ISSN:0098-4108    

DOI:10.1080/15287399509532023

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Concentrations of 2,3,7,8–substituted polychlorinated dibenzo‐p‐dioxins (PCDDs) and di‐benzofurans (PCDFs) as well as 16 polychlorinated biphenyls (PCBs) have been determined in pooled samples of breast milk from 10–12 mothers living in three different geographical areas in both Norway and Lithuania. The results indicate no apparent dependency of the PCDD/PCDF levels, expressed as toxic equivalents (TEQs), and total PCB levels on the geographical residence of the donors within a country. This confirms the findings from a corresponding Norwegian study in 1985/1986 where individual samples from the same areas were analyzed. The total TEQs, including dioxin‐like PCBs, ranged from 31 to 42 pg TEQs/g fat in Norway and from 45 to 49 pg TEQs/g fat in Lithuania. The mean concentration of PCDDs/PCDFs in the Norwegian samples (10.4 pg TEQs/g fat) was slightly lower than in the Lithuanian samples (14.8 pg TEQs/g fat). Dioxin‐like PCBs were found to contribute two to three times more to the total TEQs than the PCDDs and PCDFs. Major contributors among the dioxin‐like PCBs were PCBs 126, 156, 114, 118, and 170. Comparison of the present data with those obtained in the Norwegian study in 1985/1986 shows that for PCDDs/PCDFs the mean TEQ levels have decreased by about 37% in the 7‐yr time span, while the levels of total PCBs, as determined by packed‐column gas chromatography, have remained unchanged or only slightly decreased. Future studies are necessary to confirm this potential temporal trend.

ISSN:0098-4108    

DOI:10.1080/15287399509532024

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

A retrospective analysis of the association between skin irritancy and the potential to cause contact sensitization has been performed employing a historical database for 50 chemicals and formulations. Correlations between the results of Draize skin irritation tests and skin sensitizing activity measured with the occluded patch test of Buehler have been examined. Weak, but nevertheless statistically significant, associations between contact sensitization and skin irritancy have been demonstrated. It is proposed that such correlations are consistent with the irritant properties of a material exerting an important influence on the extent to which contact sensitization is induced.

ISSN:0098-4108    

DOI:10.1080/15287399509532025

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The present study was undertaken to further define the role of alveolar macrophages (AM) in the pulmonary response to crocidolite fibers. Briefly, groups of 4 male F344 rats were intratracheally instilled with saline or saline suspensions of crocidolite at 2 or 20 mg/kg body weight. Animals were sacrificed 3, 7, 14, and 28 d after exposure and the lung response was characterized by analysis of bronchoalveolar lavage fluid (BALF) for markers of lung injury and inflammation. AM obtained in BALF were cultured and their production of the pro‐inflammatory cytokines, tumor necrosis factor α (TNFα), and interleukin‐1 (IL‐1) were characterized along with fibronectin, a protein known to stimulate fibroblast migration and proliferation. Lung hydroxyproline content was determined 28 d after exposure and lung histopathology was characterized on d 28 and 90 after exposure. Crocidolite instillation resulted in transient dose‐related pulmonary inflammation as evidenced by increased numbers of BALF neutrophils at the low dose and neutrophils, macrophages, and lymphocytes at the high dose. Cytotoxicity and increased permeability were demonstrated by increased levels of BALF lactate dehydrogenase (LDH) and total protein, respectively. AM TNFα and IL‐1 production were increased only at the high crocidolite dose. This cytokine response was greatest at d 3 and decreased thereafter. AM TNFα and IL‐1 release were positively correlated with the increased BALF neutrophils. In contrast to TNFα and IL‐1, AM fibronectin release was increased at both the low and high doses, with the magnitude of response increasing over time. Consistent with previous acute asbestos inhalation studies, histopathology revealed inflammation localized at the level of the terminal bronchioles and alveolar ducts. Fibrosis was demonstrated at both doses by increased trichrome staining of lung tissue sections. Only the high dose resulted in a detectable increase in lung hydroxyproline. Given the bioactivities of TNFα, IL‐1, and fibronectin, their increased production after crocidolite exposure indicates they contribute to the pulmonary inflammation and fibrosis occurring with this mineral fiber. In addition, the correlation of increased AM TNFα and IL‐1 production with increased BALF neutrophils supports a role for these cytokines in crocidolite‐induced inflammatory cell recruitment. Lastly, association of a persistent increase in AM fibronectin production with an eventual increase in lung collagen deposition extends the growing database indicating this response is a predictive marker of pulmonary fibrosis.

ISSN:0098-4108    

DOI:10.1080/15287399509532026

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Acute exposure to the herbicide propanil is immunotoxic for selected immune functions, as well as causing changes in the weights of the thymus and spleen. Although spleen cellularity and weight increase with propanil exposure, the thymus: body weight ratio decreases with increasing doses of propanil. The present study analyzes the thymocyte subpopulations in the thymus, spleen, and mesenteric lymph nodes. C57BI/6 mice were treated with either 0, 100, 150, or 200 mg/kg propanil, and 7 d later thymocyte populations were analyzed by flow cytometry. In the thymus, propanil exposure resulted in a dose‐dependent decrease in total numbers of T cells, as would be expected with its reduced weight. Determination of the thymocyte subpopulation distribution in the thymus showed a significant reduction in the number of CD3+CD4+CD8−(CD3+4+8−), CD3+CD4−CD8+(CD3+4−8+), and CD3+CD4+CD8+(CD3+4+8+) cells. Percent distribution of these thymic cell subpopulations showed similar decreases only with the highest dose. Apparent dose‐related decreases in the numbers of CD3−CD4+CD8+(CD3−4+8+) cells were also noted and were attributed to the general decrease in total thymus cells. The percentage of CD3−subpopulations showed an increasing trend with dose, which suggests that at 7 d postpropanil exposure there may be a specific effect on this most immature population. Although the size and cellularity of the spleen were increased, no change in CD4+or CD8+cell distribution was observed. Similarly, mesenteric lymph nodes showed no changes in the cell subpopulation distribution between propanil‐treated and control animals.

ISSN:0098-4108    

DOI:10.1080/15287399509532027

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Benzene is a human carcinogen; exposure to benzene can result in aplastic anemia and leukemia. Data from animal models are frequently used in the risk assessment for benzene. In rodent studies, mice have been shown to be more sensitive to benzene‐induced bemato‐toxicity than rats. In this regard, we have observed that bone marrow stromal cells from mice were significantly more susceptible to the cytotoxicity induced by the benzene metabolites hydroquinone (HQ) and benzoquinone (BQ) than cells from rats. Since cellular glutathione (GSH) and quinone reductase (QR) are known to play critical roles in modulating HQ‐induced cytotoxicity, we have measured the CSH content and the QR and glutathione S‐transferase (GST) activity in stromal cells from both species. In rat cells, the GSH content and the QR specific activity were 2 and 28 times as much as those from mice, respectively. GSH and QR in both mouse and rat stromal cells were inducible by 1,2‐dithiole‐3‐thione (D3T). D3T pretreatment of both mouse and rat stromal cells resulted in a marked protection against HQ‐induced toxicity. Pretreatment of both mouse and rat stromal cells with GSH ethyl ester also provided a dramatic protection against HQ‐induced toxicity. Conversely, dicoumarol, an inhibitor of QR, enhanced the HQ‐induced toxicity in stromal cells from both mice and rats, indicating an important role for QR in modulating HQ‐induced stromal toxicity in both species. Buthionine sulfoximine (BSO), which depleted GSH significantly in both species, potentiated the HQ‐induced toxicity in mouse but not in rat stromal cells. Surprisingly, incubation of stromal cells with BSO resulted in a significant induction of QR, especially in rats. The failure of BSO to potentiate HQ‐induced toxicity in rat stromal cells may be due to the concomitant induction of QR by BSO. Overall, this study demonstrates that the differences in stromal cellular GSH content and QR activity between mice and rats contribute to their respective susceptibility to HQ‐induced cytotoxicity in vitro, and may be involved in the greater in vivo sensitivity of mice to benzene‐induced hematotoxicity.

ISSN:0098-4108    

DOI:10.1080/15287399509532028

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Increases in the use of methanol (MeOH) as a transportation fuel would result in greater potential for inhalation exposure. Because oral exposure to MeOH potentiates the hepatotoxicity of carbon tetrachloride (CCI4), we examined the ability of inhaled MeOH to potentiate CCI4hepatotoxicity and the time course of injury and recovery. Adult male F‐344 rats were exposed to 0 or to 10,000 ppm MeOH by inhalation lor 6 h and gavaged with 0.075 ml CCI4/kg 24 h later. Hepatotoxicity was assessed 0.5, 1, 1.5, 2, 3, 7, 15, 30, and 61 d after CCI4exposure. For CCI4alone, hepatotoxicity was most severe at 0.5 and 1 d, when minimal centrilobular hepatoceltular necrosis and predominately mild centrilobular hepato‐cellular vacuolar degeneration occurred. By d 3, the livers from the CCI4rats were histo‐logically normal. For MeOH + CCI4, peak seventy of hepatic injury was at 1 and 1.5 d, when moderate centrilobular necrosis and moderate/marked centrilobular degeneration occurred. MeOH + CCI4resulted in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that were increased, relative to CCI4alone, 171‐ and 113‐fold, respectively, on d 1, and 166‐ and 140‐fold, respectively, on d 1.5. Significant serum elevations in MeOH + CCI4rats, relative to CCI4alone rats, were present until d 7 and d 15 for AST and ALT, respectively. By d 3 and d 7, degeneration and necrosis, respectively.

ISSN:0098-4108    

DOI:10.1080/15287399509532029

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The mechanism(s) of liver damage initiated by ingestion of toxic components of thermally oxidized lipids was compared in a rat model with the documented mechanisms of hepatic failure and necrosis initiated by acetaminophen. Acetaminophen (50 mg/kg body weight) or oxidized lipids (0.15 ml oxidized trilinolein or 1.05 ml oxidized butter oil per rat) were intubated at 12‐h intervals to rats. Treated rats were allowed free access to food and water containing 3% ethanol. Changes in relative concentration of acute‐phase plasma proteins, determined by two‐dimensional (2D) immunoelectrophoresis, were taken as a marker of liver damage. In contrast to simple inflammation, acute‐phase plasma proteins in this study disproportionately increased or decreased as histological damage of the liver due to intubation oxidized lipids or acetaminophen. Histological examination of liver of rats intoxicated with oxidized lipids revealed severe liver cirrhosis at the end of the trial, where the remaining viable hepatocytes were separated in a matrix of collagen. [3H1JThymidine incorporation in hepatic DNA of acetaminophen or oxidized lipid intoxication increased in the early stages of intoxication, indicative of regenerative activity of the liver. Further progression of the cirrhosis inhibited continued liver regeneration and [3H1]thymidine incorporation into hepatic DNA. The cirrhotic liver at this stage failed to regenerate to the original mass upon 75% partial hepatectomy. Therefore, it may be concluded that hepatic necrosis produced by oxidized lipids or by acetaminophen may have similar mechanisms.

ISSN:0098-4108    

DOI:10.1080/15287399509532030

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Tetrandrine is a benzylisoquinoline alkaloid that has been used in China as an antifibrotic drug to treat the lesions of silicosis. Its mechanism in the treatment of silicosis is unclear. Electron spin resonance (ESR) spin trapping was employed to investigate the antioxidant properties of tetrandrine. The spin trap used was 5,5‐dimethyl‐1 ‐pyrroline N‐oxide (DMPO). Tetrandrine efficiently reacted with hydroxyl COH) radicals with a reaction rate of approximately 1.4 × 1010M−1s−1The *OH radicals were generated by the Fenton reaction [Fe(II) + H2O2) as well as by reaction of chromium(V) with H2O2. Similar results were obtained using *OH radicals generated by reaction of freshly fractured quartz particles with aqueous medium. Tetrandrine also scavenged superoxide (O2−) radicals produced from xanthine/ xanthine oxidase. The effect of tetrandrine on lipid peroxidation induced by freshly fractured quartz particles was evaluated using linoleic acid as a model lipid. The results showed that tetrandrine caused a significant inhibition on freshly fractured quartz‐induced lipid peroxidation.

ISSN:0098-4108    

DOI:10.1080/15287399509532031

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The aim of this study was to determine if a relationship existed between some inhalation anesthetics airborne exposure levels (Cl) and the concentration of anesthetics in samples of urine produced throughout the exposure time (Cu. The concentrations of nitrous oxide (N2O), halothane (fluothane), enflurane (ethrane), and isoflurane (forane) in the ambient atmosphere were determined in 190 operating theaters of 41 hospitals in Italy. Nitrous oxide, halothane, enflurane and isoflurane were detected in the urine of 1521 exposed subjects (anesthetists, surgeons, and nurses). The environmental measurements were performed using personal passive samplers, and the biological measurements were performed using the head space method. Significant correlations were found between the anesthetics concentration in urine produced during the shift collected after a 4‐h exposure (Cu, μg/L) and anesthetics environmental concentration (C1, ppm). The results show that the urinary anesthetic concentration can be used as an appropriate biological exposure index. The biological values (urinary concentration values) proposed are the following: nitrous oxide, 25 μg/L, for an environmental value of 50 ppm; halothane, 97 μg/L, corresponding to 50 ppm of environmental exposure; 6.2 μg/L, corresponding to 2 ppm of environmental exposure; enflurane, 145 μg/L for an environmental exposure of 75 ppm and 5.6 μg/L for an environmental exposure of 2 ppm; isoflurane, 5.3 μg/L for an environmental exposure of 2 ppm. The values proposed are the respectively 95% lower confidence limit and therefore should be considered as a protection for the individual, especially if each biological value is corrected according to analytical variability of the measurements. In our opinion, the method of choice in the assessment of occupational exposure to inhalation anesthetics is the measurement of the urinary anesthetic concentration.

ISSN:0098-4108    

DOI:10.1080/15287399509532032

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor