Triphenylphosphine 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

tester strains which were able to detect crosslinking/oxidising agents were not used

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Triphenylphosphine oxide

EC Number:

212-338-8

EC Name:

Triphenylphosphine oxide

Cas Number:

791-28-6

Molecular formula:

C18H15OP

IUPAC Name:

(diphenylphosphoroso)benzene

Test material form:

solid

Method

Target gene:

his-

Species / strain

Species / strain / cell type:

other: S. typhimurium TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix from Aroclor 1254 induced rat livers

Test concentrations with justification for top dose:

4, 20, 100, 500, 1000, 1500, 2000 and 2500 µg/plate

Vehicle / solvent:

Acetone

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: without S-9 mix: N-Methyl-N'-nitro-N-nitroso-guanidine for all strains; with S-9 mix: cyclophosphamide for TA 100; 2-aminoanthracene for TA 100, TA 98, TA 1537

Details on test system and experimental conditions:

METHOD OF APPLICATION: plate incorporation, two independent trials

NUMBER OF REPLICATIONS: 3

Evaluation criteria:

substances were considered as positive in the Ames test if following criteria are fulfilled:
- doubling the spontaneous mutation rate
- dose-effect-relationship observed
- reproducibility of the results

Results and discussion

Test results

Key result

Species / strain:

other: S. typhimurium TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

2000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Experiment 1

Dose (µg/plate)	Number of revertant colonies of 4 replicate plates with different strains of Salmonella typhimurium
	TA98	TA100	TA1537
	Results with S9
Aceton	47;30;30;26	141;136;136;125	10;7;11;5
4	34;24;26;42	143;146;147;141	6;11;8;7
20	33;26;24;31	119;135;118;129	10;6;10;13
100	n.d.;24;25;48	124;142;135;142	14;6;7;11
500	20;18;30;37	129;163;127;125	4;6;8;7
1000
1500
2000
2500	31;24;38;27	78;80;115;136	6;8;8;7
2-AA (10.0)	700;515;1035;520	1420;1460;1530;1550	78;78;98;68
Cyclopho. (500)		220;236;194;248
MNNG (5)
	Results without S9
Aceton	21;28;35;30	109;96;115;108	10;8;6;2
4	26;n.d.;35;32	98;130;135;116	4;7;5;3
20	32;37;27;32	149;121;113;115	5;2;6;5
100	15;44;23;30	120;145;101;102	6;5;3;5
500	20;24;23;28	134;154;114;145	3;2;5;4
1000
1500
2000
2500	n.d.;17;15;18 (B)	108;98;102;113 (B)	4;n.d.;5;n.d.
MNNG (5)		2013;2100;1950;2250	13;18;17;19

B= reduced background growth

n.d.= not determined

 

Experiment 2

Dose (µg/plate)	Number of revertant colonies of 4 replicate plates with different strains of Salmonella typhimurium
	TA98	TA100	TA1537
	Results with S9
Aceton	32;27;22;27	114;103;79;95	5;6;8;4
4
20
100	24;24;26;21	112;91;83;103	9;10;6;5
500	25;21;29;26	102;90;93;118	6;7;4;8
1000	24;33;25;20	103;87;104;91	7;7;5;4
1500	28;13;22;18	81;90;91;86	7;10;6;10
2000	21;15;24;24	56;32;57;69 (B)	7;4;6;6
2500	7;18;19;17 (B)	64;44;66;76 (B)	4;6;5;3 (B)
2-AA (10.0)	559;537;498;315	856;1000;1044;929	75;70;61;60
Cyclopho. (500)		225;218;215;198
MNNG (5)
	Results without S9
Aceton	20;54;35;30	149;144;165;155	3;6;6;3
4
20
100	61;n.d.;37;23	143;148;173;124	8;2;5;3
500	38;42;43;n.d.	136;156;120;144	4;5;3;2
1000	41;45;29;35	139;158;130;169	7;6;5;4
1500	42;51;34;n.d.	143;135;130;142	6;4;5;3
2000	35;52;n.d.21	130;n.d.;134;105	10;8;n.d.;5
2500	33;27;33;n.d.	56;96;124;85	n.d.;6;n.d.;9
MNNG (5)	1760;1600;1500;1760	2400;2560;220;2420	16;14;17;24

B= reduced background growth

n.d.= not determined

 

 

The test item was neither mutagenic in the Ames-test with metabolic activation by S-9 mix, nor without. The amount of revertants was in the range of the negative controls (differences not significant).

The test item demonstrated to be toxic for the Salmonella strains employed upon concentrations > 2000 µg/plate.

 Positive controls showed a distinct increase in revertants in all experimental approaches.

Applicant's summary and conclusion

Conclusions:

The test substance under the experimental conditions described was not mutagenic.

Executive summary:

A bacterial reverse mutation assay (plate incorporation, two independent trials) similar to OECD Guideline 471 was conducted. S. typhimurium TA 1537, TA 98 and TA 100 was exposed to test item concentrations of 4 - 2500 µg/plate. As vehicle acetone was used. In addition , negative controls, solvent controls and positive controls were performed (without S-9 mix: N-Methyl-N'-nitro-N-nitroso-guanidine for all strains; with S-9 mix: cyclophosphamide for TA 100; 2-aminoanthracene for TA 100, TA 98, TA 1537). Tester strains which were able to detect crosslinking/oxidising agents were not used. The test item was considered to be positive in the Ames test if the spontaneous mutation rate doubled, dose-effect-relationship was observed and if the results are reproducible. In result, the test item was neither mutagenic in the Ames-test with metabolic activation by S-9 mix, nor without. The amount of revertants was in the range of the negative controls (differences not significant). The test item demonstrated to be toxic for the Salmonella strains employed upon concentrations > 2000 µg/plate. Positive controls showed a distinct increase in revertants in all experimental approaches. In conclusion, these results indicate that the test substance under the experimental conditions described, was not mutagenic to Salmonella typhimurium strains TA 1537, TA 98 and TA 100 in the presence and absence of a metabolizing system.