p-phenetidine

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: No available data on GLP and deviations from guideline.

Data source

Reference

Reference Type:

publication

Title:

Mechanism of Metabolic Activation of the Analgetic Bucetin to Bacterial Mutagens by Hamster Liver Microsomes

Author:

NOHMI T, ISHIDATE M JR, HIRATSUKA A, WATABEB T

Year:

1985

Bibliographic source:

Chemical and Pharmaceutical Bulletin (Tokyo), 33, 2877, (1985)

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

At least five strains of bacteria should be used in the test, but in the study, only one strain has been used.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

p-phenetidine

EC Number:

205-855-5

EC Name:

p-phenetidine

Cas Number:

156-43-4

Molecular formula:

C8H11NO

IUPAC Name:

4-ethoxyaniline

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 100

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

PCB-treated or untreated rat or hamster S9

Test concentrations with justification for top dose:

No data

Vehicle / solvent:

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

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk

DURATION
- Preincubation period: 20 minutes at 37ºC
- Exposure duration: 2 days

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Test results 2

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'.

Any other information on results incl. tables

Mutagenic potency (data are expressed as arithmetic mean values of at least three experiments after subtracting the mean number of spontaneous revertant colonies (135/plate) (induced His+/ μmol) for p-phenetidine:

-S9 mix: 0

+S9 mix: 608

P-phenetidine, a deacylation product of bucetin, was about 6 times more mutagenic than bucetin in the presence of PCB-H-S9 mix.

 

Applicant's summary and conclusion

Conclusions:

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

The test substance was positive for mutagenic effects in cultures with metabolic activation and negative without metabolic activation.

Executive summary:

The mutagenic potency of the analgetic bucetin was investigated according to the method of Ames et al., with and without metabolic activation. Since p-phenetidine has been reported in a HPLC study to be a metabolite of bucetin, its mutagenicity has also been studied. P-phenetidine has been found to be about 6 times more mutagenic that bucetin in the presence of PCB-H-S9 mix. Therefore, there is a potential risk, since potent mutagenic metabolites could be formed from bucetin as well as from phenacetin.