2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol

Endpoint summary

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:

other: data from OECD QSAR toolbox v 3.4

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

equivalent or similar to guideline

Guideline:

other: predicted data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v 3.4

GLP compliance:

not specified

Type of study:

Buehler test

Species:

guinea pig

Strain:

Hartley

Sex:

female

Route:

epicutaneous, occlusive

Concentration / amount:

0.4ml of undiluted test material was used in induction phase

Route:

epicutaneous, occlusive

Concentration / amount:

0.4ml of undiluted test material was used in induction phase

No. of animals per dose:

Test group: 10

Positive control substance(s):

not specified

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.4 ml

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no sensitizing reactions observed

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.4 ml . No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no sensitizing reactions observed.

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes mode value from the 8 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 ( not "m") )  )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Alcohol AND Alkane, branched with tertiary carbon AND Alkene AND Allyl AND Cycloalkene AND Terpenes by Organic Functional groups

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkane, branched with tertiary carbon AND Allyl AND Cycloalkene AND Overlapping groups AND Terpenes by Organic Functional groups (nested)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

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 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 via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones and Trihydroxybenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN1 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 attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines 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 >> Haloalcohols by DNA binding by OASIS v.1.4

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 Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR AN2 OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha,beta-Unsaturated Carboxylic Acids and Esters OR Ionic interaction OR Ionic interaction >> Substituted guanidines OR Ionic interaction >> Substituted guanidines >> Guanidines OR Michael addition OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  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 by Protein binding by OASIS v1.4

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 16 - Oxygen O by Chemical elements

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 3.3

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.77

Interpretation of results:

not sensitising

Conclusions:

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not sensitizing to guinea pigs

Executive summary:

The skin sensitizing potential of 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated using OECD QSAR toolbox version 3.4

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not sensitizing to guinea pigs

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization

Skin sensitization effects by (OECD QSAR toolbox v 3.4) were observed for target (28219-60-5) in guinea pig. The skin sensitizing potential of 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated using OECD QSAR toolbox version 3.4 .The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not sensitizing to guinea pig.

Another study reported by Safety data sheet-TAKASAGO, 2015 with target substance 28219-60-5 observed in guinea pig. The skin sensitization study of 2-Buten-1-ol, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)- (CAS No: -28219-60-5) was performed in guinea pigs to observed its sensitizing efficacy by Guinea pig maximization test. The test sample was applied at concentration of 30% in ethanol. Since no skin reactions were observed, the test chemical 2-Buten-1-ol, 2-methyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl) - (CAS No: -28219-60-5) was found to be non sensitizing in guinea pigs.

According to Material Safety Data Sheet-International Flavors & Fragrances 2010, the skin sensitizing effects were reported in humans for target CAS 28219-60-5. The skin sensitization study of 2-Buten-1-ol, 2-methyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl)- (CAS No: -28219-60-5) was performed in humans to observed its sensitizing efficacy. The test sample was applied at concentration of 5% on human skin. Since no skin reactions were observed, the test chemical 2-Buten-1-ol, 2-methyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl) - (CAS No: -28219-60-5) was found to be non sensitizing in humans.

According to Danish (Q)SAR Database 2016, the sensitization effects were observed for target CAS 28219-60-5 in guinea pig and human. Based on the QSAR prediction done using the Danish (Q)SAR Database, the skin sensitization was estimated to be not sensitizing on guinea pig and human for 2-Buten-1-ol, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)- (CAS No: - 28219-60-5) . Thus it can be concluded that the substance 2-Buten-1-ol, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)- (CAS No: - 28219-60-5) has negative skin sensitization effects.

In other study by (S.P. Bhatia, C.S. Letizia, A.M. Api, 2000) with similar substance ( 98-55-5) was observed in guinea pig. The skin irritation study of alpha-Terpineol (CAS No: -98-55-5) was performed in 10 female Pirbright-white albino guinea pigs by using a modified FCA technique. Alpha-Terpineol at 30 mg was dissolved in 4 ml of FCA and emulsified with 4 ml of physiological saline. Following eleven days after induction, open epicutaneous elicitation was performed by application of 0.05 ml of pure oils using acetone as vehicle. After induction, animals were challenged. Reactions were assessed at 24, 48, and 72 h according to the rules of International Contact Dermatitis Research Group (ICDRG). The mean response (MR) was computed as the quotient of the sum of all reactions obtained, divided by the total number of guinea pigs treated at 24 and 48 h. A MR of 0–1 was considered weak. The MR to 10% alpha-terpineol was 0.01 at 24 h and no response was observed at 48 h as no reactions were observed. The guinea pigs did not produce any skin reaction during the 72 hours observation period. Therefore the test chemical alpha-Terpineol (CAS No: -98-55-5) was found to be non sensitizing on skin of female guinea pigs.

Based upon the study by (S.P. Bhatia, C.S. Letizia, A.M. Api 2008) with read across substance (115-71-9) was observed in male and female guinea pigs. The skin sensitization study of alpha-Santalol (CAS No: - 115-71-9) was performed in male and female guinea pigs by using Open epicutaneous tests (OET). During induction phase 0.1 ml of 20% a-santalol applied onto an 8 cm2area of test animals. A total of 21 applications were made for 21 days. Following induction, challenge applications were made on days 21 and 35, to the contralateral flank with 0.025 ml of the a-santalol at the minimal irritating concentration and some lower primary non-irritating concentrations onto a skin area measuring 2 cm2.The guinea pigs did not show any skin reaction. Therefore the test chemical alpha-Santalol (CAS No: - 115-71-9) was found to be non sensitizing on skin of male and female guinea pigs.

 

On the basis of available information for the target as well as read across substance and applying weight of evidence approach, the test substance can be considered as not sensitising to the skin.

Migrated from Short description of key information:

Skin sensitization effect by (OECD QSAR toolbox v 3.4) for target (28219-60-5) was observed in guinea pig. The skin sensitizing potential of 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated using OECD QSAR toolbox version 3.4 .The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not sensitizing to guinea pig.

Justification for selection of skin sensitisation endpoint:

Skin sensitization effect by (OECD QSAR toolbox v 3.4)  for target (28219-60-5) was observed in guinea pig. The skin sensitizing potential of 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated using OECD QSAR toolbox version 3.4 .The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not sensitizing to guinea pig.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The test substance 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was observed in various skin sensitizing studies. From these studies it is concluded that the test substance 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol can be classified as non skin sensitizer.