Methyl non-2-enoate

Endpoint summary

Description of key information

Skin irritation:

The dermal irritation potential of Methyl non-2-enoate (CAS No: 111-79-5) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Methyl non-2-enoate (CAS No: 111-79-5) was estimated to be not irritating to the skin of New Zealand White rabbits. Based on the estimated result Methyl non-2-enoate (CAS No: 111-79-5) can be considered to be not irritating to skin and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Eye irritation:

The ocular irritation potential of Methyl non-2-enoate (CAS No: 111-79-5) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Methyl non-2-enoate (CAS No: 111-79-5) was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result Methyl non-2-enoate (CAS No: 111-79-5) can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

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 is from peer reviewed document

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Skin irritation study of Methyl nonylenate (CAS No: 111-79-5) was performed on human subjects to examine the adverse skin effects caused by the chemical under occlusive condition.

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: Pyrazine-2-carboxylic acid
- Molecular formula: C5H4N2O2
- Molecular weight: 124.099 g/mol
- Substance type: organic
- Physical state: solid
- Smiles: c1ncc(C(=O)O)nc1
- InChI: 1S/C5H4N2O2/c8-5(9)4-3-6-1-2-7-4/h1-3H,(H,8,9)

Species:

human

Strain:

other: not applicable

Details on test animals or test system and environmental conditions:

No Data Available

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: petrolatum

Controls:

not specified

Amount / concentration applied:

20% in petrolatum

Duration of treatment / exposure:

48hr

Observation period:

48hr

Number of animals:

25 volunteers

Details on study design:

No Data Available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

48 h

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No known signs of skin irritation were observed.

Interpretation of results:

other: not irritating

Conclusions:

The test material Methyl nonylenate (CAS No: 111-79-5) was considered to be not irritating to the human skin.

Executive summary:

Skin irritation study of Methyl nonylenate (CAS No: 111-79-5) was performed on human subjects to examine the adverse skin effects caused by the chemical under occlusive condition.

 

About 20% of Methyl nonylenate in petrolatum was applied to the skin of each subject for 48 hours and later observed for skin reactions.

 

No known signs of skin irritation were observed. Hence the chemicalMethyl nonylenate (CAS No: 111-79-5)was considered to be not irritating to the human 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 version 3.3 and QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Specific details on test material used for the study:

- Name of test material: methyl (2E)-non-2-enoate
- Molecular formula: C10H18O2
- Molecular weight: 170.25 g/mol
- Smiles notation: C(\C=C\C(OC)=O)CCCCC
- InChl: 1S/C10H18O2/c1-3-4-5-6-7-8-9-10(11)12-2/h8-9H,3-7H2,1-2H3/b9-8+
- Substance type: Organic
- Physical state: Liquid

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No data available

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

No data available

Duration of treatment / exposure:

7 days

Observation period (in vivo):

7 days

Duration of post- treatment incubation (in vitro):

No data available

Number of animals or in vitro replicates:

No data available

Details on study design:

No data available

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

7 d

Reversibility:

not specified

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No irritation was observed in treated animals.

Estimation method: Takes mode value from the 8 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 "m" )  and "n" )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and ("s" and "t" )  )

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 Michael addition AND Michael addition >> Polarised Alkenes-Michael addition AND Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters by DNA binding by OECD

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as High reactive AND High reactive >> alpha,beta-carbonyl compounds with polarized multiple bonds by DPRA Cysteine peptide depletion

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Michael Addition AND Michael Addition >> Michael addition on conjugated systems with electron withdrawing group AND Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  by Protein binding by OASIS v1.3

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Polarised Alkenes AND Michael addition >> Polarised Alkenes >> Polarised alkene - esters by Protein binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Michael addition AND Michael addition >> Polarised Alkenes-Michael addition AND Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters by DNA binding by OECD

Domain logical expression index: "g"

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 >> 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 >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated aldehydes OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR No alert found 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 >> 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 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 >> Coumarins 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: "h"

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

Domain logical expression index: "i"

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: "j"

Referential boundary: The target chemical should be classified as Michael Addition AND Michael Addition >> Michael addition on conjugated systems with electron withdrawing group AND Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  by Protein binding by OASIS v1.3

Domain logical expression index: "k"

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 Acylation >> Direct acylation involving a leaving group >> Carbamates  OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> Cyanoalkenes OR No alert found OR Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones 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 v1.3

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Class 3 (unspecific reactivity) by Acute aquatic toxicity classification by Verhaar (Modified) ONLY

Domain logical expression index: "n"

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

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Carbonic acid derivative 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 Enolether OR Ether OR Hydroxy compound OR Primary alcohol OR Secondary alcohol by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

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

Domain logical expression index: "r"

Similarity boundary:Target: CCCCCCC=CC(=O)OC
Threshold=20%,
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 >= 2.75

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.64

Interpretation of results:

other: not irritating

Conclusions:

The substance Methyl non-2-enoate (CAS No: 111-79-5)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result Methyl non-2-enoate (CAS No: 111-79-5)can be considered to be not irritating to eye.

Executive summary:

The ocular irritation potential of Methyl non-2-enoate (CAS No: 111-79-5)was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance Methyl non-2-enoate (CAS No: 111-79-5)was estimated to be not irritating into the eyes of New Zealand White rabbits. Based on the estimated result Methyl non-2-enoate (CAS No: 111-79-5)can be considered to be not irritating to eye and can be classified under the category ˋ Not Classified’ as per CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

Various studieshas been investigated for the test chemicalMethyl non-2-enoate (CAS No: 111-79-5)to observe the potential for dermal irritation to a greater or lesser extent. The studies are based on in vivo experiments in rabbits and humans for target chemicalMethyl non-2-enoate (CAS No: 111-79-5) and its structurally similar read across substances2-Nonynoic acid methyl ester (CAS No: 111-80-8) and Ethyl caprylate (CAS No: 106-32-1).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

The D. L. J. Opdyke (1979) carried out skin irritation study of Methyl nonylenate (CAS No: 111-79-5) on human subjects and rabbits to examine the adverse skin effects caused by the chemical under occlusive condition as follows;.

In human test,about 20% ofMethyl nonylenate in petrolatum was applied to the skin of each subject for 48 hours and later observed for skin reactions.No known signs of skin irritation were observed. Hence the chemicalMethyl nonylenate (CAS No: 111-79-5)was considered to be not irritating to the human skin.

The skin irritation study of rabbits was conducted on intact and abraded skin under occlusive condition.Each rabbit received 100% of chemical for 24 hours exposure period and later observed for skin reactions.

No known signs of skin irritation were observed on humans while moderate skin irritation was observed in rabbits study. Hence Methyl nonylenate (CAS No: 111-79-5)was considered to be not irritating to the human skinwhile it was consideredto bemoderately irritating to theintact and abraded skin of rabbits.

 

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the skin irritation potential was estimated for test chemicalMethyl nonylenate (CAS No: 111-79-5)  .The chemical Methyl nonylenate (CAS No: 111-79-5) is estimated to be not irritating to skin of New Zealand White rabbits.

 

 

Another skin irritation studies were conducted by D. L. J. Opdyke on twostructurally similar read across substances2-Nonynoic acid methyl ester (CAS No: 111-80-8) and Ethyl caprylate (CAS No: 106-32-1) in the year 1975 and 1976 respectively which seems to support the negative result obtained for the target chemical Methyl nonylenate (CAS No: 111-79-5) as follows;

In case of Methyl octine carbonate (CAS No: 111-80-8) the intact and abraded skin of rabbits received 100% of chemical for 24 hours exposure period under occlusive condition and later observed for skin reactions.No known signs of skin irritation were observed.

Skin irritation study of Ethyl caprylate (CAS No: 106-32-1) was conducted on two different panels of human subjects to observe its irritation efficacy under occlusive condition.In this study, 2% ofEthyl caprylate in petrolatum was applied on skin of each subject under 48 hours closed patch condition and observed for skin lesions.None of the subject showed any skin reactions.

Since the chemicals did not induce any cutaneous reactions, the chemicalMethyl octine carbonate (CAS No: 111-80-8) and Ethyl caprylate (CAS No: 106-32-1)was considered to be not irritating.

 

 

Thus on the basis of available data for thetarget chemicalMethyl non-2-enoate (CAS No: 111-79-5) and its structurally similar read across substances2-Nonynoic acid methyl ester (CAS No: 111-80-8) and Ethyl caprylate (CAS No: 106-32-1),it can be concluded thatchemical Methyl non-2-enoate (CAS No: 111-79-5) is unable to cause skin irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

 

 

Eye irritation:

In different studies,the test chemicalMethyl non-2-enoate (CAS No: 111-79-5) has been investigated for potential for ocular irritationto a greater or lesser extent. The studies are based on in vivo experiments in rabbits and humans for target chemicalMethyl nonylenate (CAS No: 111-79-5) andits structurally similar read across substances2-Ethylhexyl acrylate (CAS No: 103-11-7) and dibutyl maleate (CAS No: 105-76-0).The predicted data using the OECD QSAR toolbox has also been compared with the experimental data and summarized as below;

 

 

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the ocular irritation potential was estimated for test chemicalMethyl nonylenate (CAS No: 111-79-5)  .The chemical Methyl nonylenate (CAS No: 111-79-5) is estimated to be not irritating to eyes of New Zealand White rabbits.

 

 

The MAK Collection for Occupational Health and Safety (2012) conducted an eye irritation test ofstructurally similar read across substance2-Ethylhexyl acrylate (CAS No: 103-11-7) in rabbits according to OECD Test Guideline 405. About 0.1ml of undiluted 2-Ethylhexyl acrylate was installed into the one of each animal and the observations were made at 24, 48 h and 3 days after treatment. Only slight changes were observed. The average values after 24, 48 and 72 hours for the cornea were 0/0 / 0.3; For the iris 0/0 / 0.3; For mucous redness 0.3 / 0 / 0.3 as well as for mucous membrane curl 0/0 / 0.3. All results were completely reversible after 3 days. Since all the observed effects were cleared within 3 days, the chemical 2-Ethylhexyl acrylate (CAS No: 103-11-7) was considered to be non-irritant to the eyes of rabbits.

 

 

The above results were further supported by the experimental study carried out by OECD SIDS (1996) and IUCLID Dataset (2000) onstructurally similar read across substancedibutyl maleate (CAS No: 105-76-0) in rabbits to examine the eye irritation effects caused by the chemical. In this test, Dibutylmaleinate was applicated to the mucous membrane of the eyes of rabbits. 1 - 2 minutes after application the animals were rubbing the eyes. The eyelids were closed for 10 - 15 minutes. After 1 hour all animals had a slight hyperemia of the conjunctiva. The hyperemia disappeared after 24 hours. Therefore the chemical dibutyl maleate (CAS No: 105-76-0) was considered to be not irritating to the eye of rabbits.

 

 

Thus on the basis of available data for thetarget chemicalMethyl nonylenate (CAS No: 111-79-5) andits structurally similar read across substances2-Ethylhexyl acrylate (CAS No: 103-11-7) and dibutyl maleate (CAS No: 105-76-0),it can be concluded thatchemical Methyl nonylenate (CAS No: 111-79-5) is unable to cause eye irritation and considered as not irritating.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Justification for classification or non-classification

The skin and eye irritation potential of test chemicalMethyl nonylenate (CAS No: 111-79-5) and its structurally similar read across substanceswere observed in various studies. The results obtained from these studies indicate that the chemicalMethyl nonylenateis unlikely to cause skin and eye irritation. HenceMethyl nonylenate (CAS No: 111-79-5)can be classified under the category “Not Classified” for skin and eye as per CLP.