[1S-(1α,3aβ,4α,8aβ)]-decahydro-4,8,8-trimethyl-9-methylene-1,4-methanoazulene

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Remarks:

Acute oral toxicity study in rats (14 days)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19th Dec 1983 - 2nd Jan 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

comparable with OECD test guideline 401 from 1981 (now replaced )

Deviations:

no

Principles of method if other than guideline:

- Short description of test conditions: dose range finding by given test material by gavage at a dose level of 5000 mg/kg body weight
- Parameters analysed / observed: LD50 mortality, clinical signs, body weight and gross lesions at necropsy after 14 days

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[1S-(1α,3aβ,4α,8aβ)]-decahydro-4,8,8-trimethyl-9-methylene-1,4-methanoazulene

EC Number:

207-491-2

EC Name:

[1S-(1α,3aβ,4α,8aβ)]-decahydro-4,8,8-trimethyl-9-methylene-1,4-methanoazulene

Cas Number:

475-20-7

Molecular formula:

C15H24

IUPAC Name:

4,8,8-trimethyl-9-methylenedecahydro-1,4-methanoazulene

Test material form:

liquid

Details on test material:

purity 85.3%

Specific details on test material used for the study:

-Compound description: 83-230-04 clear liquid
-Lot No: not applicable
-purity: is responsibility of the sponsor
-stability: no change during administration

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Labs, Wilmington, Massachusetts
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 80-280 grams (after fasting)
- Housing: rats housed in groups, according to sex, or individually in stainless steel wire mesh cages. Size in accordance with the 'guide for the care and use of laboratory animals' of the institute of laboratory resources, national research council.
- Diet (ad libitum): Wayne Lab Blox, checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging and scattering.
- Water (ad libitum): availability, fresh tap water, fit for human consumption, using an automatic watering system supplied by Edstrom Industries, Inc.
- Acclimation period: 5 days
- Microbiological status when known
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 30 to 70%
- Air changes (per hr):
- Photoperiod: 12 hours light, 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

compound preparation: as received
volume administration: 5 ml/kg
vehicle: as received

MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based upon results of a dose-range finding study

Doses:

1 dose of 5000 mg/kg

No. of animals per sex per dose:

5 female
5 male

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed immediately and at one, fours and tweenty-four hours after dosing and twice daily for fourteen days pharmacotoxic, CNS effects and mortality. Body weights recorded on the fourteenth day.
- Necropsy of survivors performed: yes
- Clinical signs including decreased activity, body weight, abnormal gait, poor grooming, diarrhea, abnormal stance and piloerection

Results and discussion

Preliminary study:

In a dose range finding study, four fasted animals, tow per sex, were administrated the test article at 500, 1600 and 5000 mg/kg, orally, by gavage. Signs observed included diarrhea, decreased activity and body tone, hypersensitivity and poor grooming. None of the animals dies at the 500, 1600 or 5000 mg/kg dose level.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: decreased activity, body weight, abnormal gait, poor grooming, diarrhea, abnormal stance and piloerection. After four days all animal appeared normal

Gross pathology:

no gross lesion seen

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 of Longifolene in rats is > 5 g/kg body weight. Based on these results, Longifolene is considered practically non-toxic according to the IFF Toxicity Classification System

Executive summary:

Acute oral LD50 Toxicity in rats:

Material: Longifolene

Introduction: Longifolene is an IFF propietary material which is currently active in the fragance division. this study was conducted in accordance with our policy of acquiring safety data on IFF propietary materials.

Materials and methods: Based on the results of a dose range finding study, one group of then rats (five males and five females) was given the test material by gavage at a dose level of 5000 mg/kg body weight.

Animals were observed for mortality, clinical signs, body weight gain and gross lesions at necropsy after 14 days.

Results: based on the absence of mortality the LD50 is > 5 g/kg.

Immediately after dosing most animals showed decreased activity and abnormal gait. These signs persisted for fours days after which all animals apperaed normal and exhibited normal body weight gain.

at necropsy no gross lesion was seen which was attributed to treatment.

Discussion and conclusion: the acute oral LD50 of Longifolene in rats is > 5 g/kg body weight. Based on these results, Longifolene is considered practically non-toxic according to the IFF Toxicity Classification System.