摘要:

Fiber length has been implicated as a determinant of fiber toxicity. Fibers of narrowly defined length can be generated by dielectrophoretic classifiers. Since the quantities of fibers produced are very small, we developed a rat alveolar macrophage microculture system to study the toxicity of these samples. The objective of this study was to examine the role of fiber length on the cytotoxicity of Manville code 100 (JM-100) fibers. Rat alveolar macrophages were cultured with 0-500 mug/ml of 5 lengths of JM-100 fibers on 96-well plates. After 18 h, well supernatants were removed and lactate dehydrogenase (LDH) activity was measured to assess cell damage. Chemiluminescence (CL), an assessment of macrophage function, was measured by adding lucigenin with or without zymosan, a particulate stimulus, to appropriate wells. For each fiber length the effects were concentration dependent: CL declined and LDH rose with increasing fiber concentration. Comparing the effects of different lengths showed the greatest toxicity from a relatively long fiber sample (mean length = 17 mum) . Microscopic examination of the interaction of fibers with macrophages revealed multiple macrophages attached along the length of the long fibers. This suggests that frustrated, or incomplete, phagocytosis may be a factor in the increased toxicity of longer fibers. Overall the results demonstrate that length is an important determinant of toxicity for JM-100 fibers.

ISSN:1528-7394    

DOI:10.1080/009841098158836

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

This study reports experiments designed to evaluate the dose and temporal effects of an atmospheric pollutant, sulfuric acid (H2SO4) aerosol, on the dynamic components of the respiratory cycle. Ventilation was measured in a whole-body barometric plethysmograph in unanesthetized, unrestrained animals following a 4-h exposure to H2SO4 aerosol at 14.1, 20.1, or 43.3 mg/m 3. Lung injury was assessed by histopathology and bronchoalveolar lavage (BAL) . Aerosol exposure with H SO caused marked alterations in both the magnitude and composition of the ventilatory response, which were both dose and time dependent. At the highest concentration tested, there was a significant increase in tidal volume (deltaVt) and a decrease in breathing frequency (f) immediately after exposure. Analysis of BAL fluid at this time showed increased inflammatory cells and protein in the acid exposed animals, and histology showed hyaline membranes and acute inflammatory cells in the proximal acinar region. By 24 h postexposure, f significantly increased whereas deltaVt decreased. This pattern of breathing was interspersed with short periods of apnea. The onset of rapid, shallow breathing was associated with histological evidence of diffuse pulmonary edema. By contrast, the immediate postexposure period at the lowest concentration of H SO aerosol was characterized by a significant increase in f and little or no effect on deltaVt. These effects diminished with time, and at 24 h postexposure ventilatory parameters were indistinguishable from baseline values. An apparent crossover between the effects associated with the high and low exposure concentrations was seen at the intermediate exposure concentration; however, closer inspection of these findings on an animal-by-animal basis revealed two pop

ISSN:1528-7394    

DOI:10.1080/009841098158845

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

While certain neuroactive volatile organic compounds (VOCs) have been reported to have an uneven distribution in various anatomically distinctive brain regions, this has not yet been reported for the short-chain aliphatic halogenated hydrocarbons. Therefore, the uptake and regional brain distribution of 1,1,1-trichloroethane (TRI) in mice and rats following inhalation exposure were examined. Male Sprague-Dawley rats and CD-1 mice were exposed to TRI at either 3500 or 5000 ppm for 10, 30, 60, or 120 min. Seven brain regions from rats and three from mice were sampled, and TRI concentrations in the blood and brain tissues were determined by headspace gas chromatography. In both species, the medulla oblongata was found to have the highest TRI concentrations, while cortex (in both species) and hippocampus (only sampled in rats) contained the lowest TRI concentrations. Substantial differences were also observed between the two species, as the mice exhibited higher capacity to accumulate TRI in the blood as well as in the brain regions. It appears that lipid content is a main factor influencing the differential disposition of TRI among the brains regions. Physiological differences in the respiratory systems of the two species and the physiochemical properties of the chemical favoring diffusion toward lipid-rich compartments could also have been expected to account for the patterns of regional distribution and species differences.

ISSN:1528-7394    

DOI:10.1080/009841098158854

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

Hydroquinone is a ubiquitous chemical readily available as monographed in cosmetic and nonprescription forms for skin lightening, and is an important industrial chemical. The in vivo bioavailability for 24-h application in humans was 45.3 +/- 11.2% of dose from a 2% cream formulation containing [14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h. Timed skin wash and skin tape-stripping sequences showed a rapid and continuous movement of hydroquinone into the stratum corneum of human volunteers. Plasma levels taken both ipsilateral and contralateral to the topical dosing site contained radioactivity at the first 0.5-h sampling time. Peak plasma radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous absorption with fresh viable human skin gave a bioavailability of 43.3% of dose, and flux was calculated at 2.85 mug/cm 2/h. In vitro, some of the skin samples were pretreated with the metabolic inhibitor sodium azide, which had no effect on percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were extracted and the extracts subjected to thin-layer chromatography (TLC) . Control [14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone. Receptor fluid and skin extraction had a second peak with the same R as benzoquinone, which was decreased with azide f treatment. No other peaks were found. Ethyl acetate extraction of urine from the in vivo study showed all radioactivity to be only water-soluble, free hydroquinone released following glucuronidase treatment. Risk assessment should not only involve the bioavailability of intact topical hydroquinone, but also consider phase I and phase II metabolism in both humans and any animal for which toxicity potential was assessed.

ISSN:1528-7394    

DOI:10.1080/009841098158863

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

The herbicide CIPC [N-(3-chlorophenyl) carbamate] has been shown to disrupt microtubule organization in plants, apparently by interfering with the functioning of the microtubule organizing center. Very few studies have examined the effects of CIPC on animal cell microtubules and centrosomes, however, and the effects of this cytoskeletal disrupting agent on fertilization and early development have not been studied in detail. To address these questions, fertilized sea urchin eggs were cultured in the presence of CIPC until the prism stage, and perturbations in the cytoskeleton and development were examined. It was found that Lytechinus pictus embryos are sensitive to micromolar amounts of CIPC, and that a characteristic set of cytoskeletal and developmental deficits is produced as a result of exposure to this herbicide. Mitotic spindles were truncated and randomly oriented within zygotes and blastomeres, and cytokinesis was compromised, resulting in the production of blastomeres of various sizes and ploidy. Interestingly, in spite of these cytoskeletal and nuclear alterations, spindle poles at fourth cleavage retained their ability to interact with the plasma membrane in a manner sim ilar to that norm ally characterizing the unequal division of m acromeres and micromeres. CIPC treatment resulted in unequal cell divisions at atypical times, and skeletal spicule formation in these embryos was abnormal. These results indicate that CIPC may pose a significant health risk during mammalian embryogenesis; in addition, it may be a useful tool with which to study microtubule and centrosomal functioning during animal cell division-especially in those cell types that exhibit stereotypic patterns of cell division during early development.

ISSN:1528-7394    

DOI:10.1080/009841098158872

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor