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Description of key information

LD50 was estimated to be 4184 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with butyl 12-acetoxyoctadec-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:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.4
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
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/mole
- 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:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
No data available
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
No data available
Doses:
4184 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
No data available
Statistics:
No data available
Preliminary study:
No data available
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 184 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50 % mortality observed
Mortality:
No data available
Clinical signs:
No data available
Body weight:
No data available
Gross pathology:
No data available
Other findings:
No data available

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 6 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 "l" )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and ("r" and ( not "s") )  )  and "t" )  and ("u" and ( not "v") )  )  and "w" )  and ("x" and "y" )  )

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 >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isocyanates 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 >> 5-alkoxyindoles 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 aldehydes 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 >> Alpha halo ethers (including alpha halo thioethers) 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 (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary (unsaturated) heterocyclic 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 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> 1,2-Dihaloalkanes 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 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 No superfragment by Superfragments ONLY

Domain logical expression index: "l"

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

Domain logical expression index: "m"

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: "n"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "o"

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: "p"

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: "q"

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: "r"

Referential boundary: The target chemical should be classified as Basic [0,10) AND No pKa value by Ionization at pH = 4

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as No pKb value by Ionization at pH = 4

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Not calculated by Hydrolysis half-life (pH 6.5-7.4) ONLY

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as Not categorized by US-EPA New Chemical Categories

Domain logical expression index: "v"

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

Domain logical expression index: "w"

Similarity boundary:Target: CCCCCCC(CC=CCCCCCCCC(=O)OCCCC)OC(C)=O
Threshold=80%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "x"

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

Domain logical expression index: "y"

Parametric boundary:The target chemical should have a value of log Kow which is <= 9.17

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
LD50 was estimated to be 4184 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with butyl 12-acetoxyoctadec-9-enoate.
Executive summary:

In prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for butyl 12-acetoxyoctadec-9-enoate. The LD50 was estimated to be 4184 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with butyl 12-acetoxyoctadec-9-enoate. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 184 mg/kg bw
Quality of whole database:
Data is from KIlmisch 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, butyl 12-acetoxyoctadec-9-enoate has been investigated for acute oral toxicity to a greater or lesser extent. Studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for butyl 12-acetoxyoctadec-9-enoate along with structurally similar read across substance Hexalure (CAS: 23192-42-9). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies.

In prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for butyl 12-acetoxyoctadec-9-enoate. The LD50 was estimated to be 4184 mg/kg bw when Sprague-Dawley male and female rats were orally exposed with butyl 12-acetoxyoctadec-9-enoate. 

In another prediction done by SSS (2017) using Danish QSAR (EPA Model), the acute oral toxicity was estimated for butyl 12-acetoxyoctadec-9-enoate. The LD50 was estimated to be 12000 mg/kg bw in mice and 15000 mg/kg bw in rat when mice and rat were orally exposed with butyl 12-acetoxyoctadec-9-enoate.  

Also it is further supported by experimental study conducted by Beroza et al (Toxicology and Applied Pharmacology, 31,421-429 (1975)) on structurally similar read across substance Hexalure (CAS: 23192-42-9), Sprague Dawley male and female rat were treated with Hexalure in four, five and six dose levels orally by gavage and observed for 14 days. No mortality observed at 34600 mg/kg bw. Therefore, LD50 was estimated to >34600 mg/kg bw (10250- 34600) when Sprague Dawley male and female rat were treated with Hexalure orally by gavage. 

 

Thus, based on the above studies and predictions on butyl 12-acetoxyoctadec-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, butyl 12-acetoxyoctadec-9-enoate can be “Not classified” for acute oral toxicity.

Justification for classification or non-classification

Based on the above predictions and study on butyl 12-acetoxyoctadec-9-enoate and its read across substances and by applying weight of evidence, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, butyl 12-acetoxyoctadec-9-enoate can be Not classified for acute oral toxicity.