7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one

Endpoint summary

Description of key information

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to skin of guinea pig.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 QMRF report has been attached

Qualifier:

according to guideline

Guideline:

other: estimated data

Principles of method if other than guideline:

Prediction was done by using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

not specified

Justification for non-LLNA method:

Not specified

Specific details on test material used for the study:

- Name of test material: 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one
- IUPAC name: 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one
- Molecular formula: C11H12O2
- Molecular weight: 176.214 g/mole
- Smiles : c12c(CCC(C1)=O)ccc(c2)OC
- Inchl: 1S/C11H12O2/c1-13-11-5-3-8-2-4-10(12)6-9(8)7-11/h3,5,7H,2,4,6H2,1H3
- Substance type: Organic
- Physical state: Liquid (Light yellow to yellow)

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

No data available

Route:

other: not specified

Vehicle:

not specified

Concentration / amount:

not specified

Day(s)/duration:

not specified

Adequacy of induction:

not specified

No.:

#1

Route:

other: not specified

Vehicle:

not specified

Concentration / amount:

not specified

Day(s)/duration:

not specified

Adequacy of challenge:

not specified

No. of animals per dose:

no data available

Details on study design:

no data available

Challenge controls:

not specified

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

not specified

Clinical observations:

no skin reaction 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 6 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((("a" or "b" )  and ("c" and ( not "d") )  )  and ("e" and ( not "f") )  )  and ("g" and ( not "h") )  )  and ("i" and ( not "j") )  )  and ("k" and ( not "l") )  )  and "m" )  and ("n" and "o" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Nucleophilic addition AND Nucleophilic addition >> Addition to carbon-hetero double bonds AND Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones by Protein binding by OASIS v1.4

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Class 1 (narcosis or baseline toxicity) by Acute aquatic toxicity classification by Verhaar (Modified)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR Radical 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) >> N-Hydroxylamines OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN1 >> Nucleophilic attack after nitrenium ion formation OR SN1 >> Nucleophilic attack after nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic substitution after carbenium ion formation OR SN1 >> Nucleophilic substitution after carbenium ion formation >> Monohaloalkanes OR SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> N-Hydroxylamines 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 after P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Polycyclic Aromatic Hydrocarbon and Naphthalenediimide Derivatives OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Monohaloalkanes 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 by DNA binding by OASIS v.1.4

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 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 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 by DNA binding by OECD

Domain logical expression index: "g"

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

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, non cyclic structure OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "i"

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

Domain logical expression index: "j"

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

Domain logical expression index: "k"

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: "l"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N by Chemical elements

Domain logical expression index: "m"

Similarity boundary:Target: COc1ccc2CCC(=O)Cc2c1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Parametric boundary:The target chemical should have a value of log Kow which is >= 0.336

Domain logical expression index: "o"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.29

Interpretation of results:

other: Not sensitizing

Conclusions:

7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one is considered to be non sensitizing on guinea pigs skin

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to skin of guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization:

In different studies, 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one has been investigated for potential for dermal sensitization to a greater or lesser extent. The studies are based on in vivo experiments in rabbits along with human data for target chemical 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one and its structurally similar read across substances 4-(p-methoxyphenyl)butan-2-one(104-20-1) and p- methoxyphenylacetone (122-84-2) . The predicted data using the OECD QSAR toolbox has also been compared with the experimental data.

In a prediction done by SSS (2017) using the OECD QSAR toolbox version 3.4 with log kow as the primary descriptor, the skin irritation potential was estimated for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one . It was estimated that 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was not irritating to skin of guinea pig.

The above estimation was further supported by another prediction done by using Danish QSAR database

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, 7-methoxy-1,2,3,4-tetrahydronaphthalen-2-one was considered to be non sensitizing.

The above predicted data were supported by experimental result of study conducted by Food and Cosmetics Toxicology. 12, 929, 1974 for the structurally similar read across substance 4-(p-methoxyphenyl)butan-2-one(104-20-1)

Maximization test was done to evaluate sensitization effect produce by 4-(p-methoxyphenyl) butan-2-one in human subjects.Test was carried out on 25 human volunteers. The material was tested at a concentration of 5% in petrolatum and produced no sensitization reactions. Therefore, the substance 4-(p-methoxyphenyl) butan-2-one is considered to be non-sensitizing to human skin.

The above experimental result was further supported by Food and cosmetics toxicology volume 17, supplement ,Pages 695-923 (December 1979) forstructurally similar read across substance p- methoxyphenylacetone (122-84-2)

p-methoxyphenylacetone was used as test material to evaluate skin sensitization potential by human maximization test p-methoxyphenylacetone was applied in concentration 4% in petrolatum.

No skin reaction were observed Hence p- methoxyphenylacetone can be considered as not skin sensitizer for human skin.

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,7-methoxy-1,2,3,4-tetrahydronaphthalen-2-onewas not sensitizing to skin .Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data for the target as well as read across substances and applying the weight of evidence approach,7-methoxy-1,2,3,4-tetrahydronaphthalen-2-onewas not sensitizing to skin .Comparing the above annotations with the criteria of CLP regulation, test chemical can be classified under the category “Not Classified”.