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Description of key information

The skin sensitization potential of 2-hydroxypropyl octadec-9-enoate (1330-80-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxypropyl octadec-9-enoate (1330-80-9) was predicted to be non sensitizing to the skin of 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:
Prediction is done using OECD QSAR Toolbox version 3.4 and the supporting QMRF report has been attached.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Prediction was done using OECD QSAR toolbox v3.4
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Not specified .
Specific details on test material used for the study:
- Name of the test material: 9-Octadecenoic acid, monoester with 1,2-propanediol
- IUPAC name: 2-hydroxypropyl octadec-9-enoate
- Molecular formula: C21H40O3
- Molecular weight: 340.544 g/mol
- Subsatnce type: Organic
- SMiles: C(CC(OC[C@@H](C)O)=O)CCCCC\C=C\CCCCCCCC
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
other: No data available.
Route:
other: No data available.
No. of animals per dose:
No data available.
Details on study design:
No data available.
Positive control substance(s):
not specified
Statistics:
No data available.
Reading:
1st reading
Group:
test group
No. with + reactions:
0
Clinical observations:
No skin sensitization reaction 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: Out of Domain

((((((((((((("a" or "b" or "c" or "d" or "e" )  and ("f" and ( not "g") )  )  and "h" )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and ("q" and ( not "r") )  )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and ( not "x") )  )  and ("y" and ( not "z") )  )  and ("aa" and "ab" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alcohol AND Alkene AND Allyl AND Carboxylic acid ester by Organic Functional groups

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Alcohol AND Allyl AND Carboxylic acid ester 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 Carbonyl, aliphatic attach [-C(=O)-] AND Ester, aliphatic attach [-C(=O)O] AND Hydroxy, aliphatic attach [-OH] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Alcohol AND Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester AND Hydroxy compound AND Secondary alcohol 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 >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Schiff base formers 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 >> Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Not bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Non-Metals by Groups of elements

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Halogens by Groups of elements

Domain logical expression index: "k"

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: "l"

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

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Acrylate Reactive Functional Groups OR Aldehyde Type Compounds OR Phenol Type Compounds by Oncologic Primary Classification

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Not possible to classify according to these rules by Keratinocyte gene expression

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as High gene expression OR High gene expression >> Activated esters by Keratinocyte gene expression

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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 by OASIS v.1.4

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "w"

Referential boundary: The target chemical should be classified as No alert found by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "x"

Referential boundary: The target chemical should be classified as Structural alert for nongenotoxic carcinogenicity OR Substituted n-alkylcarboxylic acids (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "y"

Referential boundary: The target chemical should be classified as Esters by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "z"

Referential boundary: The target chemical should be classified as Acid moiety OR Not Related to an Existing ECOSAR Class OR Surfactants-Nonionic by Aquatic toxicity classification by ECOSAR

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= 5.13

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.17

Interpretation of results:
other: not sensitising
Conclusions:
The skin sensitization potential of 2-hydroxypropyl octadec-9-enoate (1330-80-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxypropyl octadec-9-enoate (1330-80-9) was predicted to be non sensitizing to the skin of guinea pig.
Executive summary:

The skin sensitization potential of 2-hydroxypropyl octadec-9-enoate (1330-80-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxypropyl octadec-9-enoate (1330-80-9) was predicted to be non sensitizing to the skin of guinea pig.

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

Skin sensitization

In different studies,2-hydroxypropyl octadec-9-enoate (1330-80-9) has been investigated for its potential for dermal sensitization to a greater or lesser extent. The prediction and studies are based on in vivo experiments in guinea pig and human for target chemical 2-hydroxypropyl octadec-9-enoate (1330-80-9) and its structurally similar read across substances2,3-dihydroxypropyl octadec-9-enoate (111-03-5) and Isopropyl Myristate (110-27-0) .The predicted data using the OECD QSAR toolbox and DANISH QSAR have also been compared with the experimental data.

The skin sensitization potential of 2-hydroxypropyl octadec-9-enoate (1330-80-9) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances. 2-hydroxypropyl octadec-9-enoate (1330-80-9) was predicted to be non sensitizing to the skin of guinea pig.

 Another Prediction done by Danish QSAR (2017), to evaluate the skin sensitization potential of 2-hydroxypropyl octadec-9-enoate (1330-80-9).Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 2-hydroxypropyl octadec-9-enoate (1330-80-9) estimated to be not sensitizing when applied to human and guinea pig skin.

Further supported by experimental data conducted by Cosmetic Ingredient Review Expert Panel (JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY, 1986) on structurally similar read across substance 2,3-dihydroxypropyl octadec-9-enoate (111-03-5) on human by RIPT method.Skin sensitization for2,3-dihydroxypropyl octadec-9-enoate (111-03-5) was observed in human by repeated insult patch test. An RIPT with a sunscreen formulation containing 5% test material was conducted using an occlusive patch technique. Ten 24-h induction patches on Tuesdays, Thursdays, and Saturdays were applied. The sites were evaluated after removal of each patch. After a rest period of 12-l 6-day. A 24-h challenge patch at an adjacent site was applied. These challenge sites were then evaluated immediately after patch removal and 24 h later. None of the 15 subjects was observed with skin sensitization effect during the induction phase or when challenged. Therefore 2,3-dihydroxypropyl octadec-9-enoate (111-03-5) was considered to be non sensitizing in human.

It is further supported by Further supported by experimental data conducted by Cosmetic Ingredients Review Expert Panel  (JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY,1982) on structurally similar read across substance Isopropyl Myristate (110-27-0) on human by maximization test.Skin sensitization study for Isopropyl Myristate (110-27-0) was observed in human by maximization test.A maximization test was conducted on on 25 human volunteers using 20% concentration of Isopropyl Myristate in petrolatum. After pretreatment with sodium lauryl sulfate, the skin on the volar surface of one forearm was subjected to five sequential patches, each for 48 h with 24 h between in induction phase. While in challenge exposure ,a patch with sodium lauryl sulfate pretreatment was made after a 10 day rest period . No sensitization reactions were observed in any 25 human. Therefore Isopropyl Myristate (110-27-0) was considered to be non sensitizing in human.

 

Thus based on the above predictions on 2-hydroxypropyl octadec-9-enoate (1330-80-9) as well as its read across substances and applying weight of evidence, it can be concluded that 2-hydroxypropyl octadec-9-enoate is not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation, 2-hydroxypropyl octadec-9-enoate (1330-80-9) can be considered as ‘not classified ‘for skin sensitization effects.

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-hydroxypropyl octadec-9-enoate (1330-80-9) can be considered as ‘not classified ‘for skin sensitization effects.