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

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 5921 mg/kg bw when rats were orally exposed with 2-hydroxypropyl octadec-9-enoate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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 predicted using OECD QSAR toolbox version 3.4 and the supporting QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: as below

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.4

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

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/mole
- Subsatnce type: Organic
- SMiles: C(CC(OC[C@@H](C)O)=O)CCCCC\C=C\CCCCCCCC

Species:

rat

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

other: Oral

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

5921 mg/kg bw

No. of animals per sex per dose:

not specified

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

5 921 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

not specified

Body weight:

not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average 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 ( not "m") )  )  and "n" )  and "o" )  and "p" )  and ("q" and ( not "r") )  )  and "s" )  and "t" )  and ("u" and "v" )  )

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, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones and Trihydroxybenzenes 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 >> Michael-type conjugate addition to activated alkene derivatives OR AN2 >> Michael-type conjugate addition to activated alkene derivatives >> Alpha-Beta Conjugated Alkene Derivatives with Geminal Electron-Withdrawing Groups OR AN2 >> Nucleophilic addition reaction with cycloisomerization OR AN2 >> Nucleophilic addition reaction with cycloisomerization >> Hydrazine Derivatives OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Polarized Haloalkene Derivatives 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 AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones and Trihydroxybenzenes OR Radical OR Radical >> Generation of ROS by glutathione depletion (indirect) OR Radical >> Generation of ROS by glutathione depletion (indirect) >> Haloalkanes Containing Heteroatom OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> p-Substituted Mononitrobenzenes 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 >> Radical mechanism via ROS formation (indirect) >> Thiols OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Pyrrolizidine Derivatives OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> Single-Ring Substituted Primary Aromatic Amines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitro Azoarenes 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  OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen 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 OR SN2 >> Alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen and Sulfur Mustards OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polarized Haloalkene Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkanes Containing Heteroatom 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 >> Direct nucleophilic attack on diazonium cation OR SN2 >> Direct nucleophilic attack on diazonium cation >> Hydrazine Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Vicinal Dihaloalkanes OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) OR SN2 >> Internal SN2 reaction with aziridinium and/or cyclic sulfonium ion formation (enzymatic) >> Vicinal Dihaloalkanes OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Haloalkanes Containing Heteroatom 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 OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.4

Domain logical expression index: "h"

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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-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 >> 5-alkoxyindoles 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 >> Methylenedioxyphenyl OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones 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 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Non binder, non cyclic structure by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, without OH or NH2 group OR Strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as 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 AN2 >> Nucleophilic addition to alpha, beta - unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta - unsaturated carbonyl compounds >> Propargyl Alcohol derivatives 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 >> Conjugated systems with electron withdrawing groups  OR SN2 OR SN2 >> SN2 Reaction at a sp3 carbon atom OR SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  OR SN2 >> SN2 reaction at a sulfur atom OR SN2 >> SN2 reaction at a sulfur atom >> Thiocyanates by Protein binding by OASIS v1.4

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

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

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 Valproic acid (Hepatotoxicity) Alert by Repeated dose (HESS)

Domain logical expression index: "s"

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: "t"

Similarity boundary:Target: CCCCCCCCC=CCCCCCCCC(=O)OCC(C)O
Threshold=60%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.26

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 7.77

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 5921 mg/kg bw when rats were orally exposed with 2-hydroxypropyl octadec-9-enoate.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-hydroxypropyl octadec-9-enoate. The LD50 was estimated to be 5921 mg/kg bw when rats were orally exposed with 2-hydroxypropyl octadec-9-enoate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 921 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, 2-hydroxypropyl octadec-9-enoate has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 2-hydroxypropyl octadec-9-enoate along with the study available on structurally similar read across substance 2,3-Dihydroxypropyl 9-cis-octadecenoate (CAS no 111-03-5) and 1-Hexadecanol acetate (CAS no 629-70-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In another prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-hydroxypropyl octadec-9-enoate. The LD50 was estimated to be 5921 mg/kg bw when rats were orally exposed with 2-hydroxypropyl octadec-9-enoate.

In another prediction done by SSS (2017) using the Danish QSAR with log kow as the primary descriptor, the acute oral toxicity was estimated for 2-hydroxypropyl octadec-9-enoate. The LD50 was estimated to be 11000 mg/kg bw when rats were orally exposed with 2-hydroxypropyl octadec-9-enoate.

Also further supported by experimental study summarized by J-CHECK (Ministry of Health, Labour and Welfare", "Ministry of the Environment" and "National Institute of Technology and Evaluation, J-CHECK, 2010) on structurally similar read across substance 2,3-Dihydroxypropyl 9-cis-octadecenoate (CAS no 111-03-5), Crj:CD(SD)IGS female rat were treated with 2,3-Dihydroxypropyl 9-cis-octadecenoate in the concentration of 2000 mg/kg bw orally by gavage. No mortality was observed in treated female rat at 2000 mg/kg bw. No abnormalities in general condition, change in body weight and gross pathological abnormalities were observed in treated female rats. Therefore, LD50 was estimated to >2000 mg/kg bw when Crj:CD(SD)IGS female rats were treated with2,3-Dihydroxypropyl 9-cis-octadecenoate orally by gavage.

This is further supported by experimental study conducted by Morenoet al(Food and Chemical Toxicology, Volume 21, Issue 5, October 1983, Pages 663-665) on structurally similar read across substance 1-Hexadecanol acetate (CAS no 629-70-9), rat were treated with 1-Hexadecanol acetate in the concentration of 5000 mg/kg bw orally. No mortality was observed in treated rat at 5000 mg/kg bw. Therefore, LD50 was considered to be >5000 mg/kg bw when rat were treated with 1-Hexadecanol acetate orally.

Thus, based on the above studies and predictions on 2-hydroxypropyl octadec-9-enoate and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-hydroxypropyl octadec-9-enoate can be Not classified as acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 2-hydroxypropyl octadec-9-enoate and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 2-hydroxypropyl octadec-9-enoate can be Not classified as acute oral toxicity.