Phenetole

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Phenetole  was found to be non-genotoxic.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Qualifier:

according to guideline

Guideline:

other: Estimated data

Principles of method if other than guideline:

Prediction is done using QSAR Toolbox version 2.3.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

without

Metabolic activation system:

S9

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

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

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

The prediction was based on dataset comprised from the following descriptors: "Gene mutation"
Estimation method: Taking highest mode value from the 5 nearest neighbours
Domain logical expression:Result: In Domain

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

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Arene AND Ether AND Methyl AND Methylene by Organic functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether AND Methyl AND Methylene by Organic Functional groups (extended)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Arene AND Ether by Organic functional groups (nested)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Alkoxy AND Aryl AND Ether AND Overlapping groups by Organic Functional groups (nested)(extended)

Domain logical expression index: "e"

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 Olefinic carbon [=CH- or =C<] AND Oxygen, one aromatic attach [-O-] by Organic functional groups (US EPA)

Domain logical expression index: "f"

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

Domain logical expression index: "g"

Similarity boundary:Target: c1(OCC)ccccc1
Threshold=50%,
Dice(Atom pairs)

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 Aliphatic halides OR Aliphatic tertiary amines OR Alkyl phenols OR Allyl benzenes OR Alpha, beta- unsaturated ketones OR Arenes OR Aromatic N-hydroxylamines OR Aromatic nitro OR Aromatic nitroso OR Aromatic phenylureas OR Epoxides OR Hydroquinones OR MA: Carbenium Ion Formation OR MA: Direct Acting Epoxides and related OR MA: Epoxidation of Aliphatic Alkenes OR MA: Iminium Ion Formation OR MA: Nitrenium Ion Formation OR MA: Nitrosation_SN2 OR MA: P450 Mediated Activation to Quinones and Quinone-type Chemicals OR MA: Polarised Alkenes_Michael addition OR MA: Quinones and Quinone-type Chemicals OR MA: SN2 at an sp3 Carbon atom OR Mechanistic Domain: Michael addition OR Mechanistic Domain: SN1 OR Mechanistic Domain: SN2 OR Methylenedioxyphenyl OR Nitroso_SN2 OR N-Nitroso (alkylation) OR Phenoxy polarised alkenes OR Primary (unsaturated) heterocyclic amine OR Primary aromatic amine OR Quinones OR Secondary aromatic amine OR Sulfonates OR Tertiary aromatic amine by DNA binding by OECD

Domain logical expression index: "j"

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

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Acetates OR Activated halo-benzenes OR alpha-Halocarbonyls OR MA: Direct Acting Schiff Base Formers OR MA: Direct Acylation Involving a Leaving group OR MA: Polarised Alkenes OR MA: SN2 reaction at sp3 carbon atom OR MA: SNAr OR Mechanistic Domain: Acylation OR Mechanistic Domain: Michael addition OR Mechanistic Domain: Schiff Base Formers OR Mechanistic Domain: SN2 OR Mechanistic Domain: SNAr OR Mono-carbonyls OR Polarised alkene - aldehydes OR Thiophosphates by Protein binding by OECD

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as No alerts for carcinogenic activity by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Alkylbenzenes (Genotox) OR Halogenated benzene (Nongenotox) OR Heterocyclic Polycyclic Aromatic Hydrocarbons (Genotox) OR o-phenylphenol (Nongenotox) OR Simple aldehyde (Genotox) OR Structural alert for genotoxic carcinogenicity OR Structural alert for nongenotoxic carcinogenicity OR Substituted phenoxyacid (Nongenotox) by Carcinogenicity (genotox and nongenotox) alerts by ISS

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as (N/A) by Oncologic Primary Classification

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aromatic Amine Type Compounds OR Carbamate Type Compounds OR Phenol Type Compounds OR Polycyclic Aromatic Hydrocarbons - Homocyclic by Oncologic Primary Classification

Domain logical expression index: "p"

Parametric boundary:The target chemical should have a value of log Kow which is >= 2.47

Domain logical expression index: "q"

Parametric boundary:The target chemical should have a value of log Kow which is <= 2.71

Conclusions:

Interpretation of results (migrated information):
negative without metabolic activation

Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 100 without S9 metabolic activation it was estimated that Phenetole does not exhibit positive gene mutation effect.

Executive summary:

Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 100 without S9 metabolic activation it was estimated that Phenetole does not exhibit positive gene mutation effect.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Genetic toxicity-

Based on studies of target substance and read across reviewed for Genetic toxicity from reliable sources having Klimisch rating 2 and 4 considering weight of evidence approach. The results are summarized as follows-

Sr. No	End point	Effect	Species	Remarks
1.	Gene mutation(Ames test)	Negative without metabolic activation	S. typhimurium TA 100	Predicted data of target chemical
2.	Chromosome aberration	Negative without metabolic activation	Chinese hamster Lung (CHL)	Predicted data of target chemical
3.	Gene mutation	Negative	Mouse lymphoma	DEPA
4.	DNA damage and/or repair	Negative	Rat hepatocytes	DEPA
5.	Gene mutation	Negative	Chinese hamster ovary cell	DEPA

Based on results summarized in above table for the target phenetole, it can be concluded that the substance is non-genotoxic .Thus phenetole is considered to be not skin irritant as the criteria of CLP regulation.Thus phenetole is considered to be non-genetic toxic substance.

Justification for selection of genetic toxicity endpoint

Based on the prediction for in-vitro bacterial reverse mutation assay test on Salmonella typhimurium strain TA 100 without S9 metabolic activation it was estimated that Phenetole does not exhibit positive gene mutation effect. Also the chromosome aberration is based on the prediction for in-vitro mammalian chromosome aberration test on Chinese hamster Lung (CHL) without S9 metabolic activation it was estimated that Phenetole does not exhibit positive chromosomal effect.

Justification for classification or non-classification

Phenetole shows negative activity as is the case for chromosome abberation for the same substance.