[3aR-(3aα,5aβ,9aα,9bβ)]decahydro-3a,6,6,9a-tetramethylnaphth[2,1-b]furan-2(1H)-one

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From March 15 to May 3, 1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

The study was performed prior to the OECD test guideline No. 402 but the protocol is similar to the TG with the following exeptions: occlusive dressing (worst-case condition) was used and only 3 animals per sex were included (accepted especially in the case of rabbits). However, a repeat study under standard conditions is unlikely to show worse effects, therefore this study was considered sufficiently robust to cover this endpoint. Test material information are lacking.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

occlusive dressing

Principles of method if other than guideline:

Study was performed according to a modification of the techniques described by J.H. Draize in Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics (The association of Food and Drug Officials of the United States, 1975), pp 52-54

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[3aR-(3aα,5aβ,9aα,9bβ)]decahydro-3a,6,6,9a-tetramethylnaphth[2,1-b]furan-2(1H)-one

EC Number:

209-269-0

EC Name:

[3aR-(3aα,5aβ,9aα,9bβ)]decahydro-3a,6,6,9a-tetramethylnaphth[2,1-b]furan-2(1H)-one

Cas Number:

564-20-5

Molecular formula:

C16H26O2

IUPAC Name:

[3aR-(3aα,5aβ,9aα,9bβ)]decahydro-3a,6,6,9a-tetramethylnaphth[2,1-b]furan-2(1H)-one

Test material form:

not specified

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey, USA.
- Weight at study initiation: 1.33-2.17 kg
- Diet: Wayne animal feeds, ad libitum
- Water: Water, ad libitum
- Acclimation period: Animals were conditioned prior to use.

TEST ANIMALS
- Source: from a suitable licensed dealer.
- Age at study initiation: 3 to 4 months of age
- Weight at study initiation: 1.36 - 1.94 kg
- Fasting period before study: 18 hours.
- Housing: galvanized or stainless steel cages
- Diet: growth and maintenance ration from a commercial producer, ad libitum
- Water: ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): temperature controlled room
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Mid-dorsal area of the trunk, between the scapulae and the pelvis. The skin of half the animals (2N; 1F) remained intact; the test site of the remaining half of the animals was further prepared by abrading with a sterile 22 gauge hypodermic needle.
- % coverage: not reported
- Type of wrap if used: impermeable plastic wrap for 24 h.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test material was removed and skin gently cleansed with water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for signs of pharmacologic activity and toxicity at 1, 3, 6 and 24 h after dosing and daily thereafter for 14 days.
- Frequency of weighting: at Day 1 and Day 14
- Necropsy of survivors performed: Yes; non-survivors and animals sacrificed at the end of the 14-day observation period were subjected to gross necropsy.

Statistics:

None

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 1/6 animals died (abraded skin)

Mortality:

One male animal (abraded skin) was found dead at Day 14.

Clinical signs:

other: Slight depression was observed 3 to 6 hours after application in 4/6 animals.

Gross pathology:

The animal that died at Day 14 had its right lung filled with yellow-white pus-like substance.

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 Combined > 5000 mg/kg bw

Executive summary:

In an acute dermal toxicity, albino rabbits (3/sex, half with abraded skin) were occlusively exposed to undiluted test material at dose of 5000 mg/kg bw for 24 h. The animals were observed for mortality, clinical signs and body weight for 14 days and then necropsied for macroscopic observations.

1/6 animals (1 male, with abraded skin) died. At necropsy, its right lung was filled with yellow-white pus-like substance. No systemic or local effects were obsevred in other animals

Dermal LD50 Combined > 5000 mg/kg bw

Under the test conditions, the test material is not classified according to the Regulation EC No. 1272/2008 (CLP) and to the GHS.

This study is considered as acceptable and satisfies the requirement for acute dermal toxicity endpoint.