3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5-trimethylcyclohexyl]amino]propiononitrile

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2005-06-28 to 2005-11-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2004

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5-trimethylcyclohexyl]amino]propiononitrile

EC Number:

300-496-1

EC Name:

3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5-trimethylcyclohexyl]amino]propiononitrile

Cas Number:

93940-97-7

Molecular formula:

C16H28N4

IUPAC Name:

3-[(3-{[(2-cyanoethyl)amino]methyl}-3,5,5-trimethylcyclohexyl)amino]propanenitrile

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: V3186/1 1

Letter of Confirmation: CAS No 90530-15-7 and 93940-97-7 refer to the same substance and substance composition.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Laboratory Animal Services, Wölferstrasse 4, CH-4414 Füllinsdorf, Switzerland
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult animals (female animals approx. 8 - 12 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in stainless steel wire mesh cages, type DK-111 (Becker & Co., Castrop-Rauxel, IFIRG )
- Diet: Kliba Labordiät (Maus / Ratte Haltung "GLP"), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): fully air conditioned rooms
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a. m. - 6.00 p. m. / 6.00 p. m. - 6.00 a. m.)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10; 40 g/100 mL
- Amount of vehicle: 5 mL/kg
- Justification for choice of vehicle: Olive oil Ph. Eur./DAB had to be used to ensure homogeneity/stability of the preparation.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and its composition, no pronounced acute oral toxicity was expected. Therefore, a starting dose of 2000 mg/kg body weight has been chosen in the first step with 3 female animals. As 2 of those animals died, 500 mg/kg body weight were administered to 3 female animals in a second step. Because no animal died at the second step, 500 mg/kg body weight have been tested in a third step with another group of 3 female animals. Because all animals survived the third step the study was terminated.

Doses:

2000; 500 mg/kg bw

No. of animals per sex per dose:

3 and 6 females

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 at the end of the study. Additionally, at day of death in animals that died or were sacrificed moribund starting with study day 1.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, pathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 500 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two animals of the 2000 mg/kg bw administration group were found dead on study days 1 and 8, respectively. No mortality occurred in the 500 mg/kg bw administration groups.

Clinical signs:

other: Clinical observation in the 2000 mg/kg bw administration group revealed impaired general state, dyspnoea, staggering, tremor, piloerection, smeared fur, salivation and red clammy snout and were observed from hour 0 until including study day 9 after admini

Gross pathology:

No macroscopic pathologic findings were observed in the animals that died (2000 mg/kg bw: 2 females) and in the animals examined at termination of the study (2000 mg/kg bw: 1 female; 500 mg/kg bw: 6 females).