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EC number: 231-176-9 | CAS number: 7440-67-7
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
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
Workers - Hazard via dermal route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 11 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 200
- Modified dose descriptor starting point:
- NOAEL
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
Additional information - workers
- allometric scaling, factor 4;
- interspecies differences, factor 2.5;
- intraspecies differences (workers), factor 5;
- exposure duration, factor 2 (sub-chronic (119 days) to chronic);
- quality of whole database, factor 2. The study used was not performed on pure zirconium dioxide but for zirconium carbonate containing 20.9% zirconium dioxide
Workers long term dermal DNEL
The dermal DNEL derivation is based on the NOAEL from a 17 weeks (119 days) oral study on zirconium carbonate containing 20.9% zirconium dioxide (Harrison et al., 1951). Test animals (rats) were fed with hydrated zirconium carbonate at different doses. The NOAEL was >15100 mg HZC/kg bw/day i.e >3156 mg ZrO2/kg bw/day. The value of 3150 mg/kg bw/day was used in further calculating the DNELs.
It was assumed that the oral absorption rat = dermal absorption rat
The overall assessment factor was obtained as follows:
The overall assessment factor is: 4 x 2.5 x 5 x 2 x 2 = 200
The derived DNEL for ZrO2 is therefore: 3150 / (4 x 2.5 x 5 x 2 x 2) = 3150 /200 = 15 mg/kg bw/day.
To obtain the DNEL equivalent for Zr, a conversion factor of 1.37 need to be applicated
The derived DNEL for Zr is hence: 15 / 1.37 = 11 mg/kg bw/day
Workers long term inhalation DNEL
The study from Spiegl & al (1956) provides a NOAEC for zirconium dioxide > 11 mg Zr/m3 after 60 days of exposure and 75 mg Zr/m3 after 30 days, based on no effects observed on the several species used (cat, dog, guinea pig, rabbit and rat). Nevertheless only one dose was tested in these studies. We can only conclude that the NOAEC will be higher than these tested doses. Based on these unbounded
NOAECs, the DNEL will be unrealistically low and not representative for the toxicity of zirconium. Indeed in all available studies (read across with ZrO2), no health effects were observed even at higher doses (acute toxicity tests via oral & inhalation route). This absence of effect could be explains by the fact that, at pulmonary level, Zr particles are deposited but, as they are under an inert form (with a passivation layer surrounding them), no systemic toxicity occurs. Indeed, one of the possible effects observed is lung granuloma, sometimes found in worker exposes to Zr particles (epidemiological data): granuloma corresponds to an inflammatory chronic reaction to the deposition of the small particles in the alveolus. In addition, Zr particles are not soluble and thus own a very low bioavailability as demonstrated in the toxicokinetic assessment.
National exposure limits were defined in. In, NIOSH, ACGIH, OSHA have evaluated toxicity and defined long term and short term exposure limits for zirconium compounds. For all these organisms the same 8 hours Time Weighted Average (TWA) of 5 mgZr/m3 was set. This value was based on the results of Spiegl & al, 1956 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 dose of 3.5 mg/m3. (Unfortunately unpublished study not accessible).
So, based on all these considerations, it is considered reasonable and sufficiently conservative to use the 8 hours TWA of 5 mg/m3 as a long term systemic DNEL for workers. In addition, this value is advised by the French authorities as the limit value for exposure to dusts and was adopt for "alveolar particles". For "inhalable particles", with higher mean aerodynamic diameter, the value was set to 10 mg/m3.
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.5 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 2
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:
- 5.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 400
- Modified dose descriptor starting point:
- NOAEL
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:
- 5.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 400
- Modified dose descriptor starting point:
- NOAEL
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
Additional information - General Population
- allometric scaling, factor 4;
- interspecies differences, factor 2.5;
- intraspecies differences (population), factor 10;
- exposure duration, factor 2 (sub-chronic (119 days) to chronic);
- 2 for quality of whole database. The study used is not for pure zirconium dioxide but for zirconium carbonate containing 20.9% zirconium dioxide
General population long term dermal/oral DNEL
The dermal/oral DNEL derivation is based on the NOAEL from a 17 weeks (119 days) oral study on zirconium carbonate containing 20.9% zirconium dioxide (Harrison et al., 1951). Test animals (rats) were fed with hydrated zirconium carbonate at different doses. The NOAEL was >15100 mg HZC/kg bw/day i.e >3156 mg ZrO2/kg bw/day. The value of 3150 mg/kg bw/day was used in further calculating the DNEL.
It was assumed that the oral absorption rat = dermal absorption rat.
The overall assessment factor was obtained as follows:
The overall assessment factor is: 4 x 2.5 x 10 x 2 x 2 = 400
The derived DNEL for ZrO2 is therefore: 3150 / (4 x 2.5 x 10 x 2 x 2) = 3150 /400 = 7.5 mg/kg bw/day.
To obtain the DNEL equivalent for Zr, a conversion factor of 1.37 need to be applicated
The derived DNEL for Zr is hence: 7.5 / 1.37 = 5.5 mg/kg bw/day
General population long term inhalation DNEL
The DNEL selected for long term- systemic effect exposure of worker (i.e 5 mg/m3) is used for consumers applying an additional assessment factor of 2 for general population.The value for consumer is 2.5 mg/m3.
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