Allyl propionate

Endpoint summary

Description of key information

The skin sensitization potential of2-Propenyl Propanoate (2408-20-0)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances2-Propenyl Propanoate (2408-20-0)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig .

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

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 v3.3 and the QMRF report has been attached.

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3, 2017

GLP compliance:

not specified

Type of study:

not specified

Justification for non-LLNA method:

No data available

Specific details on test material used for the study:

- Name of the test material: 2-Propenyl Propanoate
- IUPAC name: 2-Propenyl Propanoate
- Molecular formula: C6H10O2
- Molecular weight: 114.143 g/mol
- Substance type: Organic
- Smiles: CCC(=O)OCC=C

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

No data available

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Statistics:

No data available

Positive control results:

No data available

Reading:

1st reading

Group:

test chemical

No. with + reactions:

0

Clinical observations:

No skin sensitization reaction was noted

Remarks on result:

no indication of skin sensitisation

The prediction was based on dataset comprised from the following descriptors: "Skin Sensitisation"
Estimation method: Takes highest mode 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 "p" )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

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 SN2 AND SN2 >> SN2 Reaction at a sp3 carbon atom AND SN2 >> SN2 Reaction at a sp3 carbon atom >> Activated alkyl esters and thioesters  by Protein binding by OASIS v1.3

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as SN2 AND SN2 >> SN2 reaction at sp3 carbon atom AND SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals by Protein binding by OECD

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Esters AND Vinyl/Allyl 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 OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 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 >> Schiff base formation by aldehyde formed after metabolic activation OR AN2 >> Schiff base formation by aldehyde formed after metabolic activation >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation after aldehyde release OR AN2 >> Shiff base formation after aldehyde release >> Specific Acetate Esters OR AN2 >> Shiff base formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >> Geminal Polyhaloalkane Derivatives OR AN2 >> Shiff base formation for aldehydes >> Haloalkane Derivatives with Labile Halogen OR Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Radical OR Radical >> Generation of reactive oxygen species OR Radical >> Generation of reactive oxygen species >> Thiols OR Radical >> Radical mechanism via ROS formation (indirect) OR Radical >> Radical mechanism via ROS formation (indirect) >> Geminal Polyhaloalkane Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR Radical >> Radical mechanism via ROS formation (indirect) >> Single-Ring Substituted Primary Aromatic Amines OR SN1 OR SN1 >> Carbenium ion formation OR SN1 >> Carbenium ion formation >> Alpha-Haloethers OR SN1 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Specific Acetate Esters OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic 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 >> Nitrophenols, Nitrophenyl Ethers and Nitrobenzoic Acids OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Geminal Polyhaloalkane Derivatives 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, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines 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 >> Sulfonates and Sulfates OR SN2 >> Alkylation, ring opening SN2 reaction OR SN2 >> Alkylation, ring opening SN2 reaction >> Four- and Five-Membered Lactones OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation OR SN2 >> Nucleophilic substitution at sp3 carbon atom after thiol (glutathione) conjugation >> Geminal Polyhaloalkane Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at sp3-carbon atom OR SN2 >> SN2 at sp3-carbon atom >> Alpha-Haloethers by DNA binding by OASIS v.1.3

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 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 >> Arenes OR Michael addition >> Polarised Alkenes-Michael addition 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 >> 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 SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 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 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 Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Inclusion rules not met by Skin irritation/corrosion Inclusion rules by BfR

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Not classified by Oncologic Primary Classification

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acrylate Reactive Functional Groups OR Alpha, beta-Haloether Reactive Functional Groups by Oncologic Primary Classification

Domain logical expression index: "o"

Similarity boundary:Target: CCC(=O)OCC=C
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "p"

Similarity boundary:Target: CCC(=O)OCC=C
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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<] AND Olefinic carbon [=CH2] by Organic functional groups (US EPA)

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as 2-Cyano carbonyl compound [C(C#N)CO] OR Acetylenic Carbon [#C] OR Alpha-cyano-alpha,beta-unsat. carboxylates OR Cyano, aliphatic attach [-C#N] OR Hydroxy, aliphatic attach [-OH] OR Oxygen, aliphatic attach [-O-] OR Suflur {v+4} or {v+6} OR Sulphonate, aliphatic attach [-SO2-O] OR Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.897

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.67

Interpretation of results:

other: not sensitizing

Conclusions:

The skin sensitization potential of 2-Propenyl Propanoate (2408-20-0) was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances 2-Propenyl Propanoate (2408-20-0) was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig .

Executive summary:

The skin sensitization potential of2-Propenyl Propanoate (2408-20-0)was estimated by SSS (2017) using OECD QSAR toolbox v3.4 with log kow as the primary descriptor and considering the six closest read across substances2-Propenyl Propanoate (2408-20-0)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies, 2-Propenyl Propanoate (2408-20-0) has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in mouse for target chemical, 2-Propenyl Propanoate (2408-20-0) and its structurally similar read across substancesallyl methacrylate(96-05-9) , Ethyl butyrate (105-54-4)andIsoamyl Butyrate (106-27-4), the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 2-Propenyl Propanoate (2408-20-0)was estimated by SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances2-Propenyl Propanoate (2408-20-0)was predicted to be not sensitizing to the skin of female Dunkin-Hartley guinea pig .

Prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for2-Propenyl Propanoate. Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 2-Propenyl Propanoate (2408-20-0) estimated to be not sensitizing when applied to human and guinea pig skin.

Also it is further Supported by experimental study conducted by OECD HPV Chemical Programme (OECD HPV Chemical Programme, SIDS Dossier approved at SIAM 29, 20-23 October 2009) to evaluate the skin sensitizing potential of read across substance allyl methacrylate(96-05-9) in guinea pig. The skin sensitizing study of allyl methacrylate was carried out in Hartley albino guinea pig by patch test method.10 animals in treated group and 10 animals in positive control group were observed. Dinitrochlorobenzene (DNCB) used as positive control. The repeated insult patch tests carried out either with test material or with dinitrochlorobenzene (DNCB) 4 times in 10 days. No skin reactions were observed in treated group while all the animals in positive control group were sensitized. Therefore, based on the results obtained, the allyl methacrylate(96-05-9)was considered to be non-sensitizing to skin of guinea pig.  

Also it is further Supported by experimental study conducted by D.L.J. Opdyke(Food and Cosmetics Toxicology. Vol. 12, Pg. 719, 1974) to evaluate the skin sensitizing potential of read across substance Ethyl butyrate (105-54-4) in human. In skin sensitization study, 25 volunteers were tested by maximization test at a concentration of 5 % in petrolatum. No reaction was observed therefore, the Ethyl butyrate (105-54-4) was considered to be not sensitizing to humans.

Also it is further Supported by experimental study conducted by D.L.J. Opdyke(Food and Cosmetics Toxicology. Vol. 17, Pg. 823, 1979)to evaluate the skin sensitizing potential of read across substance Isoamyl Butyrate (106-27-4) in human. In skin sensitization study, 25 volunteers were tested by maximization test at a concentration of 3% in petrolatum. No reaction was observed therefore, the Isoamyl Butyrate (106-27-4) was considered to be not sensitizing to humans.

Thus based on the above predictions on2-Propenyl Propanoate (2408-20-0)  as well as its read across and applying weight of evidence, it can be concluded that 2-Propenyl Propanoate (2408-20-0) is not a skin sensitizer. Thus comparing the above studies with the criteria of CLP regulation, 2-Propenyl Propanoate (2408-20-0) can be considered as not classified for skin sensitization.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Thus comparing the above studies with the criteria of CLP regulation, 2-Propenyl Propanoate (2408-20-0) can be considered as not classified for skin sensitization.