Tris(2,4-ditert-butylphenyl) phosphite

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:

1978-05

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:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

Only 4 strains tested.

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tris(2,4-ditert-butylphenyl) phosphite

EC Number:

250-709-6

EC Name:

Tris(2,4-ditert-butylphenyl) phosphite

Cas Number:

31570-04-4

Molecular formula:

C42H63O3P

IUPAC Name:

tris(2,4-ditert-butylphenyl) phosphite

Details on test material:

- Substance type: organic
- Physical state: solid

Method

Target gene:

his locus

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

rat liver microsomes and co-factors

Test concentrations with justification for top dose:

1, 3, 9, 27, and 81 µg/0.1 mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: acetone
- Justification for choice of solvent/vehicle: the test substance is insoluble in water

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: see below

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: none
- Exposure duration: 48 h

SELECTION AGENT (mutation assays): growth in absence of histidine

NUMBER OF CELLS EVALUATED:
In the experiments with and without the addition of microsomal activation mixture, three Petri dishes were prepared per strain and per group

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

CONTROLS:
Positive control experiments were carried out simultaneously with the following substances:
1) for Strain TA 1535: N-methyl-N'- nitro-N-nitrosoguanidine, 3 and 5 µg/0.1 ml phosphate buffer
2) for Strain TA 1537: 9(5)aminoacridine hydrochloride monohydrate, 25, 50, and 100 µg/0.l ml DMSO
3) for Strain TA 98: daunoblastin, 2.5, 5, and 10 µg/0.l ml phosphate buffer
4) for Strain TA 100: 4-nitroquinoline-N-oxide, 0.0625, 0.125, and 0.25 µg/0.l ml phosphate buffer
The activation mixture was tested with Strain TA 1535 and cyclophosphamide 100 and 250 µg/0.1 ml phosphate buffer

Evaluation criteria:

The test substances was considered to be non-mutagenic if the colony count in relation to the negative control was not doubled at any concentration

Statistics:

arithmetic mean

Results and discussion

Test results

Species / strain:

other: S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

SUMMARY OF EXPERIMENTAL RESULT

	TA 98		TA 100		TA 1535		TA 1537
Dose (µg/0.1 ml)	-S9	+S9	-S9	+S9	-S9	+S9	-S9	+S9
solvent control	13	26	78	74	8	13	6	9
1	17	17	80	84	11	14	7	10
3	17	32	75	84	11	14	4	8
9	17	26	79	87	10	12	6	9
27	21	29	78	92	10	12	9	9
81	16	28	66	84	10	13	8	10
positive controls:
solvent control	25		74		14	11	5
concentration A	63		281		68	296	43
concentration B	211		398		1067	549	396
concentration C	229		707		-		>1900
solvent control						19
concentration A						256
concentration B						478

Applicant's summary and conclusion

Conclusions:

Negative with and without metabolic activation.
In the experiments performed with and without microsomal activation, comparison of the number of histidine-prototrophic mutants in the controls and after treatment with test material revealed no marked differences.