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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2006-09-29 to 2007-05-24
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
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
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.
GLP compliance:
yes (incl. QA statement)
Remarks:
Certificate from the Department of Health of the Government of the United Kingdom
Test type:
acute toxic class method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): VRT-753136 hcl
- Molecular formula: Not applicable
- Molecular weight: Not applicable
- Smiles notation: Not applicable
- InChl: Not applicable
- Structural formula attached as image file: Not applicable
- Substance type: No data
- Physical state: White powder
- Analytical purity: 100 area %
- Impurities: 0.03 area% of unknowns
- Composition of test material, percentage of components: No data
- Isomers composition: no data
- Purity test date: 2006-09-15
- Lot/batch No.: Batch number 25515/Lot No. AF6-001
- Expiration date of the lot/batch: 2008-05-01
- Stability under test conditions: No data
- Storage condition of test material: Room temperature
- Other: No data

Test animals

Species:
rat
Strain:
other: CD (Crl:CD BR)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Obtained from Charles River (UK) Ltd, Margate, Kent, England.
- Age at study initiation: The animals were approximately eight to twelve weeks of age prior to dosing.
- Weight at study initiation: 167 to 225 g
- Fasting period before study: The day prior to dosing (Day 1)
- Housing: The cages were made of a stainless steel body with a stainless steel mesh lid and floor, and were suspended above absorbent paper which was changed at appropriate intervals. The animals were housed in groups of three rats of the same sex.
- Diet: The animals were allowed free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet), except for overnight prior to and approximately four hours after dosing.
- Water: Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23 deg C
- Humidity (%): 40 to 70%
- Air changes (per hr): not applicable
- Photoperiod (hrs dark / hrs light): Cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours

IN-LIFE DATES:
- From: 2006-10-03 To: 2006-11-03

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: purified water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The test substance was formulated at a concentration of 30 and 200 mg/mL in the vehicle.
- Amount of vehicle (if gavage): Administered at a volume of 10 mL/kg bodyweight.
- Justification for choice of vehicle: No data
- Lot/batch no.: No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED:
- No data

DOSAGE PREPARATION:
- The test substance formulations were prepared on the day of dosing. The absorption of the test substance was not determined.

CLASS METHOD
- Rationale for the selection of the starting dose: As results of the 300 mg/kg bodyweight dose level indicated the acute lethal oral dose of the test substance to be greater than 300 mg/kg bodyweight, in compliance with the study guidelines, a further two groups of three fasted female rats were similarly dosed at 2000 mg/kg to complete the study.
Doses:
300 and 2000 mg/kg bodyweight
No. of animals per sex per dose:
Two groups of three female rats received a dose level of 300 mg/kg/bodyweight as well as two groups of three fasted female rats were similarly dosed at 2000 mg/kg.
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 they were observed were recorded at each observation.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, macropathology, other: mortality

Mortality:
Cages of rats were checked at least twice daily for any mortalities

Bodyweight:
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.

Macropathology:
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:
One female (F3) dosed at 300 mg/kg died on Day 3 and one female (F12) dosed at 2000 mg/kg died on Day 1 of treatment. There were no clinical signs noted prior to death. Macroscopic examination of the decedent treated at 300 mg/kg revealed congestion (characterised by darkened tissues/organs or blood vessels injected) of the subcutaneous tissue, brain, heart, lungs and liver; together with an enlarged/swollen/thickened heart, fluid contents of the duodenum, small intestine, and thoracic cavity, and a small caecum. Examination of the decedent treated at 2000 mg/kg revealed congestion (characterised by darkened tissues/organs or blood vessels injected) of the lungs and stomach and duodenum, and fluid contents in the stomach.
Clinical signs:
Clinical signs consisted of salivation noted immediately after dosing on Day 1 occurring in two females treated at 2000 mg/kg. This sign was resolvedby approximately 30 minutes after dosing. No other clinical signs were seen in any of the remaining animals dosed at 300 or 2000 mg/kg.
Body weight:
A bodyweight loss was recorded for one female (F11) dosed at 2000 mg/kg on Day 15. Low bodyweight gain was noted for one female (F8) on Day 15 dosed at 2000 mg/kg and two females (F1 and F4) on Day 15 dosed at 300 mg/kg. All other surviving animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
no data
Other findings:
- Macroscopic examination:
Macroscopic examination at study termination on Day 15 revealed white nodules in the large intestine of two females (F10 and F11) treated at 2000 mg/kg. Congestion (characterised by darkened tissues/organs) of the spleen was noted in one female (F1) treated at 300 mg/kg. No abnormalities were revealed in any other animal, at the macroscopic examination, at this time.

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 VRT-753136 hcl was demonstrated to be greater than 2000 mg/kg bodyweight.
Executive summary:

Not applicable