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Description of key information

The skin sensitization potential of1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)was estimatedby SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)was predicted to be non 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: in vivo (non-LLNA)
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 predicted using OECD QSAR toolbox version 3.3 and the supporting QMRF report has been attached.
Reference:
Composition 1
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Principles of method if other than guideline:
Prediction is done using QSAR Toolbox version 3.3
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Not specified.
Test material information:
Composition 1
Specific details on test material used for the study:
- Name of test material: 1,1-diethoxy-3,7-dimethylocta-2,6-diene
- Molecular formula: C14H26O2
- Molecular weight: 226.35 g/mol
- Smiles notation: O(C(OCC)C=C(CCC=C(C)C)C)CC
- Substance type: Liquid
- Physical state: Organic
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
No data available.
Route:
intradermal and epicutaneous
Vehicle:
paraffin oil
Concentration / amount:
50% for
Route:
epicutaneous, occlusive
Vehicle:
paraffin oil
Concentration / amount:
100%
Day(s)/duration:
48 hour
No. of animals per dose:
Test group: 20 animals
Control group: 10 animals
Details on study design:
No data available.
Challenge controls:
No data available.
Positive control substance(s):
not specified
Statistics:
No data available.
Reading:
other: challenge
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No Skin sensitization effect were 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 10 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 ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and ("m" and ( not "n") )  )  and ("o" and ( not "p") )  )  and "q" )  and "r" )  and "s" )  and ("t" and ( not "u") )  )  and ("v" and "w" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Neutral Organics by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acetal OR Alkene OR Alkoxy OR Allyl OR Ether by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Acetal OR Alkoxy OR Allyl OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Alpha-diether [C-O-C-O-C] OR Olefinic carbon [=CH- or =C<] OR Oxygen, aliphatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Dialkylether AND Ether by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinones 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide Side Chain OR Non-covalent interaction >> DNA intercalation >> Quinones 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 >> Acridone, Thioxanthone, Xanthone and Phenazine Derivatives 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) >> 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) >> Quinones 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 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 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 after metabolic activation OR SN2 >> Acylation involving a leaving group after metabolic activation >> Geminal Polyhaloalkane Derivatives 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, nucleophilic substitution at sp3-carbon atom 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 >> DNA alkylation OR SN2 >> DNA alkylation >> Alkylphosphates, Alkylthiophosphates and Alkylphosphonates OR SN2 >> Nucleophilic substitution after carbenium ion formation OR SN2 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes 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 >> 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: "h"

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

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 (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND (!Undefined)Group C Surface Tension > 62 mN/m by Skin irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Exclusion rules not met OR Group All log Kow < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 350 g/mol OR Group C Vapour Pressure < 0.0001 Pa OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 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: "m"

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: "n"

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

Domain logical expression index: "o"

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

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Alkali Earth OR Metalloids OR Transition Metals by Groups of elements

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as Acetal AND Alkoxy AND Allyl AND Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "r"

Similarity boundary:Target: CCOC(C=C(C)CCC=C(C)C)OCC
Threshold=10%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "s"

Similarity boundary:Target: CCOC(C=C(C)CCC=C(C)C)OCC
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "t"

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

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as > 100 days OR 10 to 100 days by Ultimate biodeg

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is >= 4.06

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is <= 6.1

Interpretation of results:
other: Non sensitizing
Conclusions:
The skin sensitization potential of 1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2) 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. 1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2) was predicted to be non sensitizing to the skin of female Dunkin-Hartley guinea pig.
Executive summary:

The skin sensitization potential of1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)was estimatedby SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)was predicted to be non 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,1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)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 chemical1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2).The predicted data using the OECD QSAR toolbox and Danish QSAR has also been compared with the experimental data of target chemical.

The skin sensitization potential of1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)was estimatedby SSS (2017) using OECD QSAR toolbox v3.3 with log kow as the primary descriptor and considering the six closest read across substances.1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)was predicted to be non sensitizing to the skin of female Dunkin-Hartley guinea pig.

Another prediction done using the Danish (Q) SAR Database, the skin sensitization was estimated to be negative on guinea pig and human for1,1-diethoxy-3,7-dimethylocta-2,6-diene.Using Battery algorithm model of Danish QSAR, Allergic Contact Dermatitis for1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2) estimated to be not sensitizing when applied to human and guinea pig skin.

 It is further supported by experimental study conducted by Moreno (Food and Chemical Toxicology, ,1983) to evaluate the skin sensitizing potential of target substance1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2) in Human. Skin sensitization for1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)was assessed for its possible contact allergenic potential. For this purpose was Human maximization test was performed on 25 human. The test material was used at the concentration of 4% in petrolatum. No skin sensitization effect was observed in any human .Therefore1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2) was considered to be non sensitizing in human.

 

Thus based on the above predictions on1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2) andapplying weight of evidence, it can be concluded that 1,1-diethoxy- 3,7- dimethylocta-2,6-dieneis not a skin sensitizer. Thus comparing the above annotations with the criteria of CLP regulation,1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)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 annotations with the criteria of CLP regulation,1,1-diethoxy-3,7-dimethylocta-2,6-diene (7492-66-2)can be considered as not classified for skin sensitization.