Oleic acid, monoester with propane-1,2-diol

Endpoint summary

Description of key information

Skin Irritation:

Mild erythema and no edema was observed in rabbits during the 7 days of observation after treatment with propylene glycol oleate.

Hence, propylene glycol oleate can be considered not irritating to male albino rabbit skin.

Eye Irritation:

The ocular irritation potential of Propylene Glycol Mono oleate was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Propylene Glycol Mono oleate was estimated to be not irritating to the eyes of Himalayan rabbits.

Based on the estimated results, Propylene Glycol Mono oleate can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

A skin irritation study was conducted on male albino rabbits to assess the irritation potential of Propylene glycol oleate.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 2-hydroxypropyl octadec-9-enoate
- Molecular formula: C21H40O3
- Molecular weight: 340.544 g/mol
- Smiles notation: C(CC(OC[C@@H](C)O)=O)CCCCC\C=C\CCCCCCCC
- InChl : 1S/C21H40O3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-21(23)24-19-20(2)22/h10-11,20,22H,3-9,12-19H2,1-2H3/b11-10+
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

other: albino

Details on test animals or test system and environmental conditions:

sex: male

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

other: tetraglycol:distilled water 1:1, with and without 1% lidocaine

Controls:

not specified

Amount / concentration applied:

1% in tetraglycol:distilled water 1:1, with and without 1% lidocaine

Duration of treatment / exposure:

Day 1, 3, 5, and 7

Observation period:

The test sites were kept under occlusion except when the dressing was removed on days 1, 3, 5, and 7 only long enough for observation

Number of animals:

3 male albino rabbits

Details on study design:

Details on study design
TEST SITE
- Area of exposure: backs (clipped of hair) of the rabbits
- % coverage: exposure area diameter of 1.5 cm2
- Type of wrap if used: adhesive plasters

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data available
- Time after start of exposure: No data available

SCORING SYSTEM: No data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: Days 1, 3, 5, and 7

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Mild erythema and no edema during the seven days of observation.

Interpretation of results:

other: not irritating

Conclusions:

Mild erythema and no edema was observed in rabbits during the 7 days of observation after treatment with propylene glycol oleate.
Hence, propylene glycol oleate can be considered not irritating to male albino rabbit skin.

Executive summary:

A Skin irritation study was conducted on albino male rabbit to assess the irritation potential of propylene glycol oleate.The animals were administrated of propylene glycol oleate (1% in tetraglycol: distilled water 1:1, with and without 1% lidocaine).

Propylene glycol oleate was administered to the backs (clipped of hair) of the rabbits in adhesive plasters with an exposure area diameter of 1.5 cm2. The test sites were kept under occlusion except when the dressing was removed on days 1, 3, 5, and 7 only long enough for observation. Then sterile pads were changed and the rabbit’s back reoccluded.

Mild erythema was observed in animals and no edema was observed during the 7 days of observation after treatment with propylene glycol oleate.

Hence, propylene glycol oleate can be considered not irritating to male albino rabbit skin.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: 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 from OECD QSAR toolbox v3.4 and the QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.4

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: 2-hydroxypropyl octadec-9-enoate
- Molecular formula: C21H40O3
- Molecular weight: 340.544 g/mol
- Smiles notation: C(CC(OC[C@@H](C)O)=O)CCCCC\C=C\CCCCCCCC
- InChl : 1S/C21H40O3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-21(23)24-19-20(2)22/h10-11,20,22H,3-9,12-19H2,1-2H3/b11-10+
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

no data available

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1,24,48,72 hours

Duration of post- treatment incubation (in vitro):

no data available

Number of animals or in vitro replicates:

3

Details on study design:

no data available

Other effects / acceptance of results:

no data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

no irritation observed

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("i" and(not "j")) ) and("k" and(not "l")) ) and "m") and "n") and "o") and "p") and("q" and(not "r")) ) and("s" and(not "t")) ) and "u") and("v" and "w") )

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 OASIS v.1.4

Domain logical expression index: "g"

Referential boundary:The target chemical should be classified as AN2 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 >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Thiols OR SN1 OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN2 OR SN2 >> Acylation 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, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives 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 an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary:The target chemical should be classified as No alert found by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as alpha,beta-unsaturated aliphatic alkoxy group OR alpha,beta-unsaturated carbonyls OR Aromatic mono-and dialkylamine OR Simple aldehyde by in vitro mutagenicity (Ames test) alerts by ISS

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 OR Group 16 - Sulfur S OR Group 17 - Halogens Br OR Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Similarity boundary:Target: CCCCCCCCC=CCCCCCCCC(=O)OCC(C)O
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: CCCCCCCCC=CCCCCCCCC(=O)OCC(C)O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Referential boundary:The target chemical should be classified as Acrylates/Methacrylates (Chronic toxicity) OR Anhydrides, Carboxylic acid OR Phenols (Acute toxicity) OR Phenols (Chronic toxicity) OR Rosin by US-EPA New Chemical Categories

Domain logical expression index: "u"

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

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 6.3

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.94

Interpretation of results:

other: not irritating

Conclusions:

Propylene Glycol Mono oleate was estimated to be not irritating to the eyes of Himalayan rabbits.

Executive summary:

The ocular irritation potential of Propylene Glycol Mono oleate was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Propylene Glycol Mono oleate was estimated to be not irritating to the eyes of Himalayan rabbits.

Based on the estimated results, Propylene Glycol Mono oleate can be considered to be not irritating to eyes and can be classified under the category “Not Classified” as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

In different studies,Propylene Glycol Mono oleatehas been investigated for potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicalPropylene Glycol Mono oleateand its functionally similar read across substances, Isopropyl Myristate [CAS: 110-27-0] and Glyceryl monooleate [CAS: 111-03 -5]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

A Skin irritation study was performed by Lillian C. Becker(Cosmetic Ingredient Review Washington, DC, August 18, 2014)on albino male rabbit to assess the irritation potential of propylene glycol oleate. The animals were administrated of propylene glycol oleate (1% in tetraglycol: distilled water 1:1, with and without 1% lidocaine). Propylene glycol oleate was administered to the backs (clipped of hair) of the rabbits in adhesive plasters with an exposure area diameter of 1.5 cm2. The test sites were kept under occlusion except when the dressing was removed on days 1, 3, 5, and 7 only long enough for observation. Then sterile pads were changed and the rabbit’s back re-occluded. Mild erythema was observed in animals and no edema was observed during the 7 days of observation after treatment with propylene glycol oleate.

Hence, propylene glycol oleate can be considered not irritating to male albino rabbit skin.

Skin irritation effects were also estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for Propylene Glycol Monooleate. Based on estimation, no severe skin irritation effects were known when Propylene Glycol Monooleate was exposed to rabbit skin.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for Propylene Glycol Monooleate. Propylene Glycol Monooleate was estimated to be not irritating to skin of Himalayan rabbits.

The experimental and estimated results indicate the possibility of Propylene Glycol Monooleate being not irritating to skin.

The above results are also supported by the experimental study summarized in JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY; Volume 1, Number 4, 1982; for the functionally similar read across substance, Isopropyl Myristate [CAS: 110-27-0]. The study was performed according to Draize method.100% undiluted Isopropyl Myristate was applied to the skin of 6 rabbits. The rabbits were observed for signs of irritation (duration not mentioned). No signs of irritation observed after 100% Isopropyl Myristate was exposed to rabbit skin. Hence, Isopropyl Myristate was considered not irritating to rabbit skin.

These results are further supported by the experimental study summarized in JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY; Volume 5, Number 5, 1986; for the functionally similar read across substance, Glyceryl monooleate [CAS: 111-03-5].In a single insult occlusive patch test, 0.5 ml Glyceryl Oleate 50% in corn oil was applied to the clipped dorsal skin of 9 rabbits. Sites were graded for erythema and edema 2 and 24 h after exposure (maximum score for either erythema or edema = 4). The Primary Irritation Index after 2, 24 hours of exposure was 0.33.

Hence, Glyceryl oleate was considered to be practically not irritating to rabbit skin.

Based on the available data for the target as well as it read across substances,it can be concluded that Propylene Glycol Monooleate was not irritating to skin.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Eye Irritation:

In different studies,Propylene Glycol Mono oleatehas been investigated for potential for ocular irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with predicted data for target chemicalPropylene Glycol Mono oleateand its functionally similar read across substances, Isopropyl Myristate [CAS: 110-27-0] and Glyceryl monooleate [CAS: 111-03 -5]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for Propylene Glycol Monooleate. Propylene Glycol Monooleate was estimated to be not irritating to eyes of Himalayan rabbits.

The above results are also supported by the experimental study summarized in JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY; Volume 1, Number 4, 1982; for the functionally similar read across substance, Isopropyl Myristate [CAS: 110-27-0].100% Isopropyl myristate was instilled into the eyes of 3 rabbits. The eyes were treated daily for 3 consecutive days. The eyes were scored for signs of irritation at 24, 48 and 72 hours. The Draize scores after 24, 48 and 72 hours were 0.0 respectively.

Hence, Isopropyl Myristate was considered to be not irritating to rabbit eyes.

These results are further supported by the experimental study summarized in JOURNAL OF THE AMERICAN COLLEGE OF TOXICOLOGY; Volume 5, Number 5, 1986; for the functionally similar read across substance, Glyceryl monooleate [CAS: 111-03-5].0.1ml volume of a sunscreen formulation containing5%Glyceryl Oleate was instilled into the eyes of 6 New Zealand White rabbits. The ocular reactions were scored according to Draize method.Scoring was performed 1 h after treatment and on Days1,2, 3, and 7.

Slight conjunctivitis was observed after1h, clearing within 24 h, and no signs of irritation to other tissues were noted. Hence, Glyceryl oleate was considered to be practically not irritating to rabbit eyes.

Based on the available data for the target as well as it read across substances;and applying the weight of evidence approach, it can be concluded that Propylene Glycol Monooleate was not irritating to eyes.Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

Justification for classification or non-classification

Based on the available information,Propylene Glycol Monooleate is not likely to cause any irritation to eyes and skin. Hence, Propylene Glycol Monooleate can be classified under the category “Not Classified” as per CLP regulation.