2,2'-[(1-methylethylidene)bis(cyclohexane-4,1-diyloxymethylene)]bisoxirane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 June 2004 to 07 October 2004

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 (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[(1-methylethylidene)bis(cyclohexane-4,1-diyloxymethylene)]bisoxirane

EC Number:

236-502-3

EC Name:

2,2'-[(1-methylethylidene)bis(cyclohexane-4,1-diyloxymethylene)]bisoxirane

Cas Number:

13410-58-7

Molecular formula:

C21H36O4

IUPAC Name:

2-({[4-(2-{4-[(oxiran-2-yl)methoxy]cyclohexyl}propan-2-yl)cyclohexyl]oxy}methyl)oxirane

Test material form:

liquid: viscous

Details on test material:

- Appearance: Liquid, viscous / colourless
- Storage: Room temperature

Test animals

Species:

rat

Strain:

Wistar

Remarks:

HanBrI:WIST(SPF)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 8 -12 weeks
- Weight at study initiation: 177-179 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum .
- Housing: individually housed in stainless steel wire mesh cages, type DK-III
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24°C
- Humidity: 30 - 70%
- Photoperiod: 12h/12h (6.00 a.m. - 6.00 p.m. / 6.00 p.m. - 6 .00 a.m.)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Olive oil Ph .Eur./DAB

Details on oral exposure:

VEHICLE
- Olive oil Ph .Eur./DAB
- Justification for choice of vehicle: Inhomogeneous in aqueous preparations. Olive oil Ph .Eur./DAB had to be used to ensure homogeneity of the preparation.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

DOSAGE PREPARATION: The test material preparation was produced for each administration group shortly before administration by stirring with a magnetic stirrer. This formed a solution.

CLASS METHOD
- 2000 mg/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Recording of signs and symptoms several times on the day of administration and at least daily thereafter for 14 days.
- Individual body weights were determined shortly before administration (day 0), weekly thereafter and at the end of the study.
- A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy with gross-pathology examination was performed on the last day of the observation period after killing with CO2.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Clinical observation in the 2,000 mg/kg administration groups revealed impaired general state, dyspnoea, staggering and piloerection and were observed from hour 1 until including hour 4 after administration.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study.

Applicant's summary and conclusion

Interpretation of results:

other: Not classified in accordance with EU Criteria

Conclusions:

Under the conditions of this study, the median lethal dose of the test material after oral administration was found to be greater than 2,000 mg/kg bw in rats.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 423, EU Method B.1 tris and EPA OPPTS 870.1100, under GLP conditions.

During the study, single doses of 2,000 mg/kg body weight of test material preparations in olive oil Ph .Eur./DAB were given to two administration groups of three fasted female animals each, by gavage in a sequential manner.

No mortality occurred. Clinical observation revealed impaired general state, dyspnoea, staggering and piloerection. Findings were observed 1 to 4 hours after administration. The mean body weights of the administration groups increased throughout the study period and no macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period.

Under the conditions of this study, the median lethal dose of the test material after oral administration was found to be greater than 2,000 mg/kg bw in rats.