PubMed Health⌕ Search

Biomedical subjects

E Shibata

Publications and source records attributed to E Shibata.

At least 55 records · Page 3Linked to original sources

Toluene induces behavioral activation without affecting striatal dopamine metabolism in the rat: behavioral and microdialysis studies.

We examined the effects of toluene on the release of dopamine (DA) and its metabolites in rat striatum using microdialysis. Intraperitoneal injection of 800 mg/kg toluene significantly increased motor activity in rats, as did methamphetamine (MAP) (1 mg/kg). However, 800 mg/kg toluene did not affect the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, homovanillic acid, or 5-hydroxyindoleacetic acid. This is in contrast to MAP, which significantly increased extracellular DA and decreased the extracellular levels of its metabolites. These results suggest that toluene-induced behavioral augmentation may not be associated with alterations in DA or serotonin neurochemistry such as are associated with MAP-induced behavioral augmentation.

Animals↗

Health status of the workers using mechanized hand tools in an electric parts' maker.

The aim was to clarify the relations between the health status of the workers operating mechanized hand tools (MT). MT included electric drivers and air drivers, and the working conditions in an electric parts' maker. Fifty-nine female workers underwent the special examination for vibration hazards, made up of 39 MT operators (Group A) and 20 controls (Group B) who worked without MT at the same plant. The authors made questions about their health and working conditions and physical examinations. The measured items of the peripheral nervous system were the vibratory sensation and sensory nerve conduction velocity (SNCV) in the hand and arm. Those of the musculoskeletal function were pinching power, grasping power, back strength, and tapping ability. The frequency of the complaints "tingling of hands" and "numbness of hands" and "difficulty of finger extension" in Group A was significantly higher than in Group B. The frequency of "swelling of hands" and "heavy feeling of arms" in Group A had a higher tendency than in Group B. There was no difference in the results of physical examinations and vibratory sensation. Pinching power and grasping power (both hands) and back strength in Group A was greater than in Group B. Median SNCV in the hand in Group A was significantly slower than in Group B. The maximum vibration acceleration level (0.56-1.8 m/s2) of the MT used at the plant did not exceed the exposure guideline of ISO. The results suggest that although the vibration level was low enough, physiological changes appeared in the workers with MT.

Adult↗

Asbestos and nonasbestos fiber content in lung tissue of Japanese patients with malignant mesothelioma.

BACKGROUND: Pulmonary fiber content of both asbestos and nonasbestos types were evaluated in Japanese patients with malignant pleural mesotheliomas. METHODS: Pulmonary fiber content was analyzed in 16 patients and 16 case-matched control subjects by transmission electron microscopy with energy-dispersive X-ray analysis using a low-temperature ashing procedure. RESULTS: The geometric mean content of total asbestos was significantly higher in the patients (22.0 x 10(6) fibers/g dry lung) than in the control subjects (2.24 x 10(6) fibers/g dry lung) (P < 0.01). When the asbestos content was analyzed by fiber type, the geometric means were also consistently and significantly higher among the patients compared with the control subjects (P < 0.01). Results were as follows: (1) amosite: patients 3.94 times 10(6) versus control subjects 0.23 x 10(6); (2) crocidolite: patients 3.56 times 10(6) versus control subjects 0.35 times 10(6); (3) total amphiboles: patients 16.0 times 10(6) versus control subjects 0.77 times 10(6); and (4) chrysotile: patients 3.76 times 10(6) versus control subjects 1.01 times 10(6). However, when individual total asbestos content was considered, 7 of the 16 patients (44%) had levels lower than the highest value noted among the control subjects. Pulmonary fiber content of patients and control subjects also revealed the presence of nonasbestos fibers. The geometric mean of nonasbestos fibers was significantly higher in the patients (87.3 x 10(6)) than in control subjects (33.8 x 10(6)) (P < 0.01). The major type of nonasbestos fibers in both groups was aluminum silicates. The mean of ratios of nonasbestos fiber contents to total asbestos contents in the patients and control subjects was 7.0 and 17.3, respectively. CONCLUSIONS: The results were mainly in agreement with the findings of earlier investigations, but fiber content of both chrysotile and nonasbestos fiber as well as those of amphibole asbestos were significantly higher in the patients than in the control subjects.

Adult↗

Nerve-specific marker proteins as indicators of organic solvent neurotoxicity.

Effects of chronic exposure to n-hexane and toluene on some nerve-specific marker proteins in rat central nervous system (CNS) and peripheral nervous system (PNS) were assessed and compared. The rats were exposed to 2000 ppm n-hexane, 12 hr/day, 6 days/week, for 24 weeks, and to 1000 ppm toluene, 8 hr/day, 6 days/week, for 16 weeks. The level of neuron-specific enolase (NSE), creatine kinase-B (CK-B), and beta-S100 protein in cortex, cerebellum, spinal cord, and proximal and distal sciatic nerve was determined by enzyme immunoassay method. In n-hexane-exposed rats, the level of NSE, CK-B, and beta-S100 decreased significantly in the distal segment of the sciatic nerve, while the marker proteins in CNS and proximal sciatic nerve remained unchanged. In contrast, chronic exposure to toluene mostly affected these marker proteins in CNS tissues, displaying the increase of NSE, CK-B, beta-S100 in cerebellum, as well as the increase of beta-S100 in spinal cord. No quantitative changes of the three proteins in distal sciatic nerve were observed after exposure to toluene. n-Hexane-induced peripheral distal neuropathy and toluene-induced brain gliosis appeared to be responsible for this different pattern of biochemical changes. The present study suggests the usefulness of using these nerve-specific marker proteins to assess the solvent-related CNS and PNS neurotoxicity.

Animals↗

Modification of metabolism and neurotoxicity of hexane by co-exposure of toluene.

The effects of co-exposure of hexane and toluene were investigated in field surveys and animal experiments. One field survey suggested that increase of hexane content in adhesives might have caused an outbreak of polyneuropathy in a vinyl sandal manufacture in Japan. The animal experiments proved that co-exposure of hexane and toluene decrease hexane neurotoxicity and urinary excretion of hexane metabolites in rats. The results also suggested that toluene might inhibit metabolism of hexane. Another recent field survey indicated that the ratio of urinary 2,5-hexanedione to hexane exposure in the workers co-exposed to hexane and toluene decreased in parallel with in more crease of toluene concentration. The results indicated that urinary excretion of 2,5-hexanedione could be depressed by co-exposure of toluene even in the workers exposed to relatively low concentrations. These above-mentioned results suggest that co-exposure of hexane and toluene could inhibit hexane metabolism and decrease hexane neurotoxicity in both experimental animals and workers. Although metabolism of hexane could be easily modified by toluene or other solvents and might not be a good indicator for hexane exposure in mixed exposure, urinary 2,5-hexanedione might be a good indicator for neurotoxicity of hexane even in mixed exposure.

Adhesives↗

Comprehensive health evaluation of workers in the ceramics industry.

A cross sectional study on ceramics workers in the Seto area of Japan was conducted to determine whether there are differences in the morbidity pattern and overall health among the working populations employed by different sized companies engaged in the ceramics industry. The study population consisted of 3324 male ceramics workers (age range 40-69) who participated in the Seto occupational health screening programme in 1990. The prevalences of pulmonary diseases (silicosis and tuberculosis) and findings of some nonpulmonary diseases were compared in terms of company size by categories of 1-19, 20-49, 50-99, and 100 or more employees. The values of various screening tests were subjected to principle component analysis to extract factors representing key indices of health state. The average factor scores stratified by company size were used to quantitatively evaluate the comprehensive health level. Both prevalence and multivariate analysis showed that the employees working for smaller companies had overall worse health. The smaller the company, the higher the prevalence and the lower the health scores for silicosis and pulmonary tuberculosis tended to be; significantly increased rates and lower health scores for hypertension, anaemia, and glucosuria among small companies were also found when compared with larger companies. The high morbidity of silicosis and pulmonary tuberculosis in smaller companies contributed most to the decline in the overall health level.

Adult↗

[Inhaled nonasbestos fibers; pulmonary concentrations and fiber size in autopsied urban residents].

Nonasbestos fiber concentrations and fiber size distribution in autopsied lung tissues of 53 urban residents (34 males and 19 females) were analyzed by low temperature ashing-analytical transmission electron microscopy. The following findings were obtained. 1. Pulmonary nonasbestos fibers were found in all samples. Fiber consisting mainly of aluminum and silicon represented 80.0% of the total nonasbestos fibers observed. 2. The geometric mean concentration of nonasbestos fiber was significantly higher in males (47.6 x 10(6) fibers/g dry lung) than in females (18.2 x 10(6) fibers/g dry lung) (p < 0.05). This may be caused by differences in occupational exposure to nonasbestos fibers between males and females. 3. In females, the geometric mean concentration of nonasbestos fibers of smokers (34.6 x 10(6) fibers/g dry lung) was higher than that of nonsmokers (11.4 x 10(6) fibers/g dry lung), while, in males, the geometric mean concentration of nonasbestos fibers was lower in smokers (53.9 x 10(6) fibers/g dry lung) than in nonsmokers (89.1 x 10(6) fibers/g dry lung). These differences were not statistically significant. 4. The mean value for the ratio of nonasbestos fiber to asbestos concentration which ranged from 2.3 to 268 in males, and from 1.3 to 52.0 in females, was 30.1 and 20.2 respectively. 5. The mean length, diameter and aspect ratio for nonasbestos fibers were 1.01 microns, 0.103 microns and 11.3, respectively. Although nonasbestos fibers were almost equal in length to asbestos, the mean diameter of nonasbestos fibers was almost one-half of that of asbestos. Most of nonasbestos fibers (99.0%) were too small to be visible by light microscopy.

Adult↗

Absence of blue-yellow color vision loss among workers exposed to toluene or tetrachloroethylene, mostly at levels below occupational exposure limits.

Possible color vision loss was examined with Lanthony's new color test and Ishihara's color vision test in 261 solvent workers and 120 controls (48 men and 72 women). The solvent workers were exposed to either predominantly toluene [46 ppm as geometric mean (GM); 63 men and 111 women], tetrachloroethylene alone (13 ppm; 30 men and 34 women), or a mixture (14 men and 9 women) of tetrachloroethylene (12 ppm) and trichloroethylene (7 ppm). The only instances of color vision loss that were detected in either the exposed workers or the controls were six cases of red-green loss (all in men). These six cases of red-green loss showed an unbiased distribution between the exposed workers and the nonexposed controls.

Adult↗

Dose dependent effects of chronic exposure to toluene on neuronal and glial cell marker proteins in the central nervous system of rats.

The dose dependent effects of chronic exposure to toluene on the neuronal marker proteins (gamma-enolase, calbindin-D28k) and glial cell marker proteins (alpha-enolase, creatine kinase-B, and beta-S100 protein) were investigated in the central nervous system (CNS) of rats. Three groups of animals were exposed to 100 ppm, 300 ppm, or 1000 ppm toluene vapour eight hours a day, six days a week for 16 weeks. The contents of the marker substances were determined with enzyme immunoassays. A significant increase in the three glial cell marker proteins was noted in the cerebellum after exposure to 100 ppm toluene; a more pronounced increase occurred at the higher toluene concentrations. beta-S100 protein also exhibited a dose dependent increase in the brainstem and spinal cord. On the other hand, the two neuronal cell markers did not show a quantitative decrease in the CNS. This means that the development of gliosis, rather than neurone death, is induced by chronic exposure to toluene. The significant biochemical changes induced around the threshold limit value and the concentration dependent alterations suggest that these nerve specific marker proteins may be used to evaluate solvent related damage to the CNS.

Animals↗

Chronic exposure to n-hexane induces changes in nerve-specific marker proteins in the distal peripheral nerve of the rat.

1. After long-term n-hexane exposure (2000 ppm, 12 h d-1, 6 d week-1, for 24 weeks), the content of neuron-specific enolase (gamma-enolase), creatine kinase-B and beta-S100 protein in the cortex, cerebellum, spinal cord and proximal and distal sciatic nerves of rats was determined by enzyme immunoassay. 2. The amounts of the three proteins decreased significantly in the distal segment of sciatic nerve, whereas they remained unchanged in the brain and proximal sciatic nerve. The quantitative decline in these marker proteins in the distal sciatic nerve could be related to neurophysiological deficits in the peripheral nerves. 3. This study indicates that the biochemical changes observed are consistent with the clinical and pathological findings of n-hexane neuropathy. These nerve-specific marker proteins can be used to assess solvent-related peripheral neurotoxicity.

Animals↗

Determination of urinary 2,5-hexanedione concentration by an improved analytical method as an index of exposure to n-hexane.

2,5-Hexanedione is a main metabolite of n-hexane and is considered as the cause of n-hexane polyneuropathy. Therefore, it is useful to measure 2,5-hexanedione for biological monitoring of exposure to n-hexane. The analytical methods existing for n-hexane metabolites, however, were controversial and not established enough. Hence, a simple and precise method for determination of urinary 2,5-hexanedione has been developed. Five ml of urine was acidified to pH 0.5 with concentrated hydrochloric acid and heated for 30 minutes at 90-100 degrees C. After cooling in water, sodium chloride and dichloromethane containing internal standard were added. The sample was shaken and centrifuged. 2,5-Hexanedione concentration in an aliquot of dichloromethane extract was quantified by gas chromatography using a widebore column (DB-1701). Urinary concentration of 2,5-hexanedione showed a good correlation with exposure to n-hexane (n = 50, r = 0.973, p less than 0.001). This method is simple and precise for analysis of urinary 2,5-hexanedione as an index of exposure to n-hexane.

Adhesives↗

[Asbestos concentration and fiber size in lungs of the urban residents].

Asbestos fiber concentrations and fiber size distribution in lung tissues of 53 urban residents (males: 34, female: 19) were analyzed by low temperature ashing-analytical transmission electronmicroscopy. The following findings were obtained. 1. Pulmonary asbestos fibers were found in 51 out of 53 patients. The types of asbestos fibers were chrysotile, amosite, crocidolite, actinolite and tremolite. 2. Thirty-six of 53 patients had no history of occupational asbestos exposure, and their geometric mean concentration of asbestos fibers was 1.67 x 10(6) fibers/g dry lung. Most of these asbestos fibers are probably attributable to general environmental contamination. Thirteen patients who had a history of occupational asbestos exposure showed a geometric mean of their pulmonary asbestos concentrations (5.82 x 10(6) fibers/g dry lung) which was significantly higher than that of patients without occupational asbestos exposure (p less than 0.01). 3. The geometric mean concentration of asbestos fiber in males (2.70 x 10(6)) was higher than in females (1.59 x 10(6)), probably due to a difference in the occupational asbestos exposure between males and females. 4. Regardless of the patient's sex, the geometric mean concentration of asbestos fibers in patients without a history of smoking (male: 4.91 x 10(6), female: 1.78 x 10(6)) was higher than that in patients with a smoking history (male: 2.76 x 10(6), female: 1.37 x 10(6)). The difference, however, was not statistically significant, and no correlation was seen between the concentration of asbestos fibers and smoking history. 5. Although most asbestos fiber utilized in Japan is chrysotile, the geometric mean concentration of chrysotile (0.87 x 10(6)) was almost identical to that of amphibole asbestos fiber (0.90 x 10(6)). 6. Of the asbestos fibers observed, 95% of chrysotile and 85% of amphibole asbestos were less than 5 microns in length and 93% of the total asbestos fibers were too small to be visible by light microscopy.

Adult↗

Effects of subacute toluene exposure on neuronal and glial marker proteins in rat brain.

The behavior of marker proteins of neurons (gamma-enolase) and glial cells (alpha-enolase, beta-S100 protein and creatine kinase-B) was investigated quantitatively by using enzyme immunoassay systems in toluene-exposed rat brains. Three groups of animals were exposed to toluene vapor at 300 ppm, 1000 ppm, and 3000 ppm, respectively, 8 h/day, 6 days/week, for 2 weeks. After subacute repeated solvent exposure, both neuron-specific gamma-enolase and glial marker proteins displayed an overall concentration-dependent increase tendency in separate brain regions. In cerebrum, only the 3000 ppm group showed a significant increase in alpha-enolase by 27% and creatine kinase-B (CK-B) by 26%. alpha-Enolase and gamma-enolase exhibited a pronounced elevation in cerebellum relative to other brain regions, while beta-S100 protein appeared to be the most markedly altered marker in brainstem. The development of gliosis, which is a frequent phenomenon following CNS damage, is presumed to be responsible for the elevation of glial marker content. Energy metabolism disruption in brain tissues may also bring about the compensatory oversynthesis of glycolytic enzymes such as gamma-enolase, alpha-enolase and CK-B. The dose-dependent alteration patterns following toluene exposure suggest the feasibility of using these brain specific markers to evaluate solvent-induced CNS effects.

Animals↗

Changes in urinary n-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixed n-hexane levels.

To make clear how the n-hexane metabolism is modified by co-exposure with MEK, rats were exposed to various concentrations of MEK mixed with a fixed concentration of n-hexane. Twenty-four male Wistar rats were divided into four equal groups. Each group was exposed for 8 h to 2000 ppm n-hexane, 2000 ppm n-hexane plus 200 ppm MEK, 2000 ppm n-hexane plus 630 ppm MEK and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Free metabolites and the sum of free and conjugated metabolites of n-hexane were analyzed by gas chromatography. The main metabolite was 2-hexanol during the exposure and 2,5-hexanedione (2,5-HD) after the exposure in any group. The main metabolites, 2-hexanol and 2,5 HD, decreased in inverse proportion to the co-exposed MEK concentrations. The results suggest that augmentation of n-hexane neurotoxicity by MEK co-exposure could not be explained only by 2,5-HD. In addition, 2,5-HD is recommended as an index for biological monitoring of n-hexane exposure. However, one should be careful to evaluate the exposed n-hexane concentration by urinary 2,5-HD, because n-hexane metabolism could be largely modified by co-exposure with MEK.

Administration, Inhalation↗

Effects of MEK on kinetics of n-hexane metabolites in serum.

The neurotoxicity of n-hexane is thought to be caused ultimately by 2,5-hexanedione (2,5-HD), one of the n-hexane metabolites. The potentiation of n-hexane neurotoxicity by co-exposure with MEK, therefore, is suspected to be related to kinetics of 2,5-HD in blood. To clarify the kinetics of n-hexane metabolites in the mixed exposure of n-hexane and MEK, rats were exposed to 2000 ppm n-hexane or a mixture of 2000 ppm n-hexane and 2000 ppm MEK, and the time courses of serum n-hexane metabolites were determined. 2,5-HD in serum increased until 2 h after the end of exposure, when serum 2,5-HD concentration reached a peak of 16.35 micrograms/ml in the n-hexane-alone group. In contrast, 2,5-HD in the mixed exposure group increased much more slowly during and after exposure than in the n-hexane-alone group. It reached a peak of 2.12 micrograms/ml at 8 h after the end of exposure. Serum MBK, a precursor of 2,5-HD in the co-exposure group, was about half in the n-hexane-alone group during exposure. However, MBK decreased more slowly in the co-exposure group than in the n-hexane-alone group after the end of the exposure. The results suggest that co-exposed MEK might inhibit oxidation of n-hexane and decrease clearance of n-hexane metabolites. Co-exposed MEK did not increase serum 2,5-HD, which was considered a main neurotoxic metabolite. Therefore the enhancement of neurotoxicity could not be attributed to increased serum 2,5-HD in the co-exposed group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗