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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
3 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information
Justification:
No relevant local effects in toxicity studies
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:
8.33 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):
120
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
use of a NOAEL as a starting point
AF for differences in duration of exposure:
6
Justification:
default value for subacute to chronic exposure extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
default value for rats
AF for other interspecies differences:
1
Justification:
i.e. for other toxicokinetic differences based on ECETOC and AGS recommendations
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
complete and reliable data
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

All the data below relate to the micrometric (bulk) cerium dioxide.

 

The Derived No-Effect Levels (DNEL) were calculated using the recommendations of the ECHA "Guidance on information requirements and chemical safety assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health" (May 2008).

 

The adverse effects selected for DNEL derivation were considered to bear a threshold mode of action.

 

- ACUTE TOXICITY:

In the absence of any relevant toxic effect and in particular any acute toxicity hazard leading to Classification & Labelling, no specific DNEL was derived.

 

- IRRITATION/CORROSION:

In the absence of irritation effects related to the test substance, no specific DNEL was derived.

 

- SENSITIZATION:

In the absence of skin sensitization effects related to the test substance, no specific DNEL was derived.

 

- REPEATED DOSE TOXICITY:

(i) Dermal exposure

The study selected for dermal DNEL derivation is the OECD 422 -compliant study in rats (CIT, 2010) where no significant systemic toxicity was observed up to the highest tested dose, i.e. 1000 mg/kg bw/day.

 

* Dose descriptor: NOAEL = 1000 mg/kg bw/day in rats

 

* Corrected dose descriptor: No correction was applied (dermal NOAEL = oral NOAEL because both oral and dermal absorptions are considered negligible)

 

* Assessment factors:

Interspecies differences = 4 (default value for rats)

Other toxicokinetic differences = 1 (based on ECETOC and AGS recommendations)

Intraspecies differences = 5 (default value for workers)

Differences in exposure duration = 6 (default value for subacute to chronic exposure extrapolation) Dose-response issues = 1 (use of a NOAEL as a starting point)

Quality of the database = 1 (complete and reliable data)

 

=> Global assessment factor = 120

 

* DNEL calculation:

Worker-DNEL long-term for dermal route, systemic effects = 1000 / 120 = 8.33 mg/kg bw

 

(ii) Inhalation exposure

The study that could have been used for inhalation DNEL derivation is the 90-day repeated dose inhalation toxicity study in rats (BRL, 1994). However, the effects that were observed in this study on the respiratory tract and lymphoreticular system following prolonged inhalatory exposure to poorly soluble particles can be considered as species-specific and bearing low relevance to the human situation (Ref. ILSI Risk Science Institute. The relevance of the rat lung response to particle overload for human risk assessment: A workshop consensus report. Inhalation Toxicology, 12: 1-17, 2000). Lung overload-related inflammatory response is commonly observed in rats following inhalation exposure to poorly soluble particles. The concept of overload applies specifically to poorly soluble particles with low cytotoxicity, such as cerium dioxide. The distribution of the retained particles within the lung compartments varies between species. It has been shown that during chronic inhalation exposure, particles are retained to a greater degree in interstitial locations in lungs of non-human primates and dogs than in lungs of rats, and that the interspecies differences in particle location might contribute to corresponding differences in tissue response (Ref. Snipes MB. Current information on lung overload in non-rodent mammals: contrast with rats. Inhalation Toxicology, 8(suppl): 91 -109, 1996). These differences combined with the fact that human macrophages have five times the volume of rat macrophages are considered to account for the tendency of rats to respond to poorly soluble particles with more chronic inflammation and epithelial responses compared to humans (Ref. Oberdörster G. Toxicokinetics and effects of fibrous and non-fibrous particles. Inhalation Toxicology, 14: 29-56, 2002).

 

Therefore the critical effect for DNEL derivation was deemed irrelevant to humans. In order to set a limit exposure value, the unspecific Occupational Exposure Level (OEL) of 3 mg/m3 applicable to respirable dusts used in most of the European countries was considered instead.

 

Worker-DNEL long-term for inhalation route, systemic effects = 3 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/m³
DNEL related information
DNEL derivation method:
other: see below in "Explanation for hazard conclusion"
Overall assessment factor (AF):
2
Dose descriptor starting point:
other: OEL
Value:
3 mg/m³
AF for intraspecies differences:
2
Justification:
see below in "Explanation for hazard conclusion"
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.17 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):
240
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
use of a NOAEL as a starting point
AF for differences in duration of exposure:
6
Justification:
default value for subacute to chronic exposure extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
default value for rats
AF for other interspecies differences:
1
Justification:
i.e. for other toxicokinetic differences based on ECETOC and AGS recommendations
AF for intraspecies differences:
10
Justification:
default value for general population
AF for the quality of the whole database:
1
Justification:
complete and reliable data
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.17 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):
240
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
use of a NOAEL as a starting point
AF for differences in duration of exposure:
6
Justification:
default value for subacute to chronic exposure extrapolation
AF for interspecies differences (allometric scaling):
4
Justification:
default value for rats
AF for other interspecies differences:
1
Justification:
i.e. for other toxicokinetic differences based on ECETOC and AGS recommendations
AF for intraspecies differences:
10
Justification:
default value for general population
AF for the quality of the whole database:
1
Justification:
complete and reliable data
Acute/short term exposure
Hazard assessment conclusion:
no-threshold effect and/or no dose-response information available
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

All the data below relate to the micrometric (bulk) cerium dioxide.

 

The Derived No-Effect Levels (DNEL) were calculated using the recommendations of the ECHA "Guidance on information requirements and chemical safety assessment – Chapter R.8: Characterisation of dose [concentration]-response for human health" (May 2008).

 

The adverse effects selected for DNEL derivation were considered to bear a threshold mode of action.

 

- ACUTE TOXICITY:

In the absence of any relevant toxic effect and in particular any acute toxicity hazard leading to Classification & Labelling, no specific DNEL was derived.

 

- IRRITATION/CORROSION:

In the absence of irritation effects related to the test substance, no specific DNEL was derived.

 

- SENSITIZATION:

In the absence of skin sensitization effects related to the test substance, no specific DNEL was derived.

 

- REPEATED DOSE TOXICITY:

(i) Dermal exposure:

The study selected for dermal DNEL derivation is the OECD 422 -compliant study in rats (CIT, 2010) where no significant systemic toxicity was observed up to the highest tested dose, i.e. 1000 mg/kg bw/day.

 

* Dose descriptor: NOAEL = 1000 mg/kg bw in rats

 

* Corrected dose descriptor: No correction was applied (dermal NOAEL = oral NOAEL because both oral and dermal absorptions are considered negligible)

 

* Assessment factors:

Interspecies differences = 4 (default value for rats)

Other toxicokinetic differences = 1 (based on ECETOC and AGS recommendations)

Intraspecies differences = 10 (default value for general population)

Differences in exposure duration = 6 (default value for subacute to chronic exposure extrapolation) Dose-response issues = 1 (use of a NOAEL as a starting point)

Quality of the database = 1 (complete and reliable data)

 

=> Global assessment factor = 240

 

* DNEL calculation:

General population-DNEL long-term for dermal route, systemic effects = 1000 / 240 = 4.17 mg/kg bw

 

(ii) Inhalation exposure

The study that could have been used for inhalation DNEL derivation is the 90 -day repeat-dose inhalation toxicity study in rats (BRL, 1994). Similarly to the worker situation (see discussion above), the effects were considered as species-specific and not appropriate for DNEL derivation.

 

In order to set a limit exposure value, the unspecific Occupational Exposure Level of 3 mg/m3 applicable to respirable dusts and used in most of the European countries was considered, taking account of an additional assessment factor of 2 because of the default factors for intraspecies differences between workers (5) and general population (10).

 

General population-DNEL long-term for dermal route, systemic effects = 3/2 = 1.5 mg/m3