Isononyl acetate

Endpoint summary

Description of key information

Acute oral toxicity: 

LD50 was estimated to be 6749.5 mg/kg bw when Wistar rats were orally exposed with 7-methyloctyl acetate.

Acute Inhalation toxicity: 

LC50 was estimated to be 61.4 mg/L air (61400 mg/m³), when rat was exposed to 7-methyloctyl acetate for 4 hr.

Acute Dermal toxicity: 

LD50 was estimated to be 6847 mg/kg bw when rabbits were treated with 7-methyloctyl acetate by dermal application.

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: estimated

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 test material : 7-methyloctyl acetate
- Common name : Isononyl acetate
- Molecular formula : C11H22O2
- Molecular weight : 186.293 g/mol
- Smiles notation : C(C)(=O)OCCCCCCC(C)C
- InChl : 1S/C11H22O2/c1-10(2)8-6-4-5-7-9-13-11(3)12/h10H,4-9H2,1-3H3
- Substance type: Organic
- Physical state: Liquid

Species:

rat

Strain:

Wistar

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

oral: gavage

Vehicle:

not specified

Details on oral exposure:

not specified

Doses:

6749.5 mg/kg bw

No. of animals per sex per dose:

5

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:

6 749.5 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: 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" )  and ("e" and ( not "f") )  )  and ("g" and ( not "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 "x" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Shiff base formation after aldehyde release AND AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters AND SN1 AND SN1 >> Nucleophilic attack after carbenium ion formation AND SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters AND SN2 AND SN2 >> Acylation AND SN2 >> Acylation >> Specific Acetate Esters AND SN2 >> Nucleophilic substitution at sp3 Carbon atom AND SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Shiff base formation after aldehyde release AND AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters AND SN1 AND SN1 >> Nucleophilic attack after carbenium ion formation AND SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters AND SN2 AND SN2 >> Acylation AND SN2 >> Acylation >> Specific Acetate Esters AND SN2 >> Nucleophilic substitution at sp3 Carbon atom AND SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines 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 to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> Alpha, Beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Dicarbonyl compounds 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 for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR No alert found OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Amino Anthraquinones OR Non-covalent interaction >> DNA intercalation >> Coumarins OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Non-covalent interaction >> DNA intercalation >> Organic Azides 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 by ROS formation OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> Radical mechanism by ROS formation >> Organic Azides OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Amino Anthraquinones OR Radical >> Radical mechanism via ROS formation (indirect) >> Coumarins OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitro Azoarenes OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitroarenes with Other Active Groups OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids 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 Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines OR SN1 >> Alkylation by carbenium ion formed OR SN1 >> Alkylation by carbenium ion formed >> Diazoalkanes OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation OR SN1 >> Nucleophilic attack after diazonium or carbenium ion formation >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Amino Anthraquinones OR SN1 >> Nucleophilic attack after nitrene formation OR SN1 >> Nucleophilic attack after nitrene formation >> Organic Azides 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 >> Nitroarenes with Other Active Groups OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> p-Substituted Mononitrobenzenes OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes 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 by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Monohaloalkanes 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, 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, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes 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 >> Alkylation, ring opening SN2 reaction >> Sultones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Coumarins OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline 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 >> Haloalkanes Containing Heteroatom 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-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 OR SN2 >> SN2 attack on activated carbon Csp3 or Csp2 >> Nitroarenes with Other Active Groups by DNA binding by OASIS v.1.4

Domain logical expression index: "g"

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

Domain logical expression index: "h"

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 >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR 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 by DNA binding by OECD

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> Anhydrides (sulphur analogues of anhydrides)  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  by Protein binding by OASIS v1.4

Domain logical expression index: "m"

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

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates by Protein binding by OECD

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Esters including acrylic and methacrylic esters by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Ethylenglycolethers by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "q"

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: "r"

Referential boundary: The target chemical should be classified as Di-substituted hydrocarbons (24a) OR Known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as -CH-   [linear] AND -CH2-  [linear] AND Ester   [-C(=O)-O-C] AND Methyl  [-CH3] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Aliphatic ether  [C-O-C] by Biodegradation fragments (BioWIN MITI)

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as No Data by Ultimate biodeg

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as 1 to 10 days by Ultimate biodeg

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.61

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.56

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was estimated to be 6749.5 mg/kg bw when 5 Wistar rats were orally exposed with 7-methyloctyl acetate.

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 7-methyloctyl acetate. The LD50 was estimated to be 6749.5 mg/kg bw when 5 Wistar rats were orally exposed with 7-methyloctyl acetate.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 749.5 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.4 (2017)

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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: estimated

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 test material : 7-methyloctyl acetate
- Common name : Isononyl acetate
- Molecular formula : C11H22O2
- Molecular weight : 186.293 g/mol
- Smiles notation : C(C)(=O)OCCCCCCC(C)C
- InChl : 1S/C11H22O2/c1-10(2)8-6-4-5-7-9-13-11(3)12/h10H,4-9H2,1-3H3
- Substance type: Organic
- Physical state: Liquid

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

not specified

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

not specified

Remark on MMAD/GSD:

not specified

Details on inhalation exposure:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

not specified

Concentrations:

61.4 mg/L in air

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

male/female

Dose descriptor:

LC50

Effect level:

61.4 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: 50% mortality was observed

Mortality:

not specified

Clinical signs:

other: 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: LC50
Estimation method: Takes average 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 ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and "l" )  and "m" )  and "n" )  and ("o" and "p" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as AN2 AND AN2 >> Shiff base formation after aldehyde release AND AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters AND SN1 AND SN1 >> Nucleophilic attack after carbenium ion formation AND SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters AND SN2 AND SN2 >> Acylation AND SN2 >> Acylation >> Specific Acetate Esters AND SN2 >> Nucleophilic substitution at sp3 Carbon atom AND SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters by DNA binding by OASIS v.1.4

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Esters by Acute aquatic toxicity MOA by OASIS

Domain logical expression index: "d"

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

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 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 >> 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 SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR 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: "g"

Referential boundary: The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

Domain logical expression index: "h"

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

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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: "k"

Referential boundary: The target chemical should be classified as Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "l"

Similarity boundary:Target: CC(C)CCCCCCOC(C)=O
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "m"

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

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.76

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.87

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LC50 was estimated to be 61.4 mg/L air, when rat was exposed to 7-methyloctyl acetate for 4 hr.

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 7-methyloctyl acetate. The LC50 was estimated to be 61.4 mg/L air, when rat was exposed to 7-methyloctyl acetate for 4 hr.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

61 400 mg/m³ air

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.4 (2017)

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data from Fragrance raw materials monographs.

Qualifier:

according to guideline

Guideline:

other: as metioned below

Principles of method if other than guideline:

Acute dermal toxicity of 7-methyloctyl acetate (40379-24-6) in rabbits.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Specific details on test material used for the study:

- Name of test material : 7-methyloctyl acetate
- Common name : Isononyl acetate
- Molecular formula : C11H22O2
- Molecular weight : 186.293 g/mol
- Smiles notation : C(C)(=O)OCCCCCCC(C)C
- InChl : 1S/C11H22O2/c1-10(2)8-6-4-5-7-9-13-11(3)12/h10H,4-9H2,1-3H3
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

not specified

Type of coverage:

other: Dermal

Vehicle:

not specified

Details on dermal exposure:

not specified

Duration of exposure:

not specified

Doses:

5000 mg/kg

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:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No morality was observed

Mortality:

No morality was observed at 5000 mg/kg bw

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with 7-methyloctyl acetate by dermal application.

Executive summary:

The acute dermal toxicity study was conducted by using 7-methyloctyl acetate in rabbits at the concentration of 5000 mg/kg. No morality was observed in rabbits at 5000 mg/kg. Hence, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with 7-methyloctyl acetate by dermal application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 847 mg/kg bw

Quality of whole database:

Data is Klimicsh 2 and from QSAR Toolbox 3.4 (2017)

Additional information

Acute oral toxicity:

In different studies, 7-methyloctyl acetate (CAS no 40379-24-6) has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats and rabbits for 7-methyloctyl acetate along with the study available on structurally similar read across substance 3-Methylbutyl propionate (CAS no 105-68-0) and Octyl Acetate (CAS no 112-14-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below -

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 7-methyloctyl acetate. The LD50 was estimated to be 6749.5 mg/kg bw when 5 Wistar rats were orally exposed with 7-methyloctyl acetate.

In experimental study done on 7-methyloctyl acetate by D. L. J. Opdyke (Food and Cosmetics Toxicology, Page 716, 1979), the acute oral toxicity study was conducted by using 7-methyloctyl acetate in rat at the concentration of 4250 mg/kg. 50% morality was observed in rats at 4250 mg/kg. Hence, LD50 was considered to be 4250 mg/kg at confidential limit of 3540 - 4960 mg/kg bw, when rat was treated with 7-methyloctyl acetate orally.

In another experimental study supported by Flavor and Extract Manufacturer's Association (National Technical Information Service, VoL 1, PB86155926, 1985), for the structurally similar read across substance 3-Methylbutyl propionate (CAS no 105-68-0), the acute oral toxicity study was conducted in rabbits. 10-35 Male and Female were taken of weight 1.5 - 2.5 kg. The given test material 3-Methylbutyl propionate was dissolved in Saline at a concentration of 6924 mg/kg bw. The animals were observed for24 hrs. 50% morality was observed in treated rabbits. Therefore, LD50 was considered to be 6924 mg/kg bw, when rabbits were treated with 3-Methylbutyl propionate orally.

This is further supported by experimental study by D. L. J. Opdyke (Food and Cosmetics Toxicology, Pages 448–449, 1979), for the structurally similar read across substance 3-Methylbutyl propionate (CAS no 105-68-0), the acute oral toxicity study was conducted in rats. No morality was observed in rats. Therefore, LD50 was considered to be >5000 mg/kg bw, when rats were treated with 3-Methylbutyl propionate orally.

In another study summarized by Daughtrey et al. (Fundamental and Applied Toxicology, 12,313-320,1989), for the structurally similar read across substance Octyl Acetate (CAS no 112-14-1), rats were treated with in the concentration of 5000 mg/kg bw orally. 50% mortality was observed in treated rats at 5000 mg/kg bw. Therefore, LD50 was considered to be approximately 5000 mg/kg bw when rat were treated with Octyl Acetate orally. 

Also these results are further supported by D. L. J. Opdyke (Food and Cosmetics Toxicology. 12, 815, 1974),for the structurally similar read across substance Octyl Acetate (CAS no 112-14-1), the acute oral toxicity study was conducted in rats. Rats were treated with Octyl Acetate in the concentration of 3000 mg/kg orally. 50 % morality was observed in traded rats at 3000 mg/kg. Therefore, LD50 was considered to be 3000 mg/kg when rat were treated with Acetate C-8 orally.

Thus, based on the above studies on 7-methyloctyl acetate (CAS no 40379-24-6) 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, 7-methyloctyl acetate can be classified as category V of acute oral toxicity.

Acute Inhalation toxicity: 

In different studies, 7-methyloctyl acetate (CAS no 40379-24-6) has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rats for 7-methyloctyl acetate along with the study available on structurally similar read across substance Isobutyl acetate (CAS no: 110-19-0) and N-butyl acetate (CAS no: 123-86-4). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute inhalation toxicity was estimated for 7-methyloctyl acetate. The LC50 was estimated to be 61.4 mg/L air, when rat was exposed to 7-methyloctyl acetate for 4 hr.

In another experimental study supported by United Nations Environmental Programme (SIDS Dossier), for the structurally similar read across substanceIsobutyl acetate (CAS no: 110-19-0), the acute inhalation toxicity study was conducted at the concentration of 0, 2000, 5000, or 8000 ppm for 6 hours in 4 groups of 3 male and 3 female of Sprague-Dawley rats. The inhalation exposures were conducted in 420 L stainless steel inhalation chambers and maintained at negative pressure relative to room air. The oxygen content, airflow, temperature, humidity, and concentration were recorded every 30 minutes. The test substance was metered onto a heated glass distillation column packed with glass beads and filtered, metered conditioned air was passed through the column to generate the vapor atmosphere. Air changes were 12 -14/hour. The presence of aerosols was checked for and determined not to be present. Chamber concentrations were analysed by an infrared gas analyzer. The chamber atmosphere was checked for homogeneity and found to deviate less than 10% from the reference position and therefore was considered homogenous. Nominal concentrations were also determined. The purity of the test substance was checked with gas chromatography with flame ionization detection and was found to be greater than 99.9%. The structure of the test substance was checked by mass spectrometry. Clinical exams were conducted prior to exposure, immediately after exposure and daily thereafter for 5 days. Body weights were collected prior to exposure and daily thereafter. During Exposure Period - All groups (including the Control Group) lost weight from Day 0 to Day 1, but regained weight from Day 1 to Day 4. However, the groups exposed to the test article lost more weight (from Day 0 to Day 1) than the Control group.

During Exposure Period - At 0 ppm (Control) - No unusual clinical signs were noted during exposure in the control animals. At 2000 ppm - Minimal hypoactivity was observed during exposure from 3-6 hours and he animals responded to tapping on the side of the chamber (startle reflex stimuli). At 5000 ppm - Minimal sialorrhea and minor hypoactivity were observed within 30 minutes of exposure initiation. The severity of sialorrhea increased to moderate to severe by 1 hour and the degree of hypoactivity increased to moderate in all animals by 2 hours abd the animals had a decreased startle response to tapping stimuli beginning at 2 hours and continuing through the end of the exposure. At 8000 ppm – Moderate hypoactivity was noted at 30 minutes and this effect increased to severe hypoactivity accompanied by prostration by 2 hours in the female and 3 hours in the male animals. Minor to moderate sialorrhea and reduced response to startle stimuli were noted during the exposure in the animals.

During the post exposure period - No test substance related clinical signs were noted in either the control or 2000-ppm groups. Decreased arousal and unkempt hair coat were noted in the 5000-ppm exposure group animals until Day 4 post exposure when they were all normal. Severely decreased arousal, hypothermia, and no responsiveness to touch stimuli were noted immediately post exposure in two of three rats in both the male and female 8000-ppm groups. The remaining male rat from the 8000-ppm group had moderately decreased arousal. Abnormal gait, incomplete extension at the tarsus, decreased arousal/alertness, and unkempt hair coat were noted in the male rats during the post exposure Days 1-4. The female rats were normal during post exposure Days 1-4. At 8000 ppm – Some of the female animal was found dead at the post exposure observation time point. Therefore, LC50 was considered to be >8000 ppm (>8000000 mg/m3), when rat was exposed to N-butyl acetate for 6 hr.

Also these results are further supported by Bisesi MS, Clayton GD and Clayton FE (Patty’s industrial hygiene and toxicology, 4th ed. Vol. IID. New York, NY, J. Wiley & Sons, pp. 2967–3118, 1994), for the structurally similar read across substance N-butyl acetate (CAS no: 123-86-4),the acute inhalation toxicity study was conducted at the concentration of 14000 mg/m3 in rats. No toxicity symptoms were observed at 14000 mg/m3 when exposed for 6 hours. Therefore, LC50 was considered to be 14000 mg/m3, when rat was exposed to Isobutyl acetate for 6 hr.

Thus, based on the above studies on 7-methyloctyl acetate (CAS no 40379-24-6) and its read across substances, it can be concluded that LC50 value is greater than 20,000 ppm. Thus, comparing this value with the criteria of CLP regulation, 7-methyloctyl acetate can be classified as category V of acute inhalation toxicity.

Acute Dermal toxicity:

In different studies, 7-methyloctyl acetate (CAS no 40379-24-6) has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments in rodents, i.e. most commonly in rabbits for 7-methyloctyl acetate along with the study available on structurally similar read across substance 3-Methylbutyl propionate (CAS no 105-68-0) and Octyl Acetate (CAS no 112-14-1). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies. The studies are summarized as below –

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute dermal toxicity was estimated for 7-methyloctyl acetate. The LD50 was estimated to be 6847 mg/kg bw when 10 rabbits were treated with 7-methyloctyl acetate by dermal application.

In experimental study done on 7-methyloctyl acetate by D. L. J. Opdyke (Food and Cosmetics Toxicology, Page 716, 1979), the acute dermal toxicity study was conducted in rabbits at the concentration of 5000 mg/kg. No morality was observed in rabbits at 5000 mg/kg. Hence, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with 7-methyloctyl acetate by dermal application.

In another experimental study supported by D. L. J. Opdyke (Food and Cosmetics Toxicology, Volume 13, Issue 6, Pages 809-810, 1975), for the structurally similar read across substance 3-Methylbutyl propionate (CAS no: 105-68-0),the acute dermal toxicity study was conducted in rabbits. No morality was observed in rabbits. Therefore, LD50 was considered to be >5000 mg/kg bw, when rabbits were treated with 3-Methylbutyl propionateby dermal application.

This is further supported by experimental study by D. L. J. Opdyke (Food and Cosmetics Toxicology Volume 12, Issues 7–8, December 1974, Pages 815-816),for the structurally similar read across substance Octyl Acetate (CAS no 112-14-1). The acute dermal toxicity study was conducted in rabbits with the concentration of 5000 mg/kg dermally. No morality was observed in traded rabbits at 5000 mg/kg. Therefore, LD50 was considered to be > 5000 mg/kg when rabbits were treated with Acetate C-8 dermally.

Also these results are further supported by Daughtrey et al. (Fundamental and Applied Toxicology, 12,313-320(1989),for the structurally similar read across substance Octyl Acetate (CAS no 112-14-1). The acute dermal toxicity was conducted in rabbits at the concentration of 3000 mg/kg bw dermally. No mortality observed in treated rabbits at 3000 mg/kg bw. Therefore, LD50 was considered to be > 3000 mg/kg bw when rabbits were treated with Octyl Acetate dermally.

Thus, based on the above studies on 7-methyloctyl acetate (CAS no 40379-24-6) 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, 7-methyloctyl acetate can be classified as category V of acute dermal toxicity.

Justification for classification or non-classification

Thus, comparing these values with the criteria of CLP regulation, 7-methyloctyl acetate (CAS no 40379-24-6) can be “Not classified” for acute oral, Inhalation and dermal toxicity.