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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report Date:
1971

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
The study was conducted prior to implementation of OECD and GLP guidlines
Principles of method if other than guideline:
- Principle of test:
The twenty five amino acids were prepared as 30% solutions in water or as 30% suspensions in 1 % methyl cellulose and administered by gastric intubation at a maximum dosage volume of 53.3 ml/kg bodyweight. This gave a maximum practical dose of 16 g amino acid /kg bodyweight. The observation period was 14 days.
During the the observation period, a record was kept of all mortalities and signs of toxicity. All rats that died were examined macroscopically in an attempt to identify the target organs, and animals surviving terminally were similarly examined to detect possible residual damage. Assessment of degree of recovery from the initial toxic action of the product was made subjectively from appearance and behaviour of the animals and, more objectively, by weekly checks on bodyweight. Where the mortality data indicated that the LD50 was below the maximum practical dosage (16 g/kg bodyweight), the LD50 and its 95% confidence limits were calculated by the method of Litchfield, J.T., and Wilcoxon, F. (1949) J. Pharmac. exp. Ther, 96, 99.

- Short description of test conditions:
The rats used in these tests were of the CFY strain.
At the time of dosing they were in the weight range of 62 to 123g. Each animal was deprived of food for 20 h prior to dosing, after which food was withheld for a further 4 hours.

- Parameters analysed / observed:
Rats that died were examined macroscopically. Assessment of degree of recovery from the initial toxic action was made subjectively from appearance and behaviour of the animals, more objectively, by weekly checks on body weight. In case of death of an animal that received less than the maximum dose, the LD50 was determined.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Test animals

Species:
rat
Strain:
other: CFY strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: females: 85 and 76 g and males: 83 and 78 g
- Fasting period before study: 20 hrs prior to dosing and 4h after dosing
- Housing: caged in groups according to sex and dosage

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 30% solutions in water or 30% suspensions in 1% methyl cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: maximum concentration in vehicle: 0.3 g/mL (16 g/kg/53.3 mL/kg = 0.3 g/mL)
- Amount of vehicle (if gavage): maximum dosage volume 53.3 mL/kg bw.
Doses:
0 and 16 g/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations and weekly determination of body weight, clinical signs, mortality
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:
In case of L-asparagine no preliminary test was recorded. Only one dose was documented.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 16 000 mg/kg bw
Based on:
act. ingr.
Mortality:
no mortality observed
Clinical signs:
no clinical signs observed
Body weight:
no significant change in body weight or body weight gain compared to the control group was observed
Gross pathology:
no adverse effects were detected

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute oral toxicity study rats were administered L-asparagine at a dose of 16 g/kg bw by oral gavage. Since there was no mortality and clinical symptoms observed or recorded the LD 50 was considered to be > 16 g/kg bw.