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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material
Justification for type of information:
Read-across from a structurally similar substance.
Cross-reference
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
07 March 2012 to 22 March 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
A valid study is available for the read across substance, sodium 5-oxo-L-prolinate. It is a GLP compliant study conducted in accordance with agreed protocols, with no or minor deviations from standard testing guidelines. Read-across is considered to be suitable based on the structural similarities between the read across substance 5-oxo-DL-proline and the substance sodium 5-oxo-L-prolinate.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: CRL: (WI)
Sex:
female
Details on test animals 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
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.
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.
Interpretation of results:
other: Not classified according to EU criteria.
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.

Data source

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

Materials and methods

Test material

Reference
Name:
Unnamed
Type:
Constituent
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.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.

Applicant's summary and conclusion