摘要:

AbstractThe time development of the biodistribution and the hepatotoxicity following peroral administration of14C‐acetaminophen (APAP 400 or 800 mg.kg−1; 1μCi) was characterized in a trial procedure using male Bom:NMRI mice. APAP (400 mg.kg−1) caused a transitory hepatic glutathione (GSH) depletion while APAP 800 mg.kg−1maximally depleted hepatic GSH throughout the 12 h trial period. A lag time between the initial GSH depletion and the ensuing hepatic necrosis was seen. From 8 h post dosing a decrease of14C‐APAP or its metabolites coincided with recovery of the hepatic GSH level and the regeneration of the hepatic cells caused by APAP 400 mg.kg−1. Hepatic glycogen depletion preceded centrilobular necrosis, and irrespective of APAP dose definite kidney damage was absent. Irrespective of APAP dose the biodistribution of14C‐APAP or its metabolites was predominantly in organs associated with metabolism and excretion. After APAP (800 mg.kg−1) significant amounts of14C‐APAP or its metabolites were present up to 24 h post dosing. The operative status of the hepatic GSH conjugative system has an important influence on the rate of elimination of toxic APAP doses. Hepatic cell necrosis with a possible effect on the circulation may play an important secondary role in the elimination of toxic APAP doses. Factors which may influence the status of the hepatic GSH conjugative system and toxicokinctics of perorally administered APAP d

ISSN:0260-437X    

DOI:10.1002/jat.2550070102

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractSingle exposure of rabbits to aniline vapors caused induction of superoxide dismutase isozymes and activity as evidenced by the incorporation of radioactive amino acids and prosthetic group metals into enzymatic protein zones of electrophoreograms. Induced of a new cytosolic isozyme following aniline exposure was also evident. Xenobiotic stress indicated a close relation between free radical processes and lung biotransformation mechanisms.

ISSN:0260-437X    

DOI:10.1002/jat.2550070103

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractMale Wistar rats were exposed for 4 weeks, 5 days a week, to 0 (controls), 5 or 10 ppm formaldehyde continuously (8 hours a day), or to 10 or 20 ppm formaldehyde interruptedly (eight 30 min exposure periods separated by 30 min non‐exposure periods). Histopathology and cell proliferation studies indicated that under the conditions of exposure used, concentration rather than the total dose of formaldehyde determined the severity of the cytotoxic effects on the nasal epitheliu

ISSN:0260-437X    

DOI:10.1002/jat.2550070104

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractSporidesmin, the mycotoxin responsible for ‘facial eczema’ in ruminants, has previously been shown to generate superoxide radical and hydrogen peroxide. In the present study, the formation of the third ‘active oxygen’ species, hydroxyl radical, has been demonstrated. This species is produced both during the autoxidation of the reduced (dithiol) form of the mycotoxin and in the cyclic reduction/autoxidation reaction between sporidesmin and glutathione. In view of the exceptional reactivity of the hydroxyl radical, this substance may be the proximate agent responsible for the toxic effects of spor

ISSN:0260-437X    

DOI:10.1002/jat.2550070105

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractRats received either single oral doses of 0, 25, 50, 100 and 200 mg/kg tris(2,3‐dibromopropyl)phosphate (Tris‐BP) or repeated doses of 50, 100 and 200 mg/kg/day Tris‐BP for 7 days. Urine was collected over a 24‐hr period and subjected to13C‐NMR and biochemical examinations. Tris‐BP produced significant increases of urinary glucose and lactate. Urinary γ‐glutamyitransferase, lactate dehydrogenase and alkaline phosphatase levels were significantly elevated on the first 2 days of post‐treatment. Histopathologically, the kidney exhibited proximal tubular damage at a dose of 200 mg/kg. There was a good correlation among the histopathological, biochemical results, and the13C‐NMR urinary metabolite fingerprints in the assessment of Tris‐BP‐induced renal damage. The abnormal patterns of metabolite excretion suggested that the lesions produced by Tris‐BP were caused by changes in the metabolic function of tubular epithelial cells. The urinary excretion of lactate, enzymes and inhibition of glucose reabsorption from the tubular lumina may be attributed to necrosis and desquama

ISSN:0260-437X    

DOI:10.1002/jat.2550070106

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractRecently it has been found that homogenates ofTetrahymena thermophilacan hydrolyze the potent acetylcholinesterase inhibitorsO,O‐diisopropylphosphofluoridate (DFP) andO‐1,2,2‐trimethylpropylmethylphosphonofluoridate (soman). Upon purification of the DFP hydrolyzing activity 10‐fold it had been noted that the soman hydrolyzing activity increased only 2–3 fold. Treatment with manganous ion and comparison of the soman and DFP hydrolysis rates of the homogenate indicated that a mixture of the squid‐type and Mazur‐type DFPases may be present. Subsequent purification of the enzymatic activities within theTetrahymena‐homogenate demostrated that there are at least five functioning proteins of molecular weights 67 000 to 96 000. None are directly homologous to the DFPases found in hog kidney or squid. The enzymatic activities are designated DFPase‐1 through DFPase‐5. A hypothesis is presented that the functions of DFPases are in the normal metabolism of organophosphates naturally synthesiz

ISSN:0260-437X    

DOI:10.1002/jat.2550070107

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractMale and female albino Wistar rats were exposed to concentrations of 0, 1, 10 or 20 ppm formaldehyde vapour during 6 h/day, 5 days/wk for 13 weeks. Treatment‐related changes observed at 20 ppm included in both sexes: stared coats, uncoordinated locomotion and excitation during the first 30 minutes of each exposure, yellowing of the fur, growth retardation, a decreased level of plasma protein, severe and extensive karatinized stratified squamous metaplasia of the nasal respiratory epithelium, and focal degeneration and squamous metaplasia occasionally accompanied by keratinization of the olfactory epithelium; in males only; increased activities of plasma aspartate amino transferase (ASAT), alanine amino transferase (ALAT) and alkaline phosphatase (ALP) and squamous metaplasia of the laryngeal epithelium.Lesions seen at 10 ppm included yellowing of the fur and moderate squamous metaplasia of the nasal respiratory epithelium. The only change observed in three out of twenty 1 ppm exposed animals that might or might not be treatment‐related was minimal focal epithelial hyperplasia and squamous metaplasia of the respiratory epithelium lining the nasal septum and maxillary turbinates.No histopathological evidence of hepatotoxicity was detected in any of the formaldehyde‐treated groups.Anin vivo/in vitrocell proliferation study showed an increase in [3H]‐thymiding labeling index of the respiratory epithelium lining the nasoturbinates of rats exposed to 10 or 20 ppm formaldehyde on three successive days, whereas at the 1 ppm level the labeling index was similar to that of controls. It was concluded that under the conditions of the present 13‐week inhalation study, formaldehyde at concentrations up to 10 ppm was not hepatotoxic to rats. At the 20 ppm formaldehyde level, a slight effect on the fiver of mate rats cannot be completely excluded. The study was inconclusive with respect to 1 ppm formaldehyde being a cytotoxic or a no‐cytotoxic effect level for the nasal

ISSN:0260-437X    

DOI:10.1002/jat.2550070108

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe seed of modern cultivars ofLupinus angustifoliusnormally contain less than 0.03% alkaloids. The acute oral LD50to rats of a prorata mixture of the alkaloids ofL. angustifoliusseed was found to be 2279 mg/kg. For lupanine the LD50by oral administration was 1464 mg/kg and by intraperitoneal injection 177 mg/kg. For 13‐hydroxylupanine the LD50by intraperitoneal injection was 199 mg/kg. Since these two alkaloids comprise about 85% of the total and are known to be rapidly cleared from the body it is suggested that the alkaloids in this species do not pose a health problem for ma

ISSN:0260-437X    

DOI:10.1002/jat.2550070109

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractWe have reported that inhalation exposure of rats to toluene causes permanent hearing loss, e.g. Pryoret al. Neurobehav. Toxicol. Teratol.5, 53–62 (1983). Therefore, it was of considerable interest to examine the ototoxic potential of two structurally related solvents—mixed xylenes and styrene—compared with that of toluene. Male, weanling Fischer‐344 rats were exposed to clean air or solvents in four identical 62.5 I Pfexiglas chambers. Exposures to 800, 1000, and 1200 ppm were daily for 14 hours/day and lasted 6 weeks for mixed xylenes, 3 weeks for styrene. An additional experiment with xylenes examined the effect of exposure for only 4 (1700 ppm) or 8 (1450 ppm) hours or for 8 (1450 ppm) hours on three consecutive days to compare the results with those obtained with toluene under comparable exposure schedules. Both xylenes and styrene caused marked hearing loss as assessed by behavioral (conditioned avoidance) and electrophysiologic (brainstem auditory‐evoked response) methods. Moreover, both solvents appeared to be more potent ototoxicants than toluene, as indicated by effective concentration, effective durations of exposure, and the range of frequencies

ISSN:0260-437X    

DOI:10.1002/jat.2550070110

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractIn agreement with the inhibition of dopamine‐β‐hydroxylase by exposure to CS2, the extension of exposure time from 4 to 16 h increased dopamine concentrations in the hypothalmus and adrenals, and decreased noradrenaline concentration in the hypothalmus. The extension of exposure time also increased the toxicity of amphetamine. In conscious animals the stereotypic activity produced by 6.0 mg/kg and even that of 3.0 mg/kg amphetamine sulphate was suppressed by severe hyperthermia resulting in exhaustion, prostration and eventually death. A 16h exposure to CS2did not increase the lethal or hyperthermic effects of amphetamine in rats anaesthetized with 60 mg/kg sodium pentobarbitone. In fact the CS2exposed rats became more hypothermic than non‐expose

ISSN:0260-437X    

DOI:10.1002/jat.2550070111

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY