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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data is from authoritative database.

Data source

Reference
Reference Type:
other: Authoritative database
Title:
bacterial reverse mutation test was performed for the given test chemical
Author:
U. S. National Library of Medicine
Year:
2018
Bibliographic source:
HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC, 2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Qualifier:
equivalent or similar to guideline
Guideline:
other: EU Method B13/14
Principles of method if other than guideline:
To evaluate the mutagenic potential of test chemical in Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 according to the OECD guideline 471 and the EU Method B13/14.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium phosphinate
EC Number:
231-669-9
EC Name:
Sodium phosphinate
Cas Number:
7681-53-0
Molecular formula:
H3O2P.Na
IUPAC Name:
Sodium hypophosphite
Test material form:
solid
Details on test material:
- Name of test material: sodium phosphinate
- IUPAC name: Sodium hypophosphite
- Molecular formula: NaO2P
- Molecular weight: 87.9778 g/mole
- Smiles notation: [Na+].[O-]P=O
- InChl: 1S/Na.H3O2P/c;1-3-2/h;3H2,(H,1,2)/q+1;/p-1
- Substance type: Inorganic
- Physical state: Solid

Method

Target gene:
Histidine
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Cytokinesis block (if used):
not specified
Metabolic activation:
with and without
Metabolic activation system:
the S9 mix, prepared from a liver post-mitochondrial fraction (S9 fraction) of rats induced with Aroclor 1254.
Test concentrations with justification for top dose:
- First mutagenicity experiment with and without S9 mix: 0, 312.5, 625, 1250, 2500 and 5000 µg/plate
- Second mutagenicity experiment with and without S9 mix: 0, 625, 1250, 2500, 3750 and 5000 µg/plate
Vehicle / solvent:
vehicle was used.
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
not specified
True negative controls:
not specified
Positive controls:
yes
Remarks:
not specified
Positive control substance:
not specified
Details on test system and experimental conditions:
NUMBER OF REPLICATIONS:
- Number of cultures per concentration - triplicate
- Number of independent experiments - two independent experiments

METHOD OF TREATMENT/ EXPOSURE:
- Cell density at seeding (if applicable): No data
- Test substance added -1st experiment (+S9/-S9) and 2nd experiment (-S9): in agar (plate incorporation); 2nd experiment (+S9): preincubation method

TREATMENT AND HARVEST SCHEDULE:
- Preincubation period, if applicable: 60 minutes (only in second mutagenicity test with S9 mix)
- Exposure duration/duration of treatment: 48 to 72 hours
Rationale for test conditions:
Not specified
Evaluation criteria:
The evaluation of the toxicity was performed based on the observation of the decrease in the number of revertant colonies and/or a thinning of the bacterial lawn.
Statistics:
Not Specified

Results and discussion

Test results
Species / strain:
S. typhimurium, other: TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
True negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation and time of the determination: No precipitate was observed in the petri plates when scoring the revertants at all dose-levels.

RANGE-FINDING/SCREENING STUDIES (if applicable): A preliminary toxicity test was performed to define the dose-levels of test chemical to be used for the mutagenicity study.

Ames test:
- Signs of toxicity - No toxicity was noted towards all the strains used, both with and without S9 mix.
Remarks on result:
other: No mutagenic effects were observed

Applicant's summary and conclusion

Conclusions:
The test chemical was evaluated for its mutagenic potential in Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 according to the OECD guideline 471 and the EU Method B13/14. Under these experimental conditions the test chemical did not show any mutagenic activity in the bacterial reverse mutation assay, thus, the test chemical was considered as non-mutagenic.
Executive summary:

In Genetic toxicity in vitro study, the given test chemical was evaluated for its mutagenic potential in Salmonella typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102 according to the OECD guideline 471 and the EU Method B13/14. A preliminary toxicity test was performed to define the dose-levels of test chemical to be used for the mutagenicity study. The test chemical was then tested in two independent experiments, both with and without a metabolic activation system, the S9 mix, prepared from a liver post-mitochondrial fraction (S9 fraction) of rats induced with Aroclor 1254. Both experiments were performed according to the direct plate incorporation method except for the second test with S9 mix, which was performed according to the preincubation method (60 minutes, 37 deg C). The five strains of bacteria Salmonella typhimurium: TA 1535, TA 1537, TA 98, TA 100 and TA 102 were exposed to the following dose levels of test chemical (three plates/dose-level): 312.5, 625, 1250, 2500 and 5000 ug/plate, for the first mutagenicity experiment with and without S9 mix; 625, 1250, 2500, 3750 and 5000 ug/mL for the second mutagenicity experiment with and without S9 mix. After 48 to 72 hours of incubation at 37 deg C, the revertant colonies were scored. The evaluation of the toxicity was performed based on the observation of the decrease in the number of revertant colonies and/or a thinning of the bacterial lawn. The number of revertants for the vehicle and positive controls was as specified in the acceptance criteria. The study was therefore considered valid. No precipitate was observed in the petri plates when scoring the revertants at all dose-levels. No toxicity was noted towards all the strains used, both with and without S9 mix. The test chemical did not induce any significant increase in the number of revertants, both with or without S9 mix, in any of the five strains. Under these experimental conditions, the given test chemical did not show any mutagenic activity in the bacterial reverse mutation assay, thus, it was considered as non-mutagenic.