A mixture of: 4-(2,2,3-trimethylcyclopent-3-en-1-yl)-1-methyl-2-oxabicyclo[2.2.2]octane; 1-(2,2,3-trimethylcyclopent-3-en-1-yl)-5-methyl-6-oxabicyclo[3.2.1]octane; spiro[cyclohex-3-en-1-yl-[(4,5,6,6a-tetrahydro-3,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]furan]; spiro[cyclohex-3-en-1-yl-[4,5,6,6a-tetrahydro-4,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]]furan]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Between 07 April 1993 and 22 April 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

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:

A mixture of: 4-(2,2,3-trimethylcyclopent-3-en-1-yl)-1-methyl-2-oxabicyclo[2.2.2]octane; 1-(2,2,3-trimethylcyclopent-3-en-1-yl)-5-methyl-6-oxabicyclo[3.2.1]octane; spiro[cyclohex-3-en-1-yl-[(4,5,6,6a-tetrahydro-3,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]furan]; spiro[cyclohex-3-en-1-yl-[4,5,6,6a-tetrahydro-4,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]]furan]

EC Number:

422-040-1

EC Name:

A mixture of: 4-(2,2,3-trimethylcyclopent-3-en-1-yl)-1-methyl-2-oxabicyclo[2.2.2]octane; 1-(2,2,3-trimethylcyclopent-3-en-1-yl)-5-methyl-6-oxabicyclo[3.2.1]octane; spiro[cyclohex-3-en-1-yl-[(4,5,6,6a-tetrahydro-3,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]furan]; spiro[cyclohex-3-en-1-yl-[4,5,6,6a-tetrahydro-4,6',6',6'a-tetramethyl)-1,3'(3'aH)-[2H]cyclopenta[b]]furan]

Cas Number:

426218-78-2

Molecular formula:

C16H26O

IUPAC Name:

1-methyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)-2-oxabicyclo[2.2.2]octane; 3,6',6',6'a-tetramethyl-2',3'a,4',5',6',6'a-hexahydrospiro[cyclohexane-1,3'-cyclopenta[b]fura]-3-ene; 4,6',6',6'a-tetramethyl-2',3'a,4',5',6',6'a-hexahydrospiro[cyclohexane-1,3'-cyclopenta[b]fura]-3-ene; 5-methyl-1-(2,2,3-trimethylcyclopent-3-en-1-yl)-6-oxabicyclo[3.2.1]octane

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Equal numbers of healthy male and female CD rats of Sprague-Dawley origin (Hsd/Ola:SpragueDawley(CD)) were obtained from Harlan Olac Ltd., Bicester, Oxon, England.
They were in the weight range of 107 to 132 g and approximately four to seven weeks of age prior to dosing (Day 1) in the main study. All the rats were acclimatised to the experimental environment for a period of seven days prior to the start of the main study.
The rats were allocated without conscious bias to cages within the treatment group. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors in Building R14 Room 6.
A standard laboratory rodent diet (Biosure LAD 1) and drinking water were provided ad libitum.
Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
The batch(es) of diet used for the study was analysed for certain nutrients, possible contaminants and micro-organisms.
Results of routine physical and chemical examination of drinking water at source, as conducted, usually weekly by the supplier, were made available to Huntingdon Research Centre Ltd. (as quarterly summaries).
The mean daily minimum and maximum temperatures of the animal room were 20°C and 22°C respectively and the mean daily relative humidity value was 57% R.H. Air exchange was maintained at 10 to 15 air changes per hour and lighting was controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.
Each animal was identified by cage number and ear punching. Each cage was identified by a coloured label displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office licensee.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The appropriate dose volume of the test substance was administered to each rat by oral gavage using a syringe and plastic catheter (8 choke).

Doses:

A preliminary study was carried out at 800 mg/kg bodyweight.

Main study
A group of ten rats was treated at 2.0 g/kg bodyweight.

No. of animals per sex per dose:

Two male and two female rats were dosed at 800 mg/kg bodyweight.

Ten male and ten female rats were dosed at 2000 mg/kg bodyweight.

Control animals:

no

Details on study design:

TEST SUBSTANCE PREPARATION
The substance was administered, as supplied by the Sponsor, at a volume of 2.03 ml/kg (specific gravity 0.986) in the main study. The absorption of the substance was not determined. The homogeneity, stability and purity of the substance were the responsibility of the Sponsor.

TREATMENT PROCEDURE
Preliminary study: A preliminary study was carried out by dosing two male and two female rats at 800 mg/kg bodyweight.
Main study: A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight.
Control animals: No control animals were included in this study.

ADMINISTRATION OF TEST SUBSTANCE
The appropriate dose volume of the substance was administered to each rat by oral gavage using a syringe and plastic catheter (8 choke).
The day of dosing was designated Day 1.

OBSERVATIONS
Cages of rats were checked at least twice daily for any mortalities.
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of six hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day. This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturdays, Sundays and public holidays. The nature and severity of the clinical signs and time were recorded at each observation.
The animals on the preliminary and main studies were observed for 5 and 14 days respectively after dosing.
Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly body weight changes were calculated.

TERMINAL STUDIES
Termination: All were killed by cervical dislocation .
Macroscopic pathology: All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.

Statistics:

None recorded.

Results and discussion

Preliminary study:

The results of the preliminary study indicated that the acute lethal oral dose to male and female rats of the substance was greater than 800 mg/kg bodyweight.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95% confidence limits not reported

Mortality:

There were no deaths following a single oral dose of the substance at 2000 mg/kg bodyweight.

Clinical signs:

other: Pilo-erection was observed in all rats within three minutes of dosing and throughout the remainder of Day 1. There were no other clinical signs and recovery, as judged by external appearance and behaviour, was complete by Day 2.

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

other: Not harmful

Remarks:

in accordance with EU CLP (EC no 1272/2008 and its amendments)

Conclusions:

The substance has an LD50 of > 2000 mg/kg bw in an OECD TG 401 test

Executive summary:

The substance was tested in an acute oral toxicity test (OECD TG 401). A limit dose of 2000 mg/kg bw was used as a preliminary study indicated that the acute lethal oral dose to male and female rats of the substance was greater than 800 mg/kg bodyweight. In the main study, no mortality occurred at 2000 mg/kg bw. Pilo-erection was observed in all animals within three minutes of dosing and throughout the remainder of day 1. There were no other clinical signs and recovery, as judged by external appearance and behaviour, was complete by day 2. All animals showed expected bodyweight gain. No macroscopic abnormalities were observed. The LD50 resulted in >2000 mg/kg bw.