(S)-α-hydroxy-3-phenoxy-benzeneacetonitrile

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

441-070-6

EC Name:

-

Cas Number:

61826-76-4

Molecular formula:

C14H11NO2

IUPAC Name:

(2S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile

Method

Species / strain

Species / strain / cell type:

bacteria, other: Salmonella typhimurium TA97a, TA98, TA100, TA102 and TA1535.

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix from Aroclor 1254 induced rat livers.

Test concentrations with justification for top dose:

The following concentrations were chosen based on the results from a preliminary toxicity test:
Experiment 1 (with and without metabolic activation): 1, 3, 9, 27, 81 and 243 µg/plate
Experiment 2 /with and without metabolic activation): 3, 9, 27, 81, 243 and 729 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 4-Nitro-o-phenylene-diamine

Remarks:

without S9 mix: TA97a, 10 µg/plate

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

without S9 mix: TA98, 2 µg/plate

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

without S9 mix: TA100, 2 µg/plate; TA1535, 1 µg/plate

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: t-Butyl-hydroperoxide

Remarks:

without S9 mix: TA102, 50 µg/plate

Controls 5

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

Remarks:

with S9 mix: TA97a, 10 µg/plate

Controls 6

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with S9 mix: TA98, 1 µg/plate; TA100 and TA1535, 2µg/plate

Controls 7

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 1,8-dihydroxy-anthraquinone

Remarks:

with S9 mix: TA102, 50 µg/plate

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation)
NUMBER OF REPLICATIONS: 3 (test item and positive control), 6 (solvent control)
EXPOSURE DURATION: 2 days

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA97a, TA98, TA100, TA102 and TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

ADDITIONAL INFORMATION ON CYTOTOXICITY:
In the main test the test item was toxic to the bacteria at the 729 µg/plate samples, resulting in a missing bacterial background lawn, and at the 243 µg/plate samples without metabolisation, resulting in a reduced bacterial background lawn or microcolonies instead of a bacterial background. The addition of an external metabolising system reduced toxicity in all strains.

Any other information on results incl. tables

All positive control groups showed significantly increased mutation frequencies which demonstrate the sensitivity of the test system.

Applicant's summary and conclusion

Conclusions:

In conclusion, the test substance does not show mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium in the presence or absence of mammalian metabolic activation.

Executive summary:

In conclusion, the test substance does not show mutagenic activity in the bacterial reverse mutation test with Salmonella typhimurium in the presence or absence of mammalian metabolic activation.