Reaction mass of zinc oxide and zinc peroxide

Toxicological Summary

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

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:

 

DNEL_{oral 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

 

• 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., NOAEL_syst= 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%;
•  

NOAEL_{dermal 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:

 

DNEL_{dermal insol Zn}= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day)

 

• No further differentiation between worker and consumer DNELs is considered necessary.

 

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:

• 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., NOAEL_syst= 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 insol Zn}= 10 mg Zn/day / 20% = 50 mg Zn/day

• Corrected dose descriptor for workers considering a breathing volume of 10m³ per 8 hr shift
• 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:

o   DNEL_{inhal 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 (0.83 mg/kg bw/day)	Not required	1	50 mg Zn/day (0.83 mg/kg bw/day)
Dermal	Slightly soluble/ insoluble	50 mg Zn/day (0.83 mg/kg bw/day)	5000 mg Zn/day (83mg/kg bw/day)	1	5000 mg Zn/day (83mg/kg bw/day)
inhalation	Slightly soluble/ insoluble	50 mg Zn/day (0.83 mg/kg bw/day)	5 mg Zn/ m^3	1	5 mg Zn/ m^3

 

 

 

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

• DNEL_{oral insol Zn}= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);
• Dermal
• DNEL_{dermal insol Zn}= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day);

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:

• Inhalation - Worker
• DNEL_{inhal insoluble Zn (worker)}= 2 mg Zn/m³

 

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

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:

 

DNEL_{oral 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

 

• 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., NOAEL_syst= 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%;
•  

NOAEL_{dermal 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:

 

DNEL_{dermal insol Zn}= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day)

 

• No further differentiation between worker and consumer DNELs is considered necessary.

 

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:

• 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., NOAEL_syst= 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 insol Zn}= 10 mg Zn/day / 20% = 50 mg Zn/day

• Corrected dose descriptor for consumers considering a breathing volume of 20m³per day
• 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:

o   DNEL_{inhal 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 (0.83 mg/kg bw/day)	Not required	1	50 mg Zn/day (0.83 mg/kg bw/day)
Dermal	Slightly soluble/ insoluble	50 mg Zn/day (0.83 mg/kg bw/day)	5000 mg Zn/day (83mg/kg bw/day)	1	5000 mg Zn/day (83mg/kg bw/day)
inhalation	Slightly soluble/ insoluble	50 mg Zn/day (0.83 mg/kg bw/day)	2.5 mg Zn/ m^3	1	2.5 mg Zn/ m^3

 

 

 

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:

• Oral
• DNEL_{oral insol Zn}= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);
• Dermal
• DNEL_{dermal insol Zn}= 5000 mg Zn/day (i.e., 83 mg Zn/kg bw/day);

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

• DNEL_{inhal insoluble Zn (consumer)}= 1 mg Zn/m³