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Biomedical subjects

N Hisanaga

Publications and source records attributed to N Hisanaga.

At least 55 records · Page 3Linked to original sources

[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↗

Effects of chronic n-hexane exposure on nervous system-specific and muscle-specific proteins.

Two kinds of nervous system-specific and muscle-specific proteins, enolase and S-100 protein, were quantitatively determined in peripheral nerves and skeletal muscles of rats chronically exposed to a neurotoxic solvent - n-hexane. Three groups of animals were exposed to n-hexane vapor at three different solvent concentrations (500 ppm, 1200 ppm, 3000 ppm) for 12 h/day, 7 days/week for 16 weeks. The body weight gain and motor nerve conduction velocity (MCV) in exposure groups show progressively concentration-dependent decreases compared to control values. Histopathological examination also demonstrates the degeneration of peripheral nerves in 3000 ppm- and 1200 ppm-exposed rats. The significant decrease in the amount of S-100 protein in peripheral nerves was observed not only in the high level exposure groups (3000 ppm and 1200 ppm), but also in the lowest level group (500 ppm), although the MCV and morphological examination remained unchanged at this level. In addition, the muscle-specific S-100 protein in 3000 ppm exposed rats' soleus also displayed a significant reduction. In contrast to this, however, enolase isozymes were not significantly changed by either dosage level in both nervous tissue and skeletal muscle. The experiment suggests that beta- and alpha-S-100 proteins which are specifically localized in nervous system and muscles, respectively, are more vulnerable than enolase isozymes under treatment with n-hexane, and may possibly serve as a specific indicator to evaluate the neurotoxic effects. Further research would be worthwhile to elucidate the role of the specific S-100 protein in evaluating the neurologic damage induced by various industrial chemicals.

Animals↗

Asbestos fibers in human pulmonary and extrapulmonary tissues.

The association between asbestos fibers in human lung tissues and those in other extrapulmonary organs was studied by analysing three autopsied cases, one of whom had a high pulmonary asbestos burden, one an intermediate burden, and one a low burden. The amount, types and sizes of asbestos fibers in the tissues of lung, liver, spleen, pancreas, kidney, and gastrointestinal tract were identified and measured by transmission electron microscopy equipped with an energy dispersive X-ray analyser. The following results were obtained: 1) The concentrations of asbestos fibers in extrapulmonary organs tended to increase with that in lung tissues. 2) The types of fibers identified in lungs were approximately consistent with those in other organs. 3) A relatively large range of fiber length was observed in both lungs and other organs. The findings extend and support previous light microscopic studies comparing asbestos bodies in various organs, and may imply that persons with high levels of asbestos in their lungs are also likely to have the same types and high levels of asbestos in their other tissues.

Aged↗

Relationship between chlordane and its metabolites in blood of pest control operators and spraying conditions.

Chlordane has been widely used to protect soil and house foundations against termite infestation. Pest control operators (PCOs) are occupationally exposed to chlordane. The relationship between chlordane and its metabolites in blood of PCOs and spraying conditions were investigated. Chlordane and its metabolites were detected in the blood of some chlordane-exposed PCOs, but not in that of the controls. Trans-nonachlor and the metabolites oxychlordane and heptachlor epoxide were detected in the blood of PCOs. Total concentration of chlordane and its metabolites in blood (trans-nonachlor + oxychlordane + heptachlor epoxide) was less than 5.6 ppb (mean: 0.89 ppb). The concentration of chlordane and its metabolites in blood of chlordane-exposed PCOs was significantly correlated with the number of spraying days and the amount of chlordane sprayed, particularly with a large correlation coefficient (r = 0.81, P less than 0.001) with the spraying days in the three months prior to the medical examination. The concentration of chlordane and its metabolites in blood is considered to be a useful indicator of biological monitoring for chlordane exposed workers (PCOs).

Adult↗

Changes of n-hexane neurotoxicity and its urinary metabolites by long-term co-exposure with MEK or toluene.

It is well known that the neurotoxicity of n-hexane may be modified upon co-exposure with other organic solvents. In order to elucidate this mechanism further, rats were exposed to 500ppm n-hexane, 500ppm n-hexane plus 500ppm methyl ethyl ketone (MEK), 500ppm n-hexane plus 500ppm toluene, or air only for 8h per day for 33 weeks. The body weight, motor nerve conduction velocity (MCV) and distal latency (DL) were determined before exposure and after 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. From each group one rat was histologically examined after 33 weeks of exposure. To establish a relationship between the n-hexane neurotoxicity and changes in biotransformation, urinary metabolites (2-hexanol, methyl n-butyl ketone (MBK), 2,5-hexanedione, 2,5-dimethylfuran, and gamma-valerolactone) were measured by gas chromatography on the first exposure day, and after 1, 2, 4, 8, 12, 16, 20, 24, 29, and 33 weeks of exposure. The total amounts of metabolites of n-hexane in the urine significantly decreased upon co-exposure of n-hexane, with MEK as well as with toluene, in comparison with those of animals exposed to n-hexane alone. 2,5-Hexanedione, which is considered the ultimate neurotoxic metabolite of n-hexane, also decreased. Electrophysiological and histological studies did not reveal statistically significant differences between any two groups among the four groups. It is considered that the present results might explain the combined effects of n-hexane and toluene which decrease n-hexane neurotoxicity, but do not explain those of n-hexane and MEK. Therefore, other mechanisms of the combined effects of n-hexane and MEK should be studied.

Animals↗

[A nationwide survey on the use of organic solvents in Japan].

A total of 1,179 organic solvent products used as thinners, paint, degreasers, inks, adhesive and others, were collected nationwide from factories of various sizes and kinds in Japan, and analyzed by gas chromatography. Solvent components per sample, frequency of each solvent component, and contents of each component were analyzed and classified by use. Paints, inks, and adhesives which contained nonvolatile substances were analyzed by head space techniques. Seventy-seven percent of all samples, 93% of paints, 85% of thinners, 73% of adhesives, and 52% of degreasers contained mixed organic solvents. The average numbers of solvent components per sample were 4.14 (max. 13) in thinner, 3.29 (max. 7) in paint, 2.23 (max. 5) ink, 2.19 (max. 6) in adhesive, 1.71 (max. 6) in degreaser, when gasoline was excluded. Toluene, xylene, methylalcohol, isopropylalcohol, ethylacetate, methylethylketone, industrial gasoline were widely used in the above-mentioned products. Toluene was the most popular component in the solvent products, excluding degreasers. Many kinds of solvent components were used in thinner and paint. However, toluene, xylene and industrial gasoline were their main components and contents per sample were very high. Acetates, alcohols, ketones and glycols were frequently detected in solvent products, but their contents per sample were relatively low, because these solvent components were usually used as subordinate solvents. The chlorinated hydrocarbons such as trichloroethylene, tetrachloroethylene and 1,1,1-trichloroethane, and industrial gasoline were the most popular components in degreasers. 1,4-dioxane was detected in a relatively large number of the samples, but its content per sample was very low, because it is usually used as an additive to 1,1,1-trichloroethane. Toluene was the most popular component in ink solvents, too. In addition, isopropylacohol, methylalcohol, methylethylketone were frequently detected in inks. Toluene was also the most popular component in adhesives, and n-hexane was also frequently detected in them. In order to prevent poisoning by industrial solvents, special attention should be paid to toluene and xylene, which are frequently and largely used for wide purposes, trichloroethylene which is largely used as a degreaser and has a severe toxicity, n-hexane which is frequently used in adhesives and has a high volatility and severe neurotoxicity, and other popular and toxic solvents. The severely toxic solvents such as benzene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1,2,2-tetrachloroethane and carbon disulfide were detected in few samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adhesives↗

[Assessment of the exposure of pest control operators to organophosphorus pesticides. Organophosphorus pesticides in blood and alkyl phosphate metabolites in urine].

Pest control operators usually spray pesticides in small areas such as a kitchen in a restaurant and are exposed to various pesticides, especially those of the organophosphorus (OP) type. In order to evaluate their occupational exposure to OP pesticides during the work, OP pesticides in blood and alkyl phosphate metabolites in urine of these operators were analyzed and the relationship between pesticide exposure and analytical results were studied. OP pesticides in blood were analyzed by gas chromatography with flame photometric detector (FPD-GC) after separation of phospholipid in blood with silicagel column chromatography. OP pesticides were not detected in any blood samples (the limit of detection was 1 ng/ml). Dimethylphosphate (DMP) and dimethylthiophosphate (DMTP), being urinary metabolites of OP pesticides, were analyzed by FPD-GC after benzyl derivatization. This method eliminated interfering peaks in gas chromatograms. The ratio of two isomeric derivatives of DMTP was found to be constant. Both DMP and DMTP of the exposed group were significantly higher than those of the non-exposed group, DMP being higher than DMTP. The ratio of DMP to DMTP in the fenitrothion-dichlorvos-exposed group was significantly higher than that in the fenitrothion-exposed group. It was considered that the ratio might reflect a result of pesticide exposure. The urinary metabolites of OP pesticides tended to become lower with the lapse of time since the last exposure. However, small amounts were detected in a few samples even 5 days after the last exposure.

Adult↗

[Vibration hazards in quarry workers].

Vibration hazards were surveyed in a population of quarry workers using chipping hammers and to a lesser extent, rock drills. Sixty-nine male quarry workers, aged 49.1 +/- 8.7 and exposed to vibration for 16.4 +/- 5.1 years, were surveyed in 1981-82. They were exposed to vibration for about 2-4 hours per days, mainly under a piece-work pay system. They had a high prevalence of Raynaud's phenomenon (36.2%) and numbness in upper extremities (53.6%). It is considered that the high prevalence was mainly due to large vibration levels in chipping hammers and rock drills and long daily exposure time. The attacks of Raynaud's phenomenon were found predominantly in the left hand, which held chisels, whereas the restriction of motion in the elbow was predominantly in the right arm which pushed chipping hammers. The same 49 male quarry workers in this population were also surveyed in 1976-77 and the prevalence of their complaints between 1976-77 and 1981-82 was compared. The prevalence of Raynaud's phenomenon was the same, but the frequency of the attacks increased between the two periods. The prevalence of other complaints such as numbness, pain and chills in the upper extremities also increased. Between 1976-77 and 1981-82, the prevalence of Raynaud's phenomenon, numbness, and pain in the upper extremities increased in the population of quarriers exposed to vibration for above 2.6 hours per day and 200 days per year, or 600 hours per year. On the other hand, the prevalence of these complaints mostly decreased in the population of quarriers with less exposure.

Adult↗

A study on biological monitoring of n-hexane exposure.

n-Hexane is one of the solvents widely used in industry and well known to be neurotoxic. Recently it was clearly revealed that n-hexane is metabolized in vivo and its metabolites are excreted in the urine. However, the relationship between the exposed dose of n-hexane and the metabolites in the urine has not yet been substantially determined. Therefore, in this investigation we intended to clarify the above relationship in order to establish its usefulness for biological monitoring of n-hexane exposure. The exposed dose was measured by means of a personal monitoring badge worn by workers in seven factories manufacturing vinyl sandals. The time-weighted average (TWA) concentration of n-hexane was 0.2-47.4 ppm. The n-hexane metabolites in the urine of 22 workers were measured with modified Perbellini's method [12] in the early morning (6:00-7:00 hrs) and at 17:00 hrs. 2,5-Dimethylfuran, 2,5-hexanedione and gamma-valerolactone were identified by gas chromatography and mass spectrometory. At 17:00 hrs the means +/- SD of the metabolites were 0.21 +/- 0.11 mg/l for 2,5-dimethylfuran, 1.13 +/- 0.71 mg/l for 2,5-hexanedione, and 2.04 +/- 2.31 mg/l for gamma-valerolactone. The metabolites were also found in the urine in the early morning. 2-Hexanol was not detected in the urine of any worker examined. A strong correlation between TWA concentration of n-hexane and 2,5-hexanedione in the urine was found at 17:00 hrs (r = 0.895, P less than 0.001). The results suggest that the urinary metabolites of n-hexane, especially 2,5-hexanedione, could be useful indicators for biological monitoring of n-hexane exposure. Furthermore the present study offers the advantage of a better estimate of n-hexane TWA.

Adolescent↗