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Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) of target chemical (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) was considered to be 1950 mg/kg bw; in the range between 1600-1950 mg/kg bw; 500 mg/kg bw; Further LD50 value was predicted based on OECD QSAR toolbox, the value estimated to be 1871 mg/kg bw; LD50 value was predicted based on Danish QSAR, the value estimated to be 1500 mg/kg bw; and different studies available for the structurally similar read across substances, the LD50 was considered to be 1200 mg/kg bw; and 470 mg/kg bw. All these studies concluded that the LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one can be classified as “Category 4” for acute oral toxicity.

Acute Inhalation Toxicity: 

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Menthone ; IUPAC name;(2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no 89-80-5) ,which is reported as 0.0002775228 mmHg at temperature 25 Deg C. Thus, exposure to inhalable dust, mist and vapour of the chemical 4-tert-butylcyclohexanol is highly unlikely. Therefore this study is considered for waiver.

Acute Dermal Toxicity:

In Acute dermal toxicity, LD50 value for target substance (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) was considered to be >5000 mg/kg bw,and for differentstudies available on structurally similar read across substance was considered to be >5000 mg/kg bw. All these studies concluded that the LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) 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 peer- reviewed journal
Reference:
Composition 0
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Acute oral toxicity of (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) in rats
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- IUPAC Name: (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one- Common Name: Menthone- InChI: 1S/C10H18O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-9H,4-6H2,1-3H3- Smiles:C1([C@@H](CC[C@@H](C1)C)C (C)C)=O- Molecular formula:C10H18O - Molecular weight :154.2512 g/mole- Substance type: Organic- Physical state: Liquid
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
not specified
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
not specified
Doses:
Range of 1820-2620 mg/kg bw
No. of animals per sex per dose:
groups of 10 M and 10 F
Control animals:
not specified
Details on study design:
not specified
Statistics:
not specified
Preliminary study:
not specified
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 950 mg/kg bw
Based on:
test mat.
95% CL:
1 820 - 2 620
Remarks on result:
other: 50% mortality observed
Mortality:
50% mortality observed at 1950 mg/kg bw.
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
LD50 was considered to be 1950 mg/kg bw, with 95% confidence limit of 1820-2620 mg/kg bw, when rats were treated with (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) via oral gavage route.
Executive summary:

The acute oral toxicity study was conducted by using (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) in groups of 10 male and 10 female rats at the dose concentration range between 1820-2620 mg/kg bw.50% mortality observed at1950 mg/kg bw. Therefore, LD50 was considered to be 1950 mg/kg bw, with 95% confidence limit of 1820-2620 mg/kg bw, when rats were treated with (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) via oral gavage route.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 950 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from peer- reviewed journal.

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 peer- reviewed journal
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Acute oral toxicity of Menthone in rabbits
GLP compliance:
not specified
Test type:
other: not specified
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (IUPAC name): (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one- Common name: Menthone - Molecular formula: C10H18O- Molecular weight: 154.2512 g/mol- Smiles notation: C1([C@@H](CC[C@@H](C1)C)C(C)C)=O- InChl: 1S/C10H18O/c1-7(2)9-5-4-8(3)6-10(9)11/h7-9H,4-6H2,1-3H3- Substance type: Organic- Physical state: Liquid
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not specified
Type of coverage:
other: Dermal
Vehicle:
not specified
Details on dermal exposure:
not specified
Duration of exposure:
not specified
Doses:
5000 mg/kg bw
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 50 % mortality observed
Mortality:
No 50% mortality was observed in treated rabbits at 5000 mg/kg bw
Clinical signs:
not specified
Body weight:
not specified
Gross pathology:
not specified
Other findings:
not specified
Interpretation of results:
other: Not classified
Conclusions:
LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) by dermal application.
Executive summary:

The acute dermal toxicity study was conducted by using (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) in rabbits atthe 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 (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) by dermal application.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from peer- reviewed journal.

Additional information

Acute oral toxicity:

In different studies, (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) 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 (2R, 5S)-5-methyl-2-(propan-2-yl) cyclohexan-1-one along with the study available on structurally similar read across substances . The studies are summarized as below –

The experimental study mentioned in peer-reviewed journal (1976) and secondary source(1985) for the target chemical(2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5)was designed and conducted for acute oral toxicity.The acute oral toxicity study was conducted in groups of 10 male and 10 female rats at the dose concentration range between 1820-2620 mg/kg bw.50% mortality observed at 1950 mg/kg bw. Therefore, LD50 was considered to be 1950 mg/kg bw, with 95% confidence limit of 1820-2620 mg/kg bw, when rats were treated with (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) via oral gavage route.

The above study is supported by another experimental study mentioned in peer-reviewed journal (1996) for the target chemical(2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5)was designed and conducted for acute oral toxicity.The acute oral toxicity study was conducted by using (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) in rats at the dose concentration range between 1600-1950 mg/kg bw.50% mortality observed between 1600-1950 mg/kg bw. Therefore, LD50 was considered in range between 1600-1950 mg/kg bw, when rats were treated with (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) via oral route.

These studies are also supported by experimental study mentioned in handbook (2012);authoritative database (2017) for the target chemical (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) in rats at the dose concentration of 500 mg/kg bw. 50% mortality observed at500 mg/kg bw. Therefore, LD50 was considered to be 500 mg/kg bw, when rats were treated with (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) via oral route.

This study is further supported by QSAR prediction done using the Danish (Q)SAR Database, the acute oral toxicity was estimated for (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5). The LD50 was estimated to be 1500 mg/kg bw with Reliability Index 0.56 (0.5-0.75 = moderate prediction quality), when rats were treated with (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) via oral route.

The above experimental and prediction studies are further supported by different studies available for the structurally similar read across substances as follows –

The study is supported by experimental study mentioned in peer-reviewed journal (1996) for the structurally similar read across substance .The acute oral toxicity study was conducted in rats at the dose concentration of 1200 mg/kg bw.50% mortality observed at 1200 mg/kg bw. Therefore, LD50 was considered to be 1200 mg/kg bw, when rats were treated with test chemical via oral route.

These studies are further supported by by experimental study mentioned in peer-reviewed journal (1996) for the structurally similar read across substance. The acute oral toxicity study was conducted in rats at the dose concentration of 470 mg/kg bw.50% mortality observed at 470 mg/kg bw. Therefore, LD50 was considered to be 470 mg/kg bw, when rats were treated with test chemical via oral route.

Thus, based on the above studies on (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) and it’s read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one can be classified as “Category 4” for acute oral toxicity.

Acute Inhalation Toxicity: 

According to Annex IX of the REACH regulation, testing by the inhalation route is appropriate only if exposure of humans via inhalation is likely. Taking into account the low vapour pressure of the substance Menthone ; IUPAC name;(2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no 89-80-5) ,which is reported as 0.0002775228 mmHg at temperature 25 Deg C. Thus, exposure to inhalable dust, mist and vapour of the chemical 4-tert-butylcyclohexanol is highly unlikely. Therefore this study is considered for waiver.

Acute Dermal Toxicity:

In different experimental studies(2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5)have 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 rats and rabbits for(2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5)along with the study available on structurally similar read across substance. The studies are summarized as below –

The experimental study mentioned in peer-reviewed journal (1976) and authoritative database (2017) for the target chemical(2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5)was designed and conducted for acute dermal toxicity.The acute dermal toxicity study was conducted by using (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) in rabbits atthe 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 (2R,5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) by dermal application.

The above study is supported by another experimental study mentioned in authoritative database (2017) and peer-reviewed journal (1974) for thestructurally similar read across substancewas designed and conducted for acute dermal toxicity.The acute dermal toxicity study was conducted by using test chemical in rabbits atthe concentration of5000 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 test chemical by dermal application.

Both these experimental studies are again supported with the structurally similar read across substance.The acute dermal toxicity study was conducted by using test chemical 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 test chemical by dermal application.

Thus, based on the above summarised studies on(2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5)and it’s structurally similar read across substance, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation,(2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5)cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above studies and prediction on (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one (CAS no.: 89-80-5) and it’s read across substances, it can be concluded that LD50 value is between 300-2000 mg/kg bw for acute oral toxicity; LD50 value is >2000 mg/kg bw for acute dermal toxicity. Thus, comparing these values with the criteria of CLP regulation, (2R, 5S)-5-methyl-2-(propan-2-yl)cyclohexan-1-one can be classified as “Category 4”for acute oral toxicity and cannot be classified for acute dermal toxicity. For Acute inhalation toxicity wavier was added so, not possible to classify.