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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Additional information

Genetic toxicity in vitro

Bacterial Reverse Mutation Test:

Laus (2008) performed a bacterial reverse mutation study according to OECD guideline 471 and EU method B13/14. This study was used as key study for this endpoint. Salmonella typhimurium strains TA97a, TA98, TA100, TA102 and TA1535 were exposed to 50 to 4998 µg/plate with and without metabolic activation in 2 independent experiments. Vehicle and positive controls were valid. Zirconium dioxide did not induce mutation with and without metabolic activation and no cytotoxicity was observed.

In vitro cytogenicity in mammalian cells:

NOTOX B.V. (2010) performed a chromosome aberration test according to OECD guideline 473. Cultured peripheral human lymphocytes were exposed for 3 hours to 10, 33 and 100 µg zirconium dioxide/mL culture medium with and without S9-mix (dose range finding test/first cytogenetic assay); at 24 and 48 h continuous exposure time blood cultures were treated with 1, 3, 10, 33, 100, 333 and 1000 µg zirconium dioxide/mL culture medium without S9-mix. A second cytogenicity test was performed as follows: without S9-mix: 10, 33 and 100 µg/mL culture medium (24 and 48 h exposure time, 24 h and 48 h fixation time); with S9-mix: 10, 33 and 100 µg/mL culture medium (3 h exposure time, 48 h fixation time). Vehicle and positive control substances were tested simultaneously and considered valid. Zirconium dioxide tested negative with and without metabolic activation. No cytotoxicity was observed.

In vitro gene mutation in mammalian cells:

NOTOX B.V. (2010) performed a mouse lymphoma test according to OECD guideline 476. Mouse lymphoma L5178Y cells were exposed to 0.03, 0.1, 1, 3, 10, 33 and 100 µg/mL zirconium dioxide with and without metabolic activation. In a first experiment, cell cultures were exposed for 3 hours to zirconium dioxide in exposure medium in the absence and presence of S9-mix. In a second experiment, cell cultures were exposed to zirconium dioxide in exposure medium for 24 hours in the absence of S9-mix and for 3 hours in the presence of S9-mix. Zirconium dioxide tested negative in both experiments with and without metabolic activation. No cytotoxicity was observed and positive and vehicle controls were considered valid.

In vitro comet assay:

Braz et al. (2008) performed a Comet assay according to the following guideline: Single Cell Gel/Comet Assay: Guidelines for in vitro and in vivo genetic toxicology testing. Human lymphocytes were exposed to 1, 100 and 1000 µg/L zirconium dioxide without metabolic activation. Vehicle and positive control were tested simultaneously and considered valid. Zirconium dioxide tested negative in human lymphocytes without metabolic activation. No cytotoxicity was observed.

Genetic toxicity in vivo

No reliable data were available on the genetic toxicity in vivo endpoint. Zirconium dioxide tested negative in in vitro toxicity tests (Ames test, mammalian chromosome aberration test, mouse lymphoma assay and comet assay) and therefore no in vivo mutagenicity tests should be performed with this substance (according to column 2 of Annex VIII of the REACH Regulation).


Short description of key information:
Genetic toxicity in vitro

Bacterial Reverse Mutation Test
One reliable bacterial reverse mutation study was available (Klimisch 1) that was used as key study. The study was performed according to OECD guideline 471 and EU method B13/14. Zirconium dioxide tested negative with and without metabolic activation in Salmonella typhimurium strains.

In vitro cytogenicity in mammalian cells
One reliable test (Klimisch 1) was performed according to OECD guideline 473. Zirconium dioxide tested negative in cultured peripheral human lymphocytes with and without metabolic activation.

In vitro gene mutation in mammalian cells
One reliable mouse lymphoma test (Klimisch 1) was performed according to OECD guideline 476. Zirconium dioxide tested negative in mouse lymphoma L5178Y cells with and without metabolic activation.

In vitro Comet assay
One reliable Comet assay was available (Klimisch 2) performed according to the following guideline: Single Cell Gel/Comet Assay: Guidelines for in vitro and in vivo genetic toxicology testing. Zirconium dioxide tested negative in human lymphocytes without metabolic activation.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Zirconium dioxide did not induce any mutation or chromosome aberration in 4 different in vitro studies and therefore, the substance should not be classified for genetic toxicity.