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Toxicological information

Genetic toxicity: in vitro

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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:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
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
Species / strain:
other: TA1537, TA1535, TA98, TA100, TA102
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.