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)

The acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined in male C57BL/6J mice differing only at the Ah locus. Wild type mice (Ahb/b, "b/b") were treated once with 0, 50, 100, 200, 300, and 400 micrograms TCDD/kg po while congenic mice (Ahd/d, "d/d") received a single dose of 0, 400, 800, 1600, 2400, and 3200 micrograms TCDD/kg. Mice were checked daily, weighed twice a week, and those that survived, killed 35 days post-treatment. The LD50 values were 159 and 3351 micrograms/kg for b/b and d/d mice, respectively. Mean time to death was 22 days and was independent of dose and genotype. Decrease in body weight gain was noted in both strains 5 days after treatment and occurred at doses greater than or equal to 100 micrograms/kg in b/b mice and 1600 micrograms/kg in d/d mice. Dose-related increases in liver weight (both absolute and relative to body weight) and decreases in thymus, spleen, testes, and epididymal fat pad weights were observed at 8-24-fold higher doses in d/d than in b/b mice. A dose-related increase in segmented neutrophils was observed in both strains. Serum chemistry values indicated that 8-24X greater doses of TCDD were needed to elevate sorbitol dehydrogenase, alanine aminotransferase, and 5'-nucleotidase and to decrease total and esterified cholesterol in d/d than in b/b mice. Few effects were seen on total bile acids, serum triglycerides, glucose, or nonesterified cholesterol. In the liver, hepatocellular cytomegaly, fatty change, and bile duct hyperplasia occurred in both strains in a dose-related manner, as did thymic and splenic atrophy. Necrosis of germinal epithelium in the testes and edema in the stomach submucosa occurred at acutely toxic doses. These lesions also occurred at doses 8-24X greater in d/d than in b/b mice. Thus, the spectrum of toxicity is independent of the allele at the Ah locus, but the relative dose needed to bring about various acute responses is approximately 8-24X greater in congenic mice homozygous for the "d" allele than for the wild type animals carrying two copies of the "b" gene.
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PMID:Differential toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice congenic at the Ah Locus. 237 98

Previous studies in young normal rats have shown that intracerebral administration of the proteinase inhibitor, leupeptin, caused a rapid accumulation of lipofuscin-like pigment in lysosomes of brain cells (Ivy et al., 1984a). On the other hand, we have recently found that the administration of lovastatin, an inhibitor of HMG-CoA reductase, reduced the ceroid-like pigment and dolichol contents in the crushed epididymal fat pad of rats (Porta et al., 1988). In order to study now the possible modulating effects of these enzyme inhibitors on ceroidogenesis associated with vitamin E deficiency, two main groups of weanling Wistar female rats were respectively fed ad libitum a vitamin E-deficient basal diet, or the same diet supplemented with 16 mg% of dl-alpha-tocopherol acetate. The vitamin E-deficient and -supplemented rats were further subdivided and received for 8 weeks their diets alone or with 2, 1, or 0.5 g of lovastatin/kg of diet. Other subgroups were treated with constant peritoneal infusion of 0.5 mg/day of leupeptin by means of osmotic minipumps (Alzet 2002) consecutively implanted at days 15, 30, and 45. Lovastatin treatment to vitamin E-deficient rats was associated with dose-dependent toxicity, resulting in 100%, 75%, and 50% mortality at concentrations of 2, 1, and 0.5 g/kg diet, respectively. This mortality was mainly due to extensive hepatic necrosis. Food intake and growth rates were reduced, while the relative weights of liver, kidneys, spleen, heart and brain, as well as the serum levels of GPT and GOT were significantly increased over the values of the untreated vitamin E-deficient control rats. The volumetric densities of ceroid pigment and the dolichol contents in liver and kidneys were not significantly modified. Lovastatin toxicity was partially prevented by vitamin E supplementation. However, in these supplemented rats, lovastatin treatment did not modify the volumetric densities of hepatic and renal ceroid, although the contents of hepatic and renal dolichol were significantly increased. No correlations could be found between levels of hepatic or renal ceroid and total dolichol content in vitamin E-deficient and supplemented rats. Leupeptin treatment to vitamin E-deficient rats only slightly reduced food intake and growth rates, and did not significantly modify the relative organ weights or the serum levels of cholesterol, GOT and GPT. Although in both vitamin E-deficient and -supplemented rats the leupeptin treatment consistently showed a tendency to increase the volumetric densities of hepatic and renal ceroid pigment, the differences with the control untreated rats were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of lovastatin and leupeptin on ceroidogenesis of vitamin E-deficient and -supplemented young rats. 248 49

The effects of acute aflatoxicosis on sperm maturation in the rat were evaluated using sperm GOT, GPT and LDH activities as indices. The levels of these enzymes in sperm undergoing maturation were stable like the sperm populations in the testis and epididymis. Acute aflatoxicosis enhanced corpus epididymal sperm transaminase but not sperm transit.
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PMID:Sperm maturation and storage in the male rat after acute treatment with aflatoxin B1. 393 3

Fat-cells were prepared from rat and guinea-pig epididymal adipose tissue and compared on the basis of the intracellular distributions and activities of enzymes and with respect to their utilization of various U-(14)C-labelled substrates for lipogenesis. 1. Compared with the rat, guinea-pig extramitochondrial enzyme activities differed in that aconitate hydratase, alanine aminotransferase, ATP-citrate lyase, lactate dehydrogenase, NAD-malate dehydrogenase, NADP-malate dehydrogenase and phosphoenolpyruvate carboxykinase activities were appreciably lower, whereas aspartate aminotransferase, glucose 6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase and 6-phosphogluconate dehydrogenase activities were appreciably higher. Mitochondrial activities of citrate synthase, NADP-isocitrate dehydrogenase and pyruvate carboxylase were appreciably lower, whereas mitochondrial activities of aspartate aminotransferase, glutamate dehydrogenase, NAD-malate dehydrogenase and phosphoenolpyruvate carboxykinase were higher in the guinea pig compared with the rat. 2. In general guinea-pig fat-cells incorporated acetate and lactate into fatty acids more readily than rat fat-cells, whereas rat fat-cells incorporated glucose and pyruvate more readily than guinea-pig fat-cells. 3. Acetate stimulated the incorporation of glucose into fatty acids in rat fat-cells, but had no appreciable effect upon this process in guinea-pig fat-cells. Acetate greatly decreased the incorporation of lactate into fatty acids in cells from both species. 4. Lactate/pyruvate ratios produced by incubation of guinea-pig cells with glucose+insulin were very low compared with those found with rat cells under the same conditions. 5. With glucose (+insulin) or with glucose+acetate (+insulin) as substrates guinea-pig cells produced enough NADPH by the hexose monophosphate pathway to satisfy the NADPH requirements of lipogenesis. In rat fat-cells under the same conditions, hexose monophosphate-pathway NADPH provision was not sufficient to meet the requirements of lipogenesis. 6. These results are discussed, particularly in relationship to the disposition of cytosolic reducing equivalents in the cells.
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PMID:Lipogenesis in rat and guinea-pig isolated epididymal fat-cells. 415 67

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25 degrees C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD-isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP-malate dehydrogenase (11.0), ATP-citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP-isocitrate dehydrogenase (3.7), NAD-malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109mug/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3-6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP-citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.
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PMID:The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. 439 82

The antispermatogenic effects of 2, 4-dinitro-6-tert-. butylphenyl methanesulfonate (HE-166) were studied in Sprague-Dawley rats. They were fed 25, 100 and 400 ppm of HE-166 in the basal died for one year. Laboratory data showed no significant changes except for increases in gamma-globulin, alkaline phosphatase, GOT and GPT values in the 100 ppm group. Macroscopically, significant changes were found in the testes in the experimental group, which showed marked atrophy. Histologically, the testes were filled with fibrin exudate in the stroma and there was reduced spermatogonia, cellular debris and giant cells, and even calcification, depending on the dose of HE-166. The anti-fertility effects of HE-166 were also observed by mating rats and checking the pregnancy rate during three generations. These effects might be due to the direct cytotoxic effect of HE-166 on post-meiotic cells as epididymal spermatozoa and testicular sperm and spermatids. As far as tumor incidence was concerned, one case of fibroadenoma of the mammary gland, one case of leiomyosarcoma in the uterus in the 100 ppm group and one case of leiomyoma in the uterus in the 25 ppm group developed at around 8 months, but no other tumors developed.
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PMID:The antispermatogenic effect and toxicity of 2, 4-dinitro-6-tert-butylphenyl methanesulfonate on Sprague-Dawley rat. 609 Jun 86

In male albino mice, the petroleum ether extract of the leaves of Mentha arvensis L., at the doses 10 and 20 mg/mouse per day for 20, 40 and 60 days, when administered orally, showed a dose and duration dependent reduction in the number of offspring of the treated male mated with normal females. Negative fertility was observed in both dose regimens after 60 days of treatment. The body weight and libido of the treated ammals remain unaffected. However, a significant decrease in the weight of the testis, epididymis, cauda epididymal sperm count, motility, viability and normal morphology of the spermatozoa was observed. The levels of serum protein, bilirubin, GOT, GPT and acid phosphatase, blood urea and haematological indices were unaltered throughout the course of investigation. All the altered parameters were reversible following withdrawal of treatment. The results suggest that the petroleum ether extract of the leaves of M. arvensis possess reversible antifertility property without adverse toxicity in male mice.
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PMID:Antifertility investigation and toxicological screening of the petroleum ether extract of the leaves of Mentha arvensis L. in male albino mice. 1128 36

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

[molecular structure: see text] p-tert-Butylcatechol is used as an antioxidant, stabilizer, and polymerization inhibitor for styrene, butadiene, neoprene, and other olefins and reactive monomers. p-tert-Butylcatechol was nominated by the National Cancer Institute and the U.S. Food and Drug Administration for testing based on reports of its increasing levels of production and use and to compare the toxicity of p-tert-butylcatechol with that of similar antioxidants, butylated hydroxyanisole and butylated hydroxytoluene, which are added to food. Male and female F344/N rats and B6C3F1 mice were exposed to p-tert-butylcatechol (greater than 99% pure) in feed for 15 days or 14 weeks. Genetic toxicology studies were conducted in Salmonella typhimurium, rat bone marrow cells, and mouse peripheral blood erythrocytes. In the 15-day studies, groups of five male and five female rats and mice were fed diets containing 0, 3,125, 6,250, 12,500, 25,000, or 50,000 ppm p-tert-butylcatechol (equivalent to average daily doses of approximately 290 to 2,470 mg p-tert-butylcatechol/kg body weight to rats and 590 to 8,200 mg/kg to mice). All animals in the 50,000 ppm groups were killed moribund on day 8 (rats) or by day 7 (mice). Mean body weights of all groups of rats exposed to 6,250 ppm or greater were significantly less than those of the controls. Mean body weights of male mice exposed to 12,500 or 25,000 ppm and of 25,000 ppm female mice were significantly less than those of the controls. Female rats, male and female mice in the 25,000 ppm groups, and 12,500 ppm male mice lost weight during the studies. Feed consumption by exposed rats generally decreased with increasing exposure concentration; feed consumption by exposed mice was similar to that by the controls. Thymus weights of 25,000 ppm rats and mice were significantly less than those of the controls. Gross findings noted at necropsy included thin carcasses for three male and all female rats in the 12,500 ppm groups and all male and female rats and mice in the 25,000 and 50,000 ppm groups. No exposure-related lesions were observed microscopically. In the 14-week studies, groups of 10 male and 10 female rats and mice were fed diets containing 0, 781, 1,562, 3,125, 6,250, or 12,500 ppm p-tert-butylcatechol (equivalent to average daily doses of approximately 70 to 1,030 mg/kg to rats and 135 to 2,815 mg/kg to mice). All animals survived to the end of the studies. Mean body weights of male rats exposed to 1,562 ppm or greater, female rats exposed to 3,125 ppm or greater, male mice exposed to 12,500 ppm, and female mice exposed to 6,250 or 12,500 ppm were significantly less than those of the controls. Feed consumption by male and female rats in the 6,250 and 12,500 ppm groups at week 1 and the 12,500 ppm groups at week 14 was less than that by the controls; feed consumption by exposed and control mice was similar. An erythrocytosis, indicated by increased hematocrit values, hemoglobin concentrations, and erythrocyte counts, was observed in 6,250 and 12,500 ppm rats on day 4 and in 12,500 ppm rats on day 22. At these time points, a transient hepatic effect was demonstrated by increases in alanine aminotransferase activities and bile salt concentrations in exposed rats. In 12,500 ppm male rats, absolute left cauda epididymis, epididymis, and testis weights were decreased by 15%, 10%, and 9%, respectively, compared to the controls. The number of spermatid heads per testis and epididymal sperm motility of male rats in the 12,500 ppm group were significantly less than those of the controls. The numbers of cycling female rats and females with regular estrous cycles were decreased in the 6,250 and 12,500 ppm groups. Exposed groups of females had significantly fewer estrous cycles than did the controls. Estrous cycle length increased with increasing exposure concentration; female rats in the 6,250 and 12,500 ppm groups had significantly longer cycles and spent more time in diestrus and less time in proestrus, estrus, and metestrus than did the controls. Female mice in the 12,500 ppm group had a significantly longer estrous cycle than did the controls. The incidences of hyperkeratosis of the forestomach epithelium were significantly increased in male and female rats in all exposed groups and in 12,500 ppm female mice. The incidences of hyperplasia of the forestomach epithelium were significantly increased in male and female rats exposed to 3,125 ppm or greater, male mice exposed to 12,500 ppm, and female mice exposed to 6,250 or 12,500 ppm. The severities of the forestomach lesions were minimal to moderate in male rats and minimal to mild in female rats and in mice. All male rats exposed to 6,250 or 12,500 ppm had minimal cytoplasmic alteration in the liver. The absorption, distribution, metabolism, and excretion of p-tert-butylcatechol following intravenous injection, gavage dosing, or dermal application were determined in male F344/N rats and B6C3F1 mice. The absorption of [(14)C]-p-tert-butylcatechol following gavage dosing or dermal application was high. The percent absorption following dermal application increased with increasing dose. Peak concentrations of [(14)C]-p-tert-butylcatechol equivalents in plasma were reached 1 hour after gavage dosing (200 mg/kg) and 2 hours after dermal application (60 mg/kg); no parent compound was detected in the plasma extracts. Regardless of route of administration, p-tert-butylcatechol derived radioactivity was readily excreted in the urine and was markedly nonpersistent in the tissues. p-tert- Butylcatechol was excreted as p-tert-butylcatechol sulfate and other polar metabolites that included predominately sulfate conjugates; it was not excreted as the parent compound. One metabolite was determined to be an O-methyl- ON-sulfate of p-tert-butylcatechol. p-tert-Butylcatechol (10 to 1,000 microg/plate) was not mutagenic in any of several strains of S. typhimurium with or without rat or hamster liver S9. Bone marrow micronucleus tests in which 125 to 500 mg/kg p-tert-butylcatechol was administered three times by intraperitoneal injection to male rats gave negative results. No increases in the frequencies of micronucleated normochromatic erythrocytes were observed in the peripheral blood of male or female mice administered p-tert-butylcatechol in feed for 14 weeks. No significant alteration in the percentage of polychromatic erythrocytes in mouse bone marrow was observed. In summary, the primary toxicity of p-tert-butylcatechol was to the forestomach of rats and mice. In the 14-week study in rats, forestomach toxicity was observed at all exposure concentrations, and the no-observed-adverse-effect level (NOAEL) was not reached for this effect. In the 14-week study in mice, the NOAEL for forestomach toxicity was 1,562 ppm.
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PMID:NTP technical report on the toxicity studies of p-tert-butylcatechol (CAS No. 98-29-3) administered in feed to F344/N rats and B6C3F1 mice. 1259 14

The antifertility effects of 50% ethanol extracts of Ricinus communis have been studied in male rats. There was a drastic reduction in the epididymal sperm counts. Alteration in the motility, mode of movement and morphology of the sperms were observed. Reductions in the fructose and testosterone levels were suggestive of reduced reproductive performance. Reversibility tests showed that the antifertility effect of Ricinus communis was completely reversible on withdrawal of the drug. The ethanol extracts of Ricinus communis did not cause any hepatotoxicity since the hepatic GOT and GPT levels were unaltered.
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PMID:Antifertility effects of Ricinus communis (Linn) on rats. 1274 88


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