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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well performed GLP compliant study using a different set of tester strains as compared to actual guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Principles of method if other than guideline:
a different set of tester strains was used as compared to actual guidelines
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
p,p'-dinitrobibenzyl
EC Number:
212-001-5
EC Name:
p,p'-dinitrobibenzyl
Cas Number:
736-30-1
Molecular formula:
C14H12N2O4
IUPAC Name:
p,p'-dinitrobibenzyl

Method

Species / strain
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced rat liver S9 mix
Test concentrations with justification for top dose:
1.0, 10.0, 100.0, 500.0, 1000.0, 2500.0, 5000.0, 10000.0 µg per plate with and without metabolic activation
Vehicle / solvent:
DMSO
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: 2-Anthramine
Evaluation criteria:
(1) Strains TA-1535, TA-1537 and TA-1538
If the solvent control value is within the normal range, a test
material producing a positive response equal to or above three times the solvent
control value is considered mutagenic.

(2) Strains TA-98 and TA-l00
If the solvent control value is within the normal range, a test
material producing a positive response equal to or above twice the solvent
control value is considered mutagenic.
Statistics:
not required

Results and discussion

Test results
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
positive
Remarks:
in TA-1538, TA-98 and TA-l00 with and without metabolic activation
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

The test material exhibited genetic activity with the strains TA-1538, TA-98 and TA-100 with and without metabolic activation and was therefore considered to be mutagenic under these test conditions.
Executive summary:

The test compound was examined for mutagenic activity in a series of in vitro microbial assays employing Salmonella indicator organisms (TA 98, TA100, TA 1535, TA 1537, TA 1538). The compound was tested in the absence and in the presence of liver microsomal enzyme preparations from Aroclor-induced rats.

A negative control consisting of the solvent used for preparing the stock solutions and subsequent dilutions of the test material and specific positive compounds were also assayed concurrently with the test material. The negative control data was used as the basis for evaluating the results obtained with the test material.

Doses were selected from a preliminary study conducted with the test material at 14 doses of 1.22 µg to 10,000 µg per plate using the strain TA-100.

In the preliminary toxicity study, the test material did not exhibit toxicity to the indicator strain at any of the doses tested as evidenced by the presence of the background lawn on the minimal plates. As such, the mutagenicity assays were conducted at 8 doses of 1.0 µg to 10,000.0 µg per plate.

The test conducted on the test material in the absence of a metabolic activation system was positive with strains TA-1538, TA-98 and TA-100.

The test conducted on the test material in the presence of a rat liver activation system was positive with strains TA-1538, TA-98 and TA-100.

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