Cerium

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

8.13 mg/m³

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

5.07 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

18

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - workers

DNEL for long-term exposure, dermal and systemic effects for workers:

 

NOAEL (oral, sub-acute, rats) = 150 mgCe2(CO3)3/kg = 150 * (280,24 / 460,18) = 91,35 mg Ce /kg bw.

 

NOAEL_corrected(dermal, sub-acute) = 150 x 1 (oral to dermal) = 91,35 mg Ce/kg bw

 

Assessment factor: 3 x 6 = 18

Intra-species variability:  Allometric scaling: 1

(Any metabolism of inorganic substances can be excluded. Therefore, it is considered justified to deviate from default assessment factors accounting for a correction for difference in metabolic rate by assigning a factor of 1 instead of using the default factor of 4).

 

The remaining differences (e.g. toxicokinetics / -dynamics) have been covered by the following Intra + Inter-species factor.

 

Intra+ Inter-species variability: 3 (Eurometaux recommendation for workers)

Duration of exposure: 6 (sub-acute to chronic)

Dose response: 1 (adequate data available)

Quality of the whole data base: 1

 

DNEL_Workers(long-term, dermal, systemic effects) = 91,35 / 18 = 5,07 mg Ce/kg bw.

DNEL for long-term exposure, inhalation and systemic effects for workers:

The effects that were observed in the inhalation study (Rhodia, 1994) 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 oxide. 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 Austrian Occupational Exposure Level of 10 mg CeO2/m3 applicable to respirable dusts was considered instead.

DNEL_Workers(long-term, inhalation, systemic effects) = 10 mg CeO2/m3 = 8,13 mg Ce / m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

4.8 mg/m³

Acute/short term exposure

DNEL related information

Local effects

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.04 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.04 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

30

Modified dose descriptor starting point:

NOAEL

Acute/short term exposure

DNEL related information

Additional information - General Population

DNEL for long-term exposure,oral and systemic effects for general population:

NOAEL (oral, sub-acute, rats) = 150 mgCe2(CO3)3/kg = 150 * (280,24 / 460,18) = 91,35 mg Ce /kg bw.

 

Modification of the dose descriptor to the correct starting point is not necessary because there are no differences in human (oral) and experimental (oral) exposure conditions.

 

Assessment factor: 1 x 5 x 6 = 30

Intra-species variability:  Allometric scaling: 1

(Any metabolism of inorganic substances can be excluded. Therefore, it is considered justified to deviate from default assessment factors accounting for a correction for difference in metabolic rate by assigning a factor of 1 instead of using the default factor of 4).

 

The remaining differences (e.g. toxicokinetics / -dynamics) have been covered by the following Intra + Inter-species factor.

 

Intra+ Inter-species variability: 5 (Eurometaux recommendation for general population)

Duration of exposure: 6 (sub-acute to chronic)

Dose response: 1 (adequate data available)

Quality of the whole data base: 1

 

DNEL_{Gen Population}(long-term, oral, systemic effects) = 91,35 / 30 = 3,04 mg Ce/kg bw.

DNEL for long-term exposure, inhalation and systemic effects for general population:

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 Austrian Occupational Exposure Level of 10 mg CeO2/m3 applicable to respirable dusts was considered, taking account of an additional assessment factor because of the default factors for intraspecies differences between workers (3) and general population (5).

 

DNEL_{General Population}(long-term, inhalation, systemic effects) = 10 x (3/5) = 6 mg CeO2/m3 = 4,8 mg Ce / m3

DNEL for long-term exposure,oral and systemic effects for general population:

NOAEL (oral, sub-acute, rats) = 150 mgCe2(CO3)3/kg = 150 * (280,24 / 460,18) = 91,35 mg Ce /kg bw.

 

Modification of the dose descriptor to the correct starting point is not necessary because there are no differences in human (oral) and experimental (oral) exposure conditions.

 

Assessment factor: 1 x 5 x 6 = 30

Intra-species variability:  Allometric scaling: 1

(VC Reasoning: “Any metabolism of inorganic substances can be excluded. Therefore, it is considered justified to deviate from default assessment factors accounting for a correction for difference in metabolic rate by assigning a factor of 1 instead of using the default factor of 4”).

 

The remaining differences (e.g. toxicokinetics / -dynamics) have been covered by the following Intra + Inter-species factor.

 

Intra+ Inter-species variability: 5 (Eurometaux recommendation for general population)

 

Duration of exposure: 6 (sub-acute to chronic)

Dose response:1 (adequate data available)

Quality of the whole data base: 1

 

DNEL_{Gen Population}(long-term, oral, systemic effects) = 91,35 / 30 = 3,04 mg Ce/kg bw.