Zirconium disilicide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No data is available for Zirconium disilicide (target substance) as in the framework of an OECD 471 study the substance was not soluble in a range of solvents for preparing the dilution series of the test material. Thus, it was not possible to conduct the study with the target substance. To assess the mutagenicity potential of Zirconium disilicide available data from Zirconium oxychloride (source substance) is used in a read-across approach. In a bacterial reverse gene mutation assay the source substance was tested negative in S. typhimurium strains TA1535, TA1537, TA98 and TA100.

Link to relevant study records

Reference

Reference 1

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

Justification for type of information:

It was technically not possible to conduct an in vitro reverse mutation assay with the target substance zirconium disilicide. The target substance was not soluble in any of the solvents used (Aqua dest, DMSO, ethanol and tetrahydrofuran).
As no further data is available for the target substance to assess mutagenicity, available data from a suitable read-partner was used. The hexahydrate of zirconium dichloride oxide (ZrOCl2: CAS No. 7699-43-6; ZrOCl2 6xH2O: CAS No. 25399-81-9) was tested in an in vitro bacterial reverse mutation assay (Mortelmans, 1986).
As indicated in ECHA‘s guidance on QSAR and grouping of chemicals (ECHA Chapter R.6, 2008a), comparison of the water solubility is an important aspect in determining the similarity between compounds for purposes of the read-across strategy. This approach assumes that the extent of water solubility approximates the bioavailability of a substance. Therefore, inorganic substances of similar water solubility would have similar toxicity, based on the fact that both substances would release the same toxicological metal species. The use of source substances which have a higher water solubility compared to the target substance can be considered as an appropriate worst-case read-across approach for potential systemic and environmental effects and is adequately protective.
The source substance ZrOCl2 show a higher water solubility than ZrSi2 and hence results in a higher release of zirconium ions compared to zirconium disilicide. Thus, the used read-across partner is considered as suitable.
Despite the low water solubility of the target substance, data is available from a bio-elution test. The release of zirconium ions from ZrSi2 is very low in artificial body fluids. For human health endpoints, it is the relative bioavailability of zirconium at target site(s) that determines the potential occurrence and severity of the systemic effects to be assessed for the read-across of zirconium substances. The source substance ZrOCl2 is considered to be highly soluble in water. At physiological pH zirconium will precipitate. Therefore, the zirconium release of this substance is expected to be similar low as for the target substance under physiological conditions and thus, read-across is considered to be adequately safe and will not underestimate the toxicity.

Reason / purpose for cross-reference:

read-across source

Key result

Species / strain:

other: TA1535, TA1537, TA100 and TA98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Vehicle controls validity:

not examined

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

For detailed results please refer to table 1 in box "Any other information on results incl. tables"

Remarks on result:

other: non-mutagenic

Table 1: Summary of Results
Concentration  µg/plate		TA100						Concentration  µg/plate		TA1535
		without S9		with 10% hamster S9		with 10% rat S9				without S9				with 10% hamster S9				with 10% rat S9
		Mean	SEM	Mean	SEM	Mean	SEM			Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM
Negative Control		142	4.6	127	1	150	5.5	Negative Control		31	2.6	9	1.3	34	2.4	24	3.5	34	3.3	29	1.5
Positive Control		268	19.3	1572	41.5	742	48.2	Positive Control		344	6.9	175	23.2	505	12.5	326	15.2	223	19.9	114	6.1
10		-	-	-	-	-	-	10		28	5.2	-	-	36	2.3	-	-	45	5.8	-	-
33		-	-	-	-	-	-	33		29	3.5			36	3.2	-	-	39	2.2	-	-
100		125	8.2	158	9.5	136	4.5	100		30	2.4	22	3.0	41	3.5	33	2.3	42	6.6	30	1.0
333		108	10.9	169	10.5	126	7.1	333		30	1.0	29	6.4	38	6.1	37	3.1	35	3.7	33	3.6
1000		116	13.1	156	7.0	134	3.7	1000		30p	1.0	20	4.2	30p	0.3	35	4.9	38p	6.8	31	3.2
3333		149p	13.5	144p	14.0	77p	38.8	3333		-	-	26p	3.8	-	-	0p	0.0	-	-	29p	6.8
6666		48p	24.0	126p	5.2	35p	35.3	6666		-	-	0p	0.0	-	-	0p	0.0	-	-	0p	0.0

p= precipitation present in plates

Table 1 continued: Summary of Results
Concentration  µg/plate		TA1537						TA98
		without S9		with 10% hamster S9		with 10% rat S9		without S9		with 10% hamster S9		with 10% rat S9
		Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM	Mean	SEM
Negative Control		7	2.9	7	0.7	12	3.2	25	0.0	32	0.9	30	3.5
Positive Control		109	8.7	536	34.9	197	7.6	793	25.9	1385	100.5	556	36.2
10		-	-	-	-	-	-	-	-	-	-	-	-
33		-	-	-	-	-	-	-	-	-	-	-	-
100		8	0.9	13	4.2	7	1.2	21	4.3	34	2.7	30	0.6
333		8	1.9	8	1.9	9	2.6	28	1.5	34	2.6	32	4.2
1000		8	1.8	12	2.0	9	2.2	21	4.6	32	5.8	27	4.1
3333		9p	1.8	7p	2.5	13p	0.9	19p	1.5	30p	3.0	28p	2.2
6666		0p	0.0	0p	0.0	0p	0.0	0p	0.0	0p	0.0	0p	0.0

p= precipitation present in plates

Conclusions:

In conclusion, it can be stated that during the described mutagenicity test and under the experimental conditions reported, the test item can be considered as non-mutagenic.

Executive summary:

In a reverse gene mutation assay in bacteria conducted similar to OECD test guideline 471, strains TA98, TA100, TA1535 and TA1537 of Salmonella typhimurium were exposed to Zirconium oxychloride hexahydrate in 95% ethanol at concentrations of 10, 33, 100, 333, 1000, 3333 and 6666 µg/plate in the presence and absence of mammalian metabolic activation. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background in all tester strains. Therefore, Zirconium oxychloride hexahydrate is considered to be non-mutagenic in this Salmonella typhimurium reverse gene mutation assay.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2017-06-13 to 2017-08-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted 21st July 1997

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine locus

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 specified

Test concentrations with justification for top dose:

not specified

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

not specified

Rationale for test conditions:

not specified

Evaluation criteria:

not specified

Statistics:

not specified

Species / strain:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537

Metabolic activation:

not applicable

Genotoxicity:

not determined

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

not examined

Untreated negative controls validity:

not examined

Positive controls validity:

not examined

Additional information on results:

The test item could not be prepared in an appropriate solvent and diluted prior to treatment. Due to the properties of the material, Zirconium disilicide was not soluble in any of the solvents used (A. dest, DMSO, ethanol and tetrahydrofuran). No stable suspension which is suitable for the preparation of the dilution series could be obtained. Therefore it was not possible to perform any further steps in this study.

Remarks on result:

not measured/tested

Conclusions:

Zirconium disilicide was not soluble in any of the solvents used. Therefore, it was not possible to perform an Ames test.

Executive summary:

In this study, the test item Zirconium disilicide could not be prepared in an appropriate solvent and diluted prior to treatment. Due to the properties of the material, Zirconium disilicide was not soluble in any of the solvents used (A. dest, DMSO, ethanol and tetrahydrofuran). No stable suspension which is suitable for the preparation of the dilution series could be obtained. Therefore it was not possible to perform any further steps in this study. Since the test item could not be prepared in an appropriate solvent and diluted prior to treatment, it was not possible to perform an Ames test with Zirconium disilicide.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

No data is available for Zirconium disilicide (target substance) as in the framework of an OECD 471 study the substance was not soluble in a range of solvents for preparing the dilution series of the test material. Thus, it was not possible to conduct the study with the target substance. That the target substance is highly insoluble was also seen in a T/D test conducted in accordance with OECD 29 (see IUCLID section 4.8).

To assess the mutagenicity potential of Zirconium disilicide available data from Zirconium oxychloride (source substance) is used in a read-across approach. For justification of read-across please refer to the read-across report attached to IUCLID section 13.

In a bacterial reverse gene mutation assay, which was conducted similar to OECD test guideline 471, the source substance was tested negative in S. typhimurium strains TA1535, TA1537, TA98 and TA100.

Justification for classification or non-classification

Based on available data from a suitable read-across partner, the target substance Zirconium disilicide does not warrant classification for mutagenicity.