Phosphinate1030

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

During the described mutagenicity test and the experimental conditions reported, the source substance diethylphosphinic acid, did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. Therefore the substance is considered to be non-mutagenic in this bacterial reverse mutation assay.

The results of two independent bacterial mutagenicity tests performed with the source substance phosphinic acid, diethyl, aluminium salt lead to the conclusion that the test item is not mutagenic in the bacterial test in absence or in the presence of metabolic activation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Remarks:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9 mix

Test concentrations with justification for top dose:

For both experiments the following concentrations were used:
31.6, 100, 316, 1000, 2500 and 5000 µg/plate.
based on solubility and cytotoxicity tests

Vehicle / solvent:

Distilled water

Untreated negative controls:

yes

Remarks:

distilled water

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

methylmethanesulfonate

other: 4-nitro-o-phenylene-diamine, 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation; experiment I) and preincubation (experiment II)

DURATION
- Preincubation period: 60 min
- Exposure duration: 48 h

SELECTION AGENT (mutation assays): his

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Rationale for test conditions:

according to guideline

Evaluation criteria:

Validity:
A test ist considered acceptable if for each strain:
- the bacteria demonstrate their typical responses to ampicillin (TA 98, TA 100)
- the control plates with and without S9 mix are within the historical control ranges
- the positive controls show a distinct enhacement of revertant tates over the control plate

Evaluation of Mutagenicity:
A test item is mutagenic if:
- a clear and dose-related increase in the number of revertants occurs and/or
- a biologically relevant positive response for at least one of the dose groups occurs in at least one tester strain with or without metabolic activation

Statistics:

not mandatory

Key result

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

Key result

Species / strain:

S. typhimurium TA 1537

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

Key result

Species / strain:

S. typhimurium TA 98

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

Key result

Species / strain:

S. typhimurium TA 100

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

Key result

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

Additional information on results:

No precipitation of the test item was observed in any tester strain used in experiment I and II (with and without metabolic activation).

Conclusions:

During the described mutagenicity test and the experimental conditions reported, the source substance diethylphosphinic acid, did not cause gene mutations by base pair changes or frameshifts in the genome of the tester strains used. Therefore the substance is considered to be non-mutagenic in this bacterial reverse mutation assay.

Executive summary:

The source substance, diethyl phosphinic acid, was investigated for its potential to induce gene mutations according to the plate incorporation test and the pre-incubation test using Salmonella th. TA 98, TA 100, TA 1535, TA 1537 and tester strain E. coli WP2 uvrA.

In two independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls were tested in triplicate. The following concentrations were prepared and used in the experiments: 31.6, 100, 316, 1000, 2500 and 5000 µg/plate.

No preciptitation of the test item was observed in any tester strain used in exp. I and II (with and without metabolic activation).

No toxic effects of the test item were noted in any of the five tester strains up to the highest dose with and without metabolic activation.

No biologically relevant increases in revertant colony numbers of any of the five tester strains were observed folling the treatment at any concentration level, neither in the presence nor absence of the metabolic activation in experiment I and II.

The reference mutagens induced a distinct increase of revertant colonies indicating the validity of the experiments.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

not mandatory

Additional information

The source substance, diethyl phosphinic acid, was investigated for its potential to induce gene mutations according to the plate incorporation test and the pre-incubation test using Salmonella th. TA 98, TA 100, TA 1535, TA 1537 and tester strain E. coli WP2 uvrA.

In two independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls were tested in triplicate. The following concentrations were prepared and used in the experiments: 31.6, 100, 316, 1000, 2500 and 5000 µg/plate.

No preciptitation of the test item was observed in any tester strain used in exp. I and II (with and without metabolic activation).

No toxic effects of the test item were noted in any of the five tester strains up to the highest dose with and without metabolic activation.

No biologically relevant increases in revertant colony numbers of any of the five tester strains were observed folling the treatment at any concentration level, neither in the presence nor absence of the metabolic activation in experiment I and II.

The reference mutagens induced a distinct increase of revertant colonies indicating the validity of the experiments.

In two independent mutation tests the source substance, phosphinic acid, diethyl, aluminium salt was tested for mutagenicity in triplicate.

The test item did not cause a significant increase in the number of the tester strains either in the absence nor in the presence of S9 mix in either mutation test. No dose-dependent effect was obtained.

All positive controls produced significant increases in the number of revertant colonies. Thus, the sensitivity of the assay and the efficacy of the exogeneous metabolic activation system were demonstrated.

Justification for classification or non-classification

In conclusion, both source substances are not mutagenic in the bacterial reverse mutation assay in the presence and absence of metabolic activation and up to the limit concentration.

Therefore, the target substance does not have to be not classified for mutagenicity.