摘要:

AbstractThe acute and subchronic toxicological effects of nitazoxanide were investigated at levels near and in excess of the therapeutic dose in rats, mice, dogs and cats. Single oral gavage doses of 0.625–10 g per kg body weight were administered to rats and mice. Single oral doses of 1–10 g per kg body weight were administered in capsules to dogs and cats. Acute oral LD50values were greater than 10 g kg−1in rats, dogs and cats, and 1.4 g kg−1in mice. Systemic toxicity was evaluated in a repeated dose study in rats at doses of 50, 150 and 450 mg per kg per day for 14 weeks. The highest dose group exhibited intense salivation, increased liver and spleen weight, and decreased thymus weights. Variances between control and treated organ weights were not confirmed by histopathological evaluation. Nitazoxanide was negative when tested in the Ames Salmonella assay using five tester strains with and without metabolic activation at levels from 1 to 100 mg per plate. The drug was also shown to be non‐irritating in a test for eye irritation

ISSN:0260-437X    

DOI:10.1002/jat.2550050202

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractA series of 27 compounds, including 11 polycyclic hydrocarbons, 8 proximate carcinogens and 8 other compounds, were tested for their ability to induce epidermal nuclear enlargement in mouse skin. The materials were applied topically in methyl ethyl ketone containing 0.1% croton oil, repetitively for 3 days. Nuclear enlargement present on the fourth day was determined with the aid of a Quantiment image‐analysing computer. The results obtained indicated a close correlation between the topical carcinogenicity of the test compounds and their ability to induce epidermal nuclear enlargement in the presence of croton oi

ISSN:0260-437X    

DOI:10.1002/jat.2550050203

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractFetal chromosomal damage and toxicity were investigated in mice exposed to the atmospheric concentrations of 28.5 mg m−3, 2.9 mg m−3and 0.26 mg m−3of arsenic for 4 h per day on the 9th, 10th, 11th and 12th days of gestation. On the 18th day, the fetuses were removed, and the following parameters were examined: the number of dead fetuses, retardation in growth, osteogenesis and chromosomal aberrations in liver cells. It was found that exposure to As2O3at 28.5 mg m−3caused fetotoxic effects and chromosomal damage, while the two lower exposures produced no significant changes with the exception of a slight decrease (9.9 and 3.1%, respectively) in fetal

ISSN:0260-437X    

DOI:10.1002/jat.2550050204

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractEffects ofn‐octane andn‐nonane (1 ml per kg body weight daily) on hepatic and serum enzymes, which reflect abnormal liver function and concentration of lipid and nucleic acid (serum and liver), were studied after 2 and 7 days intraperitoneal administration to albino rats. Decreased activities of serum acetylcholine esterase and carboxyl esterase were observed, together with an increase in FDP aldolase activity. Significant decrease in the concentration of albumin, total protein, and total and esterified cholesterol in serum have been noted aftern‐octane andn‐nonane administration for 7 days. Also, free cholesterol content of liver was elevated significantly after solvents e

ISSN:0260-437X    

DOI:10.1002/jat.2550050205

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractSporidesmin, the mycotoxin responsible for “facial eczema” in ruminants, has previously been shown to generate superoxide free radical, the latter being formed during autoxidation of the reduced form of the mycotoxin, a dithiol. The autoxidation of reduced sporidesmin is catalysed by iron and by copper, although cobalt, nickel, manganese, cerium, vanadium and molybdenum were found to be without effect. The catalytic activity of copper was some 900‐fold that of iron. Cyanide and certain organic complexing agents inhibit superoxide production from reduced sporidesmin by virtue of their ability to chelate copper. Some proteins behave likewise, again through binding of the metal catalyst, although arnino acid‐bound copper was found to be as effective as ionic copper in catalysing the autoxidation reaction. From the results of the present experiments, it is suggested that any superoxide production from sporidesminin vivowould be mediated by the intracellular transport pool of copper. Furthermore, the ability of zinc to inhibit intestinal absorption of copper may be involved in the mechanism whereby salts of this metal afford protection against the harmful effects of sporidesmin in the living

ISSN:0260-437X    

DOI:10.1002/jat.2550050206

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractHexachloro‐1, 3‐butadiene (HCBD) produced a time‐ and dose‐related increase in hepatic water content following i.p. administration to male Alderley Park (Alpk/AP) mice. The increase in liver water was maximal 1–2 days after a single dose of 50 mg kg−1and had returned to normal by day 5. Associated with the increased water, there was a parallel increase in Na+and K+ions, with no overall change in intracellular cation concentration. Liver non‐protein sulphydryl content showed no consistent time‐related decrease after 50 mg kg−1HCBD. Histopathological examination of the liver showed fine cytoplasmic vacuolation of periportal hepatocytes which was more marked following 100 or 200 mg kg−1than 50 mg kg−1HCBD. In one animal, following 200 mg kg−1HCBD, the liver showed ballooning and degeneration of periportal hepatocytes. Ultrastructural changes were evident 4 h after 50 mg kg−1and consisted of mitochondrial swelling in periportal hepatocytes, whilst pericentral hepatocytes appeared normal. By 16 h, marked mitochondrial swelling and some proliferation of smooth endoplasmic reticulum were evident in periportal hepatocytes. Male mice of the C57BL/10J and C3H strains appeared to be more sensitive to HCBD‐induced hepatic hydropic change than did the male and female Alpk/AP strain and male Balbc and DBA/2 J strains. It appears that HCBD or a metabolite causes disruption of mitochondria in periportal hepatocytes which results in an influx of water and ions into the cell witho

ISSN:0260-437X    

DOI:10.1002/jat.2550050207

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractIn this study, methodologies developed for the analysis of synthetic fuel products were applied to the coal tar fractions isolated from coal tar‐based pharmaceutical products. A pharmaceutical stock solution of 20% coal tar in alcohol, a 50% coal tar bath emulsion and a 4.3% coal tar shampoo were studied. The toxicology and chemical composition of the coal tar fractions isolated from these materials were compared with an industrial coal tar and with a direct‐liquefaction coal liquid product. The coal tars and coal liquid product were fractionated into chemical classes by alumina column chromatography and individual components were identified and quantitated by high‐resolution gas chromatography. The microbial mutagenicity of these materials was measured againstS. typhimurium, TA 98. In addition, the industrial coal tar, coal‐liquid product, and coal tar isolate from the 20% coal tar in alcohol solution were tested for initiating activity in an initiation/promotion mouse skin painting assay for carcinogenicity. The chemical compositions of the coal tar‐based therapeutic agents, the industrial coal tar and direct‐liquefaction coal liquid were similar. With the exception of the 50% bath emulsion, the microbial mutagenicity and tumor‐initiating activity in mouse skin for those materials tested were

ISSN:0260-437X    

DOI:10.1002/jat.2550050208

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractThe uptake of14C‐proline by lung slices and its incorporation into trichloroacetic‐acid (TCA)‐insoluble proteins and hydroxylation in collagenous proteins were studied. They were found to be linearly increased with the incubation time for as long as 8 h. The effects of different concentrations of bleomycin on these parameters were subsequently investigated. Bleomycin at 10−3M significantly reduced the uptake of14C‐proline to 75% of the control value. The incorporation of14C‐proline into TCA‐insoluble proteins was reduced to 84%, 78% and 75% of the control at 2.5 × 10−4M, 5 × 10−4M and 10−3M concentrations of bleomycin, respectively. Bleomycin failed to alter the proline pool size of the lung slices at any of these concentrations. In addition, bleomycin also inhibited the hydroxylation of14C‐proline into collagen to 72% and 69% of the control at 5 × 10−4M and 10−3M, respectively. These findings show that bleomycin‐induced increases in collagen synthesisin vivois probably secondary to inflammatory reactions of the lung and bleomycinper sehas little effect on increased collagen synthesis

ISSN:0260-437X    

DOI:10.1002/jat.2550050209

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractTo estimate the plasma ‘filterable’ form concentration, glomerular filtration and tubular reabsorption in man for metals and organic substances, the regressions of the 24‐h urinary excretion of lead (Pb), inorganic mercury (Hg), δ‐aminolevulinic acid (ALA) and coproporphyrinogen (CP‐gen) on glomerular filtration rate were examined. The regressions were significant for ALA in two ‘healthy’ men examined and for Pb and for CP‐gen in one of them. From these data, it was estimated that the plasma concentration of ‘filterable’Pb was approximately 0.01 μg dl−1; the ALA concentration was 2.3 and 4.5 μg dl−1; and CP‐gen was 0.11 μg dl−1. Similarly, the filtered loads of Pb, ALA and CP‐gen were assumed to be nearly twice as large as their urinary excretion. Hg was not considered

ISSN:0260-437X    

DOI:10.1002/jat.2550050210

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY

摘要:

AbstractAlcide®, a liquid sterilizer, was evaluated for teratogenic potential in rats and mice. Sodium chlorite and lactic acid, the active ingredients of this compound, form chlorine dioxide when mixed. Pregnant rats and mice were administered 1 ml and 0.1 ml, respectively, of Alcide® liquid by gavage on days 6–15 of gestation. The general health of the dams was evaluated and the fetuses examined for external, visceral and skeletal malformations. There was no evidence of maternal toxicity among treated rats and mice. Fetal viability, weight, length and number of resorptions were comparable with control groups. Teratogenic toxicity was not detected in either species. There was some incidence of skeletal and visceral anomalies; however, these variances were not significantly different from control anim

ISSN:0260-437X    

DOI:10.1002/jat.2550050211

出版商:John Wiley&Sons, Ltd.    

年代:1985

数据来源: WILEY