Denatonium benzoate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic and germ cell study: gene mutation

Remarks:

Type of genotoxicity: other:

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 3.4 and the supporting QMRF report has been attached

Data source

Reference

Reference Type:

other: Predicted data

Title:

[R]: Negative; Estimation for chromosome aberration, DNA damage and/or repair for CAS 3734-33-6

Author:

Sustainability Support Services (Europe) AB

Year:

2017

Bibliographic source:

OECD QSAR Toolbox version 3.4, 2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

Prediction is done using OECD QSAR Toolbox version 3.4, 2017

GLP compliance:

no

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Denatonium benzoate

EC Number:

223-095-2

EC Name:

Denatonium benzoate

Cas Number:

3734-33-6

Molecular formula:

C21H29N2O.C7H5O2

IUPAC Name:

N-benzyl-2-[(2,6-dimethylphenyl)amino]-N,N-diethyl-2-oxoethanaminium benzoate hydrate

Details on test material:

- Name of test material (as cited in study report): Denatonium benzoate
- Molecular formula : C21H29N2O.C7H5O2
- Molecular weight :446.588 g/mole
- Substance type: Organic
- Physical state: Solid

Specific details on test material used for the study:

- Name of test material: Denatonium benzoate
- IUPAC name: N-benzyl-2-[(2,6-dimethylphenyl)amino]-N,N-diethyl-2-oxoethanaminium benzoate hydrate
- Molecular formula: C21H29N2O.C7H5O2
- Molecular weight : 446.58 g/mol
- Substance type: organic
- Physical state: Solid
- SMILES: CCN{+}(CC)(Cc1ccccc1)(CC(=O)Nc1c(C)cccc1C).O{-}C(=O)c1ccccc1

Test animals

Species:

mouse

Strain:

ICR

Details on species / strain selection:

No data

Sex:

male/female

Details on test animals or test system and environmental conditions:

No data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

No data

Details on exposure:

No data

Duration of treatment / exposure:

One single IP

Frequency of treatment:

Once

Post exposure period:

No data

Doses / concentrations

Remarks:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Positive control(s):

No data

Examinations

Tissues and cell types examined:

No data

Details of tissue and slide preparation:

No data

Evaluation criteria:

No data

Statistics:

No data

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: No mutagenic potential

Additional information on results:

No data

Any other information on results incl. tables

The prediction was based on dataset comprised from the following descriptors: "DNA damage and/or repair","chromosome aberration"
Estimation method: Takes highest mode value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((("a" or "b" )  and ("c" and ( not "d") )  )  and ("e" and "f" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Cationic (quaternary ammonium) surfactants by US-EPA New Chemical Categories

Domain logical expression index: "b"

Similarity boundary:Target: CCN{+}(CC)(Cc1ccccc1)(CC(=O)Nc1c(C)cccc1C).O{-}C(=O)c1ccccc1_O
Threshold=50%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OASIS v.1.4

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Non-covalent interaction OR Non-covalent interaction >> DNA intercalation OR Non-covalent interaction >> DNA intercalation >> DNA Intercalators with Carboxamide and Aminoalkylamine Side Chain OR Radical OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA OR Radical >> Radical mechanism by ROS formation (indirect) or direct radical attack on DNA >> Organic Peroxy Compounds OR Radical >> ROS formation after GSH depletion (indirect) OR Radical >> ROS formation after GSH depletion (indirect) >> Haloalcohols OR SN2 OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction OR SN2 >> Alkylation by epoxide metabolically formed after E2 reaction >> Haloalcohols by DNA binding by OASIS v.1.4

Domain logical expression index: "e"

Parametric boundary:The target chemical should have a value of log Kow which is >= -2.94

Domain logical expression index: "f"

Parametric boundary:The target chemical should have a value of log Kow which is <= 3.92

Applicant's summary and conclusion

Conclusions:

Denatonium benzoate was predicted to not induce gene mutation in male and female ICR mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.

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 denatonium benzoate. The study assumed the use of male and female ICR mouse. Denatonium benzoate was predicted to not induce gene mutation in male and female ICR mouse and hence, according to the prediction made, it is not likely to classify as a gene mutant in vivo.

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