Registration Dossier

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Strontium chloride have been tested in bacterial reverse mutation test. The tests show a negative response, thus strontium oxalate is not to be classified as mutagenic.

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:
key study
Study period:
The study was performed between 10 December 1996 and 03 February 1997.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information in a detailed justification report is included as attachment to the same record.

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
For the determination of analogue in this read-across approach, the following points have been considered:
- Chemical speciation and valency (common strontium cation: Sr2+).
- The water solubility, as it provides a first indication of the availability of the metal ion in the different compartments of interest. The most simplistic approach to hazard evaluation is to assume that the specific metal-containing compound to be evaluated shows the same hazards as the most water-soluble compounds.
- In fluids of organisms and in aqueous media, dissociation of strontium oxalate takes place immediately, resulting in formation of strontium cations (Sr2+) and oxalate anions. Thus, any ingestion or absorption of strontium oxalate by living organisms, in case of systemic consideration, will inevitably result of exposure to the dissociation products.
- Oxalic acid is naturally present in organisms because it is involved in biochemical reactions (Robertson 2011). Oxalic acid occurs widely in nature. It is present in the tissues of many plants and algae (US EPA 1992), serving both to excrete and store calcium. Oxalate anion (formed during the dissociation of strontium oxalate) is of low (eco)toxicological relevance when ingested and taken up systemically. Thus, any possible toxicological or ecotoxicological effect triggered by strontium oxalate exposure can be attributed to strontium.
- Counter ions: the assumption that the metal ion is responsible for the common property or effect implies that the toxicity or ecotoxicity of the counter ion present in the compound will be largely irrelevant in producing the effects to be assessed.
- Likely common breakdown products via physical and/or biological processes for the targeted substance (strontium oxalate) and the analogues identified cannot present strong differences since the structures are very simple and very similar (formation of Sr2+ or oxalate ion).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source chemical information is provided in the “source” endpoint. No impurity affecting the classification is reported for the source chemical.
Information on the impurities of the target chemical are detailed in the attached report.

3. ANALOGUE APPROACH JUSTIFICATION
The main hypothesis for the analogue approach are verified. They are presented in the detailed report attached. The experimental data performed on the substance (tests performed in this REACH registration dossier on strontium peroxide) confirms the analogue approach performed (same results on analogues).

4. DATA MATRIX
A data matrix is presented in the detailed report attached.
Reason / purpose for cross-reference:
read-across source
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No significant increase in the frequency of revertant colonies of bacteria were recorded for any of the strains of S. typhimurium used, at any dose level.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No toxicity was exhibited to any of the strains tested.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No significant increase in the frequency of revertant colonies of bacteria were recorded for any of the strains of S. typhimurium used, at any dose level.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No toxicity was exhibited to any of the strains tested.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No significant increase in the frequency of revertant colonies of bacteria were recorded for any of the strains of S. typhimurium used, at any dose level.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No toxicity was exhibited to any of the strains tested.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No significant increase in the frequency of revertant colonies of bacteria were recorded for any of the strains of S. typhimurium used, at any dose level.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No toxicity was exhibited to any of the strains tested.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Remarks:
No significant increase in the frequency of revertant colonies of bacteria were recorded for any of the strains of S. typhimurium used, at any dose level.
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No toxicity was exhibited to any of the strains tested.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
No details are reported.

RANGE-FINDING/SCREENING STUDIES:
The dose range of the test material used in the preliminary toxicity study was 0, 50, 150, 500, 1500 and 5000 µg/plate. The test material was non-toxic to the strain of S. typhimurium TA100.

COMPARISON WITH HISTORICAL CONTROL DATA:
no data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
No further details are reported.
Conclusions:
Interpretation of results : negative
In conclusion, under the test conditions described the test material, strontium chloride-6-hydrate extra pure, was considered to be non-mutagenic either with or without metabolic activation at any concentration tested. This test result is considered as relaiable and it is used in a read-across approach on strontium oxalate.
Executive summary:

S. typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100 were treated with the strontium chloride using the Ames plate incorporation method at 5 dose levels, both with and without metabolic activation. The dose range was determined in a preliminary toxicity assay and was 50 to 5000 µg/plate in the first experiment. The experiment was repeated on a separate day using the same dose range as experiment 1. The test material caused no visible reduction in the growth of the bacterial lawn at any of the dose levels to any of the strains of Salmonella tested. No significant increase in the frequency of revertant colonies was recorded for any of the bacterial strains with any of the concentrations tested, either with or without metabolic activation.

This test result is considered as relaiable and it is used in a read-across approach on strontium oxalate.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Ames test: Read across from SrCl2 to strontium oxalate is envisaged due to the fact that possible effects occurred could be regarded as strontium ion related effects. Both substances (SrCl2 and strontium oxalate) are highly soluble in water (since they dissociate with formation of Sr2+ cation). Hence, it could be concluded that read across is possible. Nevertheless, tests on the mutagenic potential of strontium compounds in bacteria are considered dispensable for principal considerations, since inorganic metal compounds are frequently negative in this assay due to limited capacity for uptake of metal ions (Guidance on information requirements and chemical safety assessment, Chapter R.7a, p. 565; HERAG facts sheet mutagenicity, Chapter 2.1).

Justification for classification or non-classification

Strontium oxalate can be regarded to have no mutagenicity / genotoxicity effects, tested in vitro. Hence, no classification and labelling is required.