N,N''-hexane-1,6-diylbis[N'-benzylurea]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP compliant guideline study, available as unpublished report, no restrictions, fully adequate for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

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:

other: Commission Regulation (EC) No 440/2008

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N,N''-hexane-1,6-diylbis[N'-benzylurea]

EC Number:

254-274-3

EC Name:

N,N''-hexane-1,6-diylbis[N'-benzylurea]

Cas Number:

39072-70-3

Molecular formula:

C22H30N4O2

IUPAC Name:

N',N'''-hexane-1,6-diylbis(1-benzylurea)

Details on test material:

- Name of test item: N,N''-Hexane-1,6-diylbis[N'-benzylurea]
- Test item No.: 11/0726-1
- Batch identification: 259-635
- Purity: 98.0 g/100 g determined by 1H NMR spectroscopy using the internal standard method
- Homogeneity: The test item was homogeneous by visual inspection.
- Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Expiry date: January 09, 2013
- Storage conditions: Room temperature; no direct sunlight; protect against humidity
- Physical state / color: Solid / white

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: Administration group 1: 163 - 178 g; administration group 2: 180 - 184 g
- Fasting period before study: at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing in Makrolon cage, type III with bedding (H 15005-29; Ssniff, Spezialitäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)) and enrichment (NGM E-022; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria)
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Day / night rhythm: 12 h / 12 h

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Olive oil Ph.Eur

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 g/100 mL
- Justification for choice of vehicle: Good homogeneity in olive oil Ph.Eur.
- Amount of vehicle (if gavage): 10 mL/kg bw

DOSAGE PREPARATION
The test item was ground with mortar and pestle. The test item preparation was produced shortly before application by stirring with a high speed homogenizer (Ultra-Turrax) and a magnetic stirrer. Additionally the homogeneity of the test item preparation during application was ensured by stirring with a magnetic stirrer.
Form of application: Suspension

SELECTION OF DOSES/CONCENTRATIONS
By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals. Because no mortality occurred, 2000 mg/kg bw were administered to another group of 3 female animals in the second step.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 female animals per administration group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation;recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Mortality at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed: No histological examinations were performed.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred in both test groups.

Clinical signs:

other: No clinical signs were observed in both test groups during clinical examination.

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.