Asparagine

Acute Toxicity: oral

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

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

Test material information

Constituent 1

Reference substance name:

Asparagine

EC Number:

200-735-9

EC Name:

Asparagine

Cas Number:

70-47-3

Molecular formula:

C4H8N2O3

IUPAC Name:

asparagine

Test material form:

not specified

Test animals

Species:

rat

Strain:

other: CFY strain

Sex:

male/female

Details on test animals or test system 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:

other: no clinical signs 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.