Dioctyl sebacate

Endpoint summary

Description of key information

Skin sensitization

The skin sensitization potential of 1,10-dioctyl decanedioate (2432-87-3)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 substances of 1,10-dioctyl decanedioate (2432-87-3)was predicted to be not sensitizing to the skin of male and female Hartley / Crl: (HA) Br 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:

guinea pig maximisation test

Justification for non-LLNA method:

No data available

Specific details on test material used for the study:

- Name of the test material: Dioctyl decanedioate / Dioctyl sebacate
- IUPAC name: 1,10-dioctyl decanedioate
- Molecular formula: C26H50O4
- Molecular weight: 426.677g/mol
- Smiles: C(=O)(OCCCCCCCC)CCCCCCCCC(=O)OCCCCCCCC
- Inchi : 1S/C26H50O4/c1-3-5-7-9-15-19-23-29-25(27)21-17-13-11-12-14-18-22-26(28)30-24-20-16-10-8-6-4-2/h3-24H2,1-2H3
- Substance type: Organic
- Physical state : Liquid (colorless to light yellow)

Species:

guinea pig

Strain:

other: Hartley / Crl: (HA) Br

Sex:

male/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 observed

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 8 nearest neighbours
Domain  logical expression:Result: In Domain

((((((((((((("a" or "b" or "c" or "d" or "e" or "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" and ( not "y") )  )  and "z" )  and ("aa" and "ab" )  )

Domain logical expression index: "a"

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

Domain logical expression index: "b"

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

Domain logical expression index: "c"

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

Domain logical expression index: "d"

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

Domain logical expression index: "e"

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: "f"

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: "g"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.3

Domain logical expression index: "h"

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 >> Coumarins 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 >> 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 (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 via ROS formation (indirect) 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) >> 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) >> 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 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 >> 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 >> Nitroarenes with Other Active Groups 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 >> Coumarins 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 >> Haloalkanes Containing Heteroatom 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 >> Ring opening SN2 reaction OR SN2 >> Ring opening SN2 reaction >> Sultones 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.1.3

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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 >> 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 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 >> 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 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 by DNA binding by OECD

Domain logical expression index: "k"

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

Domain logical expression index: "l"

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: "m"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OASIS v1.3

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as 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 >> Nucleophilic substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> Alkyl halides  OR SN2 >> Nucleophilic substitution at sp3 carbon atom >> alpha-Activated haloalkanes  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: "o"

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

Domain logical expression index: "p"

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: "q"

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: "r"

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

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m AND Group All log Kow > 9 AND Group C Aqueous Solubility < 0.0001 g/L AND Group C Melting Point > 55 C AND Group C Molecular Weight > 350 g/mol AND Group C Vapour Pressure < 0.0001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All Melting Point > 200 C OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CN Melting Point > 180 C OR Group CN Molecular Weight > 290 g/mol OR Group CN Vapour Pressure < 0.001 Pa by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "u"

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: "v"

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: "w"

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

Domain logical expression index: "x"

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: "y"

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

Domain logical expression index: "z"

Similarity boundary:Target: CCCCCCCCOC(=O)CCCCCCCCC(=O)OCCCCCCCC
Threshold=40%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is >= 7.12

Domain logical expression index: "ab"

Parametric boundary:The target chemical should have a value of log Kow which is <= 12.4

Interpretation of results:

other: not sensitizing

Conclusions:

The skin sensitization potential of 1,10-dioctyl decanedioate (2432-87-3) 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 substances of 1,10-dioctyl decanedioate (2432-87-3) was predicted to be not sensitizing to the skin of male and female Hartley / Crl: (HA)Br guinea pig.

Executive summary:

The skin sensitization potential of 1,10-dioctyl decanedioate (2432-87-3)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 substances of 1,10-dioctyl decanedioate (2432-87-3)was predicted to be not sensitizing to the skin of male and female Hartley / Crl: (HA) Br guinea pig.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization 

In different studies, 1,10-dioctyl decanedioate (2432-87-3)has been investigated for potential of skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pig and human for target chemical 1,10-dioctyl decanedioate (2432-87-3)and its structurally similar read across substances Diisopropyl sebacate (7491-02-3)andDiethylhexyl sebacate(122-62-3),the predicted data using the OECD QSAR toolbox has also been compared with the experimental data of read across.

The skin sensitization potential of 1,10-dioctyl decanedioate (2432-87-3)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 substances of 1,10-dioctyl decanedioate (2432-87-3)was predicted to be not sensitizing to the skin of male and female Hartley / Crl: (HA) Br guinea pig.

In another prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for 1,10-dioctyl decanedioate (2432-87-3).Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for 1,10-dioctyl decanedioate (2432-87-3) was estimated to be not sensitizing when applied to human and guinea pig skin.

 Also these results are further supported by the experimental study conducted in an Fiume MM, Heldreth B, Eldreth H, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler D, Marks JG, Shank RC, Slaga TJ, Snyder PW, Andersen FA (International Journal of Toxicology, Vol 31, Issue 4_suppl, pp. 5S - 76S, 2012) for the structurally similar read across substance, Diisopropyl sebacate (7491-02-3)in human .In skin sensitization study, 107 volunteers were tested by patch test at a concentration of 100 % of Diisopropyl sebacate. In induction phase test material applied for 24hr on 2cm x2cm area of skin on right upper arm of each participant as patch.Three induction application given during 1to 4 weeks. After each induction application test site was examined immediately after removal of patch. No clinically significant effect observed during this phase. During week 6, challenge application given to 105 participants and observed for skin reaction. As No skin sensitization reaction was noted therefore, the Diisopropyl sebacate (7491-02-3) was considered to be not sensitizing to humans.

Also further supported by the experimental study conducted in an Fiume MM, Heldreth B, Eldreth H, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler D, Marks JG, Shank RC, Slaga TJ, Snyder PW, Andersen FA (International Journal of Toxicology, Vol 31, Issue 4_suppl, pp. 5S - 76S, 2012) for the structurally similar read across substance, Diethylhexyl sebacate(122-62-3)in human . In skin sensitization study, 15-30 participants were tested by patch test at a concentration of 100 % of Diethylhexyl sebacate. In induction phase test material applied for 48hr as occlusive patch on each participant. No clinically significant effect observed during this phase. After 2 week, challenge application given as same concentration as induction phase and observed for skin reaction. As no skin sensitization reaction was noted after 48 hr. therefore, the Diethylhexyl sebacate(122-62-3)was considered to be not sensitizing to humans. 

Thus based on the above predictions on 1,10-dioctyl decanedioate (2432-87-3) as well as its read across and applying weight of evidence, it can be concluded that 1,10-dioctyl decanedioate (2432-87-3) is not a skin sensitizer. Thus comparing the above studies with the criteria of CLP regulation, 1,10-dioctyl decanedioate (2432-87-3) 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, 1,10-dioctyl decanedioate (2432-87-3) can be considered as not classified for skin sensitization.