Registration Dossier

Administrative data

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Acute / short-term exposure (systemic and local effects)

- Inhalation: no experimental data are available on acute toxicity after inhalation exposure. However, the substance is marketed/used in aqueous solution and is not volatile. No peak of exposure is expected for specific patterns. Therefore no DNEL for acute inhalation toxicity (systemic and local effects) needs to be derived.

- Dermal: an acute dermal toxicity test has been performed in rats (Longobardi, 2013a). No mortalities were observed. The LD50 is greater than 2000 mg/kg bw, hence not leading to classification. No peak of exposure is expected. Based on the lack of toxicity and exposure, it is not relevant to derive an acute DNEL for dermal exposure (systemic and local effects).

Long-term exposure (systemic effects):

- Dermal: no long-term dermal toxicity studies are available for zirconium acetate and this test is also waived based on the following information: a key study is available for the oral route of exposure and, according to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it was not necessary to perform a repeated dose toxicity study via the dermal route of exposure. As there is no adequate data, no DNEL dermal exposure (systemic effects) is derived. Although experimental data from an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening performed with zirconium acetate are available (Rossiello, 2013), no systemic hazard was identified up to and including the highest dose tested (limit dose as per OECD 422 guideline) that could be used to derive a DNEL using 'route-to-route extrapolation'. Based on all abovementioned considerations and the fact that there is sufficient evidence available indicating that zirconium is barely absorbed after dermal exposure (see section 7.1), no DNEL long-term (systemic effects) needs to be derived.

- Inhalation: no long-term inhalation toxicity studies are available for zirconium acetate and this test is also waived based on the following information: a key study is available for the oral route of exposure and, according to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it was not necessary to perform a repeated dose toxicity study via the inhalation route of exposure. As there is no adequate data, no DNEL inhalation exposure (systemic effects) is derived. In addition, the substance is marketed/used in aqueous solution and thus inhalation exposure is unlikely. Although experimental data from an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening performed with zirconium acetate are available (Rossiello, 2013), no systemic hazard was identified up to and including the highest dose tested (limit dose as per OECD 422 guideline) that could be used to derive a DNEL using 'route-to-route extrapolation'. Based on all abovementioned considerations and the fact that there is sufficient evidence available indicating that zirconium is barely absorbed after inhalation exposure (see section 7.1), no DNEL long-term (systemic effects) needs to be derived.

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) with zirconium dioxide 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.

Although no DNEL needs to be derived for zirconium acetate, it is advised to respect, when relevant, the generic standards for zirconium compounds mentioned above.

Long-term exposure (local effects):

No reliable repeated dose toxicity study is available for this substance via the dermal and inhalation route of exposure. Therefore, a DNEL long-term exposure, local effects cannot be derived for the dermal and inhalation route.

Hazard for the eyes

According to the criteria of the CLP Regulation, zirconium acetate is classified as Eye damage category 1 (H318). Therefore, and according to ECHA's Guidance on Information Requirements and Chemical Safety Assessment, Part E, Table E.3-1, the substance should be considered to cause medium hazard (qualitative assesment).

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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Acute / short-term exposure (systemic and local effects)

- Inhalation: no experimental data are available on acute toxicity after inhalation exposure. However, the substance is marketed/used in aqueous solution and is not volatile. No peak of exposure is expected for specific patterns. Therefore no DNEL for acute inhalation toxicity (systemic and local effects) needs to be derived.

- Dermal: an acute dermal toxicity test has been performed in rats (Longobardi, 2013a). No mortalities were observed. The LD50 is greater than 2000 mg/kg bw, hence not leading to classification. Based on the lack of toxicity and exposure, it is not relevant to derive an acute DNEL for dermal exposure (systemic and local effects).

-Oral: in a K2 study (Cochran et al., 1950), the acute oral LD50 was estimated to be 4100 mg/kg. According to the criteria of the CLP Regulation, the substance does not need to be classified for acute oral toxicity when the LD50 value is > 2000 mg/kg bw. As no adverse effect needs to be addressed, it is not required to derive an acute DNEL for oral exposure (systemic and local effects).

 

Long-term exposure (systemic effects):

- Oral: an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening has been performed with zirconium acetate (Rossiello, 2013). The test solution was administered daily, by gavage. Parental Sprague-Dawley rats (10 per sex and per dose) were treated, starting at 6-7 weeks old and ending when the animals were euthanized, at dose levels of 100, 300 and 1000 mg/kg bw/day of zirconium acetate. A control group of 10 males and 10 females was dosed with vehicle alone (deionized water). The No Observed Adverse Effect Level (NOAEL) was considered to be >=1000 mg/kg bw/day. No systemic hazard was identified up to and including the highest dose tested (limit dose as per OECD 422 guideline) that could be used to derive a DNEL. Based on all abovementioned considerations and the fact that there is sufficient evidence available indicating that zirconium is barely absorbed after oral exposure (see section 7.1), no DNEL long-term (systemic effects) needs to be derived.

- Dermal: as discussed in the 'Workers' section, no long-term dermal toxicity studies are available for zirconium acetate and this test is also waived based on the following information: a key study is available for the oral route of exposure and, according to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it was not necessary to perform a repeated dose toxicity study via the dermal route of exposure. As there is no adequate data, no DNEL dermal exposure (systemic effects) is derived. Although experimental data from an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening performed with zirconium acetate are available (Rossiello, 2013), no systemic hazard was identified up to and including the highest dose tested (limit dose as per OECD 422 guideline) that could be used to derive a DNEL using 'route-to-route extrapolation'. Based on all abovementioned considerations and the fact that there is sufficient evidence available indicating that zirconium is barely absorbed after dermal exposure (see section 7.1), no DNEL long-term (systemic effects) needs to be derived.

- Inhalation: no long-term inhalation toxicity studies are available for zirconium acetate and this test is also waived based on the following information: a key study is available for the oral route of exposure and, according to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it was not necessary to perform a repeated dose toxicity study via the inhalation route of exposure. As there is no adequate data, no DNEL inhalation exposure (systemic effects) is derived. In addition, the substance is marketed/used in aqueous solution and thus inhalation exposure is unlikely. Although experimental data from an oral combined repeated dose toxicity study with reproduction/developmental toxicity screening performed with zirconium acetate are available (Rossiello, 2013), no systemic hazard was identified up to and including the highest dose tested (limit dose as per OECD 422 guideline) that could be used to derive a DNEL using 'route-to-route extrapolation'. Based on all abovementioned considerations and the fact that there is sufficient evidence available indicating that zirconium is barely absorbed after inhalation exposure (see section 7.1), no DNEL long-term (systemic effects) needs to be derived.

 

Long-term exposure (local effects):

- No reliable repeated dose toxicity study is available for this substance via the dermal and inhalation route of exposure. Therefore, a DNEL long-term exposure, local effects cannot be derived for the dermal and inhalation route.

Hazard for the eyes

According to the criteria of the CLP Regulation, zirconium acetate is classified as Eye damage category 1 (H318). Therefore, and according to ECHA's Guidance on Information Requirements and Chemical Safety Assessment, Part E, Table E.3-1, the substance should be considered to cause medium hazard (qualitative assesment).