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Additional toxicological data

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Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
N-acetylcysteine or trolox derivative mitigate the toxic effects of methanol on the antioxidant system of rat brain.
Author:
Farbiszewski, R. et al.
Year:
2000
Bibliographic source:
Toxicology 156: 47-55
Reference Type:
publication
Title:
Ethanol and N-acetylcysteine influence on the development of liver changes in experimental methanol intoxication.
Author:
Kasacka, I. and Skrzydlewska, E.
Year:
2001
Bibliographic source:
Roczniki Akademii Medycznej w Bialymstoku 46: 133-144
Reference Type:
publication
Title:
Protective effect of N-acetylcysteine on reduced glutathione, reduced glutathione-related enzymes and lipid peroxidation in methanol intoxication.
Author:
Skrzydlewska, E. and Farbiszewski, R.
Year:
1999
Bibliographic source:
Drug Alcohol Dep 57: 61-67
Reference Type:
publication
Title:
Trolox-derivative antioxidant protects against methanol-induced damage.
Author:
Skrzydlewska, E. and Farbiszewski, R.
Year:
1997
Bibliographic source:
Fund Clin Pharmacol 11 460-465

Materials and methods

Type of study / information:
Information on the effects of N-acetylcysteine or trolox derivative to mitigate the toxic potential of methanol on the antioxidant system of rats.
Principles of method if other than guideline:
Male Wistar rats were treated with N-acetylcysteine or trolox derivative during methanol intoxication to evaluate the antioxidant defense potential.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

1. After oral application of methanol (3.0 g/kg body weight), the thiobarbituric acid-reactive substances indicating lipid peroxidation were significantly increased in brain tissue from 6 hours to 7 days after treatment. The activities of brain GSH peroxidase and GSH reductase were already reduced at 6 hours after administration. [Farbiszewski and Skrzydlewska, 2000] Also in liver, concentrations of lipid peroxidation products were increased and GSH peroxidase and GSH reductase levels were decreased. [Skrzydlewska and Farbiszewski, 1999]

2. N-Acetylcysteine exerted an protective antioxidant effect in the liver of methanol-treated rats: The total antioxidant status remained on the background-level after prior i.p. treatment with N-acetylcysteine (150 mg/kg body weight) [Farbiszewski and Skrzydlewska, 1999]. Furthermore it resulted in a lower degree of parenchymal damage [Kasacka and Skrzydlewska, 2001].

Concomitantly methanol-induced GSH-depletion was significant after 24 h and the content steadily decreased until 7 days. The toxic effects of methanol on the antioxidant system seems to be mitigated by N-acetylcysteine. In presence of N-acetylcysteine, enzyme activities involved in the removal of reactive oxygen species were also similar to the untreated control while significantly increased without protective counteraction. [Farbiszewski and Skrzydlewska, 2000].

3. A trolox derivative, an analog of alpha-tocopherol, is introduced as a beneficial antioxidant which prevents or reduces methanol-induced lipid peroxidation in rats [Skrzydlewska and Farbiszewski, 1997].

Applicant's summary and conclusion