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Biomedical subjects

N Hisanaga

Publications and source records attributed to N Hisanaga.

At least 73 records · Page 4Linked to original sources

Changes of n-hexane metabolites in urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK.

It is well known that n-hexane produces peripheral neuropathy, and 2,5-hexanedione, one of the metabolites of n-hexane, is thought to be the main causative agent. Recently, the metabolites of n-hexane in urine have been measured by gas chromatography, and 2,5-hexanedione was proved to be useful for the biological monitoring of n-hexane exposure. In the present experiment, we intended to clarify the change of n-hexane metabolites in the urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene of MEK. In the first experiment, five separate groups of five rats each were exposed to 100, 500, 1000, or 3000 ppm of n-hexane, or fresh air respectively in an exposure chamber for 8 h a day. Urinary samples were gathered during exposure, 16, 24, and 40 h after exposure. Half of each sample was analyzed by gas chromatography after hydrolysis with acid and enzymes, and the other half was analyzed without hydrolysis. 2,5-Dimethylfuran, MBK, 2-hexanol, 2,5-hexanedione, and gamma-valerolactone could be identified as n-hexane metabolites in the urine. The main metabolites were 2-hexanol and 2,5-hexanedione. 2-Hexanol was mostly excreted during exposure, while most of the 2,5-hexanedione was excreted after the end of exposure. The amount of metabolites in the urine correlatively increased with the concentration of n-hexane from 100 to 1000 ppm, but the amount of metabolites scarcely increased when the concentration of n-hexane increased from 1000 to 3000 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An experimental study of the combined effects of n-hexane and methyl ethyl ketone.

This study was intended to determine whether or not methyl ethyl ketone (MEK) enhances the neurotoxicity of n-hexane at low concentration and after long term exposure. Separate groups of eight rats were exposed to 100 ppm n-hexane, 200 ppm MEK, 100 ppm n-hexane plus 200 ppm MEK, or fresh air in an exposure chamber for 12 hours a day for 24 weeks. The body weight, motor nerve conduction velocity (MCV), distal motor latency (DL), and mixed nerve conduction velocities (MNCVs) were measured before exposure and after four, eight, 12, 16, 20, and 24 weeks' exposure. One rat of each group was histopathologically examined after 24 weeks' exposure. Exposure of 100 ppm n-hexane did not significantly decrease the functions of the peripheral nerve throughout the experiment. Exposure to 200 ppm MEK significantly increased MCV and MNCVs and decreased DL after four weeks' exposure, but at this later stage no significant changes were found throughout the experiment by comparison with the controls. Mixed exposure to 100 ppm n-hexane plus 200 ppm MEK significantly decreased by comparison with the controls. On histopathological examination of the tail nerve, however, no changes were found in any of the exposed groups or the controls. These results suggest that MEK might enhance the neurotoxicity of n-hexane at a low concentration, and mixed exposures to n-hexane and MEK should be avoided.

Animals↗

Neurotoxicity of petroleum benzine compared with n-hexane.

Petroleum benzine is one of the mixtures of organic solvents containing n-hexane. The occurrence of polyneuropathy in the workers using petroleum benzines is attributed mainly to n-hexane, though other hydrocarbons present are also suspected of having some neurotoxicity or some potential which could modify the neurotoxicity of n-hexane. The present experiment was performed in order to clarify the toxicity of petroleum benzine to the peripheral nerve and compare it with that of n-hexane. Forty rats were randomly divided into five groups. The groups were exposed to 200 ppm n-hexane, 500 ppm n-hexane, and petroleum benzine vapor containing 200 ppm n-hexane or 500 ppm n-hexane, together with aliphatic and aromatic hydrocarbons for 12 h a day for 24 weeks. The body weight, motor nerve conduction velocity, motor distal latency, and mixed nerve conduction velocities were measured before exposure and every 4 weeks of exposure. A rat from each exposed group was histopathologically examined after 24 weeks' exposure. The function of the peripheral nerve was conspicuously impaired by 500 ppm n-hexane, slightly impaired by 200 ppm n-hexane and petroleum benzine containing 500 ppm n-hexane, and even less impaired by petroleum benzine containing 200 ppm n-hexane. Degenerations of the myelin sheaths and axons were demonstrated in all exposed groups upon examination of the revealed tail nerves. Thus, the experiment revealed that petroleum benzine could impair the peripheral nerves, while some components of petroleum benzine were considered to inhibit the neurotoxicity of n-hexane.

Alkanes↗

A comparative study on the toxicity of n-hexane and its isomers on the peripheral nerve.

Commercial hexane which caused polyneuropathy in many workers contained 10-40% of 2-methylpentane, 3-methylpentane and methylcyclopentane in addition to n-hexane. The hexacarbon compounds methyl n-butyl ketone, 2,5-hexanedione and etc. were shown to be neurotoxic like n-hexane. Therefore, 2-methylpentane, 3-methylpentane and methylcyclopentane which are also hexacarbon compounds were suspected to be neurotoxic, but their neurotoxicity had not been sufficiently investigated. The present experiment was performed to clarify their neurotoxicity by measuring the nerve conduction velocity in the rat's tail. Thirty rats were divided into five groups of 5-7 rats. n-Hexane, 2-methylpentane, 3-methylpentane and methylcyclopentane were diluted with olive oil and orally administered daily for eight weeks. The body weight, motor nerve conduction velocity, motor distal latency and mixed nerve conduction velocity were measured before administration, after two, four, six and eight weeks' administration. The n-hexane group showed a distinct impairment of the functional states of the peripheral nerve. Methylcyclopentane, 2-methylpentane and 3-methylpentane group had some significant differences in comparison with the control in the experiment, although these differences were not so distinct as those in n-hexane group. The results revealed that the neurotoxicity of the three chemicals was not so severe as that of n-hexane and were in the order of n-hexane greater than methylcyclopentane greater than or equal to 2-methylpentane divided by 3-methylpentane.

Animals↗

An experimental study on the combined effects of n-hexane and toluene on the peripheral nerve of the rat.

An electrophysiological study was undertaken to determine whether toluene affected the neurotoxicity of n-hexane. Separate groups of eight rats were exposed to 1000 ppm n-hexane, 1000 ppm toulene, 1000 ppm n-hexane plus 1000 ppm toluene, of fresh air in an exposure chamber for 12 hours a day for 16 weeks. The body weight, MCV, DL, MNCVs were measured before exposure, after four, eight 12, and 16 weeks exposure; and four weeks after exposure was discontinued. Exposure to 1000 ppm n-hexane considerably impaired the function of the peripheral nerve, but exposure to a mixture of 1000 ppm n-hexane plus 1000 ppm toluene resulted in only slight impairment; 1000 ppm toluene had little effect. These results strongly suggest that toluene decreases the toxic effects of n-hexane on the peripheral nerve.

Animals↗

[An occupational health survey on dry cleaning workers (author's transl)].

In order ot clarify the working conditions and health of dry cleaning workers, we investigated dry cleaning workshops in C ward of Nagoya City. We had the responses from 52 (91%) workshops and 181 (97%) workers. 26 (50%) of the workshops used petroleum solvents, 23 (46%) perchloroethylene, two (4%) 1, 1, 2-trichloro-1, 2, 2-trifluoroethane (R 113), and one (2%) petroleum solvent plus perchloroethylene. Average amounts of solvents consumed per workshop were 1280 kg/year of petroleum solvents, 1450 kg/year of perchloroethylene, and 275 kg/year of R 113. Average number of workers employed in 19 workshops per workshop was 3.6 persons (median 2.0), and the remaining 33(63%) workshops had no employee. The workers complained of strange smell, irritation of eyes, unsteady feeling of head at high rate during week. They also had the high rate of complaints of shoulder stiffness, fatigability, lumbago, and the percentages of them were higher in the workers using petroleum solvents than those in the workers using perchloroethylene. More detailed surveys were made in 13 workshops out of 52. In these cases, average working hours were 11.1 per day and average years of using solvents were 12.9 in workshops using petroleum solvents, 8.4 in those using perchloroethylene including 3.1 years of petroleum solvents. Relatively high concentrations of solvents were detected under the nose of the workers pulling clothes out of dry cleaning machines, near the clothes just pulled out, and about 30 cm above the clothes at brushing with solvents before putting them into the machines. Perchloroethylene leaked from the dry cleaning machine in a workshop. Amount of the total trichlorinated compounds (TTC) in the urine of the workers directly engaged in dry cleaning with perchloroethylene tended to be larger than those of the indirect workers. TTC in both groups, however, were significantly larger than those in the control and in the workers using petroleum solvents. RBC, Hb, an Ht of the female workers in the petroleum solvents workshops were lower than those in perchloroethylene workshops. Liver function tests showed that the average values in the workers directly engaged in dry cleaning with perchloreothylene were significantly larger than those in the indirect workers. A case of malignant lymphoma, a case of liver dysfunction and a case of diabetes mellitus were found among workers directly engaged in dry cleaning. Workers in the small-sized dry cleaning workshops would not be prevented from exposure to organic solvents without the further improvement of administrative guidance and cooperation of the makers of dry cleaning machines and solvents.

Adult↗

A comparative study on the neurotoxicity of n-pentane, n-hexane, and n-heptane in the rat.

The neurotoxicity of n-pentane, n-hexane, and n-heptane have been studied in Wistar strain male rats after exposure to 3000 ppm of n-pentane, n-hexane, or n-heptane for 12 hours a day for 16 weeks. The nerve conduction velocity and the distal latency were measured before the beginning of the exposure and after exposure for four, eight, 12, and 16 weeks. The experiment showed that n-hexane disturbed the conduction velocity of the motor nerve and the mixed nerve and prolonged the distal latency in the rat's tail, but that n-pentane and n-heptane did not. The light and electron microscopic examination showed that the peripheral nerve, the neuromuscular junction, and the muscle fibre of the rats exposed to n-hexane were severely impaired, but those of the rats exposed to n-pentane or n-heptane showed no particular changes even after 16 weeks of exposure. These results show that n-hexane is far more toxic to the peripheral nerve of the rat than n-pentane or n-heptane. It is necessary to study the neurotoxicity of other petroleum hydrocarbons, since some reports suggest that petroleum solvents might possibly contain neurotoxic hydrocarbons other than n-hexane.

Animals↗

[Toxicity and dose-response (effect) relationship of n-hexane (author's transl)].

A large amount of n-hexane is being widely used in industry as a solvent or a component of the mixed solvents for extraction of vegetable oils, adhesives, paints, and for cleaning, etc. And, many cases of polyneuropathy due to n-hexane have been reported up to now. Recently, studies on the neurotoxicity and metabolism of n-hexane rapidly progressed in many countries. The present review covers clinical signs and symptoms, pathological changes, metabolism, dose-response (effect) in acute exposure, glue or thinner sniffers, workers, animal experiments. The joint effects and the maximal allowable concentration of n-hexane are also briefly discussed.

Animals↗

The neurotoxicity of toluene: EEG changes in rats exposed to various concentrations.

Workers exposed to toluene develop many central and autonomic nervous symptoms. It has been suggested that the effects of toluene on the central nervous system may be detectable by EEG. In the present experiments, changes in EEG and behaviour of rats exposed to toluene were monitored in an attempt to clarify the relationship between exposure to toluene and central nervous system reaction. Chronically implanted electrodes were used in Wistar albino male rats to record EEG in cortex and hippocampus, cervical EEG and pulse rate. The rats were exposed to 4000 ppm, 2000 ppm and 1000 ppm toluene vapour for four hours. The sleep cycle was divided into five phases (wakeful, spindle, slow-wave, preparadoxical and paradoxical) judged by the cortical and hippocampal EEGs, the cervical EMG, and behaviour. This classification should be useful in assessment of the effects of toluene on the central nervous system. In our experiments, the changes in the sleep cycle suggest that 4000 ppm and 2000 ppm of toluene vapour disturb the sleep, and 1000 ppm of toluene vapour prevents sleep entering the slow-wave phase but facilitates its entry into the paradoxical phase. The changes of EEG components were peculiar to each concentration. The results suggest, in effect, that analysis of the changes in the EEG components would be helpful as an index to the reaction of the central nervous system to toluene vapour.

Animals↗