3,3-dimethyl-8,9-dinorbornan-2-one

Endpoint summary

Description of key information

Skin irritation

The dermal irritation potential of target chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) was assessedin various experimental studies which were conducted on rabbits and humans for target chemical 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) and its structurally similar read across substancesFenchyl acetate (CAS No: 13851-11-1) and alpha-Fenchyl alcohol (CAS No: 512-13-0). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) 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

An ocular irritation potential of target chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) was assessedin various experimental studies which were conducted on rabbits for target chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) and its structurally similar read across substancestert-butyl acetate (CAS No: 540-88-5) andMethylcyclohexane (CAS no: 108-87-2). The predicted data usingQSAR toolboxhas also been compared with the experimental data.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) is unable to cause eye damage and thus can be 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.

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Skin irritation study of Fenchone (CAS No: 1195-79-5) was conducted on human subjects to determine the degree of skin irritancy caused by the chemical under occlusive condition.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 3,3-Dimethyl-8,9-dinorbornan-2-one
- Common name: 1,3,3-trimethylbicyclo[2.2.1]heptan-2-one / Fenchone
- Molecular formula: C10H16O
- Molecular weight: 152.2354 g/mol
- Smiles notation: C[C@@]12CC[C@@H](C1)C(C)(C)C2=O
- InChl: 1S/C10H16O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7H,4-6H2,1-3H3/t7-,10+/m0/s1
- Substance type: Organic
- Physical state: Liquid

Species:

other: Human

Strain:

other: Not applicable

Details on test animals or test system 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:

4%

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 Fenchone (CAS No: 1195-79-5) was considered to be not irritating to the skin of human subjects.

Executive summary:

Skin irritation study of Fenchone (CAS No: 1195-79-5) was conducted on human subjects to determine the degree of skin irritancy caused by the chemical.

 

Each subject was treated with 4% of Fenchone (CAS No: 1195-79-5) in petrolatum dermally for 48 hours under a closed path patch.

 

Since no known signs of irritation was observed, the chemicalFenchone (CAS No: 1195-79-5)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:

(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 version 3.4 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Specific details on test material used for the study:

Name of test material: 3,3-Dimethyl-8,9-dinorbornan-2-one
- Common name: 1,3,3-trimethylbicyclo[2.2.1]heptan-2-one / Fenchone
- Molecular formula: C10H16O
- Molecular weight: 152.2354 g/mol
- Smiles notation: C[C@@]12CC[C@@H](C1)C(C)(C)C2=O
- InChl: 1S/C10H16O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7H,4-6H2,1-3H3/t7-,10+/m0/s1
- 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:

No data available

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 hours

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No eye irritation was observed in treated rabbits.

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

(((((((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and "k" )  and "l" )  and "m" )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Carbonyl compound OR Ketone by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Carbonyl, aliphatic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Tertiary Carbon by Organic functional groups (US EPA) ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Cycloketone OR Overlapping groups OR Terpenes by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkane, branched with tertiary carbon OR Bicycloheptane  OR Bridged-ring carbocycles OR Cycloalkane OR Cycloketone OR Terpenes by Organic Functional groups ONLY

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha,beta-Unsaturated Carbonyls and Related Compounds OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes OR SN2 OR SN2 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Epoxides, Aziridines and Sulfuranes  by Protein binding by OASIS v1.4

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Similarity boundary:Target: CC1(C)C2CCC(C)(C2)C1=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Similarity boundary:Target: CC1(C)C2CCC(C)(C2)C1=O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

Similarity boundary:Target: CC1(C)C2CCC(C)(C2)C1=O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Cycloketone AND Overlapping groups AND Terpenes by Organic Functional groups (nested) ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Carbon with 4 single bonds & no hydrogens AND -CH -  [cyclic] AND -CH2-  [cyclic] AND Ketone   [-C-C(=O)-C-] AND Methyl  [-CH3] AND Number of fused acyclic rings by Bioaccumulation - metabolism alerts

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Unsubstituted Cycloalkane by Bioaccumulation - metabolism alerts

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.45

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.61

Interpretation of results:

other: not irritating

Conclusions:

The chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) was estimated using OECD QSAR toolbox version 3.4 with logPow as the primary descriptor. The chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) can be considered to be not irritating to eye and can be classified under the category ˋ 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:

Various studieshas been investigated for the test chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5)  to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and humans for target chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5)  and its structurally similar read across substancesFenchyl acetate (CAS No: 13851-11-1) and alpha-Fenchyl alcohol (CAS No: 512-13-0).The predicted data using the OECD QSAR toolbox andDanish QSAR databasehas also been compared with the experimental data and summarized as below;

 

The D. L. J. Opdyke {Food and Cosmetics Toxicology, 1979, Pages 191}carried outSkin irritation study of  Fenchone (CAS No: 1195-79-5) on rabbits and humans to determine the degree of skin irritancy caused by the chemical as below;

In human study, each subject was treated with 4% of test substance in petrolatum dermally for 48 hours under a closed path patch.No known signs of irritation were observed.

Whereas in case of rabbits,each rabbit received neatchemical 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, the chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) was considered to be mildly irritating to theintact and abraded skin of rabbits.

Even though rabbit study indicates that3,3-Dimethyl-8,9-dinorbornan-2-one/ Fenchone (CAS No: 1195-79-5) 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 Fenchone (CAS No: 1195-79-5) than the normal use, there exists a possibility of 3,3-Dimethyl-8,9-dinorbornan-2-one / Fenchone (CAS No: 1195-79-5) being of not irritating to rabbit skin at lower concentrations. So, Fenchone (CAS No: 1195-79-5) can be considered to be not irritating to 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 for test chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) . The chemical 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5)  is estimated to be not irritating to skin of New Zealand White rabbits.

 

 

The above mentioned human and predicted data were further supported by the experimental studies summarized byD.L.J. Opdykefor two read across chemicalsFenchyl acetate (CAS No: 13851-11-1) and alpha-Fenchyl alcohol (CAS No: 512-13-0)as below;

Skin irritation study of Fenchyl acetate (CAS No: 13851-11-1) was conducted on human subjects. Each subject was treated with 5% of Fenchyl acetate (CAS No: 13851-11-1) in petrolatum dermally for 48 hours under a closed path patch.Since no known signs of irritation was observed, the chemicalFenchyl acetate (CAS No: 13851-11-1)was considered to be not irritating to theskin of human subjects.

 

Another irritation study of alpha-Fenchyl alcohol (CAS No: 512-13-0) {Food and Cosmetics Toxicology 1979, Pages 384–385} was conducted on human volunteers. Approximately 4% of alpha-Fenchyl alcohol (CAS No: 512-13-0) was applied on each volunteers in petrolatum for 48 hours under a closed path patch.Since no known signs of irritation was observed, the chemicalalpha-Fenchyl alcohol (CAS No: 512-13-0)was considered to be not irritating to theskin of female volunteers.

 

Thus 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 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5)  is unable to cause skin 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”.

 

Eye irritation:

In different studies, 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) has been investigated for potential for ocular irritation to a greater or lesser extent.The studies are based on in vivo experiments in rabbits for target chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) and its structurally similar read across substancetert-butyl acetate (CAS No: 540-88-5) andMethylcyclohexane (CAS no: 108-87-2).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the eye irritation potential was estimated for test chemical3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5)  .The chemical 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) is estimated to be not irritating to eye of New Zealand White rabbits.

 

The International Programme on Chemical Safety (IPCS) {Butyl Acetates (Cicads 64, 2005);Concise International Chemical Assessment Document 64; World Health Organization; Geneva, 2005} reported an ocular irritation study on New Zealand White rabbits for read across chemicaltert-butyl acetate (CAS No: 540-88-5).Approximately, 0.1ml of test chemical was place into the conjunctival sac of each rabbitwhich causedminimal conjunctival irritation, which lasted for 96 hours. The mean Draize scores were 4.8, 3.6, 2.0, 2.0, 1.6, and 0 at observation times of 1, 24, 48, 72, and 96 h and 7 days, respectively.Since the observed effects were not persisted, the chemicaltert-butyl acetate (CAS No: 540-88-5)was considered as not irritating to the eyes.

 

The above results were further supported by the another experimental study reported bythe MAK Collection for Occupational Health and Safety{The MAK Collection for Occupational Health and Safety. 1:578–596, 2016} for same read across chemicaltert-butyl acetate in rabbits (CAS No: 540-88-5). 0.1 ml was applied to the conjunctival sac of one eye of each of 6 male New Zealand White rabbits. The rabbits were observed for effects till day 7 and scored according to Draize method. Corneal opacity was observed in one animal (reversible after 2 days), iritis was detected in 3 animals (reversible after 2 days) and all animals had conjunctival redness (reversible after 3 days). The Draize scores were 14.5, 6.8, 2.0 and 0 of a maximum of 110 after 1, 24, 48 and 72 hours and after 7 days. Hence the chemicaltert-Butyl acetate was considered as not irritating to the eyes.

 

The overall all results were further supported by the experimental study reported by The MAK Collection for Occupational Health and Safety { Methylcyclohexan [MAK Value Documentation in German language, 2000]. The MAK Collection for Occupational Health and Safety. 1–6} and in NTRL REPORT {OTS0556750 May 17. 1982} for read across chemical Methylcyclohexane (CAS no: 108-87-2). An Unwashed Primary Eye Irritation study was conducted in New Zealand White rabbits to assess an eye irritancy of read across chemical  Methylcyclohexane (CAS no: 108-87-2). The 0.1ml of undiluted Methylcyclohexane was installed into thelower 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 Methylcyclohexane (CAS no: 108-87-2) was considered to be not irritating in into the eyes of male and female New Zealand White rabbits using an unwashed procedure.

 

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 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) is unable 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 chemical 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemical 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) is unlikely to cause skin and eye irritation. Hence 3,3-Dimethyl-8,9-dinorbornan-2-one (CAS No: 1195-79-5) can be classified under the category “Not Classified” for skin and eye as per CLP.