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EC number: 910-427-2 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicological Summary
- Administrative data
- Workers - Hazard via inhalation route
- Workers - Hazard via dermal route
- Workers - Hazard for the eyes
- Additional information - workers
- General Population - Hazard via inhalation route
- General Population - Hazard via dermal route
- General Population - Hazard via oral route
- General Population - Hazard for the eyes
- Additional information - General Population
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: List of MAK and BAT Values 2015.
- Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 50 mg Zn/day is the basis for the derivation of the inhalatory DNEL.
Hence, the derivation of the inhalation DNEL requires a route to route extrapolation as described in the following: *) Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i. e., NOAELsyst= 50 mg Zn/day x 20% = 10 mg Zn/day);
*) Calculation of a inhalation exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; the following assumptions are made: bioavailability of soluble zinc compounds following inhalation exposure – 40%; bioavailability of slightly soluble/insoluble zinc compounds following inhalation exposure – 20%; NOAELinhal sol. Zn= 10 mg Zn/day / 40% = 25 mg Zn/day NOAEL inhal insol Zn=10 mg Zn/day / 20% = 50 mg Zn/day Corrected dose descriptor for workers considering a breathing volume of 10m3per 8hr shift NOAELinhal sol. Zn= 25 mg Zn/day / 10m3/day = 2.5 mg/m3 NOAEL inhal insol. Zn= 50 mg Zn/day / 10m3/day = 5 mg/m3
*) No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows: DNELinhal sol Zn (worker) = 2.5 mg/m3; DNEL inhal insol Zn (worker) = 5 mg Zn/m3
According to the List of MAK and BAT values, 2015 (List of MAK and BAT Values 2015. DFG, Deutsche Forschungsgemeinschaft), the MAK value for Zinc and its inorganic compounds (inhalable fraction, based on the D50 of approx. 136.6 µm) is 2 mg/m³. This value will be used as inhalation DNEL for workers.
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- Oral
DNEL related information
- DNEL derivation method:
- other: List of MAK and BAT Values 2015.
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:
- 83 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
- Dose descriptor starting point:
- NOAEL
- Value:
- 8.3 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 83 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The derivation of a dermal DNEL on the basis of an oral NOAEL of 50 mg Zn/day derived from human volunteer studies
requires a route to route extrapolation.In this process, the follow steps are required
*) Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i.e., NOAELsyst = 50 mg Zn/day x 20% = 10 mg Zn/day);
*) Calculation of a dermal exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; assumption: bioavailability of soluble zinc compounds following dermal exposure – 2%; bioavailability of slightly soluble/insoluble zinc compounds following dermal exposure – 0.2%; NOAELdermal sol Zn = 10 mg Zn/day / 2% = 500 mg Zn/day ; NOAELdermal insol Zn = 10 mg Zn/day / 0.2% = 5000 mg Zn/day
*) No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows: DNELdermal sol Zn = 500 mg Zn/day (i.e., 8.3 mg Zn/kg bw/day); DNELdermal insol Zn = 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day)
- AF for dose response relationship:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for differences in duration of exposure:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for other interspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for intraspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for the quality of the whole database:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for remaining uncertainties:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
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
- Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i.e., NOAELsyst= 50 mg Zn/day x 20% = 10 mg Zn/day);
- Calculation of a dermal exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; assumption: bioavailability of soluble zinc compounds following dermal exposure – 2%; bioavailability of slightly soluble/insoluble zinc compounds following dermal exposure – 0.2%;
- No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows:
- No further differentiation between worker and consumer DNELs is considered necessary.
- Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i.e., NOAELsyst= 50 mg Zn/day x 20% = 10 mg Zn/day);
- Calculation of a inhalation exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; the following assumptions are made: bioavailability of soluble zinc compounds following inhalation exposure – 40%; bioavailability of slightly soluble/insoluble zinc compounds following inhalation exposure – 20%;
- Corrected dose descriptor for workers considering a breathing volume of 10m3 per 8 hr shift
- NOAELinhal insol. Zn= 50 mg Zn/day / 10m³/day = 5 mg/m³
- No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows:
- DNELoral insol Zn= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);
- Dermal
- DNELdermal insol Zn= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day);
- Inhalation - Worker
- DNELinhal insoluble Zn (worker)= 2 mg Zn/m3
To derive the endpoint specific NOAELs for workers and consumers on the basis of the established NOAEL of 50 mg zinc/day (0.83 mg/kg bw/day based on a woman’s body weight of 60 kg), the NOAEL has to be corrected by assessment factors to account for the uncertainties of the database that led to the establishment of the NOAEL. As the toxicity of zinc compounds is well understood and the NOAEL has been based on human experience and data following chronic exposure to zinc through food supplementation, no assessment factors are considered to be required for zinc compounds
Derivation of the oral DNEL
The most relevant dose descriptor has been derived from oral human volunteer studies and human experience from the use of zinc in food supplementation. Neither correction of the dose descriptor nor the use of an assessment factor is considered necessary. Therefore, the oral DNEL for all zinc compounds (i. e., soluble or slightly soluble/insoluble) for workers and consumers equals the most relevant quantitative external dose descriptor for systemic exposure:
DNELoral insol Zn= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day)
This setting of the DNEL is fully in line with the approach and result that was concluded in the EU Risk Assessment- part II Human Health (EU RAR 2004).
Derivation of the dermal DNEL (workers)
The derivation of a dermal DNEL on the basis of an oral NOAEL of 50 mg Zn/day derived from human volunteer studies requires a route to route extrapolation. In this process, the follow steps are required
NOAELdermal insol Zn= 10 mg Zn/day / 0.2% = 5000 mg Zn/day
DNELdermal insol Zn= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day)
Derivation of the inhalation DNEL (workers)
The oral NOAEL of 50 mg Zn/day is also the basis for the derivation of the inhalatory DNEL. Hence, the derivation of the inhalation DNEL requires a route to route extrapolation as described in the following:
NOAELinhal insol Zn= 10 mg Zn/day / 20% = 50 mg Zn/day
o DNELinhal insol Zn (worker)= 5 mg Zn/m³
The following tables summarize DNELs that have been calculated for worker and consumer exposure to slightly soluble/insoluble zinc compounds according to the ECHA guidance methodology.
Corrected dose descriptor(s) per endpoint and endpoint-specific DNELs for workers
Repeated dose toxicity
|
Zinc compound category |
Most relevant quantitative external dose descriptor for systemic exposure(NOEL) |
Corrected external dose descriptor for systemic exposure |
Overall Assessment factor |
Endpoint-specific DNEL (external dose) |
oral |
Slightly soluble/ insoluble |
50 mg Zn/day |
Not required |
1 |
50 mg Zn/day |
Dermal |
Slightly soluble/ insoluble |
50 mg Zn/day (0.83 mg/kg bw/day) |
5000 mg Zn/day |
1 |
5000 mg Zn/day |
inhalation |
Slightly soluble/ insoluble |
50 mg Zn/day (0.83 mg/kg bw/day) |
5 mg Zn/ m3 |
1 |
5 mg Zn/ m3 |
In line with the rationale provided above, the DNEL’s for workers following oral or dermal exposure to soluble and slightly soluble/insoluble compounds are as follows:
Oral
These DNEL’s appropriately protect workers and consumers for the most sensitive health endpoint, i. e. reduced ESOD activity that has been observed in humans following repeated exposure to zinc compounds.
With regard to establishing the critical DNELs for inhalation exposure of workers or consumers to zinc compounds, two approaches are considered suitable:
a. the derivation of the DNEL on the basis of existing oral human dietary supplement studies requiring route to route extrapolation as illustrated above and
b. the use of existing OELs as the respective DNELs for worker exposure.
With regard to the latter, the guidance on information requirements and chemical safety assessment states that the OELs and/or the underlying information used for setting the OELs can be used to derive the DNELs for workers (ECHA, 2008).
As presented in above, existing data from human supplementary studies results in worker DNELs of 5 mg Zn/m3 for slightly soluble/insoluble zinc compounds and consumer DNELs of 2.5 mg Zn/m3.
According to the List of MAK and BAT values, 2015 (List of MAK and BAT Values 2015. DFG, Deutsche Forschungsgemeinschaft), the MAK value for Zinc and its inorganic compounds (inhalable fraction, based on the D50 of approx. 136.6 µm) is 2 mg/m³.
Taking a conservative approach it is proposed that for inhalation exposure to soluble and slightly soluble/ insoluble zinc compounds, the existing MAK values are used as the respective DNEL against which to judge the adequacy of workplace risk management measures (RMM) to control airborne exposure to zinc compounds:
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
- Route of original study:
- By inhalation
DNEL related information
- DNEL derivation method:
- ECHA REACH Guidance
- Overall assessment factor (AF):
- 1
- Dose descriptor starting point:
- NOAEC
- Value:
- 2 mg/m³
- Modified dose descriptor starting point:
- NOAEC
- Value:
- 1 mg/m³
- Explanation for the modification of the dose descriptor starting point:
The oral NOAEL of 50 mg Zn/day is the basis for the derivation of the inhalatory DNEL.
Hence, the derivation of the inhalation DNEL requires a route to route extrapolation as described in the following:
*) Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i. e., NOAELsyst= 50 mg Zn/day x 20% = 10 mg Zn/day);
*) Calculation of a inhalation exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; the following assumptions are made: bioavailability of soluble zinc compounds following inhalation exposure – 40%; bioavailability of slightly soluble/insoluble zinc compounds following inhalation exposure – 20%; NOAEL inhal sol. Zn= 10 mg Zn/day / 40% = 25 mg Zn/day NOAEL inhal insol Zn=10 mg Zn/day / 20% = 50 mg Zn/day Corrected dose descriptor for consumers considering a breathing volume of 20m3 per day NOAELinhal sol. Zn= 25 mg Zn/day / 20m³/day = 1.25 mg/m³ NOAEL inhal insol. Zn= 50 mg Zn/day / 20m³/day = 2.5 mg/m³
*) No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows: DNELinhal sol Zn (consumer) = 1.25 mg/m³; DNEL inhal insol Zn (consumer) = 2.5 mg Zn/m³
Additionally, studies on worker exposure to Zinc compounds are available which resulted in a NOAEL of 2 mg/m³. These data were used to derive a MAK value. When extrapolating this result to general population (24 h exposure, 10 m³ respiratory volume), a DNEL of 1 mg/m³ is derived for inhalation exposure of the general population.
- AF for dose response relationship:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience
- AF for differences in duration of exposure:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience
- AF for other interspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience
- AF for intraspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience
- AF for the quality of the whole database:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience
- AF for remaining uncertainties:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience
Acute/short term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 1 mg/m³
DNEL related information
- DNEL extrapolated from long term DNEL
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:
- 83 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
- Dose descriptor starting point:
- NOAEL
- Value:
- 0.83 mg/kg bw/day
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 83 mg/kg bw/day
- Explanation for the modification of the dose descriptor starting point:
The derivation of a dermal DNEL on the basis of an oral NOAEL of 50 mg Zn/day derived from human volunteer studies requires a route to route extrapolation.In this process, the follow steps are required
*) Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i.e., NOAELsyst = 50 mg Zn/day x 20% = 10 mg Zn/day);
*) Calculation of a dermal exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; assumption: bioavailability of soluble zinc compounds following dermal exposure – 2%; bioavailability of slightly soluble/insoluble zinc compounds following dermal exposure – 0.2%; NOAELdermal sol Zn = 10 mg Zn/day / 2% = 500 mg Zn/day ; NOAELdermal insol Zn = 10 mg Zn/day / 0.2% = 5000 mg Zn/day
*) No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows: DNELdermal sol Zn = 500 mg Zn/day (i.e., 8.3 mg Zn/kg bw/day); DNELdermal insol Zn = 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day)
- AF for dose response relationship:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for differences in duration of exposure:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for other interspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for intraspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for the quality of the whole database:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for remaining uncertainties:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
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:
- DNEL (Derived No Effect Level)
- Value:
- 0.83 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
- Modified dose descriptor starting point:
- NOAEL
- Value:
- 0.83 mg/kg bw/day
- AF for dose response relationship:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for differences in duration of exposure:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for interspecies differences (allometric scaling):
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for other interspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for intraspecies differences:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for the quality of the whole database:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
- AF for remaining uncertainties:
- 1
- Justification:
- No AF required; NOAEL has been derived from human experience through food supplementation
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
- Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i.e., NOAELsyst= 50 mg Zn/day x 20% = 10 mg Zn/day);
- Calculation of a dermal exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; assumption: bioavailability of soluble zinc compounds following dermal exposure – 2%; bioavailability of slightly soluble/insoluble zinc compounds following dermal exposure – 0.2%;
- No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows:
- No further differentiation between worker and consumer DNELs is considered necessary.
- Derivation of the systemic exposure reflecting the oral NOAEL considering the bioavailability of soluble zinc compounds which have been used in the human volunteer studies (i.e., NOAELsyst= 50 mg Zn/day x 20% = 10 mg Zn/day);
- Calculation of a inhalation exposure to a soluble or slightly soluble/insoluble zinc compound that results in a systemic exposure of 10 mg Zn/day; the following assumptions are made: bioavailability of soluble zinc compounds following inhalation exposure – 40%; bioavailability of slightly soluble/insoluble zinc compounds following inhalation exposure – 20%;
- Corrected dose descriptor for consumers considering a breathing volume of 20m3per day
- NOAELinhal insol. Zn= 50 mg Zn/day / 20m3/day = 2.5 mg/m3
- No assessment factor is considered to be required as the original dose descriptor has been derived from appropriate human volunteer studies; hence the DNELs are as follows:
- Oral
- DNELoral insol Zn= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);
- Dermal
- DNELdermal insol Zn= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day);
- DNELinhal insoluble Zn (consumer)= 1 mg Zn/m³
To derive the endpoint specific NOAELs for consumers on the basis of the established NOAEL of 50 mg zinc/day (0.83 mg/kg bw/day based on a woman’s body weight of 60 kg), the NOAEL has to be corrected by assessment factors to account for the uncertainties of the database that led to the establishment of the NOAEL. As the toxicity of zinc compounds is well understood and the NOAEL has been based on human experience and data following chronic exposure to zinc through food supplementation, no assessment factors are considered to be required for zinc compounds
Derivation of the oral DNEL
The most relevant dose descriptor has been derived from oral human volunteer studies and human experience from the use of zinc in food supplementation. Neither correction of the dose descriptor nor the use of an assessment factor is considered necessary. Therefore, the oral DNEL for all zinc compounds (i. e., soluble or slightly soluble/insoluble) for workers and consumers equals the most relevant quantitative external dose descriptor for systemic exposure:
DNELoral insol Zn= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day)
This setting of the DNEL is fully in line with the approach and result that was concluded in the EU Risk Assessment- part II Human Health (EU RAR 2004).
Derivation of the dermal DNEL (consumers)
The derivation of a dermal DNEL on the basis of an oral NOAEL of 50 mg Zn/day derived from human volunteer studies requires a route to route extrapolation. In this process, the follow steps are required
NOAELdermal insol Zn= 10 mg Zn/day / 0.2% = 5000 mg Zn/day
DNELdermal insol Zn= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day)
Derivation of the inhalation DNEL (consumers)
The oral NOAEL of 50 mg Zn/day is also the basis for the derivation of the inhalatory DNEL. Hence, the derivation of the inhalation DNEL requires a route to route extrapolation as described in the following:
NOAELinhal insol Zn= 10 mg Zn/day / 20% = 50 mg Zn/day
o DNELinhal insol Zn (consumer)= 2.5 mg Zn/m3;
The following tables summarize DNELs that have been calculated for worker and consumer exposure to slightly soluble/insoluble zinc compounds according to the ECHA guidance methodology.
Corrected dose descriptor(s) per endpoint and endpoint-specific DNELs for consumers
Repeated dose toxicity
|
Zinc compound category |
Most relevant quantitative external dose descriptor for systemic exposure(NOEL) |
Corrected external dose descriptor for systemic exposure |
Overall Assessment factor |
Endpoint-specific DNEL (external dose) |
oral |
Slightly soluble/ insoluble |
50 mg Zn/day |
Not required |
1 |
50 mg Zn/day |
Dermal |
Slightly soluble/ insoluble |
50 mg Zn/day (0.83 mg/kg bw/day) |
5000 mg Zn/day |
1 |
5000 mg Zn/day |
inhalation |
Slightly soluble/ insoluble |
50 mg Zn/day (0.83 mg/kg bw/day) |
2.5 mg Zn/ m3 |
1 |
2.5 mg Zn/ m3 |
In line with the rationale provided above, the DNEL’s for workers and consumers following oral or dermal exposure to soluble and slightly soluble/insoluble compounds are as follows:
These DNEL’s appropriately protect workers and consumers for the most sensitive health endpoint, i. e. reduced ESOD activity that has been observed in humans following repeated exposure to zinc compounds.
With regard to establishing the critical DNELs for inhalation exposure of workers or consumers to zinc compounds, two approaches are considered suitable:
a. the derivation of the DNEL on the basis of existing oral human dietary supplement studies requiring route to route extrapolation as illustrated above and
b. the use of existing OELs as the respective DNELs for worker exposure.
With regard to the latter, the guidance on information requirements and chemical safety assessment states that the OELs and/or the underlying information used for setting the OELs can be used to derive the DNELs for workers (ECHA, 2008).
As presented in above, existing data from human supplementary studies results in worker DNELs of 2.5 or 5 mg Zn/m³ for soluble and slightly soluble/insoluble zinc compounds respectively and consumer DNELs of 1.3 or 2.5 mg Zn/m³.
According to the List of MAK and BAT values, 2015 (List of MAK and BAT Values 2015. DFG, Deutsche Forschungsgemeinschaft), the MAK value for Zinc and its inorganic compounds (inhalable fraction, based on the D50 of approx. 136.6 µm) is 2 mg/m³. The same study was also used to derive the respective consumer DNEL by extrapolating to 24 h exposure.
o Inhalation - Consumer
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.