摘要:

AbstractThe current study was designed to assess the methacholine dose‐response behaviour of the airways and pulmonary parenchyma with the aid of alveolar capsules. The experiments were performed in eight adult female Wistar rats (155–250 g). The animals were anaesthetized with sodium pentobarbital (30 mg kg−1i.p.) and mechanically ventilated. Measurements of tracheal (ptr) and alveolar (pA) pressures and the pressure change across the airway (paw) were performed prior to and after exposing rats to aerosols generated from sequentially increasing concentrations of methacholine chloride solution (2, 4, 8, 16, 32, 64 and 128 mg ml−1) through the breathing circuit. BaselinepawandpAmean (± SD) values (6.44 ± 2.06 and 8.25 ± 3.44 cmH2O, respectively) were not statistically different (P= 0.220). The increases inptrandpAwere significant during the dose‐response study (P= 0.001), whereaspawwas not increased. The increase inpAwas significantly higher than that ofpaw(P<0.001). The relationship between the mean (± SE) values ofptrandpAcould be well described by a straight line (r= 0.990,P<0.001). There were also significant correlations based on regression equations betweenptrandpaw(r= 0.947,P<0.001) andpAandpaw(r= 0.913,P= 0.004). These findings suggest that the pulmonary tissue of rats is a major component responsible for the increase in lung impedance observed after methacholine challenge. In addition, airway and pulmonary parenchyma pressure changes were correlated, suggesting that both lung regions have a similar sensitivity to the agonist. Our results indicate that the response of peripheral tissues should be considered during bronchial challenge prot

ISSN:0260-437X    

DOI:10.1002/jat.2550120404

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractA variety of carbamates have been developed since the 1960s for use as broad‐spectrum insecticides. An easy and inexpensivein vitroassay using chick‐embryo derived cells was examined for its capability to screen and test the toxicity of these compounds. Chick embryo brain and limb bud cultures were treated with different concentrations of either carbaryl or aldicarb with or without activation (± S‐9) for 5 days. Viability and cytotoxicity using the neutral red assay, and carbamate effects on cell migration and colony spread were measured. S‐9 decreased the effects of carbaryl and aldicarb on brain cell cytotoxicity at exposures of 15–60 ppm and 40–200 ppm, respectively, as indicated by increased concentrations of neutral red. Viability of brain cell cultures was not altered by aldicarb, but was decreased by carbaryl plus S‐9 in concentrations of>40 ppm. In limb cultures, carbaryl without S‐9 was significantly toxic at 8–25 ppm, but only concentrations of>25 ppm of carbaryl plus S‐9 significantly affected cytotoxicity. In contrast, aldicarb without S‐9 caused no effect on limb cell cytotoxicity at concentrations of 40–200 ppm, but aldicarb plus S‐9 significantly reduced cellular cytotoxicity at concentrations of>160 ppm. Carbaryl ± S‐9 decreased the spread of both brain and limb colonies; aldicarb ± S‐9 caused a significant increase in the spread of the brain but not limb colonies. These results suggest that toxicities of carbaryl and aldicarb can be detectedin vitro, but that these two carbamates have a selective toxicity, with carbaryl toxic to both brain and limb buds and aldicarb more toxic to brain than limb cells. S‐9 was more likely to decrease the toxicity of carb

ISSN:0260-437X    

DOI:10.1002/jat.2550120405

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractMale CD‐1 mice were exposed to a commercial formulation of 2,4‐dichlorophenoxyacetic acid (2,4‐D), the amine derivative, in the drinking water at concentrations ranging from 0 to 0.163% of the formulated product, equivalent to approximately 0–50 mg kg−1day−12,4‐D content. The effect of 2,4‐D on urethan‐induced pulmonary adenoma formation was evaluated following a 105‐day exposure. Urethan‐induced sleeping times observed following an i.p. injection of urethan (1.5 mg g−1) after 3 weeks of 2,4‐D exposure were not altered by 2,4‐D, indicating that 2,4‐D did not influence urethan elimination. Pulmonary adenoma production, which was evaluated 84 days after urethan injection, was enhanced by 2,4‐D exposure but had no effect on tumor size. The effect of 2,4‐D on the incidence of spontaneous murine lymphocytic leukemia was evaluated during the 365‐day treatment period. Mortality associated with the leukemia virus was not altered by 2,4‐D treatment. Exposure to this commercial 2,4‐D product at moderately high levels of exposure may modify the development or expression of certain tumors in CD‐1 mice. The mechanism of the co‐carcinogenic or tumor‐promoting activity associated

ISSN:0260-437X    

DOI:10.1002/jat.2550120406

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractWe calculated the effective dietary exposure to 20 organophosphorus insecticides in a sample of residents of the Region of Murcia (Spain). Calculations were based on the contamination of 2310 specimens of citrus fruits, pitted and seedy fruits and vegetables collected in the 1985–86 and 1989 campaigns. A comparison of the results from the two campaigns showed that the mean annual insecticide ingestion determined from the mean consumption of each type of farm produce fell from 7.82 mg to 5.55 mg over the 4‐year period studied. The total annual ingestion of insecticides during the 1985–86 and 1989 campaigns was ca. 0.133 and 0.1 mg kg−1body weight; these values are well below the admissible annual ingestion of 29.565 mg kg−1bo

ISSN:0260-437X    

DOI:10.1002/jat.2550120407

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractA precise, accurate, selective and sensitive liquid chromatographic method for the determination of benzophenone‐3 in rat biological fluids and different tissues has been developed. The minimum detection limit for benzophenone‐3 was 2.0 ng ml−1and the retention time was 6.01 min. Standard curves for benzophenone‐3 were linear in a wide range of concentrations in methanol and different body fluids, ranging from 6.25 ng ml−1to 100 μg ml−1. To detect benzophenone‐3 in rat whole blood after oral administration, HCl hydrolysis was required. Benzophenone‐3 was found to produce a peak blood concentration 1 h after administration. Free benzophenone‐3 in urine represented a very small percentage during the first 12 h after administration, while a higher concentration of the glucuronide conjugate was detected in th

ISSN:0260-437X    

DOI:10.1002/jat.2550120408

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractClinical use of modern dextran solutions has been limited by concerns of anaphylactoid reactions. To assess the short‐term antigenic response to 7.5% hypertonic saline in 6% Dextran‐70 (HSD), sera were obtained from dogs involved in the acute and subacute toxicology testing of HSD and its individual components, and analyzed for IgG, IgM and C3 complement. In separate studies, beagles were infused i.v. with a single dose of HSD or its components at 20 ml kg−1(the maximum tolerated dose; MTD), or the MTD daily for 14 days, and serum was obtained prior to and at various times after infusion up to 14 days. In both studies, despite serum dextran concentrations exceeding 2000 mg dl−1, no induction of IgG, IgM or C3 complement concentrations were observed. In addition, serum IgG immunoelectrophoretic patterns were of normal curvature, position and intensity; the immunoprecipitin bands were not displaced, bowed, inhibited or thicker than the normal preinfusion immunoelectrophoretograms.The data suggest that single or multiple HSD i.v. injections, as much as five times the proposed therapeutic level for the treatment of hypovolemia, evoked no increase in antibody titers in dogs. Therefore, therapeutic use of HSD in the treatment of hemorrhagic shock should not be associated with widespread concomitant allergic compli

ISSN:0260-437X    

DOI:10.1002/jat.2550120409

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractBromophenol blue and tetrabromophenol blue are two triphenylmethane dyes. Triphenylmethane derivatives and their structurally related compounds, such as fluoresceins and xathenes, are widely used as industrial dyes for foods, drugs, cosmetics, textiles, printing inks or laboratory indicators. Since a number of these types of dyes have been reported to be genotoxic, safety concerns on these two dyes of interest have been raised. Consequently, a battery of genetic toxicology assays, including the AmesSalmonella/microsome assay, L5178Y TK+/−mouse lymphoma assay, mouse micronucleus test and mitotic recombination assay with yeastSaccharomyces cerevisiaestrain D5, has been performed on each of the two dyes. The results of the evaluations indicate that both bromophenol blue and tetrabromophenol blue were not active and can be considered non‐genotoxic for the three genetic endpoints assessed (gene mutation, chromosome aberrations and primary DNA damage). Genetic activities in some structurally related compounds of these dyes have been reported but may be attributed to the presence of mutagenic impurities rather than the compound its

ISSN:0260-437X    

DOI:10.1002/jat.2550120410

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractFenarimol administered in one single oral dose of 125 or 62.5 mg kg−1body wt. day−1, respectively, stimulated rat liver enlargement at a dose‐independent rate. Three single doses of fenarimol produced dose‐dependent liver growth, whereas five single doses caused no further increase in liver weight. This increase was accompanied by an increase in hepatic DNA synthesis and mitotic activity, with a peak on the first day after the beginning of the experiments. The increase in binuclear hepatocytes and signs of necrosis suggested that the hepatomitogenic effect reflected a compensatory hyperplasia. After both three and five single doses the hepatomitogenic effect was supressed, as a result of tolerance deve

ISSN:0260-437X    

DOI:10.1002/jat.2550120411

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractA series of 76 fiber finishes, typically composed of blends of lubricants, emulsifiers, antistatic agents and fatty acid soaps, were tested in rabbits to determine both the eye and the skin irritation potential. Each finish was classified as being either non‐, slightly, mildly, moderately or severely irritating to the target tissue during a 48‐h post‐treatment period. Seven (9.2%) of the finishes tested were severely irritating to both the skin and the eye; two (2.6%) were determined to be non‐irritating to both tissues. While occasionally finishes produced equal degrees of damage resulting in similar irritancy classifications, seven (9.2%) finishes were found to be severely irritating to the skin without producing any irritation in the eye. Conversely, one finish was found to be a severe eye irritant without producing any skin irritation. The suggested use of the skin irritation data to predict the ocular reaction needs to be carefully examined, particularly with materials such as these fiber finishes. The prediction that a severe skin irritant is also a severe eye irritant was demonstrated to be in error with 8 of 75 (10.5%) of the finishes studied. Further, there is little predictive association between the skin and eye irritation for these co

ISSN:0260-437X    

DOI:10.1002/jat.2550120412

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe metabolic effects of different concentrations of nickel hydroxycarbonate (NiHC) on guinea pig alveolar macrophages (GPAMs) were investigated. Exposure to high concentrations of NiHC (6.25 and 12.5 μg 10−6cells) led to cell vacuolization. Morphological changes were associated with a dramatic reduction in the steady‐state level of cellular adenosine triphosphate (ATP), i.e. ATP levels were reduced by 35% (P<0.001) and 53% (P<0.01), respectively. Low concentrations of NiHC (0.0625 and 0.125 μg 10−6cells) did not induce morphological changes but increased cellular ATP content by 19% (P<0.01) and 12% (P<0.05), respectively. Effects of NiHC (0.125 and 6.25 μg 10−6cells) on cell oxidative metabolism were studied. The chemiluminescence was significantly increased (P<0.001) by the lower but not the higher concentration. A slight inhibition of total superoxide dismutase (P<0.05) and a decrease of catalase activity were demonstrated (P<0.05) for the high dose, while the low dose decreased the levels of reduced and total glutathione. In conclusion, the effects of NiHC on alveolar macrophages are characterized by an overproduction of free radicals for low concentrations and the depletion of cellular reserve energy, particularly ATP, for high conc

ISSN:0260-437X    

DOI:10.1002/jat.2550120413

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY