Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-10-02 to 2007-04-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study performed according to OECD Guideline 423 (Acute Oral Toxicity - Acute Toxic Class Method) and EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method) without deviations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Remarks:
The testing facility indicated that the protocol was followed without deviation.
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
Department of Health of the Government of the United Kingdom
Test type:
other: Acute Oral Toxicity
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): VRT-126016
- Molecular formula (if other than submission substance): Not applicable
- Molecular weight (if other than submission substance): Not applicable
- Smiles notation (if other than submission substance): Not applicable
- InChl (if other than submission substance): Not applicable
- Structural formula attached as image file (if other than submission substance): Not applicable
- Substance type: No data
- Physical state: White powder
- Analytical purity: 99.8%
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: 2006-02-02
- Lot/batch No.: Lot I-4107-6-02-02/ Batch No. 25719
- Expiration date of the lot/batch: 2008-02-01
- Other: Store at room temperature

Test animals

Species:
rat
Strain:
other: CD (Crl:CD BR)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, England
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 175 to 209 g
- Fasting period before study: Overnight prior to and approximately 4 hours after exposure to test substance
- Housing: Housed in groups of three rats of the same sex
- Diet (e.g. ad libitum): Standard rodent diet (Rat and Mouse No. 1 Maintenance Diet), ad libitum
- Water (e.g. ad libitum): Potable water taken from the public supply, ad libitum
- Acclimation period: 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature (deg C): 19 to 23 deg C
- Humidity (%): 40 to 70%
- Air changes (per hr): No data
- Photoperiod: 12 hours continuous light and 12 hours continuous dark per 24 hours

IN-LIFE DATES
- From: 2006-10-05 to 2007-11-09

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 1%
- Amount of vehicle (if gavage): 10 mL/kg body weight
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED
- 10 mL/kg body weight

DOSAGE PREPARATION (if unusual)
- Not applicable

CLASS METHOD
- Rationale for the selection of the starting dose: OECD Guideline 423

Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
3 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 – morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation. The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: Yes
- Other examinations performed: Cages of rats were checked at least twice daily for any mortalities. All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Statistics:
no data

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no deaths during the study.
Clinical signs:
Clinical signs of reaction to treatment observed in animals dosed at 2000 mg/kg comprised hunched posture, abnormal gait (unsteady), piloerection and urine staining (perigenital area). In addition, underactivity seen in four females, partially closed eyelids in two females, reduced body temperature in two females, loose faeces and irregular breathing were observed in one female. These signs were first noted approximately from one to three hours after dosing. Recovery of animals, as judged by external appearance and behaviour, was complete by Day 4 or 5.
Body weight:
A bodyweight loss was noted for one animal (No. I8) dosed at 2000 mg/kg on Day 15. A low bodyweight gain was noted for one female (No. I4) on Day 15 dosed at 300 mg/kg and one female (No. I10) on Day 15 dosed at 2000 mg/kg. All other animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.
Other findings:
No data

Any other information on results incl. tables

Not applicable

Applicant's summary and conclusion

Conclusions:
The acute median lethal oral dose (LD50) to rats of the test substance was demonstrated to be greater than 2000 mg/kg bodyweight.
The test substance is included in Category 5 or unclassified, according to the Globally Harmonised System (GHS), (United Nations, 2005).
Executive summary:

Not applicable