摘要:

AbstractThe total LDH, HBDH and LDH isoenzyme activities were assessed in a number of rat tissues. HBDH did not correlate with LD1and LD2isoenzyme activity in tissues with high HBDH activity. HBDH therefore cannot be used as a marker for cardiac necrosis in the rat. In rats treated with isoprenaline and SK&F 94120 at doses producing myocardial necrosis, only the LD1isoenzymes showed any significant change but only within the first 24 h of treatment. No statistically significant differences were seen in the plasma AST, CK, CK‐MB and total LDH activitie

ISSN:0260-437X    

DOI:10.1002/jat.2550080402

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThe effect of intermittent 2 months' exposure to 2 g/m3unleaded petrol on the hypothalamo‐pituitary‐thyroid‐adrenal system was evaluated by measuring hypothalamic noradrenaline (NA), serum corticosterone (CS), thyroxine (T4) and adrenal catecholamine (CA) levels in male rats. Serum CS and adrenal CA were increased and hypothalamic NA was decreased by exposure. No changes were observed in serum T4. Exposure induced an increase in spleen, kidney, liver and lung weights; weights of adrenals and hypothalamus were not changed. All the petrol‐induced effects depended on the length of exposure. Rats exposed to petrol gained less weight than controls. The results suggest a non‐specific stress response i

ISSN:0260-437X    

DOI:10.1002/jat.2550080403

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractTrihalomethanes, Carbon tetrachloride and trichloroethylene were tested in single, binary and multi‐complex mixtures using standard tester strains TA1535, TA1537, TA98 and TA100 ofSalmonella typhimuriumwith and without addition of anin vitrometabolizing fraction S‐9. Chloroform (CHCl3) was found to be mutagenic in all strains without S‐9 activation. However, when tested with Bromoform (15%), which was nonmutagenic singly, the combined effect of the mixture was nonmutagenic. CCl4was a direct mutagen (without S‐9) in all strains except TA 1535. When combined with 85% CHCl3, only strains TA1535 and TA1537 were mutagenic. When tested with mammalian activation (S‐9), CCl4was mutagenic in all strains. However, when tested with CHCl3(CHCl3and CCl4‐ 85 : 15), the mutagenic capability was lost.With or without S‐9 Activation multi‐complex mixture of CHCl3, CCl4and TCE (85 : 8 : 7) was mutagenic for a narrow range of doses

ISSN:0260-437X    

DOI:10.1002/jat.2550080404

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThere are a wide variety of laboratory tests available to assess damage to and functional impairment of the liver, though the effectiveness of these tests varies greatly depending upon the type of damage and the animal species involved.Species differences in tissue localization, metabolism, specificity and sensitivity of parameters relating to the liver influence the choice of tests. Some tests can be applied usefully to most animal species while others may be highly specific in one species but show very low discriminatory potential in others.The tests available, and their use in veterinary and toxicological investigations have been reviewed in the light of current practice in the U.K.

ISSN:0260-437X    

DOI:10.1002/jat.2550080405

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractThe C3H/10T1/2 CL8(10T½) cell transformation assay has been used as an importantin vitrotool for screening potential carcinogens. In this paper we describe an experimental design that increases the sensitivity and specificity of the assay. One half of the total dishes was allocated to the solvent control and the other half was equally subdivided into four treatment dose groups of low to high cytotoxic effects. The transformation frequency was calculated on the basis of the number of dishes with Type III foci. Each treatment group, as well as the pooled treatment groups, was compared to the solvent control using Fisher's exact test. The sensitivity of our design, as evaluated by power analyses, greatly exceeded that of a standard test design in which about 20 dishes are allocated to each of the control and treatment groups. Furthermore, our use of an expanded number of control and treatment dishes reduces the chance for both false positive and false negative responses. Our experimental design is illustrated with data from experiments in which the transforming potential of two drugs, dimenhydrinate and SC‐32006, was examin

ISSN:0260-437X    

DOI:10.1002/jat.2550080406

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractIn mice subjected to glutathione depletion by pretreatment with phorone (diisopropylidene acetone, 200 mg/kg i.p. in 10 ml/kg olive oil) paracetamol (acetaminophen, 300 mg/kg p.o. in 10 ml/kg tylose 2 h later) led to a marked hepatotoxicity as evidenced by increased plasma activities of the liver‐specific enzymes sorbitol dehydrogenase (SDH) and glutamate‐pyruvate‐transaminase (GPT) 3 and 24 h after treatment. Nephrotoxicity was also indicated at both timepoints by an increased creatinine concentration in plasma, while neither the urine volume nor its content in γ‐glutamyl transpeptitase over 20 h were affected. Hepato‐ and nephrotoxicity were also assessed histomorphologically.In vivolipid peroxidation (LPO), as measured by ethane exhalation over 3 h, was clearly enhanced by paracetamol. Malondialdehyde content was increased and glutathione concentration diminished in the liver, but not in the kidney. Diethyldithiocarbamate (DTC, 200 mg/kg i.p.) or deferrioxamine (DFO, 500 mg/kg i.p.) both given 30 min before PA, inhibitedin vivoLPO. However, only DTC was capable of antagonizing the hepato‐ and nephrotoxic effects of paracetamol, while DFO only delayed the onset of nephrotoxicity but left the hepatotoxicity unaffected. Both agents inhibited the rise in hepatic malondialdehyde‐content, but only DTC prevented paracetamol‐induced glutathione depletion. These results indicate that LPO is not mainly responsible for paracetamol toxicity towards

ISSN:0260-437X    

DOI:10.1002/jat.2550080407

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractApproximately 125 carcinogenicity studies in Fischer 344 rats conducted by the National Toxicology Program (NTP) were examined to determine the frequency with which cage effects were associated with observed carcinogenic responses. All studies involving groups of 50 rats housed five per cage and showing evidence of chemically‐related carcinogenicity were considered. For each of these experiments, two statistical analyses were carried out for each dosed and control group: (i) a test to determine whether or not the occurrence of tumors clustered within cages; and (ii) an evaluation to determine whether or not tumor incidences differed significantly between differing cage shelf levels. These analyses showed that the numbers of statistically significant (P<0.05 orP<0.01) effects were consistent with the number expected by chance alone. Thus, cage‐related factors appeared to have little or no impact upon tumor incidence in these particular studies. Experimental design protocols now used by the NTP (which include random assignment of animals to cages; random assignment of columns of cages to dosed and control groups; and periodic rotation of cage location) further reduce the likelihood that factors associated with the housing of the animals could influence tumor incidence in current stud

ISSN:0260-437X    

DOI:10.1002/jat.2550080408

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractNewborn rat pups that inhale 500 ppm carbon monoxide (CO) for 32 days and develop increased heart mass (i.e. cardiomegaly) show persistent cardiomegaly and elevated resting heart rate as adults. Studies were carried out to explore the relationship of these phenomena to CO concentration and initial cardiomegaly using exposures of 350, 500 and 700 ppm CO. Initial cardiomegaly was greater in the right ventricle free wall (RV) than in the left ventricle plus interventricular septum (LV+S) at all three CO concentrations, and RV mass excess increased with CO concentration. Initial RV cardiomegaly was greater at 350 and 700 ppm CO in females than in males. Persistent cardiomegaly in the RV also increased with CO concentration, and was significantly greater in the females. Persistent cardiomegaly in the RV increased with initial cardiomegaly but at a decreasing rate at the higher CO concentrations, and when expressed as a percentage of initial cardiomegaly (i.e. “efficiency”), the relative response was greatest at 500 ppm CO. For LV+S, efficiency of development of persistent cardiomegaly was greatest at 350 ppm CO. Persistent tachycardia increased with CO concentration in males but failed to do so in females, and was only weakly correlated with degree of persistent cardiomegaly. Thus, persistent cardiomegaly and persistent tachycardia (in males) are related to CO concentration. Myocardial DNA content of 32‐day‐old juveniles was significantly increased at 350 and 700 ppm CO. Adult DNA content of the RV was significantly elevated at 350 ppm CO (females) and continued to rise with CO concentration. DNA concentrations of the RV and LV were increased at 700 ppm CO. The case is argued that altered cardiac DNA content and concentration indicates persistent cellular‐level changes (i.e. ‘cellular remodeling’), also related to CO

ISSN:0260-437X    

DOI:10.1002/jat.2550080409

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

摘要:

AbstractIn a three‐generation reproduction study, rats were given caprolactam in the diet of 0, 1000, 5000 and 10,000 ppm. No treatment‐related effects were observed in the parental animals with respect to mortality, clinical signs, reproductive performance or gross pathology findings. Consistently lower body weights were noted in the P2and P3mid‐ and high‐dose males and females. Consistently lower mean food consumption values were noted in the P2and P3mid‐ and high‐dose males and the high‐dose females. These differences were generally significant (P ≤ 0.05) in the high‐dose group of both sexes. Compound‐related histopathologic findings noted in the high‐dose P1males consisted of a slight increase in the severity of spontaneous nephropathies, occasionally accompanied by granular casts. The offspring data revealed no treatment‐related effect with respect to gross appearance, gross pathology, survival, number of pups, percentage of male pups or kidney weight. Analysis of the offspring body weights on Days 1, 7 and 21 of lactation revealed consistently and generally significant lower mean values in the high‐dose male and female animals of all filial generations. The mean body weights of both sexes in the mid‐dose group were generally lower than those of the controls. The effects on mean body weight, mean food consumption and the group increases in the severity of nephropathy, accompanied by the presence of granular casts in some animals, are considered to be related to the ad

ISSN:0260-437X    

DOI:10.1002/jat.2550080410

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY

ISSN:0260-437X    

DOI:10.1002/jat.2550080411

出版商:John Wiley&Sons, Ltd.    

年代:1988

数据来源: WILEY