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Description of key information

The skin sensitization potential of 3-methylbutyl benzoate (94-46-2) was estimated by using OECD QSAR toolbox v 3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methylbutyl benzoate (94-46-2) was predicted to be non sensitizing to the skin of Hartley guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation
Remarks:
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 takenfrom OECD QSAR toolboxv.3.3 and QMRF report has been attached.
Qualifier:
according to
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Data is predicted using OECD QSAR toolboxv.3.3 .
GLP compliance:
not specified
Type of study:
Draize test
Justification for non-LLNA method:
Not specified .
Specific details on test material used for the study:
- Name of test material (as cited in study report): Isoamyl benzoate (3-methylbutyl benzoate)
- Molecular formula: C12H16O2
- Molecular weight: 192.256 g/mol
- Substance type: Organic
- Physical state: Liquid
Species:
guinea pig
Strain:
Hartley
Remarks:
Hartley-English short hair cross-strain
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: 6 different distributors within 100 miles of Washington, D.C.
- Weight at study initiation: 300 - 500 g
Route:
intradermal
Vehicle:
not specified
Concentration / amount:
3%
Day(s)/duration:
20 days
Route:
intradermal and epicutaneous
Vehicle:
not specified
Concentration / amount:
3%
Day(s)/duration:
No data available.
No. of animals per dose:
23animals.
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10 intradermal injections
- Exposure period: 20 d
- Frequency of applications: every second day
- Duration: 10 single injections for on alternate days for 20 days
- Concentrations: 3%

B. CHALLENGE EXPOSURE
- No. of exposures: one intradermal injection and epicutaneous application
- Day of challenge: 34
- Exposure period: single injection and single application, not further specified
- Concentrations: 3%
- Evaluation (hr after challenge): not further specified
Challenge controls:
No data available.
Positive control substance(s):
not specified
Statistics:
No data available.
Reading:
other: challenge
Group:
test group
Dose level:
3%
No. with + reactions:
0
Total no. in group:
23
Clinical observations:
No skin sensitization reaction observerd.
Remarks on result:
no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "S M W N"
Estimation method: Takes highest mode value from the 5 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" )  and ("n" and ( not "o") )  )  and "p" )  and ("q" and ( not "r") )  )  and "s" )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Esters (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid ester AND Isopropyl by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aryl AND Carboxylic acid ester AND Isopropyl AND Overlapping groups 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 Aromatic Carbon [C] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Ester, aliphatic attach [-C(=O)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 Aromatic compound AND Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester 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 OECD

Domain logical expression index: "g"

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 >> Alkyl phenols 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 Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR SN1 OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR Acylation >> Ester aminolysis or thiolysis OR Acylation >> Ester aminolysis or thiolysis >> Activated alkyl esters  OR Acylation >> Ester aminolysis or thiolysis >> Activated aryl esters  OR Ionic interaction OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates OR Ionic interaction >> Electrostatic interaction of tetraalkylamonium ion with protein carboxylates >> Tetraalkylammonium ions 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 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 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.3

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Low (Class I) by Toxic hazard classification by Cramer (with extensions) ONLY

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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: "o"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "p"

Similarity boundary:Target: CC(C)CCOC(=O)c1ccccc1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as No superfragment by Superfragments ONLY

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.3

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.6

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.84

Interpretation of results:
other: Non sensitizer
Conclusions:
The skin sensitization potential of 3-methylbutyl benzoate (94-46-2) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methylbutyl benzoate (94-46-2) was predicted to be non sensitizing to the skin of Hartley guinea pig.
Executive summary:

The skin sensitization potential of 3-methylbutyl benzoate (94-46-2) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methylbutyl benzoate (94-46-2) was predicted to be non sensitizing to the skin of Hartley guinea pig.

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

Skin sensitization 

In different studies, 3-methylbutyl benzoate (94-46-2) 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 chemical 3-methylbutyl benzoate (94-46-2) and in vivo experiments in human for its structurally similar read across substancesEthyl benzoate (93-89-0) and Isobutyl benzoate (120-50-3).The predicted data using the OECD QSAR toolbox and Danish QSAR has also been compared with the experimental data of target chemical and read across.

The skin sensitization potential of 3-methylbutyl benzoate (94-46-2) was estimated by using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances. 3-methylbutyl benzoate (94-46-2) was predicted to be non sensitizing to the skin of Hartley guinea pig.

Another prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for3-methylbutyl benzoate. Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 3-methylbutyl benzoate (94-46-2) estimated to be not sensitizing when applied to human and guinea pig skin.

 Supported by experimental study conducted by D. L. J. OPDYKE (Food & Cosmt. Tox.,1973) to evaluate the skin sensitizing potential of target substance 3-methylbutyl benzoate (94-46-2) in Human. Skin sensitization potential for 3-methylbutyl benzoate (94-46-2) was observed in human by human maximization test. A group of 25 human volunteers were tested by maximization test at a concentration of 6% in petrolatum. No reaction was observed .Therefore, 3-methylbutyl benzoate (94-46-2) was considered to be not sensitizing to humans.

It is further supported by experimental study conducted by Bar (Food & Cosmt. Tox.,1979) to evaluate the skin sensitizing potential of read across substance Ethyl benzoate(93-89-0) in Human. Skin sensitization test of Ethyl benzoate was observed in human by Human maximization test. A group of 25 volunteers were tested by maximization test at a concentration of 8% in petrolatum. No skin sensitization reaction was observed .Therefore, Ethyl benzoate (93-89-0) was considered to be not sensitizing to humans.

It is further supported by experimental study conducted by D. L. J. OPDYKE (Food & Cosmt. Tox.,1979) to evaluate the skin sensitizing potential of read across substance Isobutyl benzoate(120-50-3) in Human. Skin sensitization test of Isobutyl benzoate was observed in human by human maximization test. Group of25 human volunteers were tested by maximization test at a concentration of 2% in petrolatum. No skin sensitization reaction was observed. Therefore, Isobutyl benzoate (120-50-3) was considered to be not sensitizing to humans.

 

Thus based on the above predictions on 3-methylbutyl benzoate (94-46-2) as well as its read across and applying weight of evidence, it can be concluded that3-methylbutyl benzoate is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 3-methylbutyl benzoate (94-46-2) 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, 3-methylbutyl benzoate (94-46-2) can be considered as not classified for skin sensitization.