Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 March 2012 to 22 March 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
sodium (2S)-5-oxopyrrolidine-2-carboxylate
Cas Number:
28874-51-3
Molecular formula:
C5H6NO3. Na
IUPAC Name:
sodium (2S)-5-oxopyrrolidine-2-carboxylate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: White to pale yellow powder.
- Storage condition of test material: Controlled room temperature (15-25 °C, below 70 RH %), protected from humidity.

Test animals

Species:
rat
Strain:
other: CRL: (WI)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10 to 11 weeks old.
- Weight at study initiation: 220 to 235 g
- Fasting period before study: Animals were fasted the night before treatment, and then returned three hours after treatment.
- Housing: In groups of three, in polypropylene/polycarbonate cages.
- Diet: Complete diet for rats and mice, ad libitum.
- Water: tap water from the municipal supply ad libitum.
- Acclimation period: At least 20 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15 - 20 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours per day, between 06:00 and 18:00 hours.

IN-LIFE DATES: From: 07 March 2012 To: 21/22 March 2012

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Distilled
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: The test amterial was freshly formulated at a concentration of 200 mg/mL in the vehicle, on the day of administration. The formulation container was stirred continuously up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: The initial dose level was selected by the study director to be that which is most likely to produce mortality in some of the dosed animals. In the lack of any preliminary toxicological information, 2000 mg/kg bw was selected to be the starting dose.

DOSING
- Method: A group of three females were tested at the dose level initially, based on the findings a second group was dosed to confirm the results.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Three females per group.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing:
> Weighing: Body weights were recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly thereafter.
> Clinical: Observations were recorded at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: Yes, and macroscopic examination was performed on all animals. After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortalities were observed in either group dosed at 2000 mg/kg bw.
Clinical signs:
No treatment related observations were made during the 14 day observation period.
Body weight:
Body weight gains of treated animals were within the expected range, and showed no indication of treatment related effects. The mean bodyweight gain for animls from groups 1 and 2 was 20.7 ± 8.0 g.
Gross pathology:
No treatment related effects were observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, no mortalities or signs of toxicity were observed in animals treated at 2000 mg/kg bw. The LD50 was therefore considered to be greater than 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of the test material was determined in a study conducted under GLP conditions and in line with OECD 423 and EU Method B. 1 tris, according to the acute toxic class method. Two groups of three females were dosed with the test material, formulated in distilled water, at 2000 mg/kg bw via oral gavage. Animals were observed for 14 days post treatment for mortality, clinical signs of toxicity, changes in body weight and macroscopic changes at necropsy.

Under the conditions of the study, no mortalities or signs of toxicity were observed in treated animals. The LD50 was therefore considered to be greater than 2000 mg/kg bw.