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Toxicological information

Neurotoxicity

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Administrative data

Endpoint:
neurotoxicity
Remarks:
acute
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: publication using subcutaneous injection (irrelevant route of exposure)

Data source

Reference
Reference Type:
publication
Title:
3-MERCAPTOPROPIONIC ACID: CONVULSANT PROPERTIES, EFFECTS ON ENZYMES OF THE 7-AMINOBUTYRATE SYSTEM IN MOUSE BRAIN AND ANTAGONISM BY CERTAIN ANTICONVULSANT DRUGS, AMINOOXYACETIC ACID AND GABACULINE.
Author:
Löscher, W.
Year:
1979
Bibliographic source:
Biochemical Pharmacology, Vol. 28, pp. 1397-1407.

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purchased from Merck (Darmstadt, Germany)

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male
Details on test animals and environmental conditions:
no data
TEST ANIMALS
- Source: Bomholtgard, Ry, Denmark
- Weight at study initiation: 24-30 g
- Fasting period before study:
- Housing: groups of 10 in Makrolon vages
- Diet (ad libitum): Altromin
- Water (e.g. ad libitum): no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24-26°C

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Frequency of treatment:
single
Doses / concentrations
Remarks:
Doses / Concentrations:
60 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
no data

Results and discussion

Applicant's summary and conclusion

Executive summary:

Subcutaneous injection of 3-mercaptopropionic acid (MP) into mice caused severe convulsions which started after about 6 min and were paralleled by a large, reversible inhibition of glutamate decarboxylase (GAD) and activation of (GABA)-a-oxoglutarate aminotransferase (GABA-T) in the brain. The central (GABA) level, determined by a newly developed gas chromatographic method, was not altered after administration of the CD 97 of MP (60 mg/kg) but decreased after doubling or tripling the dose. The results suggest a role played by the GABA system in the convulsant action of MP and in the antiseizure activity of several clinically useful anticonvulsants as well as AOAA and gabaculine. With respect to the GABA system, MP seems to be a useful tool in studies of experimental epilepsy.