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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
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: Comparable to guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
no
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ro 81-1789/000
- Purity test date: 19.03.1983
- Lot/batch No.: 564'262

Method

Target gene:
HGPRT
Species / strain
Species / strain / cell type:
Chinese hamster lung fibroblasts (V79)
Details on mammalian cell type (if applicable):
- Type and identity of media: MEM medium + 10% FCS
- Properly maintained: yes
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
S9 liver microsomal fraction obtained from Aroclor 1254-induced male Sprague-Dawley rats.
Test concentrations with justification for top dose:
5, 10, 15, 20 µg/mL
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
yes
Positive controls:
yes
Positive control substance:
other: Ethylmethanesulfonate and 7,12-Dimethylbenzanthracene

Results and discussion

Test results
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
20 µg/mL reduced the plating efficiency to 12.8%
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1: Mutagenicity and toxicity data (experiment 1)

 

Concentration [µg/mL]

S9 mix

Mean number of mutant colonies

Mutant colonies per 106cells

Plating efficiency [%]

Negative control

0.0

-

+

3.6±0.9

4.6±1.8

12.8

17.7

67.1

65.7

Negative control + solvent

0.0

-

+

3.4±1.8

3.8±1.3

9.7

18.8

70.2

65.6

Positive control (EMS)

1000

-

73.6±12.3

220.3

71.

Positive control (DMBA)

15.4

+

51.6±2.5

318.9

60.9

Test compound

5.0

-

+

4.8±2.7

4.8±1.8

17.7

19.5

68.7

65.1

 

10.0

-

+

3.8±2.2

6.7±2.3

15.4

27.7

62.4

69.6

 

15.0

-

+

8.6±1.1

3.3±2.1

38.3

12.8

52.3

67.0

 

20.0

-

+

4.0±1.7

5.4±1.5

15.3

21.1

37.6

68.6

 

Table 2: Mutagenicity and toxicity data (experiment 2)

 

Concentration [µg/mL]

S9 mix

Mean number of mutant colonies

Mutant colonies per 106cells

Plating efficiency [%]

Negative control

0.0

-

+

1.6±0.5

2.6±1.7

4.3

11.3

66.7

64.4

Negative control + solvent

0.0

-

+

4.8±1.1

3.8±1.6

12.9

9.9

68.2

69.3

Positive control (EMS)

1000

-

64.4±12.2

190.3

67.2

Positive control (DMBA)

15.4

+

28.4±5.2

105.0

53.5

Test compound

5.0

-

+

7.4±2.9

6.0±2.9

17.8

22.5

64.1

62.7

 

10.0

-

+

4.8±1.5

1.8±0.8

10.8

8.4

51.8

60.3

 

15.0

-

+

2.4±1.3

3.6±0.9

6.9

11.7

50.0

63.8

 

20.0

-

+

4.0±2.9

0.6±0.9

10.8

2.1

44.6

52.9

 

 

Applicant's summary and conclusion

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

It is concluded that under the experimental conditions described in the report neither butyl methoxydibenzoylmethane (BMDBM) per se nor one of its metabolites formed by rat liver enzymes induced mutations at the HGPRT locus in Chinese hamster cells in vitro.
Executive summary:

The test compound butyl methoxydibenzoylmethane (BMDBM) was assessed for mutagenic properties in two independent experiments in the HGPRT-test with V79 cells. In a pre-experiment concentrations of the test compound solubilised in methanol higher than 20 µg/mL lead to precipitation in the nutrient medium. However, 20 µg/mL reduced the plating efficiency (PE; = survival) to 12.8 % in the absence of S9 mix. In the presence of S9 mix the test compound was only slightly toxic: PE = 91.2 %. With the four concentrations up to 20 µg/mL no indication of mutagenic activity was recorded, neither in the presence nor in the absence of S9 mix. The variations of the mutant clonies/106 cells in both experiments do not show any tendency with regard to an enhancement of mutation rates.