摘要:

AbstractA rapid optical method for determining the quantity of soot in the lungs of rodents exposed to diluted diesel exhaust has been developed. The method is nondestructive to enzymatic components of the lung, allowing dose and biochemical assays to be done on the same sample. The lung burdens of soot were determined by comparing the extinction of light at 620 nm of lung homogenates from exposed animals to that of lung homogenates containing spiked standards.

ISSN:0260-437X    

DOI:10.1002/jat.2550070602

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe profile of urinary salicylate metabolites was determined after an oral administration of acetylsalicylic acid (ASA) to: 1, control rats; 2, rats treated with CCl4and 3, rats intoxicated with CCl4and also pretreated with colchicine for 7 days. The following enzymatic activities were determined: liver and plasma ASA‐esterase, liver UDP‐glucuronyltransferase and liver aniline hydroxylase. The time course of plasma concentration of salicylates in similar groups were followed after the intraperitoneal administration of acetylsalicylic acid (ASA), salicylic acid (SA) or gentisic acid (GA). The animals acutely intoxicated with CCl4showed a reduction in urinary excretion of glucuronates and an increased urinary excretion of gentisic and salicylic acids. The activities of plasma and liver ASA‐esterases were significantly increased in CCl4‐treated rats while the aniline hydroxylase was reduced and the UDP‐glucuronyltransferase remained unchanged. The plasma half lives of salicylates were reduced in CCl4‐treated rats regardless of the administered parent compound. Colchicine pre‐treatment completely prevented the alterations produced by acute intoxication with CCl4. The heterogeneity of liver metabolic disfunctions present in acute liver damage was evidenced. It is emphasized that the pharmacokinetic alterations produced by acute liver injury can be the result of complex factors that may involve changes in circulation, hepatic binding protein and other routes o

ISSN:0260-437X    

DOI:10.1002/jat.2550070603

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractAcute toxicity was studied by administering an encapsulated single dose to chickens (G.g. domesticus) and observing them for 21 days. Azodrin‐71 (Tech.) was found to be extremely toxic, whereas Cypermethrin‐92 (Tech.), Cypermethrin‐25 EC and Permasect‐25 EC (Form.) were practically non‐toxic based on LD50value determinations.Sub‐acute oral haemotoxicity of technical and formulation grades of these insecticides was also studied by administering encapsulated low, medium and high daily doses for 21 days to chickens and recording clinical symptoms, mortality and haematological parameters pre and post‐dosing.Clinically high doses of Azodrin‐71 (Tech.) caused tremors and ataxia among chicks on the 10th day after dosing. Synthetic pyrethroids caused slight tremours in the whole body accompanied by salivation. In general, hyperactivity to external stimuli and loss of appetite and body weight were also observed.With sab‐acute oral doses, Permasect‐25 EC (Form.) more potently affected haemoglobin (Hb), red cell (RBC) counts and chloride level. Cypermethrin‐92 (Tech.) was most potent towards thrombocytes and clotting time. Azodrin‐71 (Tech.) was more potent to white cell (WBC) counts and serum protein level.The present Haematological studies have disclosed the possible reaction of blood and blood ferming organ

ISSN:0260-437X    

DOI:10.1002/jat.2550070604

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe hepatotoxicity of atrazine was investigated by studying clinical parameters related to hepatic function and by electron microscopy. Three groups to male albino rats (Wistar strain) received 100, 209 and 400 mg of atrazine/per kg of body weight/per day, for 14 days. One group received 600 mg atrazine/per kg of body weight/per day, for 7 days. At termination of dosing, the animals were sacrificed and blood was drawn for the determination of serum total lipids, glucose, alanine aminotransferase (ALT) and alkaline phosphatase (SAP). A dose dependent decrease in serum glucose concentration was observed in all the groups. In contrast, a dose relate increase in total serum lipids, was apparent at all dose levels studied. Activity of serum ALT and SAP increased approximately 60% and 200% respectively in rats given 600 mg atrazine/kg bw for 7 days. The liver was examined grossly and microscopically. Electron microscopy disclosed no changes in the hepatocytes of rats treated with the low dose (100 mg/kg bw). At high doses, electron microscopy revealed hepatocytic proliferation and degeneration of smooth endoplasmic reticulum, lipid accumulation and alteration of bile canaliculi proportional to dose and duration of treatment.

ISSN:0260-437X    

DOI:10.1002/jat.2550070605

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe induction of unscheduled DNA synthesis (UDS) in rat primary hepatocytes is used as anin vitroscreen for genotoxicity. The purpose of this study was to develop criteria for statistical evaluation of autoradiographic grain counts from the UDS assay. Based on our historical solvent control population (N= 17), we first established a predictive two‐sided symmetric tolerance interval providing 95% confidence for coverage of 99% of the distribution of the mean net nuclear grain count for a new solvent control observation. The tolerance interval was determined to run from −2.82 to 4.03 net nuclear grains. When the concurrent solvent control (C) proves admissible (−2.82

ISSN:0260-437X    

DOI:10.1002/jat.2550070606

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractFemale Swiss mice were exposed to sodium selenite (3 μ/ml selenium content) and nickelous chloride (100 μg/ml nickel content) in the drinking water on alternate days for 15 weeks. After 3 weeks of metal exposure, the mice were administered urethan (1.5 mg/g) intraperitoneally. Pulmonary adenoma formation was evaluated 12 weeks later. Selenium exposure did not alter the tumor incidence (P= 0.059) or the tumour size (P= 0.98). Nickel exposure did not affect the tumour incidence (P= 0.25), but increased the average tumour size (P= 0.0025). Combined selenium and nickel exposure resulted in significant interactions associated with tumour size (P= 0.00075) and tumour number (P= 0.045). Urethan‐induced sleeping times were reduced by selenium exposure (P= 0.0049), but were unaffected by nickel exposure (P= 0.99). Combined metal exposure did not influence urethan‐induced sleeping times (P=

ISSN:0260-437X    

DOI:10.1002/jat.2550070607

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractArterial blood gases and the pulmonary uptake of putrescine and 5‐hydroxytryptamine (5‐HT) were studied between 6 h and 18 days after the administration to rats of an oralLD50‐dose of the pneumotoxin,O,S,S‐trimethyl phophorodithioate (OSSMe), a potential impurity in several organophosphorus insecticides.Aortic blood was sampled under pentobarbitone anaesthesia for measurements of arterial pH, and partial pressures of oxygen (PaO2) and carbon dioxide (PaCO2).PaO2was significantly decreased 4 days after OSSMe administration, i.e. at the time of maximum lethality and increases in wet lung weight. This was accompanied by a significant increase inPaCO2and acidosis. These results are compatible with an impairment of gas exchange due to diffuse lung damage. For reasons that are unclear,PaCO2was slightly increased 2, 6 and 12 days after dosing.The uptake of putrescine (1,4‐diaminobutane) and of 5‐HT was measured by incubating lung slices with several concentrations of [3H]‐putrescine and [14C]−5‐HT, so as to estimate the apparent kinetic parameters of uptake,VmaxandKm. TheVmaxfor putrescine‐uptake was significantly decreased 1,2,4,6 and 12 days after the administration of OSSMe. TheVmaxfor 5‐HT‐uptake was significantly increased 1 day and significantly decreased 4 days after OSSMe administration.The uptake of 5‐HT is an endothelial function, and the decrease in 5‐HT‐uptake at 4 days may reflect injury to the pulmonary vascular endothelium at this time. The uptake of putrescine probably reflects the function of the pulmonary (mainly alveolar) epithelium. Alveolar type I cells are the cellular targets for the toxic action of OSSMe, and their destruction is followed by type II cell proliferation. The early and prolonged decrease in putrescine‐uptake, therefore, suggests that this function is different in proliferating type II cells as opp

ISSN:0260-437X    

DOI:10.1002/jat.2550070608

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe effect of endogenous glycogen on lipid peroxidation was examined in hepatic microsomes from rats. Microsomes were prepared to retain endogenous hepatic glycogen (P g+) or to minimize it (P g−). The indices of lipid peroxidation examined included the rate of NADPH‐dependent formation of malondialdehyde (MDA) and the concomitant destruction of cytochrome P‐450 and decline in the linearity of benzphetamineN‐demethylase activity in microsomes. Cytochrome P‐450 was destroyed during benzphetamineN‐demethylation in microsomes with the loss being more extensive in P g−than in P g+. The destruction of cytochrome P‐450 and the concomitant loss in linearity of benzphetamineN‐demethylation in P g−were prevented by added EDTA. Added linoleic acid hydroperoxide (LAHP) also caused a time‐dependent loss of cytochrome P‐450 in microsomes with the rate being greater in P g−than in P g+. The results show that glycogen inhibits hepatic microsomal lipid peroxidation and suggest that variations in glycogen content may contribute to disparities inin vitrooxidative activities between different microsomal samples. Such disparities may be minimized by the removal of glycogen during the preparation of microsomes and then supplementing the incubation mixtures with EDTA. Thein vivorelevance of the observed antioxidant effect of glycogen is discussed in terms of the possible modulation by the polysaccharide of hepatotoxicity by agents whose effect

ISSN:0260-437X    

DOI:10.1002/jat.2550070609

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractMutagenic potency in the AmesSalmonellatest is an important endpoint that can be influenced by biological and technical factors. The ranking of mutagenic activity of a series of anthracyclines was measured using different conditions of exposure and mutation selection. A 20 min preincubation treatment version of the Ames test using a 0.2–2.0 μg/ml (0.36–3.60 nM/ml) dose range of each of the anthracyclines Adriamycin, Daunomycin, Carminomycin, 4′‐O‐methyldoxorubicin and 4‐demethoxydoxorubicin confirmed the order of mutagenic potency seen with the same compounds under direct plating conditions. Preincubation results also confirm direct‐plating results by showing the greater sensitivity of selection to His+reversion over 8‐azaguanine resistance to anthracycline mutagenicity. However, the order of mutagenic potency was changed by lengthening the preincubation treatment time to 2 h or reducing the population density of the treated cell inoculum by ten fold. These results suggest that certain treatment conditions enable the treated cells to diminish the phenotypic expression of anthracycline mutagenicity. For comparative purposes, daunomycin and Adriamycin mutagenicity in response to 0.1–0.2 nM/ml and 0.1–0.3 nM/ml dose ranges, respectively, were assessed in a human cell culture system with 6‐thioguanine and 5‐trifluorothymidine forward mutation selection. A daunomycin dose of 0.1 nM/ml generated approximately 25‐fold and 20‐fold increases in mutant fraction with 6‐thioguanine and 5‐trifluorothymidine selections, respectively. Equivalent dosing with Adriamycin generated approximately a 4‐fold increase in mutant fraction with 6‐thioguanine selection and little or no increase with 5‐trifluothymidine selection. Maximum increase in expression of mutant fraction within the anthracycline treated populations of cells occurred with a 10 day expression time. Plating for clone forming ability on the day of treatment showed that a standard 0.1 nM/ml treatment dose reduced cloning efficiency of the daunomycin treated cells by 90% and reduced the clone forming ability

ISSN:0260-437X    

DOI:10.1002/jat.2550070610

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

ISSN:0260-437X    

DOI:10.1002/jat.2550070613

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY