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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD 401 protocol study under GLP without significant deviations
Cross-reference
Reason / purpose:
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:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
none
Body weight:
normal weight gain for this strain
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).