6-methoxynaphthalene-2-carbaldehyde

Endpoint summary

Description of key information

The skin sensitization potential of 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated to be not sensitizing to the skin of female CBA mice. Based on the estimated result 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) can be considered to be not sensitizing to female CBA mice and can be classified under the category ˋ Not Classified’ as per CLP regulation.

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:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction was done using OECD QSAR toolbox v3.3

GLP compliance:

not specified

Type of study:

other: Estimated data

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material: 6-Methoxy-2-naphthaldehyde
- Molecular formula: C12H10O2
- Molecular weight: 186.209 g/mol
- Smiles notation: COc1ccc2cc(ccc2c1)C=O
- InChl: 1S/C12H10O2/c1-14-12-5-4-10-6-9(8-13)2-3-11(10)7-12/h2-8H,1H3
- Substance type: Organic
- Physical state: Solid

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

no data available

Route:

other: not specified

Adequacy of induction:

not specified

Route:

other: not specified

No. of animals per dose:

No data available

Details on study design:

No data available

Challenge controls:

No data available

Vehicle:

not specified

Concentration:

25-100%

No. of animals per dose:

4

Details on study design:

no data available

Positive control substance(s):

not specified

Statistics:

no data available

Positive control results:

no data available

Other effects / acceptance of results:

no data available

Parameter:

SI

Test group / Remarks:

test group

Remarks on result:

no indication of skin sensitisation based on QSAR/QSPR prediction

Cellular proliferation data / Observations:

no data available

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" )  and ("f" and ( not "g") )  )  and ("h" and ( not "i") )  )  and ("j" and ( not "k") )  )  and ("l" and ( not "m") )  )  and ("n" and ( not "o") )  )  and ("p" and ( not "q") )  )  and "r" )  and ("s" and ( not "t") )  )  and ("u" and ( not "v") )  )  and ("w" and "x" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aldehydes (Acute toxicity) by US-EPA New Chemical Categories

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aldehyde OR Aryl OR Ether OR Fused carbocyclic aromatic OR Naphtalene by Organic Functional groups ONLY

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aldehyde OR Ether OR Fused carbocyclic aromatic OR Naphtalene OR Overlapping groups by Organic Functional groups (nested) ONLY

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aldehyde, aromatic attach [-CHO] OR Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Aldehyde OR Alkylarylether OR Aromatic compound OR Carbonyl compound OR Ether by Organic functional groups, Norbert Haider (checkmol) ONLY

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 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds OR AN2 >> Nucleophilic addition to alpha, beta-unsaturated carbonyl compounds >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation OR AN2 >> Schiff base formation >> alpha, beta-Unsaturated Aldehydes OR AN2 >> Schiff base formation >> Dicarbonyl compounds OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides OR Radical OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion >> Quinone methides OR SN1 OR SN1 >> Alkylation after metabolically formed carbenium ion species OR SN1 >> Alkylation after metabolically formed carbenium ion species >> Polycyclic Aromatic Hydrocarbon Derivatives OR SN2 OR SN2 >> Alkylation, direct acting epoxides and related OR SN2 >> Alkylation, direct acting epoxides and related >> Epoxides and Aziridines OR SN2 >> Alkylation, direct acting epoxides and related after cyclization OR SN2 >> Alkylation, direct acting epoxides and related after cyclization >> Nitrogen Mustards 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 Derivatives OR SN2 >> Direct acting epoxides formed after metabolic activation OR SN2 >> Direct acting epoxides formed after metabolic activation >> Quinoline Derivatives OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives 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

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans 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 >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition 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 nitro by DNA binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Weak binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "l"

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

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Michael Addition OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group OR Michael Addition >> Michael addition on conjugated systems with electron withdrawing group >> alpha,beta-Carbonyl compounds with polarized double bonds  OR Michael Addition >> Polarised Alkenes OR Michael Addition >> Polarised Alkenes >> Polarised Alkene - alkenyl pyridines, pyrazines, pyrimidines or triazines  OR Schiff base formation OR Schiff base formation >> Schiff base formation with carbonyl compounds OR Schiff base formation >> Schiff base formation with carbonyl compounds >> Aldehydes by Protein binding by OASIS v1.3

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR p-tert-Butyl-alpha-methylhydrocinnamic aldehyde (BMHCA)-like chemicals (9a) OR Toluene and small alkyl toluene derivatives (8a) by DART scheme v.1.0

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group C Melting Point > 55 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR Group All Aqueous Solubility < 0.000005 g/L OR Group All Aqueous Solubility < 0.00002 g/L OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group C Aqueous Solubility < 0.0005 g/L OR Group CN Aqueous Solubility < 0.1 g/L OR Group CN log Kow > 4.5 OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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: "t"

Referential boundary: The target chemical should be classified as Group 14 - Metalloids Si,Ge OR Group 15 - Phosphorus P by Chemical elements

Domain logical expression index: "u"

Referential boundary: The target chemical should be classified as No alert found by rtER Expert System ver.1 - USEPA

Domain logical expression index: "v"

Referential boundary: The target chemical should be classified as Multi Cyclic Hydrocarbons by rtER Expert System ver.1 - USEPA

Domain logical expression index: "w"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.07

Domain logical expression index: "x"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.05

Interpretation of results:

other: Not sensitizing

Conclusions:

The chemical 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated to be non sensitizing to the skin of female CBA mice.

Executive summary:

The skin sensitization potential of 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated to be not sensitising to the skin of female CBA mice. Based on the estimated result 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) can be considered to be not sensitizing to female CBA mice.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studieshas been investigated for the test chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs, mice and humans for target chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) and its structurally similar read across substancesp-Anisaldehyde (CAS No: 123-11-5) and Vanillin (CAS No: 121-33-5).The predicted data using the OECD QSAR toolbox andDanish QSAR databasehas also been compared with the experimental data and summarized as below;

 

The skin sensitization potential of 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated using OECD QSAR toolbox version 3.3 with logPow as the primary descriptor. The substance 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) was estimated to be not sensitizing to the skin of female CBA mice. Based on the estimated result 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) can be considered to be not sensitizing to female CBA mice.

 

According to Danish QSAR database, skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for 6-Methoxy-2-naphthaldehyde. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, 6-Methoxy-2-naphthaldehyde was considered to be non sensitizing.

 

The G. Klecak (1985) conducted an Open Epicutaneous Test (OET) on guinea pigs to assess the skin sensitization potential ofstructurally similar read across substancep-Anisaldehyde (CAS No: 123-11-5).On day 1 during induction, 0.1 ml of the p-Anisaldehyde was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h. It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 10%.Thus the chemicalp-Anisaldehyde (CAS No: 123-11-5) was considered to be not sensitizing on skin of guinea pigs at concentration of 10 % in an Open Epicutaneous Test (OET).

 

The above results were further supported by the Mouse Local Lymphnode Assay conducted by Gerberick GF, Ryan CA, Kern PS, Schlatter H, Dearman RJ, Kimber I, Patlewicz GY, Basketter DA (2005) onstructurally similar read across substanceVanillin (CAS No: 121-33-5).The LLNA was conducted on groups of CBA mice (7-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl or to an equal volume of relevant vehicle (Acetic acid in olive oil (4:1))only. Treatment was performed daily for 3 consecutive days. Five days after initiation of exposure all mice were injected via the tail vein with 250µl of PBS containing 20µCi of tritiatied thymidine. The mice were sacrificed 5 hours later, and draining the auricular lymph nodes were excised and pooled for each experimental group or each individual animal. The incorporation of tritiated thymidine measured by β-scintillation counting and was reported in disintegrations /minute.An SI was calculated as the ratio of disintegrations/minute of the treated group to the disintegrations/minute of the concurrent vehicle control group. A substance was classified skin sensitizer, if at one or more than one concentrations, it induced a three-fold or greater increase in local lymph node proliferative activity when treated with the concurrent vehicle treated controls (SI ≥3) The approach to estimation of the relative skin sensitization potential is based on the mathematical estimation of the concentration of chemical necessary to obtain a threshold positive response (SI = 3); this is termed as the EC3 value.The relative potency index of Vanillin (CAS No: 121-33-5) was not calculated but on the basis of classification system it was considered to be >100. Thus the chemical Vanillin (CAS No: 121-33-5) was considered as non skin sensitizer.

 

Thus on the basis of available data for thetarget chemical6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) and its structurally similar read across substancesp-Anisaldehyde (CAS No: 123-11-5) and Vanillin (CAS No: 121-33-5),it can be concluded thatchemical 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) is unable to cause skin sensitization and considered as non skin sensitizer.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6)  and its structurally similar read across substancesp-Anisaldehyde (CAS No: 123-11-5) and Vanillin (CAS No: 121-33-5) were observed in various studies. From the results obtained from these studies it is concluded that the chemical 6-Methoxy-2-naphthaldehyde (CAS No: 3453-33-6) is not likely to cause skin sensitization and hence can be classified as non skin sensitizer.