2-ethoxynaphthalene-1-carbonyl chloride

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2-ethoxy-1-naphthoyl chloride (55150-29-3). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 2-ethoxy-1-naphthoyl chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

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 version 3.3 and the supporting QMRF report has been attached.

Qualifier:

according to guideline

Guideline:

other: As mention below

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.3, 2017

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- IUPAC Name: 2-ethoxynaphthalene-1-carbonyl chloride
- Mol. formula: C13H11ClO2
- Molecular Weight: 234.681 g/mole
- Smiles: O=C(c1c2c(cccc2)ccc1OCC)Cl
- InChI: 1S/C13H11ClO2/c1-2-16-11-8-7-9-5-3-4-6-10(9)12(11)13(14)15/h3-8H,2H2,1H3

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with

Metabolic activation system:

S9 metabolic activation

Test concentrations with justification for top dose:

not specified

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

not specified

Rationale for test conditions:

not specified

Evaluation criteria:

Prediction was done considering a dose dependent increase in the number of revertants/plate.

Statistics:

not specified

Species / strain:

S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

not specified

Remarks on result:

other: No mutagenic effect were observed

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Takes highest mode value from the 9 nearest neighbours
Domain  logical expression:Result: In Domain

(((((((((("a" or "b" or "c" or "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 ( not "o") )  )  and ("p" and ( not "q") )  )  and ("r" and ( not "s") )  )  and ("t" and "u" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acyl chloride OR Acyl halide OR Alkylarylether OR Aromatic compound OR Carbonic acid derivative OR Carboxylic acid derivative OR Ether OR Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] 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: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] OR Aliphatic Carbon [-CH2-] OR Aliphatic Carbon [-CH3] OR Aromatic Carbon [C] OR Carbonyl, olefinic attach [-C(=O)-] OR Carbonyl, one aromatic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] 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: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >>  Michael-type addition, quinoid structures OR AN2 >>  Michael-type addition, quinoid structures >> Quinoneimines OR AN2 >>  Michael-type addition, quinoid structures >> Quinones OR AN2 >> Carbamoylation after isocyanate formation OR AN2 >> Carbamoylation after isocyanate formation >> N-Hydroxylamines 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 >> Polarized Haloalkene Derivatives OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Haloalkenes with Electron-Withdrawing Groups OR AN2 >> Thioacylation via nucleophilic addition after cysteine-mediated thioketene formation >> Polarized Haloalkene Derivatives OR Michael addition OR Michael addition >> Quinone type compounds OR Michael addition >> Quinone type compounds >> Quinone methides 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 >> Aminoacridine DNA Intercalators OR Non-covalent interaction >> DNA intercalation >> Fused-Ring Primary Aromatic Amines OR Non-covalent interaction >> DNA intercalation >> Quinones OR Radical 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) >> Conjugated Nitro Compounds OR Radical >> Radical mechanism via ROS formation (indirect) >> Fused-Ring Primary Aromatic Amines OR Radical >> Radical mechanism via ROS formation (indirect) >> Hydrazine Derivatives OR Radical >> Radical mechanism via ROS formation (indirect) >> N-Hydroxylamines OR Radical >> Radical mechanism via ROS formation (indirect) >> Quinones OR Radical >> ROS formation after GSH depletion OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Quinoneimines 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 >> Nucleophilic attack after carbenium ion formation OR SN1 >> Nucleophilic attack after carbenium ion formation >> Acyclic Triazenes OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> Fused-Ring Primary Aromatic Amines OR SN1 >> Nucleophilic attack after metabolic nitrenium ion formation >> N-Hydroxylamines OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation OR SN1 >> Nucleophilic attack after reduction and nitrenium ion formation >> Conjugated Nitro Compounds OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on  nitrenium ion OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on  nitrenium ion >> N-Acyloxy(Alkoxy) Arenamides OR SN1 >> SN1 reaction at nitrogen-atom bound to a good leaving group or on  nitrenium ion >> N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides 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 P450-mediated metabolic activation OR SN2 >> Alkylation, direct acting epoxides and related after P450-mediated metabolic activation >> Haloalkenes with Electron-Withdrawing Groups 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 >> Direct acylation involving a leaving group OR SN2 >> Direct acylation involving a leaving group >> Acyl Halides OR SN2 >> SN2 at an activated carbon atom OR SN2 >> SN2 at an activated carbon atom >> Quinoline Derivatives OR SN2 >> SN2 at Nitrogen Atom OR SN2 >> SN2 at Nitrogen Atom >> N-acetoxyamines OR SN2 >> SN2 at sp3 and activated sp2 carbon atom OR SN2 >> SN2 at sp3 and activated sp2 carbon atom >> Polarized Haloalkene Derivatives OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group >> N-Acetoxyamines OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion >> N-Acyloxy(Alkoxy) Arenamides OR SN2 >> SN2 reaction at nitrogen-atom bound to a good leaving group or nitrenium ion >> N-Aryl-N-Acetoxy(Benzoyloxy) Acetamides by DNA alerts for AMES, MN and CA by OASIS v.1.3

Domain logical expression index: "g"

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: "h"

Referential boundary: The target chemical should be classified as AhR binders.Polycyclic aromatic hydrocarbons (PAHs) (3b-3) OR Alkenes (23c) OR Alkyl amide, urea, thiourea, nitroso urea, carbonate, guanidine and carbamate derivatives (21b1) OR Alkyl amide, urea, thiourea, nitroso urea, carbonate, guanidine and carbamate derivatives (21b1) >> Alkyl formamide analogs OR Aromatic di-amines: 2,4-diamino pyrimidine related derivatives (12a) OR Aryl triazene derivatives (12d) OR Di-substituted hydrocarbons (24b) OR Glycidyl ether derivatives (16c) OR Inorganic chemical OR Known precedent reproductive and developmental toxic potential OR Metal atoms were identified OR Metals (1a) OR Miscellaneous non-cyclic chemicals (20) OR Multi-halogenated alkyl ethers (23b) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) OR Non-steroid nucleus derived estrogen receptor (ER) and androgen receptor (AR) >> 4-alkylphenol-like derivatives (2b-3) OR Not covered by current version of the decision tree OR Toluene and small alkyl toluene derivatives (8a) OR Vinyl amide, aldehyde and ester derivatives (21a) by DART scheme v.1.0

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as (!Undefined)Group All Lipid Solubility < 0.01 g/kg AND Group CHal Melting Point > 65 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as (!Undefined)Group All log Kow < -3.1 OR (!Undefined)Group All log Kow > 9 OR (!Undefined)Group All Melting Point > 200 C OR (!Undefined)Group CN Lipid Solubility < 0.4 g/kg OR (!Undefined)Group CNHal Lipid Solubility < 400 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 < -3.1 OR Group All log Kow > 9 OR Group All Melting Point > 200 C OR Group All Molecular Weight > 650 g/mol OR Group C Aqueous Solubility < 0.0001 g/L OR Group C Aqueous Solubility < 0.0005 g/L OR Group C Melting Point > 55 C OR Group C Molecular Weight > 380 g/mol OR Group CHal log Kow > 4.5 OR Group CHal Molecular Weight > 280 g/mol OR Group CHal Molecular Weight > 370 g/mol 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 CNHal Aqueous Solubility < 0.004 g/L OR Group CNHal Aqueous Solubility < 0.1 g/L OR Group CNHal log Kow > 3.8 OR Group CNHal Molecular Weight > 370 g/mol OR Group CNS log Kow > 1.5 OR Group CNS Melting Point > 200 C OR Group CNS Melting Point > 50 C by Eye irritation/corrosion Exclusion rules by BfR

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acyl halides AND H-acceptor-path3-H-acceptor by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as 1,3-dialkoxy-benzene OR 1-phenoxy-benzene OR alpha,beta-unsaturated aliphatic alkoxy group OR alpha,beta-unsaturated carbonyls OR No alert found OR Polycyclic Aromatic Hydrocarbons OR Simple aldehyde by in vivo mutagenicity (Micronucleus) alerts by ISS

Domain logical expression index: "m"

Similarity boundary:Target: CCOc1ccc2ccccc2c1C(=O)Cl
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Not categorized by Repeated dose (HESS)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Allyl esters (Hepatotoxicity) Rank A by Repeated dose (HESS)

Domain logical expression index: "p"

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: "q"

Referential boundary: The target chemical should be classified as AN2 OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters OR AN2 >> Michael addition to alpha, beta-unsaturated acids and esters >> alpha, beta - Unsaturated Carboxylic Acids and Esters by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acylation AND Acylation >> Direct Acylation Involving a Leaving group AND Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) by Protein binding by OECD

Domain logical expression index: "s"

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

Domain logical expression index: "t"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.1

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.17

Conclusions:

2-ethoxy-1-naphthoyl chloride (55150-29-3) was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Executive summary:

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2-ethoxy-1-naphthoyl chloride (55150-29-3). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with S9 metabolic activation system. 2-ethoxy-1-naphthoyl chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Prediction model based estimation and data from read across chemical have been reviewed to determine the mutagenic nature of for 2-ethoxy-1-naphthoyl chloride. The studies are as mentioned below

Based on the prediction done using the OECD QSAR toolbox version 3.3 with log kow as the primary descriptor and considering the five closest read across substances, gene mutation was predicted for 2-ethoxy-1-naphthoyl chloride (55150-29-3). The study assumed the use of Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 with and without S9 metabolic activation system. 2-ethoxy-1-naphthoyl chloride was predicted to not induce gene mutation in Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 in the presence and absence of S9 metabolic activation system and hence, according to the prediction made, it is not likely to classify as a gene mutant in vitro.

Based on the predicted result it can be concluded that the substance is considered to not toxic as per the criteria mentioned in CLP regulation.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by National Institute of Technology and Evaluation (Japan chemicals collaborative knowledge database , 2017)to determine the mutagenic nature of Diethyl Fumarate (623-91-6). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. Genetic toxicity in vitro study was assessed for Diethyl Fumarate. For this purpose AMES test was performed according to Guidelines for Screening Mutagenicity Testing of Chemicals (Japan).The test material was exposed to Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA in the presence and absence of metabolic activation S9. The concentration of test material used in the absence of metabolic activation were 0, 9.375, 18.75, 37.5, 75, 150, 300µg/plate (TA100),0, 78.13, 156.3, 312.5, 625, 1250, 2500µg/plate(TA1535, TA98, TA1537) and 0, 156.3 312.5, 625, 1250, 2500, 5000µg/plate (WP2). While concentration used in the presence of metabolic activation were 0, 312.5, 625, 1250, 2500 5000 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore Diethyl Fumarate was considered to be non mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537, E. coli WP2 uvrA by AMES test. Hence the substance cannot be classified as gene mutant in vitro.

In a study for structurally and functionally similar read across chemical, Gene mutation toxicity study was performed by Zeiger E et al.( Environmental Mutagen,1987)to determine the mutagenic nature of1,6-Hexanediol Diacrylate (13048-33-4). The read across substances share high similarity in structure and log kow .Therefore, it is acceptable to derive information on mutation from the analogue substance. In vitro Genetic toxicity study was assessed for 1,6-Hexanediol Diacrylate to find its possible mutagenic potential. For this purpose Bacterial reverse mutation assay was performed on Salmonella typhimurium TA98, TA100, TA 1535, TA 1537 and TA97. The test material was exposed in the absence of metabolic activation at the concentration of 0, 3, 10, 33, 100, 333, 666, 1000 µg/plate while concentration used in the presence of metabolic activation were 0,3.3,10,33,100,333,1000,3333 and10000 µg/plate. No mutagenic effects were observed. Therefore 1,6-Hexanediol Diacrylate was considered to be non mutagenic in Salmonella typhimurium TA98, TA100, TA 1535, TA 1537 and TA97 Bacterial reverse mutation assay. Hence the substance cannot be classified as gene mutant in vitro.

Based on the data available for the target chemical and its read across substance and applying weight of evidence 2-ethoxy-1-naphthoyl chloride does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Justification for classification or non-classification

Thus based on the above anotation and CLP criteria for the chemical . 2-ethoxy-1-naphthoyl chloride does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.