5-methyl-3-phenylisoxazole-4-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 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2). 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. 5-methyl-3-phenylisoxazole-4-carbonyl 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.

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: 5-methyl-3-phenylisoxazole-4-carbonyl chloride
- Mol. formula: C11H8ClNO2
- Molecular Weight: 221.642 g/mol
- Smiles: c1(ccccc1)c1c(C(=O)Cl)c(on1)C
- InChI: 1S/C11H8ClNO2/c1-7-9(11(12)14)10(13-15-7)8-5-3-2-4-6-8/h2-6H,1H3
- Substance Type: Organic
- Physical State: Solid

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 5 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 "j" )  and "k" )  and "l" )  and "m" )  and "n" )  and ("o" and ( not "p") )  )  and ("q" and "r" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Acyl halide OR Allyl OR Aryl OR Ketoxime derivatives OR Oxazole/ Izoxazole by Organic Functional groups ONLY

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Acyl halide OR Allyl OR Aryl OR Ketoxime derivatives OR Overlapping groups OR Oxazole/ Izoxazole by Organic Functional groups (nested) 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 Aromatic Nitrogen, five-member ring OR Aromatic Oxygen OR Carbonyl, olefinic attach [-C(=O)-] OR Chlorine, olefinic attach [-Cl] OR Miscellaneous sulfide (=S) or oxide (=O) OR Olefinic carbon [=CH- or =C<] OR Oxygen, nitrogen attach [-O-] by Organic functional groups (US EPA) ONLY

Domain logical expression index: "d"

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

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as Acyl halides AND alpha,beta-unsaturated carbonyls by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as 9,10-dihydrophenanthrenes OR Alkyl (C<5) or benzyl ester of sulphonic or phosphonic acid OR Alkyl and aryl N-nitroso groups OR alpha,beta-unsaturated aliphatic alkoxy group OR Aromatic mono-and dialkylamine OR Aromatic ring N-oxide OR Azide and triazene groups OR Epoxides and aziridines OR Heterocyclic Polycyclic Aromatic Hydrocarbons OR Hydrazine OR Monohaloalkene OR Nitro-aromatic OR No alert found OR Polycyclic Aromatic Hydrocarbons OR Primary aromatic amine,hydroxyl amine and its derived esters OR Quinones OR Simple aldehyde by in vitro mutagenicity (Ames test) alerts by ISS

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Group 14 - Carbon C AND Group 15 - Nitrogen N AND Group 16 - Oxygen O AND Group 17 - Halogens Cl AND Group 17 - Halogens F,Cl,Br,I,At by Chemical elements

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Group 16 - Sulfur S OR Group 17 - Halogens Br by Chemical elements

Domain logical expression index: "i"

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

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonic acid derivative AND Halogen derivative by Organic functional groups, Norbert Haider (checkmol) ONLY

Domain logical expression index: "k"

Similarity boundary:Target: CC1=C(C(=O)Cl)C(c2ccccc2)=NO1
Threshold=20%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Acyl halide AND Allyl AND Aryl AND Ketoxime derivatives AND Overlapping groups AND Oxazole/ Izoxazole by Organic Functional groups (nested) ONLY

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Acyl halide AND Allyl AND Aryl AND Ketoxime derivatives AND Overlapping groups AND Oxazole/ Izoxazole by Organic Functional groups (nested) ONLY

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Acyl halide AND Allyl AND Aryl AND Ketoxime derivatives AND Overlapping groups AND Oxazole/ Izoxazole by Organic Functional groups (nested) 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 >> Michael addition to activated double bonds OR AN2 >> Michael addition to activated double bonds >> alpha, beta - Unsaturated Carbonyls and Related Compounds by Protein binding alerts for Chromosomal aberration by OASIS v1.1

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.15

Domain logical expression index: "r"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.45

Conclusions:

5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2 ) 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 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2). 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. 5-methyl-3-phenylisoxazole-4-carbonyl 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 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2) .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 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2). 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. 5-methyl-3-phenylisoxazole-4-carbonyl 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 α-methylstyrene (98-83-9). 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 α-methylstyrene . 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 presence and absence of metabolic activation0, 12.5, 25, 50, 100, 200 and 400 µg/plate. No mutagenic effects were observed in all strains, in the presence and absence of metabolic activation. Therefore α-methylstyrene 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 of Citral (5392-40-5). 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 Citral to find its possible mutagenic potential. For this purpose Bacterial reverese mutation assay was performed on Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100. The test material was exposed in the absence of metabolic activation at the concentration of 0,1,3.3,10,33,50 and 67 µg/plate while concentration used in the presence of metabolic activation were 0,3.3,10,33,50,67,100,160and 220 µg/plate. No mutagenic effects were observed. Therefore Citral was considered to be non mutagenic in Salmonella typhimurium TA 1535, TA 1537, TA 98 and TA 100 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 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2)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 annotation and CLP criteria for the target chemical . 5-methyl-3-phenylisoxazole-4-carbonyl chloride (16883-16-2)does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.