Triphenyl 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:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Triphenyl phosphite

EC Number:

202-908-4

EC Name:

Triphenyl phosphite

Cas Number:

101-02-0

Molecular formula:

C18H15O3P

IUPAC Name:

triphenyl phosphite

Constituent 2

Reference substance name:

Triphenyl phosphate

EC Number:

204-112-2

EC Name:

Triphenyl phosphate

Cas Number:

115-86-6

Molecular formula:

C18-H15-O4-P

IUPAC Name:

triphenyl phosphate

Specific details on test material used for the study:

NAME OF TEST MATERIAL: Triphenyl Phosphite
- Purity: 99.48%

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: UPL Limited, Jhagadia, India. Batch No. CO05TPI078
- Expiration date of the lot/batch: February 2018
- Purity: 99.48%
- Purity test date: March 29, 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Under ambient conditions in original container
- Solubility and stability of the test substance in the solvent/vehicle: soluble in dimethyl sulfoxide at concentration of 50 µL/mL
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Precipitation was not observed at the tested concentrations

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102

Metabolic activation:

with and without

Metabolic activation system:

Arochlor 1254-induced rat liver S9 fraction

Test concentrations with justification for top dose:

6 concentrations (three plates/concentration) between 0.15625 and 5 µL/plate both in the absence and presence (10 % v/v S9 mix) of metabolic activation.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility

Controls

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

2-nitrofluorene

sodium azide

mitomycin C

other: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
- Cell density at seeding (if applicable): approximately 1 - 2 x 10E9 bacteria/mL

DURATION
- Exposure duration: 48-hr incubation

SELECTION AGENT (mutation assays): histidine

Rationale for test conditions:

Test guideline

Evaluation criteria:

Tester strain integrity, characteristic number of spontaneous revertants, tester strain density, positive control values with and without metabolic activation, cytoxicity, responses observed

Statistics:

Simple linear regression analysis was performed to assess the dose dependent nature of any increase in revertant colonies.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

In a reliable OECD Guideline 471 GLP study, TPP was not mutagenic to any of 5 strains of S. typhimurium when tested in the absence and presence of an exogenous metabolic activation system (rat liver S9) at concentrations up the recommended maximum test concentration of 5 µL/plate.