1-[4-(1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)propane-1,3-dione

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

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

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

no

GLP compliance:

yes

Type of assay:

in vitro mammalian cell gene mutation test using the Hprt and xprt genes

Test material

Test material information

Constituent 1

Reference substance name:

1-[4-(1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)propane-1,3-dione

EC Number:

274-581-6

EC Name:

1-[4-(1,1-dimethylethyl)phenyl]-3-(4-methoxyphenyl)propane-1,3-dione

Cas Number:

70356-09-1

Molecular formula:

C20H22O3

IUPAC Name:

1-(4-tert-butylphenyl)-3-(4-methoxyphenyl)propane-1,3-dione

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:

7,12-dimethylbenzanthracene

ethylmethanesulphonate

Results and discussion

Test results

Key result

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

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 10^6cells	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 10^6cells	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:

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.