5(or 6)-methyl-7(or 8)-(1-methylethyl)bicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981-05-12 to 1981-06-03

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in accordance with generally accepted scientific principles, possibly with incomplete reporting or methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Method described by Hagan served as a guide. E.C. Hagan, "Acute Toxicity", Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (The Association of Food and Drug Officials of the United States, 1975), pp. 17 - 25.

Deviations:

not specified

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

8-isopropyl-6-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

EC Number:

267-308-7

EC Name:

8-isopropyl-6-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Cas Number:

67845-30-1

Molecular formula:

C13H20O

IUPAC Name:

8-isopropyl-6-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Constituent 2

Reference substance name:

7-isopropyl-5-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

EC Number:

299-795-7

EC Name:

7-isopropyl-5-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Cas Number:

93904-56-4

Molecular formula:

C13H20O

IUPAC Name:

7-isopropyl-5-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

impurity 1

Reference substance name:

rel-(1S,2R,4R)-1-isopropyl-4-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Cas Number:

36208-34-1

Molecular formula:

C13H20O

IUPAC Name:

rel-(1S,2R,4R)-1-isopropyl-4-methylbicyclo[2.2.2]oct-5-ene-2-carbaldehyde

Test material form:

liquid

Specific details on test material used for the study:

Test Article: Maceal U 05141

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Suitably licensed dealer
- Strain: Wistar-strain albino rats
- Age at study initiation: Approximately 6 to 9 weeks of age
- Weight at study initiation: 190 to 220 grams. Animals were selected with a fasted bodyweight between 200 and 300 grams for dosing.
- Fasting period before study: Approximately 18 hours of fasting. After test material administration rats were then returned to their cages, where food and water were available ad libitum.
- Housing: Animals were housed in galvanised cages with indirect bedding
- Diet (e.g. ad libitum): Growth and maintenance ration from a commercial producer ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Temperature controlled room
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSAGE PREPARATION (if unusual): Prior to test initiation, the test material's mass to volume relationship (specific gravity) was determined to facilitate volumetric dosing. It was found to be 1.00.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of pharmacologic activity and drug toxicity at 1, 3, 6, and 24 hours post dosage. Observations were made at least once daily thereafter.
- Necropsy of survivors performed: Yes. Animals sacrificed at the end of the 14 day observation period, as well as non-survivors, were subjected to complete gross necropsy, with all findings noted.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Three of the 5 male animals died. One animal died 1 hour post -dosing, one at 24 hours and one at 3 days. None of the female animals died.

Clinical signs:

Clinical signs observed were depression and mucoid diarrhoea. All surviving animals appeared normal from day 3 onwards.

Body weight:

The 3 male animals that died had lost bodyweight. All other animals gained weight.

Gross pathology:

The animal that died 1 hour post dosing had test material in the stomach, and the animal that died 24 hours following test material administration exhibited severely reddened intestinal mucosa. No gross changes were observed for all other animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the LD50 of the test material to rats was found to be >5000 mg/kg bodyweight.

Executive summary:

The acute oral toxicity of the test material was investigated in a study which was conducted under GLP conditions using methodology described by Hagan as a guide (E.C. Hagan, "Acute Toxicity", Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (The Association of Food and Drug Officials of the United States, 1975), pp. 17 - 25) and was equivalent to the standardised guideline OECD 401.

During the study, groups of 5 male and female Wistar-strain albino rats received a single dose of undiluted test material by gavage at a dose level of 5000 mg/kg. Animals were observed for 14 days for mortality and toxic signs. Body weights were monitored. Animals sacrificed at the end of the 14 day observation period, as well as non-survivors, were subjected to complete gross necropsy, with all findings noted.

Three of the 5 male animals died. One animal died 1 hour post -dosing, one at 24 hours and one at 3 days. None of the female animals died. Clinical signs observed were depression and mucoid diarrhoea. All surviving animals appeared normal from day 3 onwards.

The animal that died 1 hour post-dosing had test material in the stomach, and the animal that died 24 hours following test material administration exhibited severely reddened intestinal mucosa. No gross changes were observed for all other animals.

Under the conditions of this study, the LD50 of the test material to rats was found to be >5000 mg/kg bodyweight.