1-Octanol, reaction products with phosphorus oxide (P2O5), potassium salts

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:

21 March to 04 May, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

1997

GLP compliance:

yes

Remarks:

US FDA (21 CFR Parts 58, 210, 211, and 820) Regulations

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

1

Reference substance name:

Octan-1-ol, reaction products with diphosphorus pentaoxide, potassium salts

EC Number:

807-789-8

Cas Number:

111062-42-1

Molecular formula:

C8-H18-O.K.O5-P2

IUPAC Name:

Octan-1-ol, reaction products with diphosphorus pentaoxide, potassium salts

Specific details on test material used for the study:

Test Article: Agent 447C; 1-octanol, reaction products with phosphorus oxide (P2Os), potassium salts (CAS 111062-42-1 ; EC 807-789-8)

Method

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium, other: TA97A, TA98, TA100, TA1535

Species / strain 2

Species / strain / cell type:

E. coli WP2

Metabolic activation:

with and without

Metabolic activation system:

S-9, rat liver

Test concentrations with justification for top dose:

5 μL, 1.6 μL, 0.5 μL, 0.16 μL, 0.05 μL/plate

The concentrations tested were based on the OECD 471 highest recommended concentration for non-cytotoxic compounds.

Vehicle / solvent:

The test article was diluted in sterile water

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

sterile water

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 4-nitro-0-phenylenediamine (tested without S-9 metabolic activation only), 2-aminofluorene (tested with S-9 metabolic activation only), 2-aminoanthracene (tested with S-9 metabolic activation only)

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)
- Cell density at seeding: the titers of each strain culture had concentrations of approximately 10E8 CFU/mL or higher

DURATION
- Exposure duration: The plates were incubated for growth at 37 ± 2°C for 48-72 hours.

NUMBER OF REPLICATIONS: 3 replicates for each test article or control were prepared.

Evaluation criteria:

Criteria for a Mutagen:
1) A reversion rate greater than 200% of the solvent control in strains TA97a and TA 100. A reversion rate greater than 300% of the solvent control in strains TA98,TA1535, and WP2.
2) Demonstration of a clear dose related response when dilutions are tested.

Criteria for a Non-Mutagen:
1) A reversion rate less than or equal to 200% of the solvent control in strains TA97a and TA 100. A reversion rate less than or equal to 300% of the solvent control in strains TA98, TA 1535, and WP2.
2) No dose related response when dilutions are tested.

Statistics:

The results were calculated using a validated computer program. Manual calculations may have differed slightly due to rounding. All results greater than 300 colony forming units (CFU) were considered estimates.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium, other: TA97a

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

At the highest test article concentration (5 µL/plate) without metabolic activation

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Any other information on results incl. tables

The criteria for acceptance of the test and criteria for determination of a mutagen were:

1) Tested strains for phenotype verification and achieved the appropriate responses.

2) All chemical controls included in the test gave the appropriate responses.

               a) for TA97a: % of control results >200 qualify as a positive

               b) for TA98: % of control results >300 qualify as a positive

               c) for TA100: % of control results >200 qualify as a positive

               d) for TA1535: % of control results >300 qualify as a positive

               e) for WP2: % of control results >300 qualify as a positive

3) The reversion rates for each tester strain were within the historical ranges (from 2016)

Applicant's summary and conclusion

Conclusions:

The test article concentrations of 5 μL, 1.6 μL, 0.5 μL, 0.16 μL, 0.05 μL/plate did not produce a two-fold or three-fold increase in the number of revertants nor produce a clear dose related response in any of the 5 tester strains (S. typhimurium tester strains TA97a, TA98, TA100, and TA1535, and E. coli test strain WP2). The spot tests showed no zone of increased reversion or of toxicity. In summary, the test article concentrations tested against the five strains did not meet the criteria for a potential mutagen.