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Administrative data

Description of key information

Skin sensitisation:

The skin sensitization potential of 2-isopropyl-5-methylcyclohexanone (1074-95-9) was estimated using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 2-isopropyl-5-methylcyclohexanone (1074-95-9) was predicted to be non sensitizing to the skin of Dunkin-Hartley female guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
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 QSAR toolbox Version 3.4.
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3 .
GLP compliance:
not specified
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-isopropyl-5-methylcyclohexanone
- Molecular formula: C10H18O
- Molecular weight: 154.2512 g/mol
- Substance type: Organic
- Physical state: Liquid
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS:
- Strain: Dunkin-Hartley, Pirbright White, Hsd/Win:DH (SPF)
- Sex: female
- Source: Harlan Winkelmann GmbH, Borchen (Germany)
- Age: healthy young adults
- Weight at study initiation: 342 g (mean test); 345 g (mean control)
- Controls: 10 animals; treatment: vehicle
- Diet: ad libitum, special diet for guinea pigs, SSniff G
- Water: ad libitum, tab water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
100 %
Day(s)/duration:
30 hour
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
100%
Day(s)/duration:
30 hour
No. of animals per dose:
20 test
10 control
Details on study design:
No data available.
Challenge controls:
No data available.
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
30
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No sensitization observed.
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 Alkane, branched with tertiary carbon AND Cycloalkane AND Cycloketone AND Isopropyl AND Terpenes by Organic Functional groups

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds OR AN2 >> Michael-type addition on alpha, beta-unsaturated carbonyl compounds >> Four- and Five-Membered Lactones OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives OR SN2 >> Alkylation OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as 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 Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes 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 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: "j"

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

Domain logical expression index: "k"

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 Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= -0.277

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.87

Interpretation of results:
GHS criteria not met
Conclusions:
The substance 2-isopropyl-5-methylcyclohexanone is estimated to be not sensitizing in Dunkin-Hartley female guinea pig.
Executive summary:

The skin sensitization potential of2-isopropyl-5-methylcyclohexanone (1074-95-9)was estimated using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.2-isopropyl-5-methylcyclohexanone (1074-95-9)was predicted to be non sensitizing to theskin of Dunkin-Hartley female guinea pig.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin sensitization 

In different studies,2-isopropyl-5-methylcyclohexanone (1074-95-9)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical2-isopropyl-5-methylcyclohexanone (1074-95-9).The predicted data using the OECD QSAR toolbox and Danish QSAR has also been compared with the experimental data of target chemical.

The skin sensitization potential of2-isopropyl-5-methylcyclohexanone (1074-95-9)was estimated using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.2-isopropyl-5-methylcyclohexanone (1074-95-9)was predicted to be non sensitizing to theskin of Dunkin-Hartley female guinea pig.

 

Based on the QSAR prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for2-isopropyl-5-methylcyclohexanone. Thus it can be concluded that the substance2-isopropyl-5-methylcyclohexanone (1074-95-9)has negative skin sensitization effects and based on the CLP criteria for classification it can be classified as non sensitizing to skin sensitization effects.

Human Maximization test for 2-isopropyl-5-methylcyclohexanone (1074-95-9) was performed on 25 human volunteers using 2-isopropyl-5-methylcyclohexanone at 8% concentration in petrolatum. After test no sensitization reaction was observed in any human volunteers. Therefore, 2-isopropyl-5-methylcyclohexanone (1074-95-9) was considered to be non-sensitizing in human.

Thus based on the above predictions on2-isopropyl-5-methylcyclohexanone (1074-95-9) and applying weight of evidence, it can be concluded that 2-isopropyl-5-methylcyclohexanone is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation,2-isopropyl-5-methylcyclohexanone (1074-95-9)can be considered as not classified for skin sensitization.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Thus comparing the above annotations with the criteria of CLP regulation,2-isopropyl-5-methylcyclohexanone (1074-95-9)can be considered as not classified for skin sensitization.