ISSN:0260-437X    

DOI:10.1002/jat.2550080302

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractBlood samples from rats and hamsters exposed to automotive engine exhausts in the Committee of Common Market Automobile Constructors long‐term inhalation study at Battelle‐Geneva were analysed for the levels of 2‐hydroxyethylvaline (HOEtVal) and 2‐hydroxypropylvaline (HOPrVal) in hemoglobin (Hb). These adducts to theN‐terminus of the Hb chains were determined by gas chromatography‐mass spectrometry of derivatives obtained by a modified Edman degradation that specifically cleaves off alkylatedN‐terminal amino acids (valine in Hb).The adduct levels found correspond to the metabolic conversion of about 5–10% of inhaled ethene and propene to ethylene oxide and propylene oxide, respectively, in agreement with results from earlier studies on mice inhaling radio‐labelled alkenes. It is concluded that the alkenes, via epoxides, are the main sources of the observed HOEtVal and HOPrVal. From calculated doses and estimates of genotoxic potency the contribution from ethene in urban air to human cancer

ISSN:0260-437X    

DOI:10.1002/jat.2550080303

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractChanges in blood volume, heart and lung mass and composition and plasma renin activity were examined in two strains of male albino rats inhaling incrementally‐increasing concentrations of CO: 250 ppm for 17 days, 500 ppm for 13–14 days, 750 ppm for 10 days, and 1300 ppm for 10 days. Blood volume increased 86% and erythrocyte mass increased 212% at 1300 ppm, while plasma volume was unchanged or decreased slightly. “Real” hematocrit (hematocrit corrected for plasma trapping) increased from 50% in controls to a peak of 75% at 1300 ppm CO. Wet weight of right ventricle (RV) and combined right and left atria (2A) increased linearly with CO concentration, paralleling changes in blood volume; while real hematocrit increased nonlinearly. Left ventricle + interventricular septum (LV+S) wet weight increased less than RV, but more in Sprague‐Dawley than in Wistar rats. Plots of RV, LV+S and 2A weightvsreal hematocrit showed sharp upward inflections at real hematocrit 65%, suggesting a possible role of increased viscosity in CO cardiomegaly at the higher hematocrit. Assymetric septal hypertrophy was not present. Lung weight increased with CO concentration, but was not due to increased lung blood volume or edema. Hydroxyproline measurements on heart and lung failed to show increased collagen content. Plasma renin activity measured by radioimmunoassay was depressed at 500 ppm, but was normal at 750 and 1300 ppm CO. Neither heart, lung,liver nor plasma renin measurements suggest congestive heart failure, supporting previous studies in the rat with chronic carboxyhemoglobinemia, in spite of enormously increased blood volume, hematocrit and hea

ISSN:0260-437X    

DOI:10.1002/jat.2550080304

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractToxic effects of ferrous sulfate and of ferric chloride were determined in the gastrointestinal tract by measuring the induction of nuclear aberrations and micronuclei. In fasting animals ferric chloride induced a dose‐related increase of nuclear aberrations in the stomach, whereas ferrous sulfate was not active. In normally feeding animals no increase of nuclear aberrations was observed. The effects of the iron compounds on the duodenum were minimal. In fasting animals a dose‐related increase of nuclear aberrations was observed at the level of the colon, with no clear difference between ferrous and ferric compounds. A modest increase of nuclear aberrations of the colon was seen in feeding animals only with ferrous sulphate. By intrarectal administration, nuclear aberrations were induced especially by ferric chloride.An increase of the frequency of micronuclei was not observed at the level of the stomach, duodenum and colon, with the exception of ferric chloride, that induces a significant, although small increase of colon micronuclei when administered intra‐rectally. The data demonstrate that iron compounds have an intrinsic cellular toxicity when not administered with food, but do not seem to carry any genotoxic potential for the gastrointestinal

ISSN:0260-437X    

DOI:10.1002/jat.2550080305

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThis paper illustrates the effects of survival differences on the routine analysis of 2‐year animal carcinogenesis experiments using quantal response. Not adjusting for decreased survival in the higher dosed groups results in a decrease in the actual significance level for the quantal response trend test, and a corresponding decrease in sensitivity for detecting a true treatment effect. Similar results hold for estimation of carcinogenic risk. Tables of the range of survival differences found in recent National Toxicology Program carcinogenesis studies are presente

ISSN:0260-437X    

DOI:10.1002/jat.2550080306

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractTo evaluate the inhalation toxicity of Ga2O3, F344 rats were exposed nose‐only to 0.2 μm Ga2O3particles 2 h/day, 5 days/week for 4 weeks. The exposure concentration was 23 ± 5 mg/m3(mean ± SD) resulting in lung burdens of 0.8 ± 0.1 mg Ga2O3/lung (mean ± SE) at the end of 4 weeks of exposure. Analysis of bronchoalveolar lavage fluid of exposed rats showed marked responses. One day after termination of exposure, lactate dehydrogenase was increased 6‐fold, and the lysosomal enzyme, beta‐glucuronidase, was increased 38‐fold in rats exposed to Ga2O3compared to sham exposed controls. Alkaline phosphatase, glutathione reductase, glutathione peroxidase, white blood cells, acid proteinase, and protein were increased 3‐ to 4‐fold. Responses remained elevated 6 and 12 months after exposure. Lung clearance of radiolabeled tracer particles was evaluated 4 days and 6 months after the end of 4 weeks of Ga2O3exposures. Long‐term clearance half‐times were significantly longer| (3–4 fold,P<0.01) in rats exposed to Ga2O3than in the sham‐exposed control rats at both 4 days and 6 months, indicating persistent impairment of particle clearance. Histopathological lesions consisted primarily of alveolar proteinosis 1 day after 4 weeks exposure, progressing in severity to large focal lesions of alveolar histiocytosis and septal fibrosis 6 and 12 months after exposure. Inhaled Ga2O3produced cytotoxic, inflammatory, and fibrogenic responses of comparable or greater magnitude than those seen after similar exposures of rats to inhaled quartz particles in other studies. These data show that inhaled Ga2O3particles produce considerable toxicity and exposures in the work

ISSN:0260-437X    

DOI:10.1002/jat.2550080307

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractTwo aliphatic nitriles, acetonitrile and fumaronitrile were tested for their genotoxic potential in three mutagenicity test systems:the Salmonella/microsome‐assay, an assay usingSaccharomyces cerevisiae(strain D7), and the bone marrow micronucleus test.Both compounds were tested with and without metabolic activation in the yeast and the bacterial test systems using S9 preparations from phenobarbitone‐pretreated and autoinduced rats. Autoinduction was performed by chronic (7 days) application of a dose equivalent to a 5% oral LD50‐value of the respective compound.With yeast strain D7 both nitriles induced low levels of gene conversion in the presence of phenobarbitone‐induced liver homogenate. An increase in the number ofile+‐revertants was not detectable under any condition.Neither of the compounds showed mutagenic activity in the Ames test with or without metabolic activation.A weak positive effect of acetonitrile could be detected in the micronucleus test 24 h after i.p.‐injection of the compound using a dose of 60% LD50. Fumaronitrile showed positive results with a 50% LD50dose 48 h after administration to mice not preinduced. After 1 week of autoinduction these effects did not appear anymore, with the exception of acetonitrile 72 h after application of a dose amounting to 60% of the oral

ISSN:0260-437X    

DOI:10.1002/jat.2550080308

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractA comparative study was made of the cytotoxic action of quartz dustin vitroon macrophages activatedin vivoby intraperitoneal inoculation of physiological saline, thioglycolate and starch. The liberation of lactate dehydrogenase (LDH) into the supernatant culture medium, adherence to a plastic surface, extent of acid dye exclusion and ultrastructural alteration in the surface morphology of macrophages were taken as parameters of the cytotoxic action of the dusts. Thioglycolate and starch stimulated cells when exposedin vitroto quartz dust released more LDH into the supernatant culture medium and resulted in a greater decrease in macrophage adherence than similarly exposed cells derived from saline stimulated animals. No difference was observed between cells obtained from differently stimulated animals in increased acid dye uptake, loss of surface filopodia and rounding of cells which phagocytosed quartz particles. The results show that quartz is cytotoxic for macrophages, irrespective of their degree of activation and the extent of damage induced is related to the chemical agent used for activation of macrophagesin vivo.

ISSN:0260-437X    

DOI:10.1002/jat.2550080309

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractAge‐ and sex‐related differences in hepatic and renal distribution of cadmium (Cd) and the effect of Cd injection (10 μmol/kg) on tissue zinc (Zn), copper (Cu) and metallothionein (MT) levels were investigated in 2‐ to 84‐day old rats. Renal Cd accumulation increased with age of the animal. Sex differences in renal Cd accumulation were noted in young animals where the 2‐ and 8‐day old males had significantly greater concentration than the females. There were no clear effects of Cd on renal Zn. Renal Cu levels, however, were elevated in the adults. The adult females contained about twice as much MT as the adult males. Cd treatment had no effect on renal MT levels of 8‐ to 84‐day old animals but depressed the levels in 2‐day old. Age‐related increase in hepatic Cd accumulation was also found; the pattern was more clear cut in females than in males. In addition, in the females the hepatic Cd concentration was significantly higher than in the males. Cd‐injection significantly increased hepatic Zn and MT concentrations only in weaned animals. While there were no sex differences in MT levels in the young animals, the weaned females had significantly more MT than the corresponding males. Immunohistochemical staining for MT showed positive staining in both cytoplasm and nuclei of the parenchymal cells. The number of MT‐positive nuclei was dependent on the relative MT concentration of the liver. In spite of the intense nuclear staining in 2‐day old controls and 84‐day old Cd‐injected rats, less than 1% of the hepatic MT was present in the nuclear fraction. The above data on the tissue distribution of Cd point to the possible effects of sex hormones on Cd metabolism. The results of the intracellular distribution of MT suggest that nuclear MT represents only a minute fraction of the total cellula

ISSN:0260-437X    

DOI:10.1002/jat.2550080310

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractOxmetidine, a new and more potent analogue of the H2receptor antagonist, cimetidine, was recently withdrawn from clinical trials because of associated hepatotoxicity. We investigated the potential hepatotoxicity of the drugin vitroandin vivoin the rat. In addition, we investigated, inin vitroexperiments, the potential hepatoxicity of other gastric acid inhibitory drugs (cimetidine, ranitidine, omeprazole and nolinium bromide). Inin vitroexperiments, oxmetidine, at various concentrations, was added to isolated hepatocyte incubations and cytoxicity was assayed by trypan blue exclusion. Inin vivoexperiments, oxmetidine was administered both i.p. and orally, and hepatotoxicity was assessed by serum biochemical measures (transaminases, alkaline phosphatase, 5′nucleotidase, gamma glutamyl transpeptidase) and liver histopathology. In thein vitrostudies, the addition of oxmetidine to the hepatocyte incubations was associated with significant (P<0.001) dose and time dependent cytotoxicity. However, thein vivoexperiments revealed no significant changes in serum biochemistry and no significant alterations in liver histopathology up to 72 h following the administration three different dosages of oxmetidine. Of the other gastric acid inhibitory drugs, only nolinium bromide was associated with significant (P<0.001)in vitrocytotoxicity. Ourin vitroobservations establish that oxmetidine is cytotoxic to isolated rat hepatocytes and suggest that nolinium bromide be further evaluated for potential hepatotoxicit

ISSN:0260-437X    

DOI:10.1002/jat.2550080311

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY