Zirconium dioxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - workers

Acute / short-term exposure - systemic and local effects

Inhalation:

As no local or systemic effects have been observed in the available toxicological studies up to the maximal technically achievable concentration, no DNEL needs to be derived.

Dermal:

No acute toxicity study for the dermal route is available for zirconium dioxide, however, this study can be waived based on Column 2 adaptation (REACH Regulation, Annex VIII, section 8.5) (acute toxicity data via two routes available). As there are no acute toxicity data available via dermal route for zirconium dioxide, no acute/short-term DNEL could be derived. In addition, the dermal route is not the most appropriate route as exposure via inhalation is more likely and there is no indication from the physicochemical and toxicological properties of significant absorption through the skin (Annex VIII, 8.5.3, Column 2 adaptation).

Long-term exposure - systemic and local effects

Inhalation:

The study from Spiegl et al. (1956) provides a NOAEL for zirconium dioxide >= 15.4 mg/m3 after 60 days of exposure and >= 100.8 mg/m3 after 30 days, nevertheless only one dose was tested in these studies. It can be concluded from this study that the NOAEC will be higher than (or equal to) these doses tested. It is not recommended to derive a DNEL value based on these unbound NOAECs, because the DNEL will be unrealistically low and not representative for zirconium dioxide. Zirconium dioxide was shown to be a compound with extremely low potential for causing toxicity. Indeed, in none of the available studies, zirconium dioxide causes adverse health effects (acute/long-term, oral/inhalation). This is mainly driven by the fact that this substance has a very low water solubility (< 55 µg/L) and thus a very low bioavailability as demonstrated in the toxicokinetics assessment.

National exposure limits for zirconium compounds were defined in Europe by 15 national authorities and set at 5 mg/m3 (expressed as Zr). In the USA, NIOSH, ACGIH, and OSHA have evaluated toxicity and defined long-term and short-term exposure limits for zirconium dioxide. The 8-h Time Weighted Average (TWA) was set at 5 mg Zr/m3 whereas the Short Term Exposure Limit (STEL) was set at 10 mg Zr/m3. These values were based on the results of Spiegl et al. (1956) as well as on the results of the study from Hodge (1955). The study of Hodge (1955), is a 1-year experiment performed on rats with zirconium oxide dust at a a low dose of 3.5 mg/m3.Unfortunately the unpublished study was not accessible. As zirconium dioxide did not show any toxic effects in the available studies, it is considered reasonable not to derive DNELs, however, the national exposure limits as mentioned above should be respected where relevant.

Dermal:

No reliable studies are available for repeated dose toxicity via the dermal route of exposure. Testing is waived based on the following justification: a short-term (30 days) and sub-chronic (60 days) study are available for the inhalation route of exposure and, according to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (Column 2 adaptation, annex VIII, section 8.6.1). Therefore, it was not necessary to perform a repeated dose toxicity study via the dermal route of exposure.

There are no long-term dermal toxicity data available for zirconium dioxide, hence no long-term DNEL could be derived.

In addition, the dermal route is not the most appropriate route as exposure via inhalation is more likely and there is no indication from the physicochemical and toxicological properties of significant absorption through the skin (Annex VIII, 8.5.3, column 2 adaptation).

For inhalation, no long-term systemic DNEL was derived based on the above argumentation. Therefore, no dermal long-term systemic DNEL should be derived by extrapolation from inhalation studies. No extrapolation from the available oral repeated dose toxicity studies (performed with the read across substances zirconium acetate and zirconium basic carbonate) should be performed either because no adverse effects were observed in these studies up to the highest (limit) test doses.

Hazards for the eyes

Based on read across from a study with yttrium zirconium oxide, zirconium dioxide was concluded not to be classified as hazardous to eyes.

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure

DNEL related information

Additional information - General Population

Acute / short-term exposure - systemic and local effects

Inhalation:

As no local or systemic effects have been observed in the available toxicological studies up to the maximal technically achievable concentration, no DNEL needs to be derived.

Dermal:

There are no acute dermal toxicity data available for zirconium dioxide, hence no acute/short-term DNEL could be derived. There is no indication from the physicochemical and toxicological properties of significant absorption through the skin (Annex VIII, 8.5.3, column 2 adaptation). Furthermore, no indication of potential dermal toxicity is assumed from the available data.

Oral:

Based on available experimental data, there are no acute toxic effects leading to classification and labeling, hence no acute/short-term DNEL needs to be derived.

Long-term exposure - systemic and local effects

Inhalation:

Based on the available data and the same argumentation as for workers, no long-term DNEL needs to be derived for the general population. In addition, no officially set values are available for the general population.

Dermal route:

Based on the same argumentation as for workers (no long-term dermal toxicity data available, no adverse effects observed in oral and inhalation repeated dose toxicity studies), no long-term DNEL needs to be derived for the general population.

Oral:

No oral repeated dose toxicity studies are available for zirconium dioxide, however, read across can be performed from two studies with zirconium basic carbonate (another insoluble zirconium compound) and zirconium acetate (a 'water soluble' zirconium compound). In these studies, no adverse effects were observed up to the highest (limit) test dose. Therefore, it is not considered necessary to derive a long-term DNEL.

Further argumentation on read across and the overall extremely low potential of zirconium compounds for causing toxicity is given in the read across justification attached to Section 13 of IUCLID.

Hazards for the eyes

Based on read across from a study with yttrium zirconium oxide, zirconium dioxide was concluded not to be classified as hazardous to eyes.