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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Remarks:
This experimental study was performed only for one constituent (2,2'-[ethylenebis(oxymethylene)]bisoxirane, CAS 2224-15-9, EC 218-746-2) of the UVCB substance.
Adequacy of study:
supporting study
Study period:
Unknown
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
no data on historical controls provided
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: at room temperature in the dark
- Stability under test conditions: verified at the end of the study

Method

Target gene:
his operon, trp operon
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:
S9 mix, prepared from the livers of rats treated with phenobarbital and 5-6-benzoflavone
Test concentrations with justification for top dose:
TA100 and TA1535 without S9: 9.77, 19.5, 39.1, 78,1, 156.3, 312.5, 625, 1250, 2500 and 5000 μg/plate
TA100 and TA1535 with S9: 39.1, 78,1, 156.3, 312.5, 625, 1250, 2500 and 5000 μg/plate

WP2uvrA with and without S9: 78,1, 156.3, 312.5, 625, 1250, 2500 and 5000 μg/mL

TA98 and TA1537 with and without S9: 312.5, 625, 1250, 2500 and 5000 μg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water for injection
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 2AA (2-aminoanthracene) for strains with S9, AF-2 [2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide] for TA98, TA100 and WP2uvrA without S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; preincubation

DURATION
- Preincubation period: 20 minutes
- Exposure duration: 48 h

NUMBER OF REPLICATIONS: 3 replications


Evaluation criteria:
A test substance was considered positive in the Ames test if:
a) the vehicle control result was within mean ± 2 S.D. according to background data,
b) the positive result was more than 2-fold increase in compared with the vehcile control,
c) the increase was dose-related and reproducible, and
d) there was no other influence on the test system
Statistics:
Mean ± standard deviation

Results and discussion

Test results
Species / strain:
other: TA98, TA100, TA1535 and WP2urvA
Metabolic activation:
with and without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
5000 µg/plate with and without S9 in WP2uvrA
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: no precipitation

RANGE-FINDING/SCREENING STUDIES:
Dose-finding test was performed with 5, 15, 50, 150, 500, 1500 and 5000 μg/plate in all strains.

HISTORICAL CONTROL DATA (with ranges, means and standard deviation and confidence interval (e.g. 95%)
- Negative (solvent/vehicle) historical control data: not provided

Any other information on results incl. tables

Table 1.

Applicant's summary and conclusion