4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with fatty acids, C18-unsatd., dimers

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:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to the O.E.C.D. test guideline 471 with GLP compliance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of fatty acids, C18-unsaturated, dimers and 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

EC Number:

701-484-2

Cas Number:

67989-52-0

Molecular formula:

(C15H16O2.C3H5ClO.Unspecified)x

IUPAC Name:

Reaction products of fatty acids, C18-unsaturated, dimers and 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Test material form:

liquid: viscous

Details on test material:

As per IUCLID5 Sections 1.1. 1.2. and 4.1.

Method

Target gene:

histidine synthesis

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

Phenobarbitone/B3-Naphthoflavone induced rat liver S9 metabolic activation.

Test concentrations with justification for top dose:

0, 0.15, 0.5, 1.5, 5, 15, 50, 150, 500, 1500 and 5000 ug/plate

Vehicle / solvent:

acetone

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

N-ethyl-N-nitro-N-nitrosoguanidine

benzo(a)pyrene

other: 2-aminoanthracene

Details on test system and experimental conditions:

The test substance was tested in Salmonella strains TA98, TA100, TA1535, and TA1537 and E. coli strain WP2uvrA without metabolic activation and with liver S9 preparations from Phenobarbitone/B3-Naphthoflavone-induced rats in a liquid incubation protocol. The Salmonella tester strains were grown up over night in nutrient broth to late log phase. The main study was performed at 6 doses, using triplicate plates. Tests were repeated at least once. S9 metabolic activation mix or buffer and vehicle, positive control substance or test substance dilution were added culture tubes. The appropriate tester strain was then added to the cultures tubes. Following this liquid preincubation treatment, approximately 2 mL of molten minimal soft agar were added to each tube followed by vortexing. The contents of the culture tubes were poured over minimal medium agar plates. The plates were allowed to harden and then incubated at approximately 37 C for 48-72 hr.

Evaluation criteria:

A positive response was defined as a reproducible, dose-related increase in his+ revertants over the solvent control level.

Statistics:

No

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: TA100

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
positive

The test substance induced a reproducible, dose-related increase of the his+ revertant frequency in Salmonella strain TA100 without liver S9 metabolic activation preparation. Strain TA1535 and WP2urvA induced an increase with and without S9 metabolic acitivation. The data suggest that the test substance is mutagenic without liver S9 metabilic activation under the conditions of the study.

Executive summary:

The test item, EPIKOTE 872 (4,4'-lsopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with fatty acids, C18-unsatd., dimers/CAS No. 67989-52-0) , was considered to be mutagenic under the conditions of this test.