1994 Fiscal Year Final Research Report Summary
Dose-effect relation and mechanism of effects at central and peripheral nervous system of volatile organic solvents as industrial substance.
| Project/Area Number |
05454233
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Public health/Health science
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| Research Institution | TOHO University |
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Principal Investigator |
OMOTO Miyako Toho University School of Medicine Professer, 医学部, 教授 (20057491)
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| Co-Investigator(Kenkyū-buntansha) |
OTAHARA Yumi Toho University School of Medicine Assistant, 医学部, 助手
IMAI Tsunehiko Toho University School of Medicine Assistant, 医学部, 助手 (90104215)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Organic solvents / Toluene / n-Hexane / Receptor / Neuron specific enolase / Cholin acetyl tsansferase / Binding assay / Immunohistochonistry |
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| Research Abstract |
Among the industrial toxic materials some organic solvents are extremely frequently and abundantly employed in the actual industrial field and handled without much care because they have too many uses in dissolving and cleansing. In addition it is known that some organic solvents affect central and peripheral nervous systems even through the exposure at relatively low concentrations. For the purpose of clarifying this mechanism, the rat was examined under various conditions of exposure using different indices concerning the nervous system.
Items examined : (1) Binding of the substance transmitting nerve impulses to receptors in the cerebrum : (2) histological findings of cerebrum ; (3) immunohistochemical findings of cerebral ChAT ; and (4) quantity of nervous apecific protein in the cerebellum and the peripheral nervous systems.
Substances used for exposure : Toluene, n-hexane, and mixture of toluene and n-hexane.
Method of exposure : (1) Inhalation in the perfuse type exposure chamber p
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urchased with this subsidy. This chamber can vary the concentration and the flowing amount of gases and can make precise measurement.
Results and discussion : 1) Effects on specific binding of cerebral nerve tranmitting chemical substance to receptors :
Toluene, high concentration, short single exposure - binding to receptors Adralpha1 -- decrease ; Adralpha2 -- increase ; Cho.Mus.-- increase
Toluene, low concentration, subchronic exposure - binding to receptor Adralpha2 -- decrease ; CABAa -- decreasing tendency
Toluene, high concentration, chronic exposure - binding to receptor Adralpha1 -- decrease
n-Hexane, low concentration, chronic exposure - binding to receptor Adralpha1 -- decrease
Other than above cases, no effects were observed on receptors setotonin 5HT2 and dopamine. 2) Cerebral histological findings : In high concentration exposure group, shrinkage of nerve cell body and axon was observed. In low concentration subchronic exposure group, large changes were not observed. 3) In immunohistological observations of cerebral ChAT,the effects of chronic exposure was not observed. 4) In measurement of neuron specific enolase, toluene of high concentration showed an increase in enolase in cerebellum, and chronic exposure at low concentration, an increase was observed in peripheral nerves (sciatic nerve).
As a results, it was suggested that high concentration acute exposure mainly affects adrenergic receptor and cholinergic receptor in the central nervous system and the low concentration chronic exposure affects the peripheral nervous systems. The subsidy we were granted this time was not enough to purchase many inhalation chambers on the market to make sufficient exposures possible. Furthermore we were not able to handle enough number of subjects for observing many items. We need to increase the observation examples and investigate other markers, too. Less
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