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

Endpoint summary

Description of key information

Acute toxicity: oral: Rat LD50 (combined) > 5000 mg/kg bw (K, rel. 2)

Acute toxicity: dermal: Rabbit LD50 (combined) > 5000 mg/kg bw (K, rel. 2)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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. 401 but the protocol is similar to the TG. Test material information are lacking.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

Study was performed according to procedure suggested by Hagan 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 17-45

GLP compliance:

no

Remarks:

pre-GLP

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: from a suitable licensed dealer.
- Age at study initiation: 6 to 8 weeks of age
- Weight at study initiation: 180-258 g
- Fasting period before study: 18 hours.
- Housing: galvanized cages with indirect bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 2 days

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

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25%

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1, 3, 6 and 24 hours after treatment, and dialy thereafter.
- 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:

No

Preliminary study:

Not applicable

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Mortality:

0/5 (M); 0/5 (F)

Clinical signs:

other: No effect

Gross pathology:

One animal showed fibrous tissue encrasing heat. No effects in the others.

Other findings:

None

None

Interpretation of results:

GHS criteria not met

Conclusions:

Oral LD50 Combined > 5000 mg/kg bw

Executive summary:

In an acute oral toxicity study, groups of Wistar rats (5/sex/dose) were administered a single oral (gavage) dose of test material suspended at 25% in corn oil at 5000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

The test material was not toxic orally to rats under conditions of this test. The internal organ on superficial examination appeared normal, excep for a deposit of fibrous tissue in the thoracic cavity of one animal.

Oral 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 oral toxicity endpoint.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The key study is comparable to guideline study with acceptable restrictions (Klimisch score = 2)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

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.

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

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

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

Preliminary study:

Not applicable

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

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The key study is comparable to guideline study with acceptable restrictions (Klimisch score = 2)

Additional information

Acute toxicity: oral:

A key study was identified (Consumer Product Testing, 1979). This acute oral toxicity study was performed prior to the OECD test guideline No. 401 but the protocol is similar to that guidance.

The test material was not toxic orally to rats under conditions of this test. The internal organ on superficial examination appeared normal, excep for a deposit of fibrous tissue in the thoracic cavity of one animal.

Oral LD50 Combined > 5000 mg/kg bw.

Acute toxicity: dermal:

A key study was identified (Consumer Product Testing, 1979). This acute dermal toxicity study was performed prior to the OECD test guideline No. 402 but the protocol is similar to that guidance with the following exeptions: occlusive dressing (worst-case condition) was used and only 3 animals per sex were included. However, a repeat study under standard conditions is unlikely to show worse effects, therefore this study was considered sufficiently robust to cover this endpoint.

Rabbits were given a single dermal application of the undiluted test material to intact or abraded skin for 24 hours.

1/6 animals (1 male, with abraded skin) died. At necropsy, it's 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

Justification for classification or non-classification

Harmonised classification:

The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).

Self-classification:

Acute toxicity (Oral):

Based on the available data, the substance is not classified according to the CLP and the GHS as the LD50 is > 5000 mg/kg bw.

Acute toxicity (Dermal):

Based on the available data, the substance is not classified according to the CLP and the GHS as the LD50 is > 5000 mg/kg bw.

Acute toxicity (Inhalation):

No information was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the CLP and to the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the CLP and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No data was available. However, the registered substance is not a skin or an eye irritant, therefore respiratory tract irritation is not expected.

 

Aspiration hazard:

The substance is not a hydrocarbon and no effects were observed on lungs in oral studies, therefore the criteria for aspiration toxicity according to the CLP and to the GHS are not met.