摘要:

AbstractThe object of this investigation was to study the relationship between acute hepatic injury and blood coagulation. Most of the clotting factors are synthesised by the hepatocytes and therefore it would seem likely that hepatic injury would lead to an impairment of blood clotting.Dimethylnitrosamine (DMN) and carbon tetrachloride (CCI4) were selected as model hepatotoxins to induce an acute hepatic lesion. Single doses of each compound were administered to male rats and groups of animals killed 3, 6, 16 and 24 h later in order to study the morphological development of the lesion and to relate this to changes in the haematological profiles. Both compounds produced a centrilobular necrosis, but with DMN there was a haemorrhagic component due to damage to endothelial cells, which contrasts with the classical coagulative necrosis produced by CCI4. After 6 h apoptosis was commonly seen in the centrilobular areas of the DMN treated rats. This process of cell death has not previously been demonstrated in chemically induced acute hepatic injury and was not seen in the CCI4treated rats. Significantly prolonged clotting times were seen in both DMN and CCI4treated rats and occurred in parallel with some of the early morphological changes but prior to the appearance of extensive haemorrhagic or coagulative necrosis. This preliminary data suggests that the measurement of blood coagulation times may provide a relatively specific and sensitive indicator of acute hepatic injury in rats.

ISSN:0260-437X    

DOI:10.1002/jat.2550070402

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractA reconstituted water medium was developed for use in the Frog Embryo Teratogenesis Assay—Xenopus(FETAX). FETAX solution was then tested on three compounds with known mammalian teratogenicity (ethanol, caffeine, and 5‐fluorouracil) as was a non‐teratogen (saccharin). The results obtained were then compared with results from tests on these compounds in two other media that had previously been used in the assay. Saccharin was not teratogenic. Ethanol and caffeine were weak and moderate teratogens, respectively. 5‐fluorouracil was a strong teratogen. The results compare favorably with those obtained in mammalian studies. The amount of growth inhibition in embryos in the 96 h tests was positively correlated with the degree of teratogenicity of the compound. Final validation of FETAX will allow it to be used to screen and rank compounds for further testing and as a tool for studying the basic mechanisms of terato

ISSN:0260-437X    

DOI:10.1002/jat.2550070403

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe acute oral toxicity in rats was estimated for seven isomers or isomeric ratios of tetramethylcyclohexane (TMCH). Lack of sufficient mortality at the highest dosage test (15.8 g/kg) precluded evaluation of an LD50 for mixedcis, trans‐isomers of 1,2,3,4‐TMCH, 1,2,3,5,‐TMCH, 1,2,4,5‐TMCH and 1,1,2,3‐TMCH, for the separatecis‐ ortrans‐forms of 1,1,3,5‐TMCH or a 1:1 mixture ofc,t−1,1,3,5‐TMCH andc,t−1,2,3,4‐TMCH. Mixed (c,t‐combined) isomeric TMCH was administered oraiiy to rats (30/group) and dogs (8/group) for 90 days at dietary levels of 0, 3000, 10 000 and 30 000 ppm TMCH and 0, 100, 300 and 1000 ppm TMCH, respectively. Administration of up to 30 000 TMCH to rats produced no discernible effects on survival, behavior, growth, food consumption, clinical blood picture or urine analysis. Absolute kidney weights of male but not female rats were elevated at all test levels. TMCH‐related microscopic lesions were confined to the kidney of male rats in all treated groups. These histopathologic changes were characteristic of tubular nephrosis. No treatment‐related effects were observed in groups of dogs fed up

ISSN:0260-437X    

DOI:10.1002/jat.2550070404

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractAdministration of Di(2‐ethylhexyl)phthalate (DEHP) at doses of 250, 500, 1000 and 2000 mg/kg to adult rats was found to significantly increase the activity of γ‐glutamyl transpeptidase (GGT) in liver and serum in a dose‐dependent manner. The data indicate that DEHP can be hepatotoxic since an increase in serum GGT levels are indicative of hepatobiliary dysfunction and liver malignancy. An assay of GGT in serum of the individuals exposed to DEHP could be helpful in early detection of liver disorders due to this widely used plast

ISSN:0260-437X    

DOI:10.1002/jat.2550070405

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe influence of repeated aluminium (Al) administration (0.05 or 0.5 mg 100 g−1b.w.t. i.p. 5 times weekly for 12 weeks) on the lysosomal enzymesN‐acetyl‐beta‐D‐glucosaminidase (β‐NAG) and beta‐glucuronidase (β‐Gluc) in serum, liver, spleen and kidneys of adult female rats with intact kidneys, (NR), or following partial nephrectomy (5/6 NX) was investigated. After Al loading, at the high dose only, the β‐NAG in serum and the free β‐NAG in liver, spleen and kidneys increased. Latent β‐NAG levels decreased in all three organs the effect being dose related. Following Al loading no elevation in total enzyme activity was observed, with one exception. Depending on Al doses the spleen of the non‐operated animals, the liver of both groups of animals and the serum showed a decrease in β‐Gluc activity. No effect on β‐Gluc activity was observed in the spleen of 5/6 NX animals or in the kidneys of either group of animals. The results confirm that high doses of Al induce toxic effects and damage the lysosomes in the liver, the spleen and the kidneys. The results indicate that the extent of lysosomal damage correlates with dose and duration of Al loading. Repeated administration of Al also interferes

ISSN:0260-437X    

DOI:10.1002/jat.2550070406

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractThe industrial chemical 1,6‐Hexane Diamine, or hexamethylenediamine (HMD), has an acute oral LD50of 980 mg kg−1in rats. Dietary administration of HMD to groups of rats for 3 months at dosages of 0, 50, 150, and 500 mg kg−1resulted in a modest retardation in weight gain at the two higher test levels. No other obvious signs of toxicity or changes in the peripheral blood picture or selected clinical pathology parameters were found at any test level throughout the study. Evaluation of absolute and relative weights of 10 selected organs, as well as complete necropsies and microscopic evaluation of over 30 selected tissues and organs, revealed no changes considered related to treatment. The administration of HMD by gavage to pregnant rats at 0, 112, 184 and 300 mg kg−1day−1on days 6–15 of pregnancy (day 1 = day sperm detected) did not induce any teratogenic effects. Signs of maternal toxicity were observed only at 300 mg kg−1day−1. Embryotoxicity was observed at both the 300 and 184 mg HMD kg−1day−1dosage levels. No treatment‐related effects were observed at

ISSN:0260-437X    

DOI:10.1002/jat.2550070407

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractSprague–Dawley rats were exposed to aerosolized diesel fuel (ADF) to determine the potential health effects in military troops during exposure to this visual obscurrant. Acute range finding studies were performed to estimate exposure conditions at which minimal (<1%) mortality would occur. This information was used in the design of a repeated exposure study to test the relative significance of the frequency of exposures, the duration of exposure, and aerosol concentration in any toxicity which might occur. Animals were exposed once or three times per week for a total of nine times to concentrations ranging from 1.3 mg ADFI−1to 6 mg ADFI−1and exposure durations of 2 or 6 h. Body weight and food consumption were recorded at weekly intervals during the exposure period and in animals that were retained for 2 weeks after the last exposure. Animals were used for a variety of endpoints, including neurotoxicological tests, pulmonary function tests, hematology, clinical chemistry, organ weights, and histopathology, either within 2 days of the last exposure or after the 2‐week recovery period. Animals exposed to ADF showed an initial depression in body weight followed by a slower rate of growth than the sham exposed controls. No exposure related changes were observed in any of the neurotoxicology assays. The lung was the primary site of toxicity. Focal accumulations of pulmonary free cells were observed histologically, with thickening and hypercellularity of nearby alveolar walls. The number of lavaged pulmonary free cells increased similarly. Both pulmonary wet and dry weights increased. Lung volumes were altered by exposure, including increased FRC and decreased TLC. Carbon monoxide diffusing capacity was decreased. Histologic abnormalities were not observed in any other organs. Of the exposure parameters tested, the frequency of exposure appeared to be the most significant in relation to degree of t

ISSN:0260-437X    

DOI:10.1002/jat.2550070408

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractRat striatal synaptosomes (P2‐fraction) were subjected to lipoperoxidation by the addition of 120 μM Fe2+and 200 μM ascorbic acid. This preparation (pretreated synaptosomes) was used to investigate the interaction of Pb2+and Mn2+on the uptake of tritiated catecholamines, Na+, K+‐ATPase activity and malondialdehyde (MDA) formation in order to understand the mechanism of enhanced neurotoxocity by concurrent exposure to these metals. The combination of Pb2+and Mn2+(25 μM + 100 μM, respectively) produced a significant increase in the uptake of3H‐Dopamine only in the untreated synaptosomes. No significant effect was noted on the uptake of3H‐Norepinephrine in either pretreated or untreated synaptosomes. However, the combination of Pb2+and Mn2+produced a pronounced decrease in the activity of Na+, K+‐ATPase, but the magnitude of the change was the sum of the individual metal effects. Metal interaction did not produce any significant change in the formation of MDA compared to the control (without addition of metals). These results indicate that Pb2+and Mn2+interaction may produce inhibition in the activity of transport ATPase in both the preparation of synaptosomes, with more pronounced effect of synaptosomes subjected to lipoperoxidation and these changes may be responsible for the disruption in the physiology of nerve impulse

ISSN:0260-437X    

DOI:10.1002/jat.2550070409

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractAn experiment was undertaken to determine the teratogenic effect of oral administration of T‐2 toxin, a trichothecene mycotoxin. Firstly, a dose response study using 0,0.5, 1.0, 2.0, 3.0, 3.5 and 4.0 mg/kg T‐2 toxin in propylene glycol, on day 9 of pregnancy, was undertaken. Maternal deaths and toxicity was noted in the 4.0 and 3.5 mg/kg groups post‐toxin administration. These groups gained less weight throughout gestation than the rest of the groups, because no fetuses were found in the 4.0 mg/kg group and the 3.5 mg/kg group had significantly fewer fetuses than the remaining groups. The total fetal weight was similar among all groups with fetuses, and normal sex ratio of offspring was seen. More major and minor defects were seen in the 3.0 mg/kg T‐2 toxin treated group than any other group. Secondly, a day response trial using a single dose of 3.0 mg/kg T‐2 toxin given on either days 6, 7, 8, 10, 11 or 12 of gestation was undertaken. Maternal mortality, with placental hemorrhage, was observed. Fetal loss was greater in the T‐2 toxin treated groups than in the starved controls. The greatest number of dead term fetuses was seen in mice treated on day 9 of gestation. Normal sex ratios were present in the offspring. Major skeletal defects were more numerous in mice treated on day 7 of gestation, whereas minor defects, retardations and variants were more common in mice treated on day 8. It was concluded that a single oral dose of T‐2 toxin in propylene glycol is primarily maternotoxic and embryolethal, and that defective development was possibly secondary to mate

ISSN:0260-437X    

DOI:10.1002/jat.2550070410

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY

摘要:

AbstractTen oils of differing origin, degree of refinement and carcinogenicity, were examined for their ability to produce nuclear enlargement in mouse skin following repeated topical exposure over a 3 day period. Application of the oils was made in a vehicle of methyl ethyl ketone incorporating a promoter and assessment of epidermal nuclear size was made on tissue sections using a Quantimet 720 image analyser.One of the oils reported to be non‐carcinogenic; was examined initially and its inability to induce enlargement of nuclei beyond the size seen in hyperplastic skin was confirmed. The same oil was then examined in combination with benzo(a)pyrene (BaP) and, from the dose–response obtained, it was clear that the oil did not prevent BaP induced nuclear enlargement.The other nine oils were examined by comparing them with the previously tested non‐carcinogenic oil. Two oils gave rise to clear nuclear enlargement; these were non‐solvent refined and gave rise to skin tumours in reported long‐term studies. One solvent‐refined oil, which gave a single papilloma in reported long‐term studies, gave borderline (non‐significant) nuclear enlargement; whereas the other solvent‐refined oils, including five reported as non‐carcinogenic and one reported as having weak (questionable) carcinogenic activity, gave no nuclear enlargement.Further examination of the data suggested that, within the limited series of oils examined, nuclear enlargement under these test conditions correlated well with carcinogenicity and might be used for predicting the skin carcinogenicity of an oil. Studies on a further 23 oils, on which long‐term studies have been carried out but not published, su

ISSN:0260-437X    

DOI:10.1002/jat.2550070411

出版商:John Wiley&Sons, Ltd.    

年代:1987

数据来源: WILEY