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Administrative data

Description of key information

Skin Irritation:

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for butyl 12-acetoxyoctadec-9-enoate Based on estimation, No severe skin irritation effects were known when butyl 12-acetoxyoctadec-9-enoate was exposed to rabbit skin.

Eye Irritation:

The ocular irritation potential of butyl 12-acetoxyoctadec-9-enoate was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Butyl 12-acetoxyoctadec-9-enoate was estimated to be not irritating to the eyes of Kleinrussen Chbb:HM rabbits.

Based on the estimated results, butyl 12-acetoxyoctadec-9-enoate 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:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
data is from modelling databases
Qualifier:
equivalent or similar to
Guideline:
other: estimated data
Principles of method if other than guideline:
To estimate the skin irritation potential of butyl 12-acetoxyoctadec-9-enoate
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of test material (as cited in study report): butyl 12-acetoxyoctadec-9-enoate
- Molecular formula: C24H44O4
- Molecular weight: 396.6076 g/mol
- Smiles notation: CCCCCC[C@H](C\C=C/CCCCCCCC(=O)OCCCC)OC(=O)C
- InChl : 1S/C24H44O4/c1-4-6-8-15-18-23(28-22(3)25)19-16-13-11-9-10-12-14-17-20-24(26)27-21-7-5-2/h13,16,23H,4-12,14-15,17-21H2,1-3H3/b16-13-/t23-/m1/s1
- Substance type: Organic
- Physical state: Liquid
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
no data available
Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
no data available
Duration of treatment / exposure:
no data available
Observation period:
no data available
Number of animals:
no data available
Details on study design:
no data available
Other effects / acceptance of results:
no data available
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: no data available
Score:
0
Reversibility:
not specified
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
no irritation observed

Table showing skin irritation estimation by three different models i.e, Leadscope, battery and SciQSAR &CASE Ultrathe average skin irritation results was given by the fourth model i.e, Battery model.

DK

Battery

SciQSAR

CASE Ultra

Leadscope

Skin irritation in rabbit

NEG

NEG

INC

NEG

Domain

IN

IN

OUT

IN

 

Where,

IN = inside applicability domain, INC - Inconclusive

Interpretation of results:
other: not irritating
Conclusions:
No severe skin irritation effects of butyl 12-acetoxyoctadec-9-enoate were estimated in rabbit skin by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database.
Executive summary:

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for butyl 12-acetoxyoctadec-9-enoate Based on estimation, No severe skin irritation effects were known when butyl 12-acetoxyoctadec-9-enoate wasexposed to 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:
equivalent or similar to
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 (as cited in study report): butyl 12-acetoxyoctadec-9-enoate
- Molecular formula: C24H44O4
- Molecular weight: 396.6076 g/mol
- Smiles notation: CCCCCC[C@H](C\C=C/CCCCCCCC(=O)OCCCC)OC(=O)C
- InChl : 1S/C24H44O4/c1-4-6-8-15-18-23(28-22(3)25)19-16-13-11-9-10-12-14-17-20-24(26)27-21-7-5-2/h13,16,23H,4-12,14-15,17-21H2,1-3H3/b16-13-/t23-/m1/s1
- Substance type: Organic
- Physical state: Liquid
Species:
rabbit
Strain:
other: Kleinrussen , Chbb:HM
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 h
Observation period (in vivo):
72 h
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:
72 h
Score:
0
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") and("e" and(not "f")) ) and("g" and(not "h")) ) and("i" and(not "j")) ) and("k" and(not "l")) ) and "m") and "n") and "o") and("p" and(not "q")) ) and "r") and("s" and "t") )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary:The target chemical should be classified as Allyl AND Carboxylic acid ester AND Overlapping groups by Organic Functional groups (nested)

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 Carbonyl, aliphatic attach [-C(=O)-] AND Ester, aliphatic attach [-C(=O)O] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary:The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

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

Domain logical expression index: "f"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems 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 >> 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 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 azo OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Epoxides 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 OR SN2 >> SN2 at an sp3 Carbon atom >> Phosphonic esters OR SN2 >> SN2 at an sp3 Carbon atom >> Sulfonates by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary:The target chemical should be classified as Moderate binder, OH grooup OR 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 OR Very strong binder, OH group OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary:The target chemical should be classified as Acylation OR Acylation >> Ester aminolysis OR Acylation >> Ester aminolysis >> Amides OR 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 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 >> Direct acting Schiff base formers OR Schiff base formation >> Direct acting Schiff base formers >> 1,2-Dicarbonyls and 1,3-Dicarbonyls  OR SN2 OR SN2 >> Interchange reaction with sulphur containing compounds OR SN2 >> Interchange reaction with sulphur containing compounds >> Thiols and disulfide compounds  OR SN2 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> (Thio)Phosphates  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Phosphonates OR SN2 >> Protein and/or DNA alkylation OR SN2 >> Protein and/or DNA alkylation >> Dialkyl Alkylphosphonates 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 v1.4

Domain logical expression index: "k"

Referential boundary:The target chemical should be classified as Not possible to classify according to these rules (GSH) by Protein binding potency

Domain logical expression index: "l"

Referential boundary:The target chemical should be classified as Highly reactive (GSH) OR Highly reactive (GSH) >> Miscellaneous Alkyl 2-halo alkenoates (SN2) by Protein binding potency

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary:The target chemical should be classified as Carbonic acid derivative AND Carboxylic acid derivative AND Carboxylic acid ester by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary:The target chemical should be classified as Alcohol OR Dialkylether OR Ether OR Hydroxy compound OR Primary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "r"

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

Domain logical expression index: "s"

Parametric boundary:The target chemical should have a value of log Kow which is >= 8.12

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 10.6

Interpretation of results:
other: not irritating
Conclusions:
Butyl 12-acetoxyoctadec-9-enoate was estimated to be not irritating to the eyes of Kleinrussen Chbb:HM rabbits.
Executive summary:

The ocular irritation potential of butyl 12-acetoxyoctadec-9-enoate was estimated using OECD QSAR toolbox v3.4 with logPow as the primary descriptor.

Butyl 12-acetoxyoctadec-9-enoate was estimated to be not irritating to the eyes of Kleinrussen Chbb:HM rabbits.

Based on the estimated results, butyl 12-acetoxyoctadec-9-enoate 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,butyl 12-acetoxyoctadec-9-enoatehas 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 chemicaland its structurally similar read across substances tributyl O-acetylcitrate [CAS: 77-90-7]and Dibutyl adipate [CAS: 105-99-7]. The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

Skin irritation effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for butyl 12 -acetoxyoctadec-9-enoate Based on estimation, No severe skin irritation effects were known when butyl 12-acetoxyoctadec-9-enoate wasexposed 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 forButyl 12 -acetoxyoctadec-9-enoate. Butyl 12-acetoxyoctadec-9-enoate was estimated to be not irritating to the skin of New Zealand White rabbits.

Both the estimated data suggests the possibility of Butyl 12-acetoxyoctadec-9-enoate being not irritating to skin.

These results are further supported by the experimental study summarized in Review of Exposure and Toxicity Data for Phthalate Substitutes; Versar, Inc, Exposure and Risk Assessment Division and Syracuse Research Corporation (SRC); 2010, for thestructurally similar read across substance tributyl O-acetylcitrate [CAS: 77-90-7].Tributyl O-acetylcitrate was tested for dermal irritation and sensitization in 59 men and women volunteers ranging in age from 21 to 60 years. Tributyl O-acetylcitrate was applied to the human skin and effects were observed. There was no evidence of irritation in the initial patch tests. Hence, tributyl O-acetylcitrate can be considered as not irritating to human skin.

The above results are also supported bythe experimental study summarized in Int J Toxicol; 2012 Jul-Aug;31(4 Suppl):5S-76S, for thestructurally similar read across substance Dibutyl adipate [CAS: 105-99-7].Dibutyl adipate 10% in acetone was applied daily for 10 days to the ears of 5 hairless mice and effects were observed. No adverse effects were observed after 10 days. Hence, dibutyl adipate can be considered as not irritating to skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,Butyl 12-acetoxyoctadec-9-enoate 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,butyl 12-acetoxyoctadec-9-enoatehas 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 chemicaland its structurally similar read across substances tributyl O-acetylcitrate [CAS: 77-90-7]and Bis(2 -ethylhexyl) adipate [CAS: 103-23-1]. 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 forButyl 12 -acetoxyoctadec-9-enoate. Butyl 12-acetoxyoctadec-9-enoate was estimated to be not irritating to the eyes of Kleinrussen Chbb:HM rabbits

This result is supported by the experimental study summarized in Review of Exposure and Toxicity Data for Phthalate Substitutes; Versar, Inc, Exposure and Risk Assessment Division and Syracuse Research Corporation (SRC); 2010, for thestructurally similar read across substance tributyl O-acetylcitrate [CAS: 77-90-7]. 0.1 ml Tributyl O-acetylcitrate was instilled into the left conjunctival sac of three male albino rabbits, with the contra-lateral eyes serving as controls. Moderate erythema was observed in two of the three test rabbits within 20 minutes. The erythema subsided in one of the rabbits after 5 hours, but persisted beyond 24 hours in the other. No irritation was observed in any rabbit at 48 or 72 hours post instillation. Hence, Tributyl O-acetylcitrate can be considered as not irritating to rabbit eyes.

The above results are further supported by the experimental study summarized in Int J Toxicol; 2012 Jul-Aug;31(4 Suppl):5S-76S, for thestructurally similar read across substance Bis(2-ethylhexyl) adipate [CAS: 103-23-1].0.1ml undiluted diethylhexyl adipate was instilled into the eyes of 6 albino rabbits, the eyes remained unwashed and the effects were observed (duration not specified). Undiluted diethylhexyl adipate was not irritating to rabbit eyes.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,Butyl 12-acetoxyoctadec-9-enoate 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

Available data for Butyl 12-acetoxyoctadec-9-enoate suggests that it is not likely to cause any irritation to eyes and skin.

Butyl 12-acetoxyoctadec-9-enoate can be classified under the category “Not Classified” as per CLP regulation.