4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid

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:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid

EC Number:

500-130-2

EC Name:

4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, esters with acrylic acid

Cas Number:

55818-57-0

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Reaction product of (4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane) and 2-propenoic acid

Test material form:

liquid: viscous

Method

Target gene:

n/a

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Additional strain / cell type characteristics:

not applicable

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

24.0 µg - 6,000 µg/plate (SPT); 4.8 µg - 3000 µg/plate (PIT)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: Due to the limited solubility of the test substance in water, DMSO was selected as the vehicle, which has been demonstrated to be suitable in bacterial reverse mutation tests and for which historical control data are available.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene (2-AA)

Remarks:

with S-9 mix for strains TA 1535, TA 100, TA 1537, TA 98 and E.coli WP2 uvrA

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: N-methyl-N'nitro-N-nitrosoguanidine (MNNG)

Remarks:

without S-9 mix for strains TA 1535 and TA 100

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 4-nitro-o-phenylendiamine (NOPD)

Remarks:

without S-9 mix for strain TA 98

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

without S-9 mix for strain TA 1537

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

without S-9 mix for strain E.coli WP2 uvrA

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation); preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48-72 hours

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

The test chemical is considered positive in this assay if the following criteria are met:
A dose-related and reproducible increase in the number of revertant colonies, i.e. about doubling of the spontaneous mutation rate in at least one
tester strain either without S-9 mix or after adding a metabolizing system.

A test substance is generally considered nonmutagenic in this test if:
The number of revertants for all tester strains were within the historical negative control range under all experimental conditions in two experiments
carried out independently of each other.

Statistics:

no data

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

A weak bacteriotoxic effect was occasionally observed depending on the strain and test conditions from about 600 µg - 3000 µg/plate onward.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

A weak bacteriotoxic effect was occasionally observed depending on the strain and test conditions from about 600 µg - 3000 µg/plate onward.

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

A weak bacteriotoxic effect was occasionally observed depending on the strain and test conditions from about 600 µg - 3000 µg/plate onward.

The maximum increase in the number of revertant colonies of 1.6, which was observed in a single incidence without a dose response relationship was well below a doubling of the number of revertant colonies and as the criteria for a positive result were not met, the test substance is not mutagenic in the Ames test.

Applicant's summary and conclusion

Conclusions:

Under the test conditions, DGEBA diacrylate is not considered as mutagenic in bacterial reverse mutation test.

Executive summary:

In a GLP study performed according to OECD guideline 471, DGEBA diacrylate was tested for mutagenicity using Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and E.coli WP2 uvrA with the plate incorporation and preincubation methods in the presence and absence of metabolic activation system.

A concentration range from 24.0 µg to 6000 µg/plate was used with the plate incorporation technique and concentrations from 4.8 µg to 3000 pg/plate were tested with the preincubation method. Precipitation was found from about 3000 µg/plate and higher. A weak bacteriotoxic effect was occasionally observed depending on the strain and test conditions from about 600 pg to 3000 pg/plate.

The positive controls induced the appropriate responses in the corresponding strains. DGEBA diacrylate showed no substantial increases in revertant colony numbers over control count obtained with any of the tester strains at any concentrations in either presence or absence of S-9.

Under the test conditions, DGEBA diacrylate is not considered as mutagenic in this bacterial system.