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Administrative data

Description of key information

Skin irritation

The dermal irritation potential of target chemical Menthone (CAS no: 89-80-5) was assessedin various experimental studies which were conducted onrabbits, guinea pigs and humansfor target chemicalMenthone (CAS no: 89-80-5)  and its structurally similar read across substances.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical Menthone (CAS no: 89-80-5) is unable to cause skin irritation and thus considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Menthone (CAS no: 89-80-5). Based on the summarized studies for target chemical Menthone (CAS no: 89-80-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

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 journal
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Skin irritation study of Menthone (CAS no: 89-80-5) was conducted on human subjects to determine the degree of skin irritancy caused by the chemical.
GLP compliance:
not specified
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:
other: Human
Strain:
other: Not applicable
Details on test animals and environmental conditions:
No data available
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
other: Petrolatum
Controls:
not specified
Amount / concentration applied:
8%
Duration of treatment / exposure:
48 hours
Observation period:
48 hours
Number of animals:
No Data Available
Details on study design:
No Data Available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
48 h
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No known signs of skin irritation were observed.
Interpretation of results:
other: Not irritating
Conclusions:
The test material Menthone (CAS no: 89-80-5) was considered to be not irritating to the skin of human subjects.
Executive summary:

Skin irritation study of Menthone (CAS no: 89-80-5) was conducted on human subjects to determine the degree of skin irritancy caused by the chemical.

 

Each subject was treated with 8% of Menthonein petrolatum dermally for 48 hours under a closed path patch.

 

Since no known signs of irritation was observed, the chemicalMenthone (CAS no: 89-80-5)was considered to be not irritating to theskin of human subjects.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
experimental data of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally similar read across chemicals
Reason / purpose:
read-across source
Related information:
Composition 1
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
WoE report is based on 2 eye irritation studies as- WoE-2 and WoE-3. An eye irritation study of test chemical was conducted on rabbits to assess its eye irritating effects.
GLP compliance:
not specified
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:
other: 1.New Zealand White 2.not specified
Details on test animals or tissues and environmental conditions:
1.TEST ANIMALS- Source: Dutchland laboratory Animals, Inc.- Age at study initiation: Young adult- Weight at study initiation: - Fasting period before study:- Housing: Individual- Diet (e.g. ad libitum): Purina lab Rabbit Chow. ad libitum. Feed will be periodically analyzed for concentrations of specified heavy metals, antibiotics, aflatoxin, pesticides, and nitrosamines.- Water (e.g. ad libitum): Tap water, ad libitum. The water is routinely-analyzed on a retrospective basis for specified microorganisms, pesticides, heavy metals, alkalinity, and halogens.- Acclimation period: Minimum of one week.ENVIRONMENTAL CONDITIONS- Temperature (°C): 70 ± 4°;- Humidity (%):40-60%- Photoperiod (hrs dark / hrs light): 12 hour light-dark cycle
Vehicle:
other: 1.unchanged (no vehicle) 2.Olive oil
Controls:
yes
Amount / concentration applied:
1.Liquid: Amount: 0.1 ml. concentration applied: 100%Solid or pastes - 100 mg. sample as a normal saline slurry.2.60% (1ml)
Duration of treatment / exposure:
1.TEST SITE- Area of exposure: the Lower conjunctival sac of the left eye of each test animal:REMOVAL OF TEST SUBSTANCE- Washing (if done): not rinsed - Time after start of exposure:7 days SCORING SYSTEM: According to the Draize system of scoring (Draize, J.H., 1959.Dermal Toxicity, pp. 46-59. In Appraisal of the Safety of Chemicals In Foods, Drugs, and cosmetics. Association of Food and Drug Officials of the U.S•• Austin. Texas.). (refer table given below)2.1 minute
Observation period (in vivo):
1.At one, 24, 48. and 72 hours, and at 4 and 7 days after treatment2.1 minute
Number of animals or in vitro replicates:
1.6/group (3/sex)2.8 rabbits
Details on study design:
1.TEST SITE- Area of exposure: the Lower conjunctival sac of the left eye of each test animal:REMOVAL OF TEST SUBSTANCE- Washing (if done): not rinsed - Time after start of exposure:7 days SCORING SYSTEM: According to the Draize system of scoring (Draize, J.H., 1959.Dermal Toxicity, pp. 46-59. In Appraisal of the Safety of Chemicals In Foods, Drugs, and cosmetics. Association of Food and Drug Officials of the U.S•• Austin. Texas.). (refer table given below)2.Substance was initially applied in 10, 20 and 30 % solution. The eyes of 4 animals were rinsed 1 minute after application with physiological saline, substance remained in the eyes of 4 animals. In a second step animals were treated with concentration of 40, 50 and 60 %.
Irritation parameter:
other: 1.overall irritation score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
110
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritation parameter:
other: 2.overall irritation score
Basis:
mean
Time point:
other: 1 minute
Score:
0
Reversibility:
other: Not applicable
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
1.Only conjunctival redness was observed in few treated rabbits.2.No signs of eye irritation were observed.

1.

DRAlZE SCALE FOR SCORING OCULAR LESIONS

Cornea Grade

(A)Opacity: degree of density (readings should be taken from most dense area)*

No ulceration or opacity = 0

Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris slightly obscured = 1

Easily discernible translucent area; details of iris slightly obscured = 2

Opalescent area; no details of iris visible; size of pupil barely discernible = 3

Opaque cornea; iris not discernible through the opacity = 4

(B) Area Of Cornea Involved

One quarter (less than ) but not zero=1

Greater than one quarter but less than half=2

Greater than one half quarter but less than three quarter =3

Greater than three quarter upto whole area=4

Score equals: A X B X 5                                                                                                  Maximum Score=80

Iris

Normal = 0

Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia; or injection; iris reactive to light (a sluggish reaction is considered to be an effect = 1

Hemorrhage, gross destruction, or no reaction to light = 2

Score equals: A X 5                                                                                                           Maximum Score: 10

Conjunctivae

(A)Redness (refers to palpebral and bulbar conjunctivae; excluding cornea and iris)

Vessels Normal = 0

Vessels definitely injected above normal = 1

Diffuse, crimson colour; individual vessels not easily discernible = 2

Diffuse beefy red = 3

(B )Chemosis

Swelling (refers to lids and/or nictating membranes)

Normal = 0

Any swelling above normal (includes nictating membrane)= 1

Obvious swelling, with partial eversion of lids = 2

Swelling, with lids about half closed = 3

Swelling, with lids more than half closed= 4

(C)Discharge

No discharge =0

Any amount different from norm al (does not include small amounts observed in inner canthus of nomal animals) =1

Discharge with moistening of the lids and hairs just adjacent to lids = 2

Discharge with moistening of the lids and hairs. and considerable area around the eye =3

Score equal s (A + B+ C) x 2                                                                                         Maximum Score: 20

 

The overall Maximum Possible Score is the sum of scores obtained for the cornea. iris and conjunctivae. Total maximum score possible = 110

2.Not specified

Interpretation of results:
other: Not irritating
Conclusions:
The test chemical Menthone (CAS no: 89-80-5) was considered to be not irritating into the eyes of rabbits.
Executive summary:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Menthone (CAS no: 89-80-5). The studies are as mentioned below:

 

An Unwashed Primary Eye Irritation study was reported in New Zealand White rabbits to assess an eye irritancy of chemical structurally similar read across substance. The 0.1ml of undiluted chemical was installed into the lower conjunctival sac of the left eye of each test animal. The untreated right eye of each rabbits served as a control. The ocular reactions were scored at one, 24, 48 and 72 hours, and at 4 and 7 days after treatment according to Draize system. The left eye of six albino rabbits will be examined 24 to 72 hours prior to instillation of the test material with fluorescein dye solution. Animals showing corneal damage will not be used on the test. After the reading at 24 hours, the eyes of the rabbits were examined with fluorescein dye solution. Any corneal damage was reconfirmed by examination with fluorescein dye solution at subsequent readings. The treated eye of each animal was re-examined at termination using the fluorescein dye solution to confirm the absence or presence of any corneal damage. The chemical induced only conjunctival redness in few treated rabbits with overall irritation score of 0.0 over a period of 7 days. Therefore the test chemical was considered to be not irritating in into the eyes of male and female New Zealand White rabbits using an unwashed procedure.

 

 

The above result was supported by the experimental study carried out for anotherstructurally similar read across substanceon rabbits to assess the degree of eye irritancy caused by the chemical according to Draize method.During the test,the test substance was initially applied in 10, 20 and 30 % solution. The eyes of 4 animals were rinsed 1 minute after application with physiological saline, substance remained in the eyes of 4 animals. In a second step animals were treated with concentration of 40, 50 and 60 %. No signs of eye irritation were observed. Hencethe test chemicalwas considered to be not irritating to theeyes of rabbits.

 

Based on the above summarized studies for target chemical Menthone (CAS no: 89-80-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

Various studieshas been investigated for the test chemicalMenthone (CAS no: 89-80-5)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits, guinea pigs and humans for target chemicalMenthone (CAS no: 89-80-5) and its structurally similar read across substances.The predicted data using theDanish QSAR databasehas also been compared with the experimental data and summarized as below;

 

The D. L. J. Opdyke (1979) conducted skin irritation studies in humans and rabbits for target chemical Menthone (CAS no: 89-80-5) as follows;

In human Skin irritation study of Menthone (CAS no: 89-80-5), each subject was treated with 8% of Menthone in petrolatum dermally for 48 hours under a closed path patch. No known signs of irritation were observed.

In skin irritation study of Menthone (CAS no: 89-80-5) conducted on rabbits,each rabbit received neatMenthone on intact and abraded skin for 24 hours under occlusive condition and later observed for skin lesions.The treated rabbits showed mild signs of irritation.

Hence the chemicalMenthone (CAS no: 89-80-5)was considered to be mildly irritating to theintact and abraded skin of rabbits while it was considered as not irritating on human skin.

 

According to Danish QSAR database , the skin irritation effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within for menthone (CAS no: 89-80-5) . Based on estimation, no severe skin irritation effects were known when menthone was exposed to rabbit skin. Hence, Menthone (CAS no: 89-80-5) can be considered not irritating to skin.

 

The above results were supported by the experimental study carried out by peer reviewed journalfor structurally similar read across substancewhich was conducted on intact and abraded skin of rabbits to assess its skin irritation potential.About 8% ofchemical in petrolatum was applied on theintact and abraded skin of each rabbit for 24 hours under occlusive condition. No signs of skin irritation were observed. Hencethe test chemicalwas considered to be not irritating to theintact and abraded skin of rabbits.

 

 

The last study was reported by OECD HPV Chemicals Programme (2003) for anotherstructurally similar read across substanceon guinea pigs which further supports the above mentioned results.During the test, theRacementhol was rubbed into the skin of 20 guinea pigs for 30 s once daily for 5 days (2 x 5 days) under non-occlusive condition. Skin lesions were observed for 14 days.No known signs of skin lesions were observed in treated guinea pigs during the 14 days observation period. Hence the chemicalRacementhol(CAS no: 89-78-1) wasconsidered to benot irritating to theguinea pigs’ skin.

 

Even though rabbit study indicates that Menthone is mildly irritating to rabbit skin but human data concludes that it is not irritating to human skin. Since, in the rabbit study skin was exposed to higher concentration of Menthone than the normal use, there exists a possibility of Menthone being of not irritating to rabbit skin at lower concentrations. Thus on the basis of the available data for the target and read across substances and applying the weight of evidence approach,the chemicalMenthone (CAS no: 89-80-5) can be considered to be not irritating to skin. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Eye irritation:

Data available for the structurally and functionally similar read across chemicals has been reviewed to determine the ocular irritation potential of the test chemical Menthone (CAS no: 89-80-5). The studies are as mentioned below:

 

An Unwashed Primary Eye Irritation study was reported in New Zealand White rabbits to assess an eye irritancy of chemical structurally similar read across substance. The 0.1ml of undiluted chemical was installed into the lower conjunctival sac of the left eye of each test animal. The untreated right eye of each rabbits served as a control. The ocular reactions were scored at one, 24, 48 and 72 hours, and at 4 and 7 days after treatment according to Draize system. The left eye of six albino rabbits will be examined 24 to 72 hours prior to instillation of the test material with fluorescein dye solution. Animals showing corneal damage will not be used on the test. After the reading at 24 hours, the eyes of the rabbits were examined with fluorescein dye solution. Any corneal damage was reconfirmed by examination with fluorescein dye solution at subsequent readings. The treated eye of each animal was re-examined at termination using the fluorescein dye solution to confirm the absence or presence of any corneal damage. The chemical induced only conjunctival redness in few treated rabbits with overall irritation score of 0.0 over a period of 7 days. Therefore the test chemical was considered to be not irritating in into the eyes of male and female New Zealand White rabbits using an unwashed procedure.

 

 

The above result was supported by the experimental study carried out for anotherstructurally similar read across substanceon rabbits to assess the degree of eye irritancy caused by the chemical according to Draize method.During the test,the test substance was initially applied in 10, 20 and 30 % solution. The eyes of 4 animals were rinsed 1 minute after application with physiological saline, substance remained in the eyes of 4 animals. In a second step animals were treated with concentration of 40, 50 and 60 %. No signs of eye irritation were observed. Hencethe test chemicalwas considered to be not irritating to theeyes of rabbits.

 

Based on the above summarized studies for target chemical Menthone (CAS no: 89-80-5) and its structurally similar read across substances,it can be concluded that the testchemical is not able to cause eye irritation and considered as not irritating. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemicalMenthone (CAS no: 89-80-5) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemicalMenthoneis unlikely to cause skin and eye irritation. HenceMenthone (CAS no: 89-80-5)can be classified under the category “Not Classified” for skin and eye as per CLP.