Levoglutamide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

Dec. 1970 to 1971-09-20

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: 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)

Principles of method if other than guideline:

An OECD or other international guideline for acute oral toxicity was not available at the the year of the study. The study is similiar to OECD 403.
Groups of ten rats (five males and five females) were administered 0 and 16g/kg bw L-glutamine and observed during two weeks for mortality.

GLP compliance:

no

Remarks:

study performed prior to implementation of GLP

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Levoglutamide

EC Number:

200-292-1

EC Name:

Levoglutamide

Cas Number:

56-85-9

Molecular formula:

C5H10N2O3

IUPAC Name:

L-glutamine

Test animals

Species:

rat

Strain:

other: CFY strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Carworth Europe, Alconbury, Huntingdon
- Weight at study initiation: 62 - 123 g
- Fasting period before study: 20 hours before dosing (and 4 hours after dosing)
- Housing: caged in groups according to sex and age

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

or water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30% solution in water or 30% suspension in 1% methyl cellulose

MAXIMUM DOSE VOLUME APPLIED:
Maximum dosage volume of 53.3 ml/kg bodyweight, equivalent to a maximum practical dose of 16g amino acid /kg bodyweight.
Dosage volumes in excess of 20 ml/kg were given in divided doses at two hourly intervals.

Doses:

0 and 16 g/kg bw.
Rats dosed with the vehicle alone served as controls.

No. of animals per sex per dose:

5 males and 5 females

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: once a week
- Necropsy of survivors performed: yes
- Other examinations performed: body weight/behaviour

Statistics:

Method of Litchfield J.T., Wilcoxon F (1949), J. Pharmac. exp. Ther. 96, 99

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Based on:

test mat.

Effect levels 3

Dose descriptor:

approximate LD50

Effect level:

ca. 16 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: median Iethal oral dose

Mortality:

One male rat died within two hours of dosing. Death was preceded by coma. Autopsy dld not reveal any specific cause of death.

Clinical signs:

other: Recovery of survivors, as judged by external appearance and behaviour was apparently complete within 24 hours.

Gross pathology:

Negative autopsy findings.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

An acute oral toxicity study was performed with groups of 5 male and 5 female rats. The results indicate that the median lethal oral dose (LD 50) of L-glutamine is ca. 16g/kg bw.