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

Endpoint summary

Description of key information

Available studies on 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol indicates that it is not irritating to skin, but has an irritating effect on eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

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

Species:

other: reconstituted human epidermis

Strain:

other: not applicable

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

10 µl of the test material

Duration of treatment / exposure:

15 minutes

Observation period:

no data

Number of animals:

The test was conducted In Vitro.

Details on study design:

The test was conducted In Vitro.

Irritation / corrosion parameter:

other: overall irritation score

Run / experiment:

15 min

Value:

0

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other:

Remarks:

Basis: mean. Time point: 15 minutes. Remarks: not irritating . (migrated information)

Estimation method: Takes mode value from the 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((("a" or "b" or "c" or "d" )  and "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 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 superfragment by Superfragments ONLY

Domain logical expression index: "f"

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: "g"

Referential boundary: The target chemical should be classified as Group 1 - Alkali Earth Li,Na,K,Rb,Cs,Fr OR Group 12 - Trans.Metals Zn,Cd,Hg OR Group 15 - Nitrogen N OR Group 16 - Sulfur S OR Group 17 - Halogens Cl OR Group 17 - Halogens F OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "h"

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: "i"

Referential boundary: The target chemical should be classified as 2-Oxyalkyl-1,2-ethanediol deriv. [HOCH2CH(OH)CO] OR Alcohol, olefinic attach [-OH] OR Aldehyde, aliphatic attach [-CHO] OR Aliphatic 1,2,3-triol [-C(COH)(COH)C-OH] OR Aliphatic Carbon [C] OR Beta-hydroxy-carbonyl compound [CC(=O)C-OH] OR Carbonyl, aliphatic attach [-C(=O)-] OR Carbonyl, olefinic attach [-C(=O)-] OR Cyclic ester OR Cyclic esters, olefinic type  OR Dihydroxy-aceton derivative [HOCC(=O)CO-] OR Dihydroxy-aceton derivative [HOCC(=O)COH] OR Ester, aliphatic attach [-C(=O)O] OR Ether-alcohols [-OC(COH)CO-] OR Fused Aliphatic ring unit  OR Ketone in a ring, olefinic aromatic attach OR Miscellaneous sulfide (=S) or oxide (=O) OR Multi alcohol  OR Olefinic carbon [=CH2] OR Oxycarbonyl compound [CCCOC-O-] OR Oxycarbonyl compound [-OCCOC-O] OR Oxygen, aliphatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "l"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.17

Domain logical expression index: "m"

Parametric boundary:The target chemical should have a value of log Kow which is <= 5.8

Interpretation of results:

not irritating

Conclusions:

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not irritating when tested in an in vitro model

Executive summary:

The skin irritation 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

Reconstituted human epidermis was used to assess the irritation potential.

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not irritating when tested in an in vitro model.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

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 doneusing OECD QSAR toolbox v 3.4

GLP compliance:

not specified

Species:

other: Reconstituted Human Corneal model

Strain:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

30 µl

Duration of treatment / exposure:

10 minutes

Observation period (in vivo):

no data

Number of animals or in vitro replicates:

Test was carried out in vitro.

Details on study design:

Test was carried out in vitro.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 10 minutes

Remarks on result:

other: irritating

Estimation method: Takes mode value from the 7 nearest neighbours
Domain  logical expression:Result: In Domain

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

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 (!Undefined)Group All Lipid Solubility < 0.01 g/kg by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Aqueous Solubility < 0.000005 g/L OR (!Undefined)Group All Aqueous Solubility < 0.00002 g/L OR (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 g/kg OR Exclusion rules not met OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group All Molecular Weight > 650 g/mol 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 OR Group CHal Melting Point > 65 C OR Group CHal Molecular Weight > 280 g/mol OR Group CHal Molecular Weight > 370 g/mol OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Molecular Weight > 290 g/mol OR Group CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNS log Kow < -2 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Ethionine (Hepatotoxicity) Alert OR Ethyleneglycol alkylethers (Hemolytic anemia) Rank A OR Halobenzenes (Hepatotoxicity) Rank A OR Halobenzenes (Renal toxicity) Rank A OR Thiocarbamates/Sulfides (Hepatotoxicity) No rank OR Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "j"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.205

Domain logical expression index: "k"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.93

Interpretation of results:

irritating

Conclusions:

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be irritating when tested in an in vitro model.

Executive summary:

The ocular irritation 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

Reconstituted Human Corneal model was used to assess the irritation potential.

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be irritating when tested in an in vitro model.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation:

The skin irritation 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

Reconstituted human epidermis was used to assess the irritation potential.

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not irritating when tested in an in vitro model.

Based on the QSAR prediction done using the Danish (Q)SAR Database, the skin irritation was estimated to be not irritating on rabbits for 2-Methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)but-2-en-1-ol .Thus it can be concluded that the substance 2-Methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)but-2-en-1-ol has no skin irritation effects and based on the CLP criteria for classification it can be classified as non irritant to skin irritation effects.

A skin irritation study of 2-Buten-1-ol, 2-methyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl) was performed (Safety data sheet-TAKASAGO-Revision No: 1, Revision Date: 27 May 2015) in guinea pigs to observe its irritation efficacy. The test sample was applied at concentration of 0.5% in petrolatum under 48 hours closed patch. Since no known skin reactions were noted, the test chemical 2-Buten-1-ol, 2-methyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl) reported to be non irritant in guinea pigs.

A skin irritation study was performed in 30 volunteers for similar substance 98-55-5 (Contact Dermatitis: 51: 1–4, 2004). The observation period for the study was 72 hours.A 0.2 ml sample of neat alpha-terpineol was applied to a 25 mm Hill Top Chambers containing a Webril pad which was then applied to the skin of the upper outer arm of 30 volunteers for up to 4 hours. alpha-Terpineol was applied progressively from 15 and 30 minutes through 1, 2, 3, and 4 hours. Each progressive application (0.2 ml sample of neat alpha-terpineol was placed on a new skin site. Sodium dodecyl sulfate (SDS) at 20% was the positive control. The reactions were assessed at 24, 48, and 72 h after patch removal. When reactions were greater than or similar to SDS reactions, alpha-terpineol was determined to be irritant and when reactions were less than the SDS reactions the alpha- terpineol was non-irritant. No known skin reactions were observed. Hence the test chemical alpha-Terpineol can be concluded as non irritant on skin of 30 volunteers.

A skin irritation study was performed in human subjects for another similar substance 115 -71 -9 (Food and Cosmetics Toxicology, Volume 12, Issues 7–8, December 1974, Pages 991-992) to determine its irritation potential. The test sample was applied at concentration of 20% in petrolatum for 48 hours closed patch and observations were made. Since no known skin reactions were observed, the test chemical alpha-Santalol was evaluated to be not irritating on human subjects.

Another skin irritation study was performed on similar substance115 -71 -9 (Food and Cosmetics Toxicology Volume 12, Issues 7–8, December 1974, Pages 991-992) in rabbit to determine its irritation potential. The test sample was applied in full strength to intact or abraded rabbit skin for 24 hour under occlusion. Since no known skin reactions were observed, the test chemical alpha-Santalol was determined to be not irritating on rabbit skin.

Based on the available information for the target chemical as well as it various read across substances, and applying the weight of evidence approach; the test substance,2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was considered to be not irritating to skin.

 

Eye Irritation:

The ocular irritation 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

Reconstituted Human Corneal model was used to assess the irritation potential.

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be irritating when tested in an in vitro model.

An eye irritation study in rabbits was performed (Material Safety Data Sheet, INTERNATIONAL FLAVORS & FRAGRANCES, 02/14/2011) to assess the irritation potential. Undiluted test sample was instilled into rabbit eyes. Effects were observed.2-Methyl-4-(2, 2, 3-trimethyl-3-cyclopenten-1-yl)but-2-en-1-ol was considered to be moderately irritating to rabbit eyes.

An eye irritation study in rabbits was performed (Safety data sheet, Kao Specialties Americas LLC, effective date- 03-30-2015) in accordance with Draize test. Undiluted test sample was instilled into rabbit eyes. Washing of the eyes was performed for some rabbits (number unspecified). Reactions were scored according to the Draize test.MAS score for washed and unwashed eyes were 10.0 and 19.8 respectively. Based on the MAS score, 2-Methyl-4-(2, 2 , 3-trimethyl-3-cyclopenten-1-yl)but-2-en-1-ol was considered to be irritating to rabbit eyes.

An eye irritation study was carried out on similar substance 515-69-5 (Food and Chemical Toxicology 46 (2008) S72–S76 and International Journal of Toxicology, 18 (Suppl. 3), 33–40, 1999) to assess the irritation potency.

Undiluted α-bisabolol was instilled into conjunctival sac of 3 rabbits. The eyes remained unwashed. Reactions were read at 1, 24, and 48 h readings. Well-defined conjunctival redness was noted in all rabbits at all the readings. Increased discharge was noted in all animals at the 1 h reading; the reaction cleared in two rabbits and was reduced to a ‘‘slight increase” in one rabbit at the 24 h reading, and was not noted in any rabbit at subsequent observations. No changes were noted in the cornea or iris at any observation. No effects were noted in the 72 hour reading.

Based on these observations, it was concluded that α-bisabolol was mildly irritating to rabbit eyes.

An eye irritation study in rabbits was performed on another similar substance 8000-41-7 (Food and Chemical Toxicology 46 (2008) S275–S279) in accordance with Draize test. The test was conducted in three healthy albino rabbits using 12.5% terpineol. A 0.1 ml sample of 12.5% terpineol in Specially Denatured Alcohol (SDA) 39 °C was instilled into the right eye of each animal, while the left eye served as an untreated control. Reactions were observed every 24 h for four days and on the seventh day. Intense conjunctival irritation involving chemosis and discharge occurred. No corneal opacity or iris congestion was observed. All eyes were normal on day 7. Based on these observations, 12.5% terpineol was considered to be moderately irritating to rabbit eyes.

 

An eye irritation study in rabbits was performed on the similar substance 8000-41-7 (8EHQ-11-18270, Submitted to EPA on 25 February, 2011) in accordance with OECD 405. The test was conducted in rabbit (New Zealand White). The test substance, terpineol was instilled pure into the eye of three rabbits at the dose level of 0.1 ml. At the conjunctivae level, a moderate redness was noted 24 hours after the test substance instillation and was totally reversible between the 6^thand 7^thday of the test, associated with a moderate chemosis, noted 1 hour after the test substance instillation and totally reversible between the 5th and the 6th day of the test. At the corneal level, a moderate opacity was registered 24 hours after the test substance instillation and was totally reversible between the 3rd and the 6th day of the test. The ocular reactions observed during the study have been moderate, and totally reversible in the three animals. Based on the results obtained in the experimental conditions, it was concluded that terpineol was irritating to rabbit eyes.

Based on the available information for the target chemical as well as it various read across substances, and applying the weight of evidence approach; the test substance,2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was considered to be an eye irritant.

Justification for selection of skin irritation / corrosion endpoint:

The skin irritation 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

Reconstituted human epidermis was used to assess the irritation potential.

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be not irritating when tested in an in vitro model.

Justification for selection of eye irritation endpoint:

The ocular irritation 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

Reconstituted Human Corneal model was used to assess the irritation potential.

The substance, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol was estimated to be irritating when tested in an in vitro model.

Effects on eye irritation: irritating

Justification for classification or non-classification

Available studies on 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-1-yl)-2-buten-1-ol indicates that it is not irritating to skin, but has an irritating effect on eyes and can be classified under Eye irritation Category 2 as per the CLP criteria.