Carbonic acid, diphenyl ester, reaction products with bisphenol A

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is comparable to OECD guideline study with accepatable restrictions (details of results not documented due to publication inherent shortening; positive control not concurrent and no positive control for TA98; partly limited documentation, e.g. no data about purity of test substance)

Data source

Reference

Reference Type:

publication

Title:

Multiple activation pathways of benzene leading to products with varying genotoxic characteristics

Author:

Glatt H, Padykula R, Berchtold GA, Ludewig G, Platt KL, Klein J, Oesch F

Year:

1989

Bibliographic source:

Environ Health Perspect 82: 81-89

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

Principles of method if other than guideline:

Study according to Glatt HR, Seidel A, Bochnitschek W, Marquardt H, Marquardt H, Hodgson RM, Grover PL, Oesch F (1986) Mutagenic and cell-transforming activities of triol-epoxides as compared to other chrysese metabolites. Cancer Res. 46: 4556-4565

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Phenol

EC Number:

203-632-7

EC Name:

Phenol

Cas Number:

108-95-2

Molecular formula:

C6H6O

IUPAC Name:

phenol

Details on test material:

No details given

Method

Target gene:

His-

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA97, TA98, TA100, TA102, TA104, TA1535

Metabolic activation:

with and without

Metabolic activation system:

NADPH-fortified postmitochondral fraction from liver homogenate of Aroclor 1254 treated rats

Test concentrations with justification for top dose:

100-5000 µg/plate (without S-9 mix); 20-5000 µg/plate (with S-9 mix)

Vehicle / solvent:

no details but presumably buffer

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

other: concurrent positive controls were not tested but in parallel experiments benzene metabolites were tested and positive results were obtained with exception of TA98

Details on test system and experimental conditions:

Test substance, bacteria, and S9-mix (or buffer) were preincubated for 20 minutes at 37°C and then added to minimal agar plates; colonies counted after incubation for 3 days.
The toxicity was determined (LD50 value in µg/plate) using his+ mutants as an internal standard.

No further details were documented on methods.

Evaluation criteria:

At least 2-fold increase in TA98 and TA1535 or at least 1.5-fold increase of revertants in other strains.

Statistics:

No data but minor restriction in this study

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA97, TA98, TA100, TA102, TA104, TA1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

LD50 = 3000 µg/plate without S9-mix and LD50 = 1800 µg/plate with S9-mix

Vehicle controls validity:

other: no historical controls but valid compared to parallel experiments

Positive controls validity:

other: positive results obtained in parallel experiments (except for TA98)

Additional information on results:

No further details presented on results (not documented due to publication inherent shortening).

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

No induction of gene mutation in the bacterial reverse mutation assay at concentrations up to 5 mg/plate (max. recommended dose level in OECD 471).

Executive summary:

The study is comparable to OECD guideline study with acceptable restrictions (details of results not documented due to publication inherent shortening; positive control not concurrent and no positive control for TA98; partly limited documentation, e.g. no data about purity of test substance).

S. typhimurium strains TA97, TA98, TA100, TA102, TA104, and TA1535 were exposed with and without metabolic activation to varying concentrations of phenol (100 -5000 µg/plate without S-9 mix and 20 -5000 µg/plate with S-9 mix). Cytotoxic effects (LD50 measured in his+ mutants as internal standards) were detected at 3000 µg/plate without S9 -mix and at 1800 µg/plate with S9 -mix. No genotoxic effects were recorded in any strain (increase in revertants less than 1.5 -2 -fold).

Conclusion: No induction of gene mutation in the bacterial reverse mutation assay at concentrations up to 5 mg/plate (max. recommended dose level in OECD 471).