[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate

Endpoint summary

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) was considered to be >5000 mg/kg bw, based on experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology, Vol. 12, Pg. 839, 1974), Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set, 2012), U.S. National Library of Medicine (ChemIDplus,2017) and U.S. Environmental Protection Agency (Chemistry Dashboard, 2018); predicted study based on OECD QSAR toolbox 4069 mg/kg bw and different studies available on structurally similar read across substances [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate (CAS no: 77-54-3) 44750 mg/kg bw; and 2-tert-butylcyclohexyl acetate (CAS no: 88-41-5) 4600 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate cannot be classified for acute oral toxicity.

Acute Inhalation toxicity: 

[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) has very low vapour pressure (0.00036 mmHg), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity: 

Acute Dermal toxicity dose (LD50) of [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) was considered to be >5000 mg/kg bw, based on experimental study conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology, Vol. 12, Pg. 839, 1974), Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set, 2012) and U.S. National Library of Medicine (ChemIDplus,2017); predicted study based on OECD QSAR toolbox 6103 mg/kg bw and different studies available on structurally similar read across substances [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate (CAS no: 77-54-3) >5000 mg/kg bw; and 2-tert-butylcyclohexyl acetate (CAS no: 88-41-5) >5000 mg/kg bw. All these studies concluded that the LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate cannot be classified for acute dermal toxicity.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute oral toxicity study of [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) in Rat.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- IUPAC Name: [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate
- InChI: 1S/C17H28O2/c1-12(18)19-17-8-5-7-16(4,11-17)9-6-13-14(17)10-15(13,2)3/h13-14H,5-11H2,1-4H3/t13-,14+,16+,17-/m1/s1
- Smiles: CC(=O)O[C@@]12CCC[C@@](C)(CC [C@@H]3[C@@H]1CC3(C)C)C2
- Common Name of test material :Caryophyllene acetate
- Molecular formula:C17H28O2
- Molecular weight:264.4062 g/mol
- Substance type: Organic
- Physical state: Colorless slightly viscous liquid with a mild fruity woody odor.

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: unspecified

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

not specified

Doses:

5000 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed at 5000 mg/kg bw.

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute oral LD50 value was considered to be >5000 mg/kg bw, when rats were treated with [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) via oral route.

Executive summary:

Acute oral toxicity study of[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) was conducted in rats at the concentration of 5000 mg/kg bw. No mortality was observed in treated rats at5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate via oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

other:

Endpoint conclusion

Quality of whole database:

Waiver

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from publication.

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Acute Dermal toxicity study of [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) in Rabbit.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- IUPAC Name: [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate
- InChI: 1S/C17H28O2/c1-12(18)19-17-8-5-7-16(4,11-17)9-6-13-14(17)10-15(13,2)3/h13-14H,5-11H2,1-4H3/t13-,14+,16+,17-/m1/s1
- Smiles: CC(=O)O[C@@]12CCC[C@@](C)(CC [C@@H]3[C@@H]1CC3(C)C)C2
- Common Name of test material :Caryophyllene acetate
- Molecular formula:C17H28O2
- Molecular weight:264.4062 g/mol
- Substance type: Organic
- Physical state: Colorless slightly viscous liquid with a mild fruity woody odor.

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

other: Dermal

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

not specified

Duration of exposure:

not specified

Doses:

5000 mg/kg

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed at 5000 mg/kg bw.

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

other: Not classified

Conclusions:

The acute Dermal LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) by dermal application.

Executive summary:

Acute Dermal toxicity study of [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) was conducted in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from publication.

Additional information

Acute oral toxicity:

In different studies, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate along with the study available on structurally similar read across substances [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate (CAS no: 77-54-3) and 2-tert-butylcyclohexyl acetate (CAS no: 88-41-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

The experiment conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology, Vol. 12, Pg. 839, 1974), Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set, 2012), U.S. National Library of Medicine (ChemIDplus, 2017) and U.S. Environmental Protection Agency (Chemistry Dashboard, 2018), acute oral toxicity dose (LD50) was considered by using target chemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5] dodecan-1-yl acetate (CAS no: 57082-24-3) in rats at the concentration of 5000 mg/kg bw. No mortality was observed in treated rats at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate via oral route.

The above study is supported by the prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3). The LD50 was estimated to be 4069 mg/kg bw, when 5 male and female Osborne-Mendel rats were treated with [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5] dodecan-1-yl acetate via oral gavage route.

This above experimental and prediction study of target substance [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) is supported by Jenner et al.(Food and Cosmetics Toxicology, Vol. 2, page 327-343, 1964), D. L. J. Opdyke (Food and Cosmetics Toxicology, Vol. 12, Pg. 847, 1974) and U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate (CAS no: 77-54-3). Acute oral toxicity study was conducted in Groups of 10 male and female Osborne-Mendel rats at the test concentration of 44750 mg/kg (Range of 33650-59520mg/kg). All animals were maintained under close observation for recording toxic signs and time of death. Such observation was continued until animals appeared normal and showed weight gain. Animals were observed for general clinical signs. LD50's were computed by the method of Litchfield & Wilcoxon (1949). 50% mortality was observed at 44750 mg/kg bw within 4hr to 11days of observation period. Clinical signs such as, scrawny appearance, rough, wet fur and general depressed activity were observed in treated rats. Therefore, LD50 value was considered to be 44750 mg/kg bw, with 95% confidence limit of 33650-59520 mg/kg bw, when male and female Osborne-Mendel rats were treated with [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate via oral gavage route.

These above studies are further supported by D. L. J. Opdyke (Food and Chemical Toxicology, Vol. 30, Pg. 13S, 1992) and U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 2-tert-butylcyclohexyl acetate (CAS no: 88-41-5). Acute oral toxicity study was conducted in rats at the concentration of 4600 mg/kg (Range of 2700-7800 mg/kg). 50% mortality was observed in treated rats at 4600 mg/kg bw. Therefore, LD50 was considered to be 4600 mg/kg bw, with the 95% confidence limit of 2700-7800 mg/kg bw, when rats were treated with2-tert-butylcyclohexyl acetate (CAS no: 88-41-5) via oral route.

Thus, based on the above studies on [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate cannot be classified for acute oral toxicity.

 

Acute Inhalation toxicity: 

[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) has very low vapour pressure (0.00036 mmHg), so the potential for the generation of inhalable vapours is very low. Also the normal conditions of use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be highly unlikely and therefore this end point was considered for waiver.

Acute Dermal toxicity:

In different studies, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate along with the study available on the structurally similar read across substances [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate (CAS no: 77-54-3) and 2-tert-butylcyclohexyl acetate (CAS no: 88-41-5). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

The experiment conducted by D. L. J. Opdyke (Food and Cosmetics Toxicology, Vol. 12, Pg. 839, 1974), Richard J. Lewis (Sax's Dangerous Properties of Industrial Materials, 12th Edition, 5 Volume Set, 2012) and U.S. National Library of Medicine (ChemIDplus, 2017), acute dermal toxicity dose (LD50) was considered by using target chemical [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5] dodecan-1-yl acetate (CAS no: 57082-24-3) in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed in treated rabbits at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with[1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate by dermal application.

The above study is supported by the prediction done by SSS (2018) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3). The LD50 was estimated to be 6103 mg/kg bw, when 3 male and female New Zealand White rabbits were treated with [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo[6.3.1.02,5] dodecan-1-yl acetate for 24 hours by dermal application occlusively.

This above experimental and prediction study of target substance [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) is supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Vol. 12, Pg. 847, 1974) and U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate (CAS no: 77-54-3). Acute Dermal toxicity study was conducted in rabbits at the concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Therefore, LD50 value was considered to be >5000 mg/kg bw, when rabbits were treated with [3R-(3α,3aβ,6α,7β,8aα)]-Octahydro-3,6,8,8-tetramethyl-1H-3a,7-methanoazulen-5-yl acetate by dermal application.

These above studies are further supported by D. L. J. Opdyke (Food and Chemical Toxicology, Vol. 30, Pg. 13S, 1992) and U.S. National Library of Medicine (ChemIDplus, 2017), for the structurally similar read across substance 2-tert-butylcyclohexyl acetate (CAS no: 88-41-5). Acute Dermal toxicity study was conducted in rabbits at the concentration of 5000mg/kg bw. No mortality was observed in treated rats at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with 2-tert-butylcyclohexyl acetate (CAS no: 88-41-5) by dermal application.

Thus, based on the above studies on [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate (CAS no: 57082-24-3) and it’s read across substances, it can be concluded that LD50 value is >2000 mg/kg bw for acute oral and dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, [1R-(1α,2α,5β,8β)]-4,4,8-trimethyltricyclo [6.3.1.02,5]dodecan-1-yl acetate cannot be classified for acute oral and dermal toxicity. For Acute Inhalation toxicity wavier was added so, not possible to classify.