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Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro:

- Bacterial reverse mutation assay:

Dillon (1994) performed a bacterial reverse mutation assay using a method similar to OECD 471 with Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 1538 and TA 100 with and without metabolic activation to test the mutagenic potential of a solution of zirconium orthosulfate. Zirconium orthosulfate solution was diluted in sterile ultra-pure water to achieve concentrations of 0.15, 0.5, 1.5, 5, 15 and 50% (here % is equal to µL/plate). Concentrations were tested in triplicate in 2 independent tests. Negative controls and positive controls were run in triplicate and the values were withing the normal ranges experienced in the laboratory and reported in the literature with these strains. Both tests were performed using a plate-incorporation method. According to the results of the study, the test substance was not mutagenic to Salmonella typhimurium with and without metabolic activation when tested at concentrations exceeding the toxic range.

- In vitro chromosome aberration in mammalian cells:

Ciliutti (2013) performed an in vitro Chromosome Aberration test in Chinese hamster ovary cells (OECD 473). Two experiments were performed using different test concentrations with and without S9 activation (3 h exposure and harvested at 20 h in experiment I; continuous exposure until harvest at 20 h for experiment II).

For the experiment I, dose levels of 2.00, 1.00, 0.500, 0.250, 0.125, 0.0625, 0.0313, 0.0156 and 0.00781 mM (corresponding to 567, 284, 142, 70.9, 35.4, 17.7,8.86 , 4.43 and 2.21 µg of zirconium sulfate/mL), were employed in the presence and absence of S9 metabolism. The dose levels of 1.00, 0.500, 0.250, 0.125, 0.0625, 0.0313, 0.0156 and 0.00781 mM (corresponding to 284, 142, 71.0, 35.5, 17.7, 8.86, 4.43 and 2.21 µg zirconium sulfate/mL) were used for the experiment II.

Both negative and positive controls were considered to be valid. On the basis of the results obtained, it was concluded that zirconium sulfate did not induce structural chromosome aberrations after in vitro treatment and under the reported conditions, and this both in the absence and presence of metabolic activation.

- In vitro mammalian cell gene mutation:

Bisini (2013) performed an in vitro mammalian gene mutation assay in L5178Y TK+/- lymphoma cells using the fluctuation method with the read across substance zirconium acetate. The test was performed according to OECD Guideline 476. Two experiments were performed using different concentrations with and without metabolic S9 activation (experiment I) and without metabolic S9 activation (experiment II). Plates were tested in duplicate. Plates were exposed for 3 h (experiment I) and 24 h (experiment II). The positive and negative (vehicle) controls were considered to be valid. It was concluded that the test substance did not induce mutation at the TK locus of L5178Y mouse lymphoma cells in vitro in the absence or presence of S9 metabolic activation under the experimental conditions.

Genetic toxicity in vivo:

According to REACH Annex IX section 8.4, column 2, no further in vivo testing is required as no positive results were obtained in any of the three in vitro studies performed according to REACH Annexes VII and VIII section 8.4.


Justification for selection of genetic toxicity endpoint
There are 3 different types of in vitro key studies available. Therefore not a single study could be selected as key study.

Short description of key information:
In vitro genetic toxicity:
- Bacterial reverse mutation assay: performed using a method similar to OECD 471 with Salmonella typhimurium TA 1535, TA 1537, TA 98, TA1538 and TA 100 (Dillon, 1994). Zirconium orthosulfate solution was not mutagenic with and without metabolic activation.
- In vitro mammalian chromosome aberration test: performed with zirconium sulfate according to OECD Guideline 473 in Chinese hamster ovary cells (Ciliutti, 2013). The test item was not clastogenic in the absence and presence of metabolic activation.
- In vitro mammalian cell gene mutation test: the read across substance zirconium acetate (another 'water soluble' zirconium compound with similar toxicokinetic behaviour as zirconium sulfate) was tested for mutation using L5178Y TK+/- mouse lymphoma cells (fluctuation method). The test was performed according to OECD Guideline 476. The test item was not mutagenic under the experimental conditions, in the absence and presence of metabolic activation.

Genetic toxicity in vivo:
No further in vivo testing is required as no positive results were obtained in any of the three in vitro studies (REACH Annexes VII and VIII section 8.4)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the available data and according to the criteria of the DSD and CLP Regulation, zirconium sulfate should not be classified for mutagenicity.