Methyl hydrogen octadecylphosphonate

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:

03 August 2005 to 16 September 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

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:

Methyl hydrogen octadecylphosphonate

EC Number:

246-905-6

EC Name:

Methyl hydrogen octadecylphosphonate

Cas Number:

25371-55-5

Molecular formula:

C19H41O3P

IUPAC Name:

methoxy(octadecyl)phosphinic acid

impurity 1

Reference substance name:

Octadecylphosphonic acid

EC Number:

225-216-4

EC Name:

Octadecylphosphonic acid

Cas Number:

4724-47-4

Molecular formula:

C18H39O3P

IUPAC Name:

octadecylphosphonic acid

impurity 2

Reference substance name:

Dimethyl octadecylphosphonate

EC Number:

246-904-0

EC Name:

Dimethyl octadecylphosphonate

Cas Number:

25371-54-4

Molecular formula:

C20H43O3P

IUPAC Name:

dimethyl octadecylphosphonate

Test material form:

solid

Method

Species / strain

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2

Additional strain / cell type characteristics:

not applicable

Metabolic activation:

with and without

Metabolic activation system:

S-9 mix

Test concentrations with justification for top dose:

Salmonella strains, with and without s9-mix: 5, 15, 50,150,500, 1500 and 5000 ug/plateE.coli strain, WP2uvrA with and without s9-mix - 50, 150, 500, 1500 and 5000 ug/plateThe top dose was selected based on the results of a preliminary test to determine the toxicity of the test material.

Vehicle / solvent:

Tetrahydrofuran

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Evaluation criteria:

There are several criteria for determining a positive result such as a dose-related increase in revertant frequency over the dose range tested and/or a reproducible increase at one or more concentrations in at least one bacterial strain with or without metabolic activation. Biological relevance of the results will be considered first, statistical methods, as recommended by UKEMS can also be used as an aid to evaluation, however, statistical significance will not be the only determining factor for a positive response.The test material will be considered non-mutagenic (negative) in the test system if the above criteria are not met.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative 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, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation. The test material was considered to be non-mutagenic under the conditions of this test.

Executive summary:

Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and Escherichia coli strain WP2uvrA were treated with the test material using the Ames plate incorporation method at up to seven dose levels, in triplicate, both with and without metabolic the addition of a rat liver homogenate metabolising system. The dose ranging study for the first experiment was determined in a preliminary toxicity assay and ranged between 5 and 5000 µg/plate, depending on strain type.

The vehicle (tetrahydrofuran) control plates gave counts of revertant colonies within the normal range. All of the positive control chemicals used in the test induced marked increases in the frequency of revertant colonies, both with or without metabolic activation. Thus, the sensitivity of the assay and the efficacy of the S9 -mix were validated.

The test material caused a visible reduction in the growth of bacterial background lawn to all of the Salmonella strains initially at 5000 µg/plate and 500 µg/plate, with and without the presence of S9 -mix, respectively. No toxicity was observed to tester strain WP2uvrA. the test material was therefore tested up to the maximum recommended dose level of 5000 µg/plate or the toxic limit, depending on bacterial strain type, presence or absence of S9 -mix and experiment number.

No significant increases in the frequency of revertant colonies were recorded for any of the bacterial strains, with any dose of the test material, either with or without metabolic activation.