Diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide

EC Number:

278-355-8

EC Name:

Diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide

Cas Number:

75980-60-8

Molecular formula:

C22H21O2P

IUPAC Name:

(mesitylcarbonyl)(diphenyl)phosphine oxide

Details on test material:

- Name of test material (as cited in study report): Lucirin LR 8728
- Analytical purity: not reported
- Physical state: pale yellow powder
- Lot/batch No.: 010213
- Storage condition of test material: stored in brown glass screw-top jars at approximately 4°C in the dark (handling time restricted to 15 minutes under fluorescent light)

Method

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:

Aroclor 1254 induced rat liver S9

Test concentrations with justification for top dose:

0, 312.5, 625, 1250, 2500 and 5000 µg/plate (in the preliminary toxicity study);
0, 8, 40, 200, 1000, and 5000) µg/plate (first experiment);
0, 312.5, 625, 1250, 2500, and 5000) µg/plate (second experiment)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: ethanol

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

9-aminoacridine

other: N-methyl-n-nitro-n-nitrosoguanidine

Remarks:

without S9

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with S9

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours at 37°C

SELECTION AGENT (mutation assays): histidine (or tryptophan in the case of WP2uvrA-)

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: 0.1 ml of bacterial suspension (TA100 or WP2uvrA-) and 0.1 ml of test solution were added to 2 ml of molten, trace histidine or tryptophan supplemented media (histidine/biotin or tryptophan & top agar) and overlayed onto sterile plates of Vogel-Bonner agar (minimal agar -25 ml/ plate). Five doses of the test substance and a solvent control were tested in duplicate. After 48-72 hours incubation the plates were scored for revertant colonies and examined for a thinning of the background lawn.

Evaluation criteria:

- The test chemical is considered positive in this assay if it induces a dose-related and statistatistically significant increase in mutation rate (of at least twice the spontaneous reversion rate) in one or more strains of bacteria in the presence and/or absence of the S-9 microsomal enzymes in both experiments.
- The test substance is generally considered non-mutagenic in this test if the number of induced revertants compared to spontaneous revertants is less than 2-fold at each dose level employed, the intervals of which should be between 2 and 5 fold and extend to the limits imposed by toxicity or solubility or up to the maximum recommended dose of 5000 µg/plate.

Results and discussion

Test results

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: observed at the highest tested dose (5000 µg/plate)

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Mean maximum revertants/plate and the corresponding concentration with/without S-9 mix are resumed below:

- First experiment:

	Mean maximum revetants observed/plate [corresponding test concentration (µg/plate)]
	Solvent control		Test substance		Positive control (substance)
Strains	with	without	with	without	with	without
TA100	78	87	90 [40]	83 [40]	732 [3.3] (2-AA)	472 [2.0] (MNNG)
TA1535	18	9	19 [40, 5000]	12 [40, 1000]	49 [3.3] (2-AA)	139 [2.0] (MNNG)
WP2uvrA-	24	30	31 [40]	31 [8]	126 [10.0] (2-AA)	734 [3.3] (4NQO)
TA98	25	18	27 [200, 1000]	22 [200]	501 [3.3] (2-AA)	803 [10.0] (4NOPD)
TA1537	6	4	6 [8]	4 [8, 200, 1000]	48 [3.3] (2-AA)	202 [50.0] (9-AA)

The spontaneous reversion counts/plate was 17.7, 8.3, 29, 107.7 and 33 respectively for TA1535, TA1537, TA 98, TA100 and WP2uvrA-.

- Second experiment

	Mean maximum revetants observed/plate [corresponding test concentration (µg/plate)]
	Solvent control		Test substance		Positive control (substance)
Strains	with	without	with	without	with	without
TA100	70	75	78 [5000]	79 [312.5]	1060 [3.3] (2-AA)	599 [2.0] (MNNG)
TA1535	14	11	14 [312.5]	12 [312.5, 2500]	74 [3.3] (2-AA)	289 [2.0] (MNNG)
WP2uvrA-	24	21	27 [312.5]	22 [625]	127 [10.0] (2-AA)	823 [3.3] (4NQO)
TA98	23	19	24 [2500]	19 [5000]	444 [3.3] (2-AA)	741 [10.0] (4NOPD)
TA1537	7	6	7 [625]	6 [5000]	59 [3.3] (2-AA)	134 [50.0] (9-AA)

The spontaneous reversion counts/plate was 15.5, 5, 23.7, 83.3 and 148.3 respectively for TA1535, TA1537, TA 98, TA100 and WP2uvrA-.

Applicant's summary and conclusion

Conclusions:

Under the experimental conditions in this study, the test substance is not a mutagenic agent in a bacterial reverse mutation test in vitro.