Phosphonic acid, P-2-propen-1-yl-, diethyl ester

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The test substance did not induce mutations (base-pair substitution and frame-shift type) in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 as well as in E. coli WP2 uvr A both in presence and absence of metabolic activation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 Nov 2014 to 01 Dec 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study according to the guidelines under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.5100 - Bacterial Reverse Mutation Test (August 1998)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Salmonella typhimurium: histidine
E-coli: tryptophan

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

S9 from rats induced with Phenobarbitone/ß-Naphthoflavone

Test concentrations with justification for top dose:

Experiment 1 (plate incorporation): 1.5, 5, 15, 50, 150, 500, 1500 and 5000 ug/plate with and without metabolic activation
Experiment 2 (preincubation): 50, 150, 500, 1500 and 5000 ug/plate with and without metabolic activation

Vehicle / solvent:

sterile distilled water

Negative solvent / vehicle controls:

yes

Remarks:

sterile distilled water

Positive controls:

yes

Remarks:

for TA100, TA1535 and WP2uvrA without metabolic activation

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Negative solvent / vehicle controls:

yes

Remarks:

sterile distilled water

Positive controls:

yes

Remarks:

for TA1537 without metabolic activation

Positive control substance:

9-aminoacridine

Negative solvent / vehicle controls:

yes

Remarks:

sterile distilled water

Positive controls:

yes

Remarks:

for TA100, TA1535, TA 1537 and WP2uvrA with metabolic activation

Positive control substance:

other: 2-aminoanthracene

Negative solvent / vehicle controls:

yes

Remarks:

sterile distilled water

Positive controls:

yes

Remarks:

for TA98 without metabolic acivation

Positive control substance:

4-nitroquinoline-N-oxide

Negative solvent / vehicle controls:

yes

Remarks:

sterile distilled water

Positive controls:

yes

Remarks:

for TA98 with metabolic activation

Positive control substance:

benzo(a)pyrene

Details on test system and experimental conditions:

METHOD OF APPLICATION: 1st test in agar (plate incorporation); 2nd test preincubation

DURATION
- Preincubation period: 20 min at 37±3°C
- Exposure duration: 48 hours at 37± 3°C

NUMBER OF REPLICATIONS: 3/concentration

DETERMINATION OF CYTOTOXICITY
- Method: growth rate + presence of bacterial background lawn

COLONY COUNT:
Colony counter (microscopically for thinning and in exp 2 manual counting (due to bubbles in agar)

Evaluation criteria:

A test item will be considered mutagenic (positive) in the test system if one or more of these criteria are met
1. A dose-related increase in mutant frequency over the dose range tested (De Serres and Shelby (1979)).
2. A reproducible increase at one or more concentrations.
3. Biological relevance against in-house historical control ranges.
4. Statistical analysis of data as determined by UKEMS (Mahon et al (1989)).
5. Fold increase greater than two times the concurrent solvent control for any tester strain (especially if accompanied by an out-of-historical range response).

Statistics:

Not specified according to UKEMS

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

exp 1 precipitate at 5000 ug/plate; exp 2 no precipitate

Vehicle controls validity:

valid

Positive controls validity:

valid

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

exp 1 precipitate at 5000 ug/plate; exp 2 no precipitate

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

In exp 2 a significant increase of TA98 was observed at 1500 ug/plate with metabolic activation. In absence of a dose response relationship this finding was considered to be of no biological relevance.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results (migrated information):
negative without metabolic activation
negative with metabolic activation

The test substance did not induce mutations (base-pair substitution and frame-shift type) in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537 as well as in E. coli WP2 uvr A both in presence and absence of metabolic activation.

Executive summary:

The test substance was tested in an Ames test in the Salmonella strains TA98, TA100, TA1535 and TA1537and E. coli WP2 uvr A. In a plate incorporation (exp 1 1.5 to 5000 ug/plate (precipitate at 5000 ug/plate)) and a pre-incubation assay (exp 2 50 -5000 ug/plate (no precipitate)), both performed in triplicate, with and without metabolic activation, the test substance did not induce mutations (base-pair substitution and frame-shift type) in Salmonella typhimurium strains TA98, TA100, TA1535 and TA1537, as well as in E. coli WP2 uvr.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Justification for selection of genetic toxicity endpoint
guideline study under GLP

Justification for classification or non-classification

The available data do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC.