Registration Dossier

Administrative data

Endpoint:
neurotoxicity: acute oral
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
circa 1994
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study did not differentiate between a direct effect or due to hypoxia.

Data source

Reference
Reference Type:
publication
Title:
Neurochemical Profile of Effects of 28 Neurotoxic Chemicals on the Central Nervous System in Rats (1) Effects of Oral Administration on Brain Contents of Biogenic Amines and Metabolites
Author:
Kanada, M., Miyagawa, M., Sato, M., Hasegawa, H., and Honma, T.
Year:
1994
Bibliographic source:
Industrial health 32:145-164

Materials and methods

Principles of method if other than guideline:
Two hours after a single acute oral dose of nitroethane, the profile of several neurochemicals in the brain was examined.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purchased from Wako Pure Chemicals Industries Ltd., Japan. No information on purity provided.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Rats received a single dose, 275 mg/kg (one quarter of the LD50 value), via oral gavage.
Frequency of treatment:
One dose
Doses / concentrations
Remarks:
Doses / Concentrations:275 mg/kgBasis:other: nominal dose via oral gavage
No. of animals per sex per dose:
4-5 animals in each group
Control animals:
yes, concurrent no treatment

Results and discussion

Any other information on results incl. tables

Not applicable.

Applicant's summary and conclusion

Conclusions:
Increased levels of medulla oblongata 3- methoxy-4-hydroxyphenylglycol (MHPG), and Medulla 5-hydroxyindoleacetic acid (5HIAA) were observed two hours after oral gavage administration of 275 mg/kg nitroethane.
Executive summary:

We investigated the effects of oral administration of 28 organic chemical agents, all of which possess neurotoxicity and most of which are used as industrial solvents, on monoamine neurotransmitters and metabolites in the rat brain. Each chemical was administered to rats singly at a dose of one-quarter the LD50 value. Two hours after administration, acetylcholine, 3,4-dihydroxyphenylalanine (DOPA), dopamine, 3,4 -dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), serotonin, and 5-hydroxyindoleacetic acid (5HIAA) contents in the small-brain regions were measured.

Increased levels of medulla oblongata 3- methoxy-4-hydroxyphenylglycol (MHPG), and Medulla 5-hydroxyindoleacetic acid (5HIAA) were observed two hours after oral gavage administration of 275 mg/kg nitroethane. The significance of this is unknown.