(±)-menthone

Endpoint summary

Description of key information

Skin Irritation:

A Closed-patch test was performed on human volunteers to assess the irritation potential of 2-isopropyl-5-methylcyclohexanone. 2-isopropyl-5-methylcyclohexanone was applied at 8% in petrolatum for 48 hrs. After 48 hrs 2-isopropyl-5-methylcyclohexanone was observed to cause no irritation in humans. 

Therefore, 2-isopropyl-5-methylcyclohexanone was considered to be not irritating to human skin.

Eye Irritation:

The ocular irritation potential of 2-isopropyl-5-methylcyclohexanone was estimated using OECD QSAR toolbox v3.4

2-isopropyl-5-methylcyclohexanone was estimated to be not irritating to New Zealand White rabbit eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

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 journals

Qualifier:

equivalent or similar to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

A Closed-patch test was performed on human volunteers to assess the irritation potential of 2-isopropyl-5-methylcyclohexanone

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 2-isopropyl-5-methylcyclohexanone [(±)-menthone]
- Molecular formula: C10H18O
- Molecular weight: 154.2512g/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:

other: humans

Strain:

not specified

Details on test animals or test system and environmental conditions:

no data available

Type of coverage:

occlusive

Preparation of test site:

other: closed patch

Vehicle:

other: petrolatum

Controls:

not specified

Amount / concentration applied:

8% in petrolatum

Duration of treatment / exposure:

48 hours

Observation period:

48 hours

Number of animals:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation observed

Interpretation of results:

GHS criteria not met

Conclusions:

2-isopropyl-5-methylcyclohexanone was considered to be not irritating to human skin.

Executive summary:

A Closed-patch test was performed on human volunteers to assess the irritation potential of 2-isopropyl-5-methylcyclohexanone. 2-isopropyl-5-methylcyclohexanone was applied at 8% in petrolatum for 48 hrs. After 48 hrs 2-isopropyl-5-methylcyclohexanone was observed to cause no irritation in humans.

 

Therefore, 2-isopropyl-5-methylcyclohexanone was considered to be not irritating to human skin.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification

Justification for type of information:

data is from OECD QSAR toolbox v3.4 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction was done using the OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

Name of test material: 2-isopropyl-5-methylcyclohexanone
- Molecular formula: C10H18O
- Molecular weight: 154.2512 g/mol
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single exposure

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

1 male and 2 females

Details on study design:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Score:

0

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation observed

Estimation method: Takes mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" and ("b" and ( not "c") )  )  and ("d" and ( not "e") )  )  and "f" )  and ("g" and ( not "h") )  )  and "i" )  and "j" )  and ("k" and ( not "l") )  )  and ("m" and "n" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "i"

Similarity boundary:Target: CC(C)C1CCC(C)CC1=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "j"

Similarity boundary:Target: CC(C)C1CCC(C)CC1=O
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Ketones by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.41

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.18

Interpretation of results:

GHS criteria not met

Conclusions:

2-isopropyl-5-methylcyclohexanone was estimated to be not irritating to New Zealand White rabbit eyes.

Executive summary:

The ocular irritation potential of 2-isopropyl-5-methylcyclohexanone was estimated using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the five closest read across substances.

2-isopropyl-5-methylcyclohexanone was predicted to be not irritating to the eyes of New Zealand White Rabbits.

On the basis of the estimated result,2-isopropyl-5-methylcyclohexanone can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

In different studies, 2-isopropyl-5-methylcyclohexanone has been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical and its functionally similar read across substance 4-tert-butylcyclohexanone (CAS: 98-53-3). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

A Closed-patch test was performed (Food and Cosm. Toxicology Vol 14, 1976, Pp 475-476,1976) on human volunteers to assess the irritation potential of 2-isopropyl-5 -methylcyclohexanone. 2 -isopropyl-5-methylcyclohexanone was applied at 8% in petrolatum for 48 hrs. After 48 hrs 2-isopropyl-5-methylcyclohexanone was observed to cause no irritation in humans.  Therefore, 2-isopropyl-5-methylcyclohexanone was considered to be not irritating to human skin.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for2-isopropyl-5 -methylcyclohexanone. It was estimated that2-isopropyl-5-methylcyclohexanone was not irritating to skin of New Zealand White rabbits.

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 2-isopropyl-5 -methylcyclohexanone. Based on estimation, No severe skin irritation effects were known when 2-isopropyl-5-methylcyclohexanone was exposed to rabbit skin.

The experimental and estimated data are in agreement with each other, suggesting that 2-isopropyl-5-methylcyclohexanone is not irritating to skin.

These results are further supported by the 2 experimental studies summarized in Food and Cosmetics Toxicology; Volume 13, Issue 6, 1975, Pages 729 for the functionally similar read across substance 4-tert-butylcyclohexanone (CAS: 98-53-3).

4-tert-butylcyclohexanone when applied full strength to intact or abraded rabbit skin for 24 hr under occlusion did not produce any irritation. When 4-tert butylcyclohexanone was tested at6%in petrolatum, on human subjects in a 48-hr closed-patch test; no irritation was observed.

Hence, 4-tert-butylcyclohexanone can be considered not irritating to rabbit and human skin.

Based on the available data for the target as well as it read across substances,it can be concluded that for 2-isopropyl-5-methylcyclohexanonewas not irritating to skin.Comparing the above annotations with the criteria of CLP regulation,2-isopropyl-5-methylcyclohexanonecan be classified under the category“Not Classified”.

 

Eye Irritation:

In different studies, 2-isopropyl-5-methylcyclohexanone has been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemical and its functionally similar read across substance 4-tert-butylcyclohexanone (CAS: 98-53-3). The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for2-isopropyl-5 -methylcyclohexanone. It was estimated that2-isopropyl-5-methylcyclohexanonewas not irritating to eyes of New Zealand White rabbits.

This result was supported by the experimental study conducted by Saltigo GmBH (4-tert-butylcyclohexanone, Saltigo GmbH, 1982) for the functionally similar read across substance 4-tert-butylcyclohexanone (CAS: 98-53-3). The study was performedaccording to OECD Guideline 405 Acute Eye Irritation / Corrosion. 6 male New Zealand White rabbits were used for the study. 100 mg of test chemical was instilled into the eyes of rabbits and the effects were observed till 7 days. The untreated eyes served as control. The ocular observations were noted and scored at 2 h, and 1, 2, 3, 4, and 7 days. In all experimental animals showed a marked redness and swelling of the conjunctiva excepted for 1 animal that showed a very strong redness (grade3) were observed. 3 animals presented mild hyperemia of the iris. In 5 animals after instillation of drop per fluorescein (2%) has been an erosion of the cornea.

The mean irritation scores over 24, 48 and 72 hours were as follows: cornea = 0.8/10; iris =0.1/2; conjunctivae = 1.2/3; chemosis = 0.4/4. All the effects observed were fully reversible within 7 days.

Based on the scores, 4-tert-butylcyclohexanone can be considered to be not irritating to New Zealand White rabbit eyes.

Based on the available data for the target as well as it read across substances,it can be concluded thatfor 2-isopropyl-5-methylcyclohexanonewas not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation,2-isopropyl-5-methylcyclohexanonecan be classified under the category“Not Classified”.

 

Justification for classification or non-classification

Available studies for 2-isopropyl-5-methylcyclohexanone indicate that it is not likely to cause any irritation to skin and eyes.

Hence, 2-isopropyl-5-methylcyclohexanonecan be evaluated as “Non - Irritant” to eyes and skin and it can be classified under the category “Not Classified” as per CLP regulation.