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Toxicological information

Genetic toxicity: in vitro

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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

Reference
Name:
Unnamed
Type:
Constituent
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 resultsopen allclose all
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
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
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
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
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.