trend in female rats, and the incidence was significantly increased in the 1.0 mg/m(3) group and exceeded the historical control range. The incidence of mononuclear cell leukemia was significantly increased in females exposed to 1.0 mg/m(3) and exceeded the historical control range. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed by inhalation to gallium arsenide particulate at concentrations of 0, 0.1, 0.5, or 1.0 mg/m(3), 6 hours per day, 5 days per week, for 105 (males) or 106 (females) weeks. Survival and Body Weights: Survival of male and female mice was similar to the chamber controls. Mean body weights of exposed groups of males were similar to those of the chamber controls throughout the study; mean body weights of exposed groups of females were greater than those of the chamber controls from week 13 until the end of the study. Pathology Findings: Exposure-related nonneoplastic lesions in the lung of all groups of exposed mice included suppurative focal inflammation, chronic focal inflammation, histiocyte cellular infiltration, alveolar epithelial hyperplasia, and proteinosis. Increased incidences of minimal lymphoid hyperplasia of the tracheobronchial lymph node occurred in mice exposed to 1.0 mg/m(3) and in 0.5 mg/m(3)mg/m(3) males. GENETIC TOXICOLOGY: Gallium arsenide was not mutagenic in several strains of Salmonella typhimurium, with or without S9 metabolic activation enzymes, and no increase in the frequency of micronucleated erythrocytes was observed in peripheral blood of male or female mice exposed to gallium arsenide by inhalation for 14 weeks. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was no evidence of carcinogenic activity of gallium arsenide in male F344/N rats exposed to 0.01, 0.1, or 1.0 mg/m(3). There was clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of benign and malignant neoplasms in the lung. Increased incidences of benign neoplasms of the adrenal medulla and increased incidences of mononuclear cell leukemia were also considered to be exposure related. There was no evidence of carcinogenic activity in male or female B6C3F1 mice exposed to 0.1, 0.5, or 1.0 mg/m(3). Exposure to gallium arsenide caused a spectrum of nonneoplastic lesions in the lung of rats and mice, the larynx of male rats and hyperplasia of the tracheobronchial lymph node in mice. Synonym: Gallium monoarsenide.
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PMID:NTP Toxicology and Carcinogenesis Studies of Gallium Arsenide (CAS No. 1303-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1256 48

Oxymetholone is a synthetic anabolic steroid used to treat a variety of conditions, including hypogonadism and delayed puberty. It is also used to correct hereditary angioneurotic edema, manage carcinoma of the breast, promote a positive nitrogen balance following injury or surgery, and stimulate erythropoiesis. Considerable amounts of androgens are consumed by athletes in attempts to improve athletic performance. The National Institute of Environmental Health Sciences and the National Cancer Institute nominated oxymetholone for study based on its extensive illicit pharmaceutical use and the limited evidence that it is a potential human carcinogen. Male and female F344/N rats received oxymetholone (greater than 99% pure) in 0.5% methylcellulose by gavage for 16 days, 14 weeks, or 2 years, and male and female B6C3F1 mice received oxymetholone in 0.5% methylcellulose by gavage for 16 days or 14 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were administered 0, 160, 315, 625, 1,250, or 2,500 mg oxymetholone/kg body weight in 0.5% methylcellulose by gavage for 16 days. All male rats survived to the end of the study; one 2,500 mg/kg female died on day 14. The mean body weights of all dosed groups of males were significantly less than those of the vehicle controls, while those of 160 and 315 mg/kg females were significantly greater. 16-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were administered 0, 320, 630, 1,250, 2,500, or 5,000 mg/kg in 0.5% methylcellulose by gavage for 16 days. All mice survived to the end of the study. The final mean body weights of all dosed groups of females were greater than those of the vehicle controls. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were administered 0, 80, 160, 315, 625, or 1,250 mg/kg in 0.5% methylcellulose by gavage for 14 weeks. One male rat each in the 625 and 1,250 mg/kg groups died before the end of the study. The mean body weights of males administered 160 mg/kg or greater were significantly less than those of the vehicle controls; in contrast, the mean body weights of all dosed groups of females were significantly greater. A dose-related erythrocytosis, evidenced by increases in erythrocyte counts, total hemoglobin concentrations, and hematocrit values, occurred in dosed groups of rats at week 14. A dose-related hypocholesterolemia occurred at all time points in all dosed groups of rats. Dose- and time-related decreases in 5 -nucleotidase activity occurred in treated rats. There was a transient, treatment-related increase in the activity of alanine aminotransferase in males and females. For male rats administered oxymetholone, cauda epididymis, epididymis, and testis weights and spermatid counts and total spermatid heads per testis were significantly less than those of the vehicle controls, and total spermatid heads per gram testis were significantly greater. Female rats in the 80 mg/kg group spent more time in diestrus and less time in estrus than did the vehicle controls. Kidney weights of males and females and liver and uterus weights of females were increased compared to vehicle controls in rats that received 315 mg/kg or greater; thymus weights of males and females and sartorius muscle and testis weights of males were less. Compared to the vehicle controls, rats that received 160 mg/kg or greater had increased incidences of nonneoplastic lesions of the kidney and mammary gland, and the incidences of hydrometra of the uterus and dysgenesis of the ovary were increased in dosed groups of females. Female rats administered 315 mg/kg or greater had increased incidences of cytoplasmic vacuolization of the adrenal gland and myocardial degeneration of the heart. The severities of these lesions generally increased with increasing dose. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were administered 0, 160, 320, 630, 1,250, or 2,500 mg/kged 0, 160, 320, 630, 1,250, or 2,500 mg/kg in 0.5&percnt; methylcellulose by gavage for 14 weeks. All mice administered oxymetholone survived until the end of the study. The mean body weights of all dosed groups were similar to those of the vehicle controls. The percentages of motile sperm in 1,250 and 2,500 mg/kg males were significantly less than those of the vehicle controls. The estrous cycle lengths of 630, 1,250, and 2,500 mg/kg females were significantly longer, and females in the 1,250 and 2,500 mg/kg groups spent more time in diestrus and less time in estrus. Kidney and liver weights of males and females were greater and thymus weights of females were less than those of the vehicle controls. All dosed females had hyperplasia of the clitoral gland, metaplasia of the parietal layer epithelium of the Bowman's capsule in the kidney, and cytoplasmic alteration of the submandibular gland; these lesions were not observed in the vehicle control group. The incidences of hypoplasia of the ovary in 320 mg/kg or greater females and of parotid gland atrophy in 1,250 and 2,500 mg/kg females were increased. The results of the 14-week oral gavage studies were generally similar in rats and mice, but rats were much more sensitive to oxymetholone. Because it was not likely that a long-term mouse study would provide significant additional toxicity information, the NTP decided to conduct a 2-year study in rats only. 2-YEAR STUDY IN RATS: Groups of 90 male F344/N rats were administered 0, 3, 30, or 150 mg/kg in 0.5&percnt; methylcellulose by gavage, and 90 female F344/N rats were administered 0, 3, 30, or 100 mg/kg in 0.5&percnt; methylcellulose by gavage for up to 104 weeks, with 9 or 10 rats per group evaluated at 3, 6, 12, or 18 months. Survival and Body Weights: Survival of all dosed groups was similar to that of the vehicle controls. The mean body weights of the 30 mg/kg male group were generally within 10&percnt; of those of the vehicle controls, but those of the 150 mg/kg group were markedly decreased. Mean body weights of 3 and 30 mg/kg females were generally greater than those of the vehicle controls throughout the study. Determinations of Oxymetholone in Plasma: The concentrations of oxymetholone in plasma of male and female rats receiving 3 mg/kg for 6, 12, or 18 months were generally below the limits of quantification; therefore, all plasma concentrations in the 3 mg/kg group are considered to be estimates (Table 8). The plasma concentrations at 30 mg/kg were approximately one order of magnitude greater than those of the estimates for males and females receiving 3 mg/kg. There were no dose-related differences in plasma concentrations in female rats receiving 30 or 100 mg/kg, but plasma concentrations in males were significantly elevated in the 150 mg/kg group. It was concluded that oxymetholone kinetics was saturated at 30 mg/kg in female but not male rats. Pathology Findings: A wide spectrum of neoplasms and nonneoplastic lesions was seen in rats administered oxymetholone for 2 years. The incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined) were significantly increased in 100 mg/kg females as were the incidences of basophilic and clear cell foci in 150 mg/kg males and 100 mg/kg females compared to vehicle controls. The incidences of alveolar/bronchiolar adenoma and adenoma or carcinoma (combined) were significantly increased in 30 mg/kg females. The incidences of mineralization in the lung of 150 mg/kg males and 30 and 100 mg/kg females were significantly increased. The incidence of keratoacanthoma was increased in 30 mg/kg females, and the combined incidence of squamous cell papilloma, keratoacanthoma, basal cell adenoma, squamous cell carcinoma, or carcinoma of the sweat gland was significantly increased in 100 mg/kg females. The incidences of subcutaneous tissue fibroma and fibroma or fibrosarcoma (combined) were significantly increased in 3 mg/kg males. At 2 years, the incidences of benign pheochromocytoma and benign or malignant pheochromocytoma (combined) of the adrenal gland in 150 mg/kg males and medullary hyperplasia in 100 mg/kg females were significantly increased. The incidences of cytoplasmic vacuolization of adrenal cortical cells were significantly increased in 30 and 150 mg/kg males at 18 months and 2 years and in 100 mg/kg females beginning at 12 months and in 30 mg/kg females at 2 years. The incidences of renal tubule adenoma in 3 and 150 mg/kg males were slightly increased. An extended evaluation of the kidney was conducted, and additional incidences of renal tubule adenoma were observed in step sections in vehicle control and dosed male rats. The combined single- and step-section incidence of renal tubule adenoma was significantly increased in 3 mg/kg males. The incidences of nephropathy were significantly increased in 30 and 150 mg/kg males at 2 years and in 100 mg/kg females beginning at 3 months. The severities of nephropathy were significantly increased in dosed groups of males at 2 years and in 100 mg/kg females at 18 months and 2 years. The incidences of mineralization of the kidney were significantly increased in 150 mg/kg males at all time points. The incidences of ovarian dysgenesis were significantly increased in 100 mg/kg females beginning at 3 months and in 30 mg/kg females beginning at 6 months, and severities increased with increasing dose. The incidences of chronic myocardial degeneration (cardiomyopathy) were significantly increased in 100 mg/kg females at 6 months and 2 years and the severity was increased at 2 years. The incidences of lobular hyperplasia were increased in 150 mg/kg males at 18 months and 2 years and in 30 and 100 mg/kg females at all time points. The incidences of seminiferous tubule degeneration were significantly increased in 30 and 150 mg/kg males at 2 years, and the incidences of mineralization of the testis were increased in 150 mg/kg males at 12 months and in 30 mg/kg males at 18 months and at 2 years. Decreased incidences of neoplasms occurred in male and female rats. The incidence of uterine stromal polyp or stromal sarcoma (combined) was significantly decreased in 100 mg/kg females at 2 years. The incidences of mammary gland fibroadenoma and fibroadenoma or carcinoma (combined) were significantly decreased in all dosed groups of females. The incidences of pituitary gland pars distalis adenoma were significantly decreased in 30 and 100 mg/kg females at 2 years. The incidences of testicular interstitial cell adenoma were significantly decreased in 30 and 150 mg/kg males at 18 months and in all dosed groups at 12 months and 2 years. The incidences of mononuclear cell leukemia were significantly decreased in 30 and 150 mg/kg males and 100 mg/kg females at 2 years. GENETIC TOXICOLOGY: Oxymetholone was not mutagenic in S. typhimurium strain TA97, TA98, TA100, or TA1535, with or without S9 metabolic activation. It did not induce chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9, and no increase in the frequency of micronucleated normochromatic erythrocytes was noted in peripheral blood samples from male or female mice treated for 14 weeks with oxymetholone. CONCLUSIONS: Under the conditions of this 2-year gavage study, there was equivocal evidence of carcinogenic activity of oxymetholone in male F344/N rats based on increased incidences of subcutaneous tissue fibromas and fibromas or fibrosarcomas (combined) of the skin, variably increased incidences of benign and benign or malignant pheochromocytomas (combined) of the adrenal gland, and increased incidences of renal tubule adenomas. There was clear evidence of carcinogenic activity of oxymetholone in female F344/N rats based on increased incidences of hepatocellular neoplasms. Increased incidences of alveolar/bronchiolar neoplasms and skin neoplasms in female rats were also related to oxymetholone administration. Decreased incidences of alveolar/bronchiolar neoplasms and testicular interstitial cell adenomas in males; uterine stromal polyps or stromal sarcomas (combined), mammary gland neoplasms, and pituitary gland pars distalis adenomas in females; and mononuclear cell leukemia in males and females were related to oxymetholone administration. In addition, gavage administration of oxymetholone to male and female F344/N rats resulted in a spectrum of nonneoplastic effects frequently reported with administration of synthetic anabolic androgens. Synonyms: Adroidin; anadroyd; anasteron; anasteronal; anasterone; androstan-3-one, androstano[2,3-c]1,2,5-oxadiazol-17-ol, 17-methyl-, (5-a,17-b)-; becorel; 4,5-dihydro-2-hydroxymethylene-17-a-methyltestosterone; dynasten; HMD; 17b-hydroxy-2- (hydroxymethyl)-17-methyl-5-a-androstan-3-one; 17-hydroxy-2-(hydroxymethylene)-17-methyl-(5-a,17-b)-; 17-hydroxy- 2-(hydroxymethylene)-17-methyl-5-a-17-b-androst-3-one; 17b-hydroxy-2-(hydroxymethylene)-17-a-methyl-5-a-androstan-3-one; 17b-hydroxy-2-(hydroxymethylene)-17-methyl-5a-androstan-3-one; 17-hydroxy-2-(hydroxymethylene)-17-methyl-5-a-17- b-androstan-3-one; 17b-hydroxy-2-hydroxymethylene-17a-methyl-3-androstanone; 2-hydroxymethylene-17-a-methyl-5- a-androstan-17-b-ol-3-one; 2-hydroxymethylene-17a-methyl dihydrotestosterone; 2-hydroxymethylene-17-a-methyl-17-b- hydroxy-3-androstanone; methabol; 17a-methyl-2-hydroxymethylene-17-hydroxy-5-a-androstan-3-one; oximetholonum; oximetolona; oxitosona-50; oxymethenolone; roboral; zenalosyn Trade names: Adroyd; Anadrol; Anapolon; Anapolon 50; Nastenon; Pardroyd; Pavisoid; Plenastril; Protanabol; Synasteron
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PMID:NTP Toxicology and Carcinogenesis Studies of Oxymetholone (CAS NO. 434-07-1) in F344/N Rats and Toxicology Studies of Oxymetholone in B6C3F1 Mice (Gavage Studies). 1257 78

Pyridine is used as a denaturant in alcohol and anti freeze mixtures, as a solvent for paint, rubber, and polycarbonate resins, and as an intermediate in the manufacture of insecticides, herbicides, and fungicides. It is used in the production of piperidine, an intermediate in the manufacture of rubber and mepiquat chloride, and as an intermediate and solvent in the preparation of vitamins and drugs, dyes, textile water repellants, and flavoring agents in food. Pyridine was nominated for study because of its large production volume and its use in a variety of food, medical, and industrial products. Male and female F344/N rats, male Wistar rats, and male and female B6C3F1 mice were exposed to pyridine (approximately 99% pure) in drinking water for 13 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse bone marrow cells. 13-WEEK STUDY IN F344/N RATS: Groups of 10 male and 10 female F344/N rats were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 5, 10, 25, 55, or 90 mg pyridine/kg body weight). Two females exposed to 1,000 ppm died during week 1. Final mean body weights of 1,000 ppm males and females and 500 ppm females were significantly less than controls. Water consumption by female rats exposed to 1,000 ppm was less than that by controls. At study termination, evidence of anemia persisted in the 500 and 1,000 ppm males and all exposed groups of females. There was evidence of hepatocellular injury and/or altered hepatic function demonstrated by increased serum alanine aminotransferase and sorbitol dehydrogenase activities and bile acid concentrations in 500 and 1,000 ppm rats. The estrous cycle length of 1,000 ppm females was significantly longer than that of the controls. Liver weights of males and females exposed to 250 ppm or greater were significantly greater than controls. In the liver, the incidences of centrilobular degeneration, hypertrophy, chronic inflammation, and pigmentation were generally increased in 500 and 1,000 ppm males and females relative to controls. In the kidney, the incidences of granular casts and hyaline degeneration (hyaline droplets) were significantly increased in 1,000 ppm males and slightly increased in 500 ppm males; these lesions are consistent with 2u-globulin nephropathy. Additionally, there were increased incidences and/or severities of protein casts, chronic inflammation, mineralization, and regeneration primarily in 500 and 1,000 ppm males. 13-WEEK STUDY IN MALE WISTAR RATS: Groups of 10 male Wistar rats were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 5, 10, 30, 60, or 100 mg/kg). One male rat exposed to 500 ppm died during week 1. Final mean body weights of rats exposed to 250, 500, or 1,000 ppm were significantly less than those of the controls. Water consumption by rats exposed to 1,000 ppm was lower than that by controls. There was evidence of hepatocellular injury and/or altered hepatic function in the 500 and 1,000 ppm groups, similar to that observed in the 13-week study in F344/N rats. Incidences of centrilobular degeneration, hypertrophy, chronic inflammation, and pigmentation in the liver of rats exposed to 500 or 1,000 ppm were significantly increased relative to controls. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 50, 100, 250, 500, or 1,000 ppm (equivalent to average daily doses of 10, 20, 50, 85, or 160 mg/kg for males and 10, 20, 60, 100, or 190 mg/kg for females). One female mouse exposed to 250 ppm died during week 2. Final mean body weights of female mice exposed to 1,000 ppm were significantly less than those of controls. Water consumption by exposed female mice was lower than that by controls at week 1 but generally slightly higher than controls at week 13. Sperm motirm motility in exposed male mice was significantly decreased relative to controls. Liver weights were significantly increased relative to controls in males exposed to 100 ppm or greater and in 250 and 500 ppm females. No chemical-related lesions were observed in male or female mice. 2-YEAR STUDY IN F344/N RATS: Groups of 50 male and 50 female F344/N rats were exposed to pyridine in drinking water at concentrations of 0, 100, 200, or 400 ppm (equivalent to average daily doses of 7, 14, or 33 mg/kg) for 104 (males) or 105 (females) weeks. Survival, Body Weights, and Water Consumption Survival of exposed males and females was similar to that of controls. Mean body weights of 400 ppm males and females were generally less than those of the controls throughout the study, and those of 200 ppm males and females were less during the second year of the study. Water consumption by males and females exposed to 200 or 400 ppm was generally greater than that by controls. Pathology Findings Incidences of renal tubule adenoma and renal tubule adenoma or carcinoma (combined) in male rats exposed to 400 ppm were significantly increased compared to controls and exceeded the historical control ranges. The findings from an extended evaluation (step section) of the kidneys did not reveal additional carcinomas, but additional adenomas were observed in each group of males. In the standard evaluation, an increased incidence of renal tubule hyperplasia was observed in 400 ppm males compared to controls. Incidences of mononuclear cell leukemia in female rats were significantly increased in the 200 and 400 ppm groups, and the incidence in the 400 ppm group exceeded the historical control range. Exposure concentration-related nonneoplastic liver lesions were observed in males and females, and the incidences were generally increased in groups exposed to 400 ppm. These included centrilobular cytomegaly, cytoplasmic vacuolization, periportal fibrosis, fibrosis, centrilobular degeneration and necrosis, and pigmentation. Bile duct hyperplasia occurred more often in exposed females than in controls. 2-YEAR STUDY IN MALE WISTAR RATS: Groups of 50 male Wistar rats were exposed to pyridine in drinking water at concentrations of 0, 100, 200, or 400 ppm (equivalent to average daily doses of 8, 17, or 36 mg/kg) for 104 weeks. Survival, Body Weights, and Water Consumption Survival of rats exposed to 200 or 400 ppm was significantly less than that of the controls. Mean body weights of rats exposed to 100, 200, or 400 ppm were significantly less than controls. Water consumption was similar by control and exposed rats. Pathology Findings The incidence of testicular interstitial cell adenoma in rats exposed to 400 ppm was significantly increased compared to controls. Incidences of interstitial cell hyperplasia were observed in control and exposed groups and were slightly, but not significantly, increased in rats exposed to 200 or 400 ppm. Severity of nephropathy was marked in all groups, and additional evidence of kidney disease, including mineralization in the glandular stomach, parathyroid gland hyperplasia, and fibrous osteodystrophy, was observed in 100 and 200 ppm rats. The incidences of hepatic centrilobular degeneration and necrosis, fibrosis, periportal fibrosis, and/or pigmentation were increased in one or more exposed groups. 2-YEAR STUDY IN MICE: Groups of 50 male B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 250, 500, or 1,000 ppm (equivalent to average daily doses of 35, 65, or 110 mg/kg) for 104 weeks, and groups of 50 female B6C3F1 mice were exposed to pyridine in drinking water at concentrations of 0, 125, 250, or 500 ppm (equivalent to average daily doses of 15, 35, or 70 mg/kg) for 105 weeks. Survival, Body Weights, and Water Consumption Survival of exposed males and females was similar to that of the controls. Mean body weights of 250 and 500 ppm females were less than controls. Water consumption by males exposed to 250 or 500 ppm was generally greater than that by controls during the last year of the study; male mice exposed to 1,000 ppm consumed less water than controls throughout the study. Water consumption by exposed females was generally lower than that by controls during the first year of the study, but greater than controls during the second year. Pathology Findings Hepatocellular neoplasms, including hepatoblastomas, in exposed male and female mice were clearly related to pyridine exposure. Additionally, many mice had multiple hepatocellular neoplasms. The incidences of hepatocellular neoplasms in exposed males and females generally exceeded the historical control ranges for drinking water studies. Neoplasms from control mice, 1,000 ppm males, and 500 ppm females were negative when stained for p53 protein. GENETIC TOXICOLOGY: Pyridine was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 or in L5178Y mouse lymphoma cells, with or without S9 metabolic activation, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. Pyridine was tested for induction of sex-linked recessive lethal mutations in adult male Drosophila melanogaster, and mixed results were obtained. In one experiment, administration by injection gave negative results, but feeding produced an equivocal response. A second experiment generated negative results by injection and feeding. A third experiment showed significant increases in sex-linked recessive lethal mutations in flies treated with pyridine by injection but not by feeding. Overall, results of the sex-linked recessive lethal mutations test in Drosophila melanogaster were considered negative by feeding and equivocal by injection. Results of a single reciprocal translocation test in male Drosophila melanogaster were negative. No induction of chromosomal aberrations or micronuclei was noted in bone marrow cells of male mice administered pyridine via intraperitoneal injection. CONCLUSIONS: Under the conditions of these 2-year drinking water studies, there was some evidence of carcinogenic activity of pyridine in male F344/N rats based on increased incidences of renal tubule neoplasms. There was equivocal evidence of carcinogenic activity of pyridine in female F344/N rats based on increased incidences of mononuclear cell leukemia. There was equivocal evidence of carcinogenic activity in male Wistar rats based on an increased incidence of interstitial cell adenoma of the testis. There was clear evidence of carcinogenic activity of pyridine in male and female B6C3F1 mice based on increased incidences of malignant hepatocellular neoplasms. In F344/N rats, exposure to pyridine resulted in increased incidences of centrilobular cytomegaly and degeneration, cytoplasmic vacuolization, and pigmentation in the liver of males and females; periportal fibrosis, fibrosis, and centrilobular necrosis in the liver of males; and bile duct hyperplasia in females. In male Wistar rats, pyridine exposure resulted in increased incidences of centrilobular degeneration and necrosis, fibrosis, periportal fibrosis, and pigmentation in the liver, and, secondary to kidney disease, mineralization in the glandular stomach and parathyroid gland hyperplasia. Synonyms: Azabenzene, azine
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PMID:NTP Toxicology and Carcinogenesis Studies of Pyridine (CAS No. 110-86-1) in F344/N Rats, Wistar Rats, and B6C3F1 Mice (Drinking Water Studies). 1257 3


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