Propanenitrile, 2,3,3,3-tetrafluoro-2-(trifluoromethyl)-

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted in compliance with OECD GLP regulations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Materials and methods

Test guideline

Qualifier:

according 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:

MTDID 28136

IUPAC Name:

MTDID 28136

Test material form:

other: Gas

Details on test material:

- Name of test material (as cited in study report): MTDID 28136
- Substance type: Mono-constituent
- Physical state: Gas
- Analytical purity: 99.97
- Purity test date: 26 December 2013
- Lot/batch No.: Lot 2

Method

Target gene:

Salmonella thyphimurium strains: Histidine operon, Escherichia coli: thyptophan operon

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:

Arclor 1254 induced rat liver S9 mix

Test concentrations with justification for top dose:

0.0781, 0.156, 0.313, 0.625, 1.25, 2.50, 5.00, 10.0, 20.0, and 40.0 % v/v

Vehicle / solvent:

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

Controls

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Strain Specific

Remarks:

TA100, TA1535, WP2 uvrA: Chloroethane, TA1537: ICR-191 acridine, TA98: 2-nitrofluorene

Details on test system and experimental conditions:

METHOD OF APPLICATION: Incubation in a bag containing the test article at the appropriate concentration.

DURATION
- Preincubation period: None
- Exposure duration: 2 days
- Expression time (cells in growth medium): 2 days
- Selection time (if incubation with a selection agent): NA
- Fixation time (start of exposure up to fixation or harvest of cells): 2 days

SELECTION AGENT (mutation assays): None

NUMBER OF CELLS EVALUATED: All

DETERMINATION OF CYTOTOXICITY
- Method: A concentration was considered cytotoxic if it caused a >50% reduction in the mean number of revertants per plate as compared to the mean vehicle control accompanied by an abrupt concentration-dependent drop in the mean number of revertants or a significant reduction in the background lawn

Evaluation criteria:

The test substance was considered positive for mutagenicity if it induced an increase of revertants per plate with increasing concentration. The increases should be at least two times the vehicle control substance background frequency for strains with high spontaneous levels (TA100) and three times for those with low spontaneous levels (TA1537, TA98, TA1535, and WP2 uvrA). Increases should be seen in at least two or more successive concentrations or the response should be repeatable at a single concentration.

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:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not examined

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: A rangefinding assay was conducted at concentrations of 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10 and 30% v/v. Cytotoxicity was observed at concentrations at and above 3% in TA100 with and without metabolic activation and WP2 uvrA with metabolic activation and at 10% or greater in WP2 uvrA without metabolic activation.

COMPARISON WITH HISTORICAL CONTROL DATA: Controls were consistent with historical data.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Based on the results of the test, the test article was not mutagenic in the Bacterial Reverse Mutation Assay in either the presence or absence of metabolic activation.

Executive summary:

The mutagenic potential of the test article was evaluated in the Bacterial Reverse Mutation Assay with S. typhimurium strains TA98, TA100, TA1535, and TA1537 and E. coli strain WP2 uvrA in the presence and absence of a metabolic activation system (S9-mix rat liver induced by Arclor 1254). The study was performed in compliance with OECD GLP. The test method was based on OECD No. 471 and ICH S2A and S2B.  Plates were exposed to the test substance via incubation in a sealed bag containing the test article at the appropriate concentration. Strains TA100, TA1535 and WP2 uvrA were exposed to chloroethane as a positive control. A dose range-finding test was performed with concentration up to 30% v/v test article in the absence and presence of metabolic activation in strains TA100 and WP2uvrA. Based on the results of the dose range finding test, the test article was tested at concentrations of 0 (control) 0.0781, 0.156, 0.313, 0.625, 1.25, 2.50, 5.00 and 10.0% v/v test article in TA1537 and TA100 with metabolic activation and at 10 % v/v in TA100 and WP2 uvrA without metabolic activation and TA1535 with and without metabolic activation. A confirmatory assay was performed at 0.0781, 0.156, 0.313, 0.625, 1.25, 2.50, 5.00, 10.0, 20.0, and 40.0 % v/v in strains TA98, TA1537 and WP2 uvrA. All treatments were performed in triplicate. No increase in revertant colonies was observed in either the presence or absence of metabolic activation in any strain tested. All criteria for a valid test were met as described in the protocol. Based on the results of the test, the test article was not mutagenic in the Bacterial Reverse Mutation Assay in either the presence or absence of metabolic activation.