1H-Imidazole, 5,5'-[1,1'-biphenyl]-4,4'-diylbis[2-(2S)-2-pyrrolidinyl-, hydrochloride (1:4)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

August 2 to 30, 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Read across to 01 - non-salt form. The -02 being registered is a HCL salt. Read across justification: Based on physiology of the digestive system, toxicokinetics and the gastric pH of the stomach, the read across of this substance to its HCL salt form is justifiable as when taken orally the non-salt form will associate with the HCL in the stomach. Therefore the acute oral toxicity for the non-salt form will be representative of the acute oral toxicity of the substance being registered as the HCL salt of the tested substance. The HCL salt will be neutralized upon exiting the stomach, thereby converting to non- HCL salt form for elimination.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Automatically generated during migration to IUCLID 6, no data available

Cas Number:

1623405-26-4

IUPAC Name:

Automatically generated during migration to IUCLID 6, no data available

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report):
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Smiles notation (if other than submission substance):
- InChl (if other than submission substance):
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type:
- Physical state:
- Analytical purity:
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.:
- Expiration date of the lot/batch:
- Radiochemical purity (if radiolabelling):
- Specific activity (if radiolabelling):
- Locations of the label (if radiolabelling):
- Expiration date of radiochemical substance (if radiolabelling):
- Stability under test conditions:
- Storage condition of test material:
- Other:

Test animals

Species:

rat

Strain:

other: Sprague-Dawley CD

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: bodyweights fell within an inteval of +/- 20% of the mean initial bodyweight of the first treated group.
- Fasting period before study: Overnight fast
- Housing: Groups of three in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Certified Rat and Mouse Diet supplied by BCM IPS Ltd., London, UK
- Water (e.g. ad libitum): drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70 %
- Air changes (per hr): At least 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: Aug. 2nd, 2007 To: Aug. 30th, 2007

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
dose level: 300, 2000, 2000 mg/kg
concentration: 30, 200, 200 mg/ml

Doses:

dose level: 300, 2000, 2000 mg/kg

No. of animals per sex per dose:

3 females per dose

Control animals:

no

Details on study design:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered was calculated
according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to
confirm the survival of the previously dosed animals. The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after the
final dose and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after
treatment. At the end of the observation period the animals were killed by ascending concentrations of carbon dioxide followed by cervical
dislocation. All animals were subjected to gross necropsy examination. This consisted of external examination and opening of the abdominal and
thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities were recorded. No tissues were retained.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no signs of system toxicity.

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral median lethal dose (LD50) of the test material in the female Sprague-Dawley CD strain rat was estimated to be greater than 2000 mg/kg bodyweight. The test material does not meet the criteria for classification according to EU labelling regulations Commission Directive 2001/59/EC
for classification and labelling of dangerous substances.