Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Effect of Selected Amino Acids on Ethanol Toxicity in Rats
Author:
Breglia R J
Year:
1973
Bibliographic source:
Journal of Pharmaceutical Sciences, vol. 62(1), pp. 49-55

Materials and methods

Principles of method if other than guideline:
- Principle of test:
Determination of acute toxicity by Seventy-Two-Hour LD50 calculation. The number dead at 72 hr. was counted and analyzed by the method of Litchfield and Wilcoxon (J. T. Litchfield, Jr., and F. Wilcoxon, J. Pharmacol. Exp Ther., 96, 99(1949))
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 2 months
- Weight at study initiation: 125-150 g
- Fasting period before study: 24 h
- Housing: no data
- Diet (e.g. ad libitum): Ad libitum.
- Water (e.g. ad libitum): Ad libitum.
- Acclimation period: 1 week

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
(distilled water)
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 6 ml
- Concentration in vehicle: 10 and 20 % (w/v)
- Justification for choice of vehicle: Destilled water has no impact on its own

MAXIMUM DOSE VOLUME APPLIED: 6 ml

Doses:
10 and 20 % (w/v) in vehicle
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 72 hours
- Frequency of observations and weighing: mortality at 72 h.
- Other examinations performed: ataxia and sleeping time.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
12 400 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 12.40 ± 0.61 (calculated by the method of Litchfield and Wilcoxon)
Mortality:
Not specified.
Clinical signs:
Some signs of toxicity did appear such as ataxia, dyspnea, decreased muscle tonus, and loss of righting reflex. Toxicity signs were first observed 11 g/kg bw.
Body weight:
Not specified.
Gross pathology:
not specified.

Applicant's summary and conclusion

Interpretation of results:
other: No category (CLP Regulation EC no. 1272/2008)
Conclusions:
LD50 of L-argine-HCl was determined to be 12400 mg/kg b.w. in a toxicity study with rats.
Executive summary:

The acute oral toxicity of L-argine-HCl was investigated with Sprague-Dawley rats. Test item was administered at two dose levels of 10 and 20% (w/v) in distilled water (five males and five females per group). After 72 hours, neurological parameters like ataxia or sleeping time were observed and the number of dead was counted and analyzed by the method of Litchfield and Wilcoxon.Some signs of toxicity were reported such as ataxia, dyspnea, decreased muscle tonus, and loss of righting reflex. Toxicity signs were first observed 11 g/kg bw. LD50 of L-argine-HCl was determined to be 12400 mg/kg b.w.