Diphenyl carbonate

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:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

Plate incorporation assay

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Diphenyl carbonate

EC Number:

203-005-8

EC Name:

Diphenyl carbonate

Cas Number:

102-09-0

Molecular formula:

C13H10O3

IUPAC Name:

diphenyl carbonate

Details on test material:

purity assumed to be > 99 %

Method

Target gene:

Histidine gene (S. typhimurium), Tryptophan gene (E. coli WP2)

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli strain (WP2)

Metabolic activation:

with and without

Metabolic activation system:

S9 rat liver microsomal fraction

Test concentrations with justification for top dose:

0, 0.5, 1.5, 5, 15, 50, 150, 500, 1500, 5000 µg/plate
Because of strong cytotoxicity at >= 500 µg/plate in a non-activation range-finding study, the concentrations were limited to 150 µg/plate.
exp. I and II without S9-mix: 0.5 - 150 µg/plate
exp. I and II with S9-mix: 15 - 5000 µg/plate

Vehicle / solvent:

DMSO

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

as appropriate (see below)

Remarks:

Appropriate reference mutagens (sodium azid, 9-aminoacridine, 2-AA, ENNG, 2-NF) were used as positive controls

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 72 hours

NUMBER OF REPLICATIONS: 2

Evaluation criteria:

A test result was considered positive if for any strain a significant increase (2- to 3-fold in dependence on strain) over the negative control in the number of revertants per plate was observed which was concentration-dependent.

Statistics:

none

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli strain (WP2)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: >= 500 µg/plate without S9 mix, 5000 µg/plate with S9 mix

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Without metabolic activation: diphenyl carbonate was toxic to all four Salmonella strains at the dose levels of 0.15 mg/plate and higher.  At 0.05 mg/plate, slight toxicity was seen in strains TA 98 and TA 1537.  E. coli showed no toxicity at any dose.  No bacterial strain demonstrated any mutagenicity in conjunction with DPC.  All test plate counts remained within acceptable historical background parameters.  
With metabolic activation: Extreme toxicity was seen in all four Salmonella typhimurium strains at 5 mg/plate.  In addition, TA1535 and TA1537 also showed increased toxicity to the test chemical at 1.5 mg/plate.  Slight toxicity was also observed at 1.5 and 0.5 mg/plate in the Salmonella strains.  E. coli was not affected by the test chemical at any dose level.  As with the non-activated assay, no mutagenicity was observed at any dose level.

Applicant's summary and conclusion

Conclusions:

Diphenyl carbonate showed no mutagenic properties in the Ames Test with S. typhimurium TA 1535, TA 1537, TA 98, TA 100 or E. coli WP2.

Executive summary:

The mutagenic potential of the substance was investigated in a study which was conducted in accordance with OECD 471.

During the study S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 and E. coli WP2 were exposed to the test material in DMSO. Due to strong cytotoxicity at 500 µg/plate in a non-activation range-finding study, the concentrations were limited to 150 µg/plate. Experiments I and II were performed without S9 mix in the test concentration range of 0.5 to 150 µg/plate; Experiments I and II were performed with S9 mix in the test concentration range of 15 to 5000 µg/plate.

Without metabolic activation, diphenyl carbonate was toxic to all four Salmonella strains at dose levels of 0.15 mg/plate and higher. At 0.05 mg/plate, slight toxicity was seen in strains TA 98 and TA 1537. E. coli showed no toxicity at any dose. No bacterial strain demonstrated any mutagenicity in conjunction with the test material. All test plate counts remained within acceptable historical background parameters. 

With metabolic activation, extreme toxicity was seen in all four Salmonella typhimurium strains at 5 mg/plate. In addition, TA1535 and TA1537 also showed increased toxicity to the test chemical at 1.5 mg/plate. Slight toxicity was also observed at 1.5 and 0.5 mg/plate in the Salmonella strains. E. coli was not affected by the test chemical at any dose level. As with the non-activated assay, no mutagenicity was observed at any dose level.

Under the conditions of this study, diphenyl carbonate did not cause a positive response in either the presence or absence of metabolic activation and is therefore non-mutagenic in the Ames test.