Iron tris(phosphinate)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Gene mutation in vitro:

Data available for read across chemicals has been reviewed to determine the mutagenic nature of Ferric hypophosphite (CAS no 7783 -84 -8). The studies are as mentioned below:

Ames mutagenicity test was conducted for read across chemical to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with dose concentration of 100-10000 µg/plate in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose level from 100-10000 µg/plate. The plates were incubated for 48 h at 37±2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. For a test article to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose response to increasing concentrations of the test chemical. The test chemical did not induce gene mutation in the Salmonella typhimurium TA98, TA100, TA1535, TA1537, and TA1538 both in the presence and absence of S9 activation system and hence the chemical is not likely to be a gene mutant.

In another study, Ames mutagenicity test was conducted for read across chemical to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA97a, TA98, TA100, TA102, TA1535, TA1537 and TA1538 in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose levels. The plates were incubated for 48 h at 37±2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. For a test article to be considered positive, it must induce at least a doubling (TA97a, TA98, TA100, TA102, and TA1535) in the mean number of revertants per plate of at least one tester strain for it to be considered positive. This increase in the mean revertants per plate must be accompanied by a dose response to increasing concentrations of the test chemical. The test chemical did not induce gene mutation in the Salmonella typhimurium TA97a, TA98, TA100, TA102, TA1535, TA1537, and TA1538 both in the presence and absence of rat and hamster liver S9 activation system and hence the chemical is not likely to be a gene mutant.

Based on the data available for the read across chemicals, the test chemical Ferric hypophosphite (CAS no 7783 -84 -8) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally and functionally similar read across chemicals

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Version / remarks:

WoE derived based on the experimental data from similar read across chemicals

Principles of method if other than guideline:

WoE report is based on two gene mutation in vitro studies for similar read across chemicals

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material: Ferric hypophosphite
- IUPAC name: iron(3+) ion triphosphinate
- Molecular formula: FeO6P3
- Molecular weight: 250.8084 g/mole
- Smiles : [Fe+3].[O-]P=O.[O-]P=O.[O-]P=O
- Inchl: 1S/Fe.3H3O2P/c;3*1-3-2/h;3*3H2,(H,1,2)/q+3;;;/p-3
- Substance type: Inorganic
- Physical state: Solid powder (white to grey)

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA1538

Remarks:

RA 1

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium, other: TA97a, TA98, TA100, TA102, TA1535, TA1537, and TA1538

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

No data

Metabolic activation:

with and without

Metabolic activation system:

Liver S9 homogenate was prepared from male Sprague-Dawley rats and Syrian golden hamsters that had been injected with Aroclor 1254 at 500 mg/kg body weight

Test concentrations with justification for top dose:

1. 100-10000 µg/plate
2. No data

Vehicle / solvent:

1. No data
2.
- Vehicle(s)/solvent(s) used: Yes, water or DMSO
- Justification for choice of solvent/vehicle: The test chemical was dissolved in water or DMSO

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

No detailed data available

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Water or DMSO

True negative controls:

not specified

Positive controls:

not specified

Positive control substance:

not specified

Details on test system and experimental conditions:

1 and 2. METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: No data available
- Exposure duration: 48 h
- Expression time (cells in growth medium): 48 h
- Selection time (if incubation with a selection agent): No data available
- Fixation time (start of exposure up to fixation or harvest of cells): No data available

SELECTION AGENT (mutation assays): No data available
SPINDLE INHIBITOR (cytogenetic assays): No data available

STAIN (for cytogenetic assays): No data available

NUMBER OF REPLICATIONS: Triplicate

NUMBER OF CELLS EVALUATED: No data available

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other: No data available

OTHER EXAMINATIONS:
- Determination of polyploidy: No data available
- Determination of endoreplication: No data available
- Other: No data available

OTHER: No data available

Rationale for test conditions:

No data

Evaluation criteria:

1. The criteria used to evaluate a test were as follows: for a test article to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose response to increasing concentrations of the test chemical. If the study showed a dose response with a less than 3-fold increase on TA1537 or TA1538, the response had to be confirmed in a repeat experiment.

2. The criteria used to evaluate a test stipulated that a test article must induce at least a doubling (TA97a, TA98, TA100, TA102, and TA1535) in the mean number of revertants per plate of at least one tester strain for it to be considered positive. This increase in the mean revertants per plate must be accompanied by a dose response to increasing concentrations of the test chemical. If the study shows a dose–response, but with a less than 3-fold increase on TA1537 or TA1538, the response must be confirmed in a repeat experiment.

Statistics:

1. No data available
2. No data available

Species / strain:

S. typhimurium, other: TA98, TA100, TA1535, TA1537, and TA1538

Metabolic activation:

with and without

Genotoxicity:

not specified

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Species / strain:

S. typhimurium, other: TA97a, TA98, TA100, TA102, TA1535, TA1537, and TA1538

Remarks:

RA 2

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

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: No data
- Effects of osmolality: No data
- Evaporation from medium: No data
- Water solubility: No data
- Precipitation: No data
- Other confounding effects: No data

RANGE-FINDING/SCREENING STUDIES:
1. and 2. The doses that were tested in the mutagenicity assay were selected based on the levels of cytotoxicity observed in a preliminary dose range-finding study using strain TA100. Ten dose levels of the chemical, one plate per dose, were tested in both the presence and the absence of induced hamster S9. If no toxicity was observed, a total maximum dose of 10 mg of test chemical per plate was used.

COMPARISON WITH HISTORICAL CONTROL DATA: No data

ADDITIONAL INFORMATION ON CYTOTOXICITY: No data

Remarks on result:

other: No mutagenic potential

Conclusions:

Ferric hypophosphite (CAS no 7783 -84 -8) does not exhibit gene mutation in vitro in the Salmonella typhimurium tester strains used in the presence and absence of S9 metabolic activation system. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.

Executive summary:

Data available for read across chemicals has been reviewed to determine the mutagenic nature of Ferric hypophosphite (CAS no 7783 -84 -8). The studies are as mentioned below:

Ames mutagenicity test was conducted for the test chemical to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with dose concentration of 100-10000 µg/plate in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose level from 100-10000 µg/plate. The plates were incubated for 48 h at 37±2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. For a test article to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose response to increasing concentrations of the test chemical. The test chemical did not induce gene mutation in the Salmonella typhimurium TA98, TA100, TA1535, TA1537, and TA1538 both in the presence and absence of S9 activation system and hence the chemical is not likely to be a gene mutant.

In another study, Ames mutagenicity test was conducted for the test chemical to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA97a, TA98, TA100, TA102, TA1535, TA1537 and TA1538 in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose levels. The plates were incubated for 48 h at 37±2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. For a test article to be considered positive, it must induce at least a doubling (TA97a, TA98, TA100, TA102, and TA1535) in the mean number of revertants per plate of at least one tester strain for it to be considered positive. This increase in the mean revertants per plate must be accompanied by a dose response to increasing concentrations of the test chemical. The test chemical did not induce gene mutation in the Salmonella typhimurium TA97a, TA98, TA100, TA102, TA1535, TA1537, and TA1538 both in the presence and absence of rat and hamster liver S9 activation system and hence the chemical is not likely to be a gene mutant.

Based on the data available for the read across chemicals, the test chemical Ferric hypophosphite (CAS no 7783 -84 -8) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Gene mutation in vitro:

Data available for the read across chemicals have been reviewed to determine the mutagenic nature of Ferric hypophosphite (CAS no 7783 -84 -8). The studies are as mentioned below:

Ames mutagenicity test by Seifried et al (Chemical Research in toxicology, 2006) was conducted for read across chemical ferric orthophosphate (RA CAS no 51833 -68 -2) to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 with dose concentration of 100-10000 µg/plate in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose level from 100-10000 µg/plate. The plates were incubated for 48 h at 37±2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. For a test article to be considered positive, it had to induce at least a doubling (TA98, TA100, and TA1535) in the mean number of revertants per plate of at least one tester strain. This increase in the mean revertants per plate had to be accompanied by a dose response to increasing concentrations of the test chemical. Ferric orthophosphate did not induce gene mutation in theSalmonella typhimurium TA98, TA100, TA1535, TA1537, and TA1538 both in the presence and absence of S9 activation system and hence the chemical is not likely to be a gene mutant.

In another study by Dunkel et al (Environmental and Molecular Mutagenesis, 1999), Ames mutagenicity test was conducted for read across chemical ferric phosphate (RA CAS no 13463 -10 -0) to evaluate its genetoxic effects when exposed to Salmonella typhimurium strains TA97a, TA98, TA100, TA102, TA1535, TA1537 and TA1538 in plate incorporation assay. Based on the preliminary study conducted, the test compound was used at a five dose levels. The plates were incubated for 48 h at 37±2 °C. Five doses of test chemical, together with the appropriate concurrent solvent and positive controls, were tested in triplicate on each tester strain without metabolic activation and also with activation by induced rat and hamster liver S9 preparations. For a test article to be considered positive, it must induce at least a doubling (TA97a, TA98, TA100, TA102, and TA1535) in the mean number of revertants per plate of at least one tester strain for it to be considered positive. This increase in the mean revertants per plate must be accompanied by a dose response to increasing concentrations of the test chemical.Ferric phosphatedid not induce gene mutation in theSalmonella typhimurium TA97a, TA98, TA100, TA102, TA1535, TA1537, and TA1538 both in the presence and absence of rat and hamster liver S9 activation system and hence the chemical is not likely to be a gene mutant.

Based on the data available for the read across chemicals, the test chemical Ferric hypophosphite (CAS no 7783 -84 -8) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.

Justification for classification or non-classification

Based on the data available for the read across chemicals, the test chemical Ferric hypophosphite (CAS no 7783 -84 -8) does not exhibit gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant as per the criteria mentioned in CLP regulation.