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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
Beta W 7 A 1.0 is not mutagenic in an OECD 471 study.
Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline Study
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
Salmonella typhimurium strains
TA 98 hisD3052 rfa uvrB +R,
TA 100 hisG46 rfa uvrB +R,
TA 1535 hisG46 rfa uvrB,
TA 1537 hisC3076 rfa uvrB
Metabolic activation system:
S9 Mix
Test concentrations with justification for top dose:
Concentration range in the main test (with metabolic activation): 4, 20, 100, 500, 2500, 5000 µg/plate
Concentration range in the main test (without metabolic activation): 4, 20, 100, 500, 2500, 5000 µg/plate
Vehicle / solvent:
dissolved in double-distilled water at appropriate concentrations immediately before use
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: 2-aminoanthracene
Details on test system and experimental conditions:
The test compound was dissolved in double-distilled water and a stock solution of
50 mg/ml was prepared for the highest concentration, which provided a final
concentration of 5000 µg/plate. Further dilutions of 2500, 500, 100, 20 and 4 µg/plate
were used in all experiments.
The test compound did not precipitate on the plates up to the highest investigated dose
of 5000 ug/plate.
The test compound proved to be not toxic to the bacterial strains.
A toxicity test using histidine-enriched agar plates and a dilution of the tester strain
TA 100 (designated TA 100 D) was performed in parallel with the second experiment.
The test compound proved to be not toxic to the bacterial strain.
Species / strain:
other: as specified above
Metabolic activation:
with
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(> 5000 µg/plate)
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
other: as specified above
Metabolic activation:
without
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
(> 5000 µg/plate)
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
The strain TA 1535 showed an increased number of revertants
at concentrations 4 and 100 µg/plate. This effects was not
reproducible in a second test nor in a further one with TA1535.
Remarks on result:
other:
Remarks:
Migrated from field 'Test system'.

The 59 fraction was prepared by the department conducting the study according to

Ames et. al (1975). Male 5prague Dawley rats (200-300 g), supplied by Harlan

Winkelmann, Gartenstrasse 27,33178 Borchen, Germany, received a single

intraperitoneal injection of Aroclor 1254 (500 mglkg body weight) 5 days before killing.

The livers were removed from at least 5-6 animals at approx. 0 to 4 °C using cold

sterile solutions and glassware, and were then pooled and washed in approx. 150 mM

KCI (approximately 1 ml/g wet liver). The washed livers were cut into small pieces and

homogenized in three volumes of KCl. The homogenate was centrifuged at approx.

9000 g for 10 minutes. The supernatant was the 59 fraction. This was divided into

small portions, rapidly frozen and stored at approx. - 80°C for not longer than six

months. The protein content was determined for every batch. Also for every batch of

59 an independent validation was performed with a minimum of two different

mutagens, e.g., 2-aminoanthracene and dimethylbenzanthracene to confirm metabolic

activation by microsomal enzymes.

Conclusions:
Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

The results lead to the conclusion that Beta W 7 A 1.0 is not mutagenic in these
bacterial test systems either in the absence or in the presence of an exogenous
metabolizing system.

Executive summary:

Beta W 7 A 1.0 was tested for mutagenicity with the strains TA 100, TA 1535, TA 1537

and TA 98 of Salmonella typhimurium.

Two independent mutagenicity studies were conducted, each in the absence and in the

presence of a metabolizing system derived from a rat liver homogenate.

Additionally a third assay was performed with the strain TA 1535 in the presence of

S9-mix.

For all studies, the compound was dissolved in double-distilled water, and each

bacterial strain was exposed to 6 dose levels.

Doses for all studies ranged from 4 to 5000 ug/plate.

Control plates without mutagen showed that the number of spontaneous revertant

colonies was within the laboratory's historical control range and similar to that

described in the literature. All the positive control compounds showed the expected

increase in the number of revertant colonies.

Toxicity: In the mutagenicity experiments toxicity was not observed.

A toxicity test using histidine-enriched agar plates and a dilution of the tester strain

TA 100 (designated TA 100 D) was performed in parallel with the second experiment.

The test compound proved to be not toxic to the bacterial strain.

Mutagenicity: In the absence and in the presence of the metabolic activation system

Beta W 7 A 1.0 did not result in relevant increases in the number of revertants in any

of the bacterial strains.

Summarizing, it can be stated that Beta W 7 A 1.0 is not mutagenic in these bacterial

test systems either with or without exogenous metabolic activation at the dose levels

investigated.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

The results lead to the conclusion that Beta W 7 A 1.0 is not mutagenic in these

bacterial test systems either in the absence or in the presence of an exogenous

metabolizing system.


Justification for selection of genetic toxicity endpoint
OECD Guideline Study

Justification for classification or non-classification