6-methoxynaphthalene-2-carbaldehyde

Endpoint summary

Description of key information

Acute oral toxicity:

LD50 was estimated to be 3116 mg/kg bw when Wistar female rats were orally exposed with 6-Methoxy-2-naphthaldehyde. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 3.3

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

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:

rat

Strain:

Wistar

Sex:

female

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

not specified

Doses:

3116 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

not specified

Statistics:

not specified

Preliminary study:

not specified

Sex:

female

Dose descriptor:

LD50

Effect level:

3 116 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 50 % mortality observed

Mortality:

not specified

Clinical signs:

other: not specified

Gross pathology:

not specified

Other findings:

not specified

The prediction was based on dataset comprised from the following descriptors: LD50
Estimation method: Takes average value from the 5 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 ("o" and ( not "p") )  )  and "q" )  and ("r" and ( not "s") )  )  and ("t" and ( not "u") )  )  and "v" )  and "w" )  and ("x" and ( not "y") )  )  and ("z" and "aa" )  )

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 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 >> Haloalkane Derivatives with Labile Halogen 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 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 SN2 OR SN2 >> Acylation OR SN2 >> Acylation >> Specific Acetate Esters OR SN2 >> Acylation involving a leaving group  OR SN2 >> Acylation involving a leaving group  >> Haloalkane Derivatives with Labile Halogen 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 >> Alkylation, nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation, nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives with Labile Halogen OR SN2 >> Nucleophilic substitution at sp3 Carbon atom OR SN2 >> Nucleophilic substitution at sp3 Carbon atom >> Specific Acetate Esters 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: "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 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 Acylation OR Acylation >> Direct acylation involving a leaving group OR Acylation >> Direct acylation involving a leaving group >> (Thio)Acyl and (thio)carbamoyl halides and cyanides  OR 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 Nucleophilic addition OR Nucleophilic addition >> Addition to carbon-hetero double bonds OR Nucleophilic addition >> Addition to carbon-hetero double bonds >> Ketones 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 High (Class III) by Toxic hazard classification by Cramer (original) ONLY

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as No alert found by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles OR AN2 >> Nucleophilic addition to pyridonimine tautomer of aminopyridoindoles or aminopyridoimidazoles >> Heterocyclic Aromatic Amines OR Radical mechanism OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base OR Radical mechanism >> ROS generation and direct attack of hydroxyl radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SE reaction (CYP450-activated heterocyclic amines) OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base OR SE reaction (CYP450-activated heterocyclic amines) >> Direct attack of arylnitrenium cation to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines OR SR reaction (peroxidase-activated heterocyclic amines) OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base OR SR reaction (peroxidase-activated heterocyclic amines) >> Direct attack of arylnitrenium radical to the C8 position of nucleoside base >> Heterocyclic Aromatic Amines by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "q"

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

Domain logical expression index: "r"

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

Domain logical expression index: "s"

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

Domain logical expression index: "t"

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: "u"

Referential boundary: The target chemical should be classified as Group 15 - Nitrogen N OR Group 15 - Phosphorus P OR Group 16 - Sulfur S by Chemical elements

Domain logical expression index: "v"

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

Domain logical expression index: "w"

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

Domain logical expression index: "x"

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

Domain logical expression index: "y"

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

Domain logical expression index: "z"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.62

Domain logical expression index: "aa"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.81

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 was estimated to be 3116 mg/kg bw when Wistar female rats were orally exposed with 6-Methoxy-2-naphthaldehyde. 

Executive summary:

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 6-Methoxy-2-naphthaldehyde. The LD50 was estimated to be 3116 mg/kg bw when Wistar female rats were orally exposed with 6-Methoxy-2-naphthaldehyde. 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 116 mg/kg bw

Quality of whole database:

Data is Klimisch 2 and from OECD QSAR toolbox

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

In different studies, 6-Methoxy-2-naphthaldehyde has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 6-Methoxy-2-naphthaldehydealong with the study available on structurally similar read across substance Methyl 2-naphthyl etheris (CAs no 93-04-9) andAnethole(CAs no 4180-23-8). The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies

In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the acute oral toxicity was estimated for 6-Methoxy-2-naphthaldehyde. The LD50 was estimated to be 3116 mg/kg bw when Wistar female rats were orally exposed with 6-Methoxy-2-naphthaldehyde. 

In another experimental study conducted bySustainability Support Services (Europe) AB (2014) on structurally similar read across substance Methyl 2-naphthyl etheris (CAs no 93-04-9), Study was performed as per OECD No. 423. Six female Wistar rats were fasted for minimum 16-18 hours prior to dosing and for 4 hours post dosing, with food withheld but drinking water providedad libitum. The time intervals between dosing were determined by the onset, duration and severity of toxic signs. Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. Hence, further dosing was stopped. Mean body weight of all six animals was observed with gain on day 7 and 14. Normal clinical signs were observed throughout the experimental period. No external and internal gross pathological examinations were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice. Hence the LD50 value was considered to be >2000 mg/kg bw.

This further supported by experimental study conducted by Levensteinet al(Food and Cosmetics Toxicology. Vol. 13, Pg. 885, 1975.) and summarized by ACToR and RTECS database (2011-12) on structurally similar read across substance Methyl 2-naphthyl etheris (CAs no 93-04-9), rat were treated with Methyl 2-naphthyl etheris in the concentration of 5000 mg./kg bw orally. No mortality was observed at 5000 mg/kg bw in treated rats. Therefore, LD50 was considered to be > 5000 mg/kg bw when rats were treated with Methyl 2-naphthyl etheris orally.

Further supported by experimental study given by Opdyke  et al(Food and Cosmetics Toxicology, 1979, Pages 92-93) on structurally similar read across substanceAnethole(CAs no 4180-23-8),,In a acute oral toxicity study, rat were treated withAnethole,50 % mortality observed at2090mg/kg bw . Therefore,LD50 was considered to 2090 mg/kg bw when rat were treated with Anethole orally.  

Thus, based on the above studies and predictions on 6-Methoxy-2-naphthaldehyde and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 6-Methoxy-2-naphthaldehyde can be classified as category V of acute oral toxicity.

Justification for classification or non-classification

Based on the above studies and predictions on 6-Methoxy-2-naphthaldehyde and its read across substances, it can be concluded that LD50 value is greater than 2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, 6-Methoxy-2-naphthaldehyde can be classified as category V of acute oral toxicity.