Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Modified dose descriptor starting point:
NOAEC
Value:
132 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to inhalation NOAEC: 150 mg/kg/day x [1/0.38 x 50/100 x 6.7/10] = 132 mg/m3
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
132 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to inhalation NOAEC: 150 mg/kg/day x [1/0.38 x 50/100 x 6.7/10] = 132 mg/m3
AF for dose response relationship:
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1

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:
DNEL (Derived No Effect Level)
Value:
0.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to dermal NOAEL: 150 mg/kg/day x [oral absorption 50% / dermal absorption 25%] = 300 mg/kg/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to dermal NOAEL: 150 mg/kg/day x [oral absorption 50% / dermal absorption 25%] = 150 mg/kg/day
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1

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

Justification for endpoint selection:

- Reproductive toxicity: effects on fertility (oral): The key study was conducted in compliance with GLP and in accordance with the OECD Guideline for the Testing of Chemicals Number 422 on the structural analogue cerium carbonate.

- Reproductive toxicity: effects on fertility (dermal): The data obtained from oral exposure is deemed sufficient to address this endpoint.

- Reproductive toxicity: effects on fertility (inhalation): The data obtained from oral exposure is deemed sufficient to address this endpoint.

- Reproductive toxicity: developmental toxicity (oral): The key study was conducted in compliance with GLP and in accordance with the OECD Guideline for the Testing of Chemicals Number 422 on the structural analogue cerium carbonate.

- Reproductive toxicity: developmental toxicity (dermal): The data obtained from oral exposure is deemed sufficient to address this endpoint.

- Reproductive toxicity: developmental toxicity (inhalation): The data obtained from oral exposure is deemed sufficient to address this endpoint.

Acute toxicity: the registered substance is not acutely toxic, as the acute dermal LD50 was determined to be greater than 2000 mg/L and the acute oral LD50 is greater than 1000 mg/kg (1000mg/kg bw/day was tested in a repeat dose toxicity study).

Skin and eye irritation/corrosion; skin sensitisation: The registered substance was not irritating to skin and did not show sensitising potential.

Repeat-dose toxicity: a fully compliant 28-d toxicity study is available on the structural analogue cerium cerbonate (Davies, R, 2008), performed according to OECD guideline 422. The study established a NOEL at 150 mg/kg/day, because treatment caused effects on the stomach in both sexes at 1000 mg/kg/day and at 450 mg/kg/day in males.

Reproductive and developmental toxicity: a fully compliant OECD 422 study is available on the structural analogue cerium cerbonate (Davies, R, 2008). The study established a NOEL for reproduction and developmental toxicity of 1000 mg/kg/day based on the absence of effects at the highest dose tested.

Oral and dermal absorption: 50%, 25%

Inhalation absorption: 100%

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.22 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Modified dose descriptor starting point:
NOAEC
Value:
65.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to inhalation NOAEC: 150 mg/kg/day x [1/1.15 x 50/100] = 65.2 mg/m3
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.3 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEC
Value:
65.2 mg/m³
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to inhalation NOAEC: 150 mg/kg/day x [1/1.15 x 50/100] = 65.2 mg/m3
AF for dose response relationship:
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1

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:
DNEL (Derived No Effect Level)
Value:
0.25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to dermal NOAEL: 150 mg/kg/day x [oral absorption 50% / dermal absorption 25%] = 300 mg/kg/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Convert oral NOAEL to dermal NOAEL: 150 mg/kg/day x [oral absorption 50% / dermal absorption 25%] = 300 mg/kg/day
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1

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:
DNEL (Derived No Effect Level)
Value:
0.13 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.75 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
200
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
150 mg/kg bw/day
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
2
AF for remaining uncertainties:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

Justification for endpoint selection:

- Reproductive toxicity: effects on fertility (oral): The key study was conducted in compliance with GLP and in accordance with the OECD Guideline for the Testing of Chemicals Number 422 on the structural analogue cerium carbonate.

- Reproductive toxicity: effects on fertility (dermal): The data obtained from oral exposure is deemed sufficient to address this endpoint.

- Reproductive toxicity: effects on fertility (inhalation): The data obtained from oral exposure is deemed sufficient to address this endpoint.

- Reproductive toxicity: developmental toxicity (oral): The key study was conducted in compliance with GLP and in accordance with the OECD Guideline for the Testing of Chemicals Number 422 on the structural analogue cerium carbonate.

- Reproductive toxicity: developmental toxicity (dermal): The data obtained from oral exposure is deemed sufficient to address this endpoint.

- Reproductive toxicity: developmental toxicity (inhalation): The data obtained from oral exposure is deemed sufficient to address this endpoint.

Acute toxicity: the registered substance is not acutely toxic, as the acute dermal LD50 was determined to be greater than 2000 mg/L and the acute oral LD50 is greater than 1000 mg/kg (1000mg/kg bw/day was tested in a repeat dose toxicity study).

Skin and eye irritation/corrosion; skin sensitisation: The registered substance was not irritating to skin and did not show sensitising potential.

Repeat-dose toxicity: a fully compliant 28-d toxicity study is available on the structural analogue cerium cerbonate (Davies, R, 2008), performed according to OECD guideline 422. The study established a NOEL at 150 mg/kg/day, because treatment caused effects on the stomach in both sexes at 1000 mg/kg/day and at 450 mg/kg/day in males.

Reproductive and developmental toxicity: a fully compliant OECD 422 study is available on the structural analogue cerium cerbonate (Davies, R, 2008). The study established a NOEL for reproduction and developmental toxicity of 1000 mg/kg/day based on the absence of effects at the highest dose tested.

Oral and dermal absorption: 50%, 25%

Inhalation absorption: 100%