cis-4-[3-(p-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09. - 12.2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 17, 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

certified by Umweltministerium Baden-Württemberg

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

cis-4-[3-(p-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine

EC Number:

266-719-9

EC Name:

cis-4-[3-(p-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine

Cas Number:

67564-91-4

Molecular formula:

C20H33NO

IUPAC Name:

(2R,6S)-4-[3-(4-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han)

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
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adult animals (approx. 10 weeks)
- Weight at study initiation: 168.0 g mean bw of test group 2000 mg/kg; 188.3 g mean bw of test group 500 mg/kg (1); 182.7 g mean bw of test group 500 mg/kg (2)
- Fasting period before study: at least 16 hours
- Housing: Animals were single housed
- Diet: VRF1 (P), ad libitum except for the day of administration
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days
- Method of randomisation in assigning animals to test and control groups : not applicable

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): not specified
- Photoperiod (12h dark /12h light): 6.00 a.m. - 6.00 p.m. / 6.00 p.m. - 6.00 a.m.

IN-LIFE DATES
- From: 2010-09-22
- To: 2010-10-19

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25 g /100 mL
- Amount of vehicle (if gavage): 500 mg/kg bw (0.5% solution of CMC in deionized water)
- Justification for choice of vehicle: good homgeneity in water could not be guaranteed
- Purity: not specified

MAXIMUM DOSE VOLUME APPLIED: 2.12 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: By the request of the sponsor a starting dose of 500 mg/kg bw was chosen in the first step with 3 female animals.

Doses:

2000 mg/kg bw (undiluted); 500 mg/kg bw (emulsion)

No. of animals per sex per dose:

3 female animals per 2000 mg/kg; 6 female animals per 500 mg/kg

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: Recording of clinical signs several times on the day of administration and at least once daily thereafter each workday.
- Frequency of weighing: On day 0 shortly before administration, thereafter weekly and on the last day of observation. Additionally, at day of death in animals that diet starting with study day 6.
- Necropsy of survivors performed: yes
- Clinical signs including body weight : yes
- Other examinations performed: check for mortality once each workday

Statistics:

No statistical analysis was conducted.

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:

- 500 mg/kg bw test group: No mortality occured in the six females
- 2000 mg/kg bw test group: A delayed mortality was observed in two out of three animals at study day 6 after the administration

Clinical signs:

other: - 500 mg/kg bw test group: Impaired general state, dyspnoea and piloerection from hour 3 to hour 5 after administration in four out of six animals. Two out of six animals did not show any clinical signs. - 2000 mg/kg bw test group: Impaired general state,

Gross pathology:

There were no macroscopic pathological findings in the animals which died or were sacrified at the end of the observation period.