Yttrium oxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Acute toxicity: the registered substance is not acutely toxic, as the acute inhalation LC50 was determined to be greater than 5.09 mg/L (OECD 436, Klimisch 1) and the acute oral LD50 is greater than 5000 mg/kg (OECD 401, Klimisch 1).

As no effects were observed in these acute toxicity studies by inhalation and by oral route, no hazard was identified and a DNEL is not required.

Furthermore, according to the process of production and uses at industrial sites, the risk of inhalation exposure is very low (packaging and final use under controlled conditions).

Skin and eye irritation/corrosion:

A publication (Lambert, 1993), evaluated as Klimisch 2, showed that yttrium oxide is not a skin irritating. In the same study, yttrium oxide is slightly irritating to the eye, but not classified according to EU criteria. Furthermore, a Klimisch 1 study (Guillot, 1986), testing yttrium oxide on guinea pig showed that yttrium oxide is not a skin Sensitizer.

The registered substance was not irritating to skin and showed very limit effect on eyes which allow to conclude to no classification. Furthermore, Yttrium oxide did not show skin sensitising potential.

Repeat-dose toxicity:

Concerning the oral route, the key study, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; klimisch 1) is available by oral route, showing no effect up to 1000 mg/kg bw/day (highest tested dose) after at least 28 days of exposure.

There were no statistically significant changes noted nor for animal weight, haematological and coagulation parameters nor clinical biochemistry parameters of male and female treated groups when compared to corresponding control.

The urinalysis performed in male animals revealed no test item related effect in the treated groups when compared to the control

At terminal sacrifice, macroscopic organ findings noted were few in both males and females, and none of them was considered to test item related.

Concerning the inhalation route, a publication (Reece, 1967), quoted Klimlisch 2, testing yttrium oxide by repeated inhalation on dogs, showed no systemic effect due to the tested substance. During the exposure period yttrium oxide concentration was arbitrarily set at 15 mg/cu.m. to maintain this concentration, daily sampling was required and adjustments were made accordingly

According to the ECHA Guidance on information requirements and chemical safety assessment, Part B: Hazard assessment (version 2.1, December 2011) and the part R.8 (i. e. Characterisation of dose[concentration]-response for human health, version 2.1, November 2012) in case there was no effect at any of the exposure ranges, the study should not be used for derivation of the NOAEL, because there is no need to set a DNEL. As no effects were observed in these studies, no hazard was identified and a DNEL is not required.

Reproductive toxicity:

The key study, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; klimisch 1) is available by oral route, showing no effect up to 1000 mg/kg bw/day (highest tested dose). There were no treatment related changes noted for the fertility index (%), reproduction efficiency or on pups. The data obtained by oral route is deemed sufficient to address the dermal and inhalation routes too.

According to the ECHA Guidance on information requirements and chemical safety assessment, Part B: Hazard assessment (version 2.1, December 2011) and the part R.8 (i. e. Characterisation of dose[concentration]-response for human health, version 2.1, November 2012) in case there was no effect at any of the exposure ranges, the study should not be used for derivation of the NOAEL, because there is no need to set a DNEL. As no effects were observed in this study, no hazard was identified and a DNEL is not required for this part.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

Acute toxicity: the registered substance is not acutely toxic, as the acute inhalation LC50 was determined to be greater than 5.09 mg/L (OECD 436, Klimisch 1) and the acute oral LD50 is greater than 5000 mg/kg (OECD 401, Klimisch 1).

ECHA Guidances on information requirements and chemical safety assessment, Part B: Hazard assessment (version 2.1, December 2011) and the part R.8 (i. e. Characterisation of dose [concentration]-response for human health, version 2.1, November 2012) in case there was no effect at any of the exposure ranges, the study should not be used for derivation of the NOAEL, because there is no need to set a DNEL.

As no effects were observed in these acute toxicity studies by inhalation and by oral route, no hazard was identified and a DNEL is not required.

Furthermore, according to the process of production and uses at industrial sites, the risk of inhalation exposure is very low (packaging and final use under controlled conditions).

Skin and eye irritation/corrosion:

A publication (Lambert, 1993), evaluated as Klimisch 2, showed that yttrium oxide is not a skin irritant. In the same study, yttrium oxide is slightly irritating to the eye, but not classified according to EU criteria.

Furthermore, a Klimisch 1 study (Guillot, 1986), testing yttrium oxide on guinea pig for skin sensitization properties showed that yttrium oxide does not induce skin sensitizer.

The registered substance was not irritating to skin and showed very limited effects on eyes which allow to conclude to no classification. Furthermore, Yttrium oxide did not show skin sensitising potential.

Repeat-dose toxicity:

Concerning the oral route, the key study, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; klimisch 1) is available by oral route, showing no effect on the tested animals up to 1000 mg/kg bw/day (highest tested dose) after at least 28 days of exposure : there were no statistically significant changes noted nor for animal weight, haematological and coagulation parameters nor clinical biochemistry parameters of male and female treated groups when compared to corresponding control.

The urinalysis performed in male animals revealed no changes in treated groups when compared to the control.

At terminal sacrifice, macroscopic organ findings noted were few in both males and females, and none of them was considered to test item related.

Therefore, according to these results the NOAEL for male and female, systemic toxicity was considered to be 1000 mg/kg bw/day

Concerning the inhalation route, a publication (Reece, 1967), quoted Klimlisch 2, testing yttrium oxide by repeated inhalation on dogs, showed no systemic effect due to the tested substance. During the exposure period yttrium oxide exposure was arbitrarily set at 15 mg/cu.m. to maintain this concentration, daily sampling was required and adjustments were made accordingly

No gross pathology, no histopathology and no effect on thoracic radiology were observed.

Lungs exposed dogs were reddish gray compared to controls. Bronchial lymph nodes in exposed dogs were enlarged 8 - 10 times.

Other body lymph nodes were normal in size and with regards to gross appearance, other organs were normal.

Significant increase of white blood cells, dust-laden macrophages in the bronchial lymph nodes & decrease of the erythrocyte volume which should indicated Y2O3 was being transported from the lungs to other tissues, having negative erythropoiesis effect.

The observed effects were rather consistent with a probable local inflammatory phenomenon of lung as a response to inhalation of poorly soluble particles of low toxicity and resulting "portal-of-entry" effects. No systemic effects were observed during the whole study. These limited and not significant effects are not relevant to the human occupational situation given the levels of exposure.

Therefore no systemic effects were observed in this study conducted by exposing dogs during 30 days at a concentration up to 20.63 mg/m3 of Yttrium Oxide by inhalation.

According to the ECHA Guidance on information requirements and chemical safety assessment, Part B: Hazard assessment (version 2.1, December 2011) and the part R.8 (i. e. Characterisation of dose[concentration]-response for human health, version 2.1, November 2012) in case there was no effect at any of the exposure ranges, the study should not be used for derivation of the NOAEL, because there is no need to set a DNEL. As no effects were observed in these studies, no hazard was identified and a DNEL is not required.

Reproductive toxicity:

The key study, a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test (OECD 422; klimisch 1) is available by oral route, showing no effect up to 1000 mg/kg bw/day (highest tested dose). There were no treatment related changes noted for the fertility index (%), reproduction efficiency or on pups. The data obtained by oral route is deemed sufficient to address the dermal and inhalation routes too.

According to the ECHA Guidance on information requirements and chemical safety assessment, Part B: Hazard assessment (version 2.1, December 2011) and the part R.8 (i. e. Characterisation of dose[concentration]-response for human health, version 2.1, November 2012) in case there was no effect at any of the exposure ranges, the study should not be used for derivation of the NOAEL, because there is no need to set a DNEL. As no effects were observed in this study, no hazard was identified and a DNEL is not required for this part.