摘要:

AbstractA long‐term exposure study with hamsters, mice and rats inhaling filtered and unfiltered diesel engine exhaust was carried out to investigate effects of chronic toxicity and, predominantly, carcinogenicity in the respiratory tract. The level of diesel exhaust in the exposur chambers corresponded to a concentration close to 4 mg m−3in the unfiltered diesel exhaust. Satellite groups of animals were additionally treated with BaP, DBahA or nitrosamines in order to check for syncarcinogenic effects.In hamsters and rats, alveolar lung clearance and mechanical lung function tests as well as biochemical and cytological measurements in lung lavage fluids showed significant changes only after exposure to unfiltered diesel exhaust and, predominantly, in rats.No lung tumors were found in hamsters. Spontaneous tumor rates occurred in mice and both types of diesel exhaust increased the incidence of adenocarcinomas in the lungs. In rats, only the unfiltered diesel exhaust caused a lung tumor incidence. It amounted to 16% with no tumors in the controls.The heavy load of particulate matter in the lungs of rats was caused by an exposure‐related impairment of the alveolar lung clearance and may have been instrumental in the induction of squamous cell tumors. However, an effect of particle‐associated PAH cannot be excluded. Syncarcinogenic effects of diesel exhaust after initial carcinogen treatment were found only in the respiratory tract

ISSN:0260-437X    

DOI:10.1002/jat.2550060602

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractUptake of cadmium as109CdCl2,109Cd‐cysteine,109Cd‐albumin and109Cd‐metallothionein was studied in isolated kidney cells from rat. Cd as109CdCl2and109Cd‐albumin was taken up at similar rates. The uptake of cadmium as109Cd‐cysteine was greater and that of109Cd‐metallothionein lower compared with that of the other substances. These observations were made on non‐pretreated cells. In cells taken from rats pretreated with CdCl2in vivo, the uptake of cadmium as109CdCl2,109Cd‐cysteine and109Cd‐albumin was lower than in cells from non‐pretreated rats. However, the uptake of109Cd‐metallothionein was considerably enhanced in pretreated cells. In pretreated kidney cells the decreased uptake of Cd (as Cd‐albumin) might be related to protection of the kidney against acute Cd toxicity and increased uptake of metallothionein‐Cd might contribute to the explanation of renal damage

ISSN:0260-437X    

DOI:10.1002/jat.2550060603

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractParathion toxicity has been attributed to its metabolic product paraoxon which is formed in the mammal liver through the multiple oxidase enzymes. These are induced by barbiturates and inhibited by SKF 525 A and cimetidine. We assessed the effects of these drugs on the acute toxicity of parathion in rats by measuring the rate of survival at 24 h after the administration of the oral LD50 of parathion to four groups of rats: control and pretreated with the aforementioned drugs. Additional rats of these groups were used to measure the capability of liver isolated microsomes to transform p‐nitroanisole to p‐nitrophenol. In the control and cimetidine groups we also measured the transformation of parathion to paraoxon and p‐nitrophenol by the liver microsomes. Phenobarbital increased the survival 100% whereas cimetidine and SKF 525 A dramatically potentiated parathion toxicity. Phenobarbital increased the formation of p‐nitrophenol but cimetidine and SKF‐525 A produced the opposite effect. Paraoxon and p‐nitrophenol from parathion were decreased by cimetidine. Our results strongly suggest that parathion itself is largely responsible of its toxicity and the inhibition of its metabolism is harmful rather than

ISSN:0260-437X    

DOI:10.1002/jat.2550060604

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe recovery process of pathological changes in the respiratory mucosa following exposure to styrene were experimentally studied to improve the understanding of the respiratory toxicity of styrene. Thirty male SD rats were exposed to 150 ppm or 1000 ppm of styrene for 4 h a day over 3 weeks (5 days a week). They were killed for examination at 1 day or 12 weeks after completion of the exposure sequence. Bilateral mucosal samples from the nasal septum and the trachea of the animals were examined for ciliary activity and subjected to electron microscopy, Complete functional and morphological recovery of the nasal and tracheal mucosa was observed at the 12th week post‐exposure to 150 ppm of styrene. After exposure to 1000 ppm of styrene, almost normal function and morphology of the tracheal mucosa was found at the 12th week post‐exposure, but the nasal mucosa continued to show decreased ciliary activity and an affected morphol

ISSN:0260-437X    

DOI:10.1002/jat.2550060605

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractImpiramine administration (50 mg kg−1, i.p.) to Sprague–Dawley male rats (240–290 g) 6 or 10 h after CCl4(1 ml kg−1, i.p.) partially prevents liver necrosis induced by the hepatotoxin. When imipramine is given 30 min before CCl4, it inhibits in part the CCl4‐inhibits in part the CCl4‐induced lipid peroxidation and the covalent interactions of reactive metabolites with microsomal lipids or proteins and partially prevents CCl4‐induced cytochrome P‐450 destruction, but not glucose 6 phosphatase activity depression.Impiramine administration prior to CCl4does not modify levels of the hepatotoxin reaching the liver or the body temperature of CCl4treated animals. Early preventive effects of imipramine on cytochrome P‐450, might be attributed to inhibition of covalent interactions of reactive metabolites.The hypothesis that imipramine exerted late preventive effects by interfering with calcium deleterious effects or by modulation of protein and phospholipid synthesis or degrad

ISSN:0260-437X    

DOI:10.1002/jat.2550060606

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractThe dependence of fluorescent porphyrin levels on the concentration of lead in blood, liver and kidney has been examined as functions of both the level and duration of dosing. Individually housed male Wistar COBS rats of 200 g were randomly selected for 3, 7, 21 and 35 day dosing periods in groups of: control, 50, 100 and 1000 ppm dosing in drinking water. The plot of all data points for porphyrin concentration against measured lead burden covers the same range of levels and closely resembles the scatter of data observed in humans. However, subsets of this plot defined by individual dose levels and durations yield well‐defined linear relationships. At all dose levels at 7 days the correlation of porphyrin concentration to lead tissue burden is negative in all tissues, showing a direct inhibition of hemopoiesis with lead burden. Depending on the tissue the slope becomes less negative, or, as in blood, positive at 21 and 35 days at all doses. This compensation is most rapid in blood, then liver and is least evident in kidney. The time at which compensation is observed is the same for all doses in each tissue and seems therefore, to depend on the rate of protein turnover in different tissue types.These results suggest that a direct correlation of porphyrin concentration to lead burden is not valid without knowledge of the dosing history. As well, evidence of compensation in one tissue does not imply successful compensation in other affected tissues where regeneration rates are slower. However, these observations do suggest that a correlation could be made between the extent of compensation in blood and that implicit for less accessible systems. Since blood compensation is most rapid, caution will be necessary in establishing tolerable lead levels for tissues at higher ris

ISSN:0260-437X    

DOI:10.1002/jat.2550060607

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractFemale Swiss mice were exposed to cadmium in the drinking water at concentrations ranging from 0 to 50 ppm for 105 or 280 day time periods. In the 105 day study, the effect of cadmium on urethan‐induced pulmonary adenoma formation was evaluated. Urethan‐induced sleeping times observed following i.p. injection of urethan after 3 weeks of cadmium exposure were not affected by cadmium indicating that chronic cadmium exposure did not alter the eliminaton of urethan. Pulmonary adenoma formation which was evaluated 84 days later was not affected by cadmium. The size and number of tumors remained unchanged. This suggests that the immunosuppressive actions of cadmium do not influence urethan‐induced adenoma formation. In the 280‐day study, the effects of cadmium on the incidence of spontaneous murine lymphocytic leukemia was evaluated. Mortality from the leukemia virus was greater in the cadmium‐exposed mice. Mice exposed to 10 or 50 ppm cadmium experienced 33% more deaths from the virus. The average time till death was unaffected. It appears that the immunosuppressive effects of cadmium impair immunosurveillance mechanisms that control expression of the murine lymphocytic leuke

ISSN:0260-437X    

DOI:10.1002/jat.2550060608

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractAdult male rabbits were exposed to high concentrations (750 ppm, 12 hours daily for 7 days) of toluene, xylenes, styrene, ethylbenzene, vinyltoluene (3‐methylstyrene), and 7‐methyl‐styrene vapours or were dosed with 4 mM/kg/day i.p. of hippuric, methylhippuric, mandelic, phenylglyoxylic, and 7‐methyl‐mandelic acids. Styrene, vinyltoluene and ethylbenzene caused a marked depletion of striatal and tuberoinfundibular dopamine. Such an effect was also caused by treatment with phenylglyoxylic and mandelic acids. Dopamine depletion was associated with an increase in homovanillic acid concentration in the same regions. These results indicate that dopamine metabolism is a target for the neurotoxic effects of some monocyclic aromatic hydrocarbons and their metabolites, a lateral vinyl‐ or ethyl‐chain being crucial for the structure/activity relationship of s

ISSN:0260-437X    

DOI:10.1002/jat.2550060609

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractPlatelet counts are routinely assessed from whole blood samples and recent technical advances enable the total platelet counts to be complemented by additional information which fully profiles the platelet population. In this report the platelet count, mode and mean platelet volumes and platelet profile histograms are presented for eight mammalian species. Species and strain variation in platelet profiles and the degree of volume heterogeneity are presented, and a platelet profile is presented for the marmoset which is previously unreported. The significance of these parameters and their potential importance to the toxicologist are disussed in the light of an observation of a drug‐induced altertaino in a platelet population profil

ISSN:0260-437X    

DOI:10.1002/jat.2550060610

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY

摘要:

AbstractMale Wistar rats were exposed continuously for 1 or 2 months to 25 or 100 ppm CO. The concentrations of noradrenaline in the hypothalamus, corticosterone and thyroxine in serum and of adrenal catecholamines were estimated. After exposure to 25 ppm CO no significant changes were observed in the serum corticosterone and thyroxine, hypothalamic noradrenaline, adrenal catecholamines levels, or in the weights of lung, spleen adrenal glands, liver and the whole body. Exposure to 100 ppm CO induced a decrease in hypothalamic noradrenaline and serum thyroxine and an increase in adrenal catecholamines and serum corticosterone. Whole‐body and organ weights were unchanged except for a slight decrease in liver weight. The results suggest a non‐specific stress response in the rat to 100 ppm CO whilst concentration of 25 ppm CO was without any stress eff

ISSN:0260-437X    

DOI:10.1002/jat.2550060611

出版商:John Wiley&Sons, Ltd.    

年代:1986

数据来源: WILEY