Tetrasodium N,N-bis(carboxylatomethyl)-L-glutamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD 401 protocol study under GLP without significant deviations

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrasodium N,N-bis(carboxylatomethyl)-L-glutamate

EC Number:

257-573-7

EC Name:

Tetrasodium N,N-bis(carboxylatomethyl)-L-glutamate

Cas Number:

51981-21-6

Molecular formula:

C9H9NO8Na4

IUPAC Name:

tetrasodium 2-[bis(carboxylatomethyl)amino]pentanedioate

Details on test material:

Contains more impurities than submission substance

Sponsor's identification : GBS-5
Batch number : GLS 30P
Date received : 23 June 1994
Description : white powder
Storage conditions : room temperature over silica gel

Composition according to Certificate of Analysis (see the CoA in the report attached)
Glutamic acid - N,N -diacetic acid, tetrasodium salt 70.70%

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 6-9weeks
- Weight at study initiation: males 131-150 g females 124-135 gr
- Fasting period before study: 1 night
- Housing: groups of 5 by sex in polyprop cages with woodflakes
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): at lib
- Acclimation period:five days min.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23
- Humidity (%): 48-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From:July 4 1994 To: July 19, 1994

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: high water solubility
- Lot/batch no. (if required):
- Purity: distilled


MAXIMUM DOSE VOLUME APPLIED:
10 ml/kg equals ~ 1.5 ml for the heaviest animals

Doses:

2000 mg /kg

No. of animals per sex per dose:

5 M / 5 F

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 0.5, 1, 2 and 4 hrs after dosing, then daily for 14 days
- weighing: day ) day 0, pre-dosing, days 1,2,3,7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

not applicable

Results and discussion

Preliminary study:

500 and 2000 mg/kg bw (sequential, 24 hr interval)
1 female per dose
observations: 0.5, 1,2,4 hrs post-dosing, daily for 7 days
No clinical signs of toxicity at 2000 mg/kg bw.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

none

Clinical signs:

other: none

Gross pathology:

none

Other findings:

None

Any other information on results incl. tables

In a separate study on this compound (Micronucleus test; Durward, 1995) mice were orally dosed with GBS-5 at levels of 2500 or 5000 mg/kg bw (1 male and 1 female per level). There was no mortality. Clinical signs were observed i n animals dosed with GBS-5 via the oral route and were as follows: hunched posture, lethargy, decreased respiratory rate, ptosis and splayed gait.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Acute median lethal dose (LD50) > 2000 mg/kg bw . As there were no toxic signs at all at this level, no classification in category V (GHS) is needed.

Executive summary:

The study was performed to assess the acute toxicity of the test material, GBS-5, following a single oral administration to the Sprague-Dawley strain rat. The procedure permitted identification of the ‘discriminatory dose’ (the highest of the pre-set dose levels which could be administered without causing compound related mortality). The study was performed according to Method B1 bis of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). Following a range-finding study, a group of ten fasted animals (five male and five female) was given a single, oral dose of the test material at a dose level 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of dosing and were then killed for gross pathological examination. There were no deaths. No clinical signs of toxicity were noted. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. The acute median lethal dose (LD50) of the test material was found to be greater than 2000 mg/kg bodyweight. The test material was considered not to have significant acute toxicity. Because of the absence of effects at 2000 mg/kg, the test material was not classified in Category V according to OECD-GHS (2000 -5000 mg/kg bw).