Zinc dilaurate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

36 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEC

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

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

593 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEL

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

ZINC DILAURATE:

It is assumed that after intake zinc dilaurate is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities.The toxic potential of the fatty acid chain, i.e. laurate, is assumed to be negligible.Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

1. Zinc dilaurate is a zinc salt of a medium-chained fatty acid containing 12 C-atoms. Thus, read-across of data available for zinc salts of shorter-chained (C8) and longer-chained (C16-18) fatty acids based on structural similarity, water solubility and zinc content and

applying bridging principles in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of zinc dilaurate (C12).

2. Toxicity endpoints 7.2 to 7.4, including acute toxicity endpoints as well as sensitisation, irritation and corrosion are addressed with substance-specific information and/or data read-across from relevant zinc soaps (zinc salts of shorter-chained (C8) and longer-chained (C16-18) fatty acids) as well as supporting information from slightly soluble/insoluble zinc compounds.

3. Chronic endpoints, including 7.5 to 7.8 are addressed with data read-across from relevant slightly soluble/insoluble zinc compounds. A full read-across of data and conclusions based on a molecular weight correction and the solubility of zinc dilaurate (being slightly soluble/insoluble) is considered, see the hazard assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in Appendix 1 of the CSR and cited in excerpts below. The DNEL values for zinc dilaurate were derived based on the DNEL values for slightly soluble/ insoluble zinc compounds (as described below) assuming an average zinc content of zinc dilaurate of 14%.

Workers
DNEL-Dermal:               83 mg/ kg bw/ d zinc      --> 593 mg/kg bw/d zinc dilaurate

DNEL-Inhalation:          5 mg/m³ zinc                   --> 36 mg/m³ zinc dilaurate

ZINC:

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, the assessment factors to be used for zinc compounds are relatively small. The following table provides an overview of the assessment factors under consideration for zinc compounds.

Table-Assessment factors (AF) for zinc compounds

Uncertainties	Assessment Factor	Justification
Interspecies	1	No AF required; NOAEL has been derived from human experience through food supplementation
Intraspecies -worker	1	No AF required; NOAEL has been derived from human experience through food supplementation
Intraspecies –general population	1	No AF required; NOAEL has been derived from human experience through food supplementation
Exposure duration	1	No AF required; NOAEL has been derived from human experience through food supplementation
Dose response and endpoint specific/severity issues	1	No spefic AF required; NOAEL is considered to be reliable.
Quality of database	1	No specific AF required; limitations of all available studies have been identified and accounted for.

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 sol Zn}= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day)

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, http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1).

Derivation of the dermal DNEL (workers, 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 sol Zn}= 10 mg Zn/day / 2% = 500 mg Zn/day

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 sol Zn}= 500 mg Zn/day (i.e., 8.3 mg Zn/kg bw/day)

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 inhalatory DNEL (workers, 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 inhalatory 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 inhalatory 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 inhalatory exposure – 40%; bioavailability of slightly soluble/insoluble zinc compounds following inhalatory 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 workers considering a breathing volume of 10m³per 8hr shift

NOAEL_{inhal 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

Corrected dose descriptor for consumers considering a breathing volume of 20m³per day NOAEL_{inhal 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:

DNEL_{inhal sol Zn (worker)}= 2.5 mg/m³;

DNEL_{inhal insol Zn (worker)}= 5 mg Zn/m³;

DNEL_{inhal sol Zn (consumer)}= 1.25 mg/m³;

DNEL_{inhal insol Zn (consumer)}= 2.5 mg Zn/m³;

The following two tables summarize DNELs that have been calculated for worker and consumer exposure to soluble and slightly soluble/insoluble zinc compounds according to the ECHA guidance methodology.

Table - Corrected dose descriptor(s) per endpoint and endpoint-specific DNELs for workers

Endpoint		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)
Repeated dose toxicity	Oral	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	Not required	1	50 mg Zn/day (0.83 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	500 mg Zn/day (8.3mg/kg bw/day)	1	500 mg Zn/day (8.3 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	2.5 mg Zn/m^3	1	2.5 mg Zn/m^3
		Slightly soluble/ insoluble	50 mg Zn/day (0.83 mg/kg bw/day)	5 mg Zn/ m^3	1	5 mg Zn/ m^3

Table - Corrected dose descriptor(s) per endpoint and endpoint-specific DNELs for consumers

Endpoint		Zinc compound category	Most relevant quantitative dose descriptor for systemic exposure	Corrected dose descriptor for systemic exposure	Overall Assessment factor	Endpoint-specific DNEL (external dose)
Repeated dose toxicity	Oral	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	Not required	1	50 mg Zn/day (0.83 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	500 mg Zn/day (8.3mg/kg bw/day)	1	500 mg Zn/day (8.3 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	1.3 mg Zn/m^3	1	1.3 mg Zn/m^3
		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

Selection of the critical DNEL(s) for critical health effects

In line with the rationale provided in section 5.11.2 of the CSR, 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 sol Zn}= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);

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

Dermal

DNEL_{dermal sol Zn}= 500 mg Zn/day (i.e., 8.3 mg Zn/kg bw/day);

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 inhalatory 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 in chapter 5.11.2 of the CSR 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 chapter 5.11.2 of the CSR, existing data from human supplementary studies results in worker DNELs of 2.5 or 5 mg Zn/m³for soluble and slightly soluble/insoluble zinc compounds respectively and consumer DNELs of 1.3 or 2.5 mg Zn/m³.

The hazard assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in Appendix 1 of the CSR provides an overview of existing OELs for soluble zinc compounds represented by zinc chloride (i.e., CSR Zinc, Table "OELs for zinc chloride") as well as slightly soluble/insoluble zinc compounds represented by zinc oxide (i.e., CSR Zinc, Table "OELs for zinc oxide". While a detailed scientific justification for the OELs is not available, these values have ensureds workers safety for decades which correlates with the DNELs derived from the human volunteer studies. Taking a conservative approach it is proposed that for inhalatory exposure to soluble and slightly soluble/ insoluble zinc compounds, the existing OEL 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 soluble Zn (worker)}= 1 mg Zn/m³;

DNEL_{inhal insoluble Zn (worker)}= 5 mg Zn/m³;

Inhalation – Consumer

DNEL_{inhal soluble Zn (consumer)}= 1.3 mg Zn/m³;

DNEL_{inhal insoluble Zn (consumer)}= 2.5 mg Zn/m³;

[EU RAR Zinc distearate (CAS-No.: 557-05-1 & 91051-01-3 EINECS-No.: 209-151-9 & 293-049-4) Part II - Human Health (Final report, May 2008;http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1)]

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

18 mg/m³

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEC

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

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

593 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEL

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:

5.93 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

Overall assessment factor (AF):

1

Modified dose descriptor starting point:

NOAEL

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

ZINC DILAURATE:

It is assumed that after intake zinc dilaurate is changed (at least in part) to ionic zinc and that only ionic zinc is determining biological activities. The toxic potential of the fatty acid chain, i.e. laurate, is assumed to be negligible. Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

1. Zinc dilaurate is a zinc salt of a medium-chained fatty acid containing 12 C-atoms. Thus, read-across of data available for zinc salts of shorter-chained (C8) and longer-chained (C16-18) fatty acids based on structural similarity, water solubility and zinc content and applying bridging principles in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of zinc dilaurate (C12).

2. Toxicity endpoints 7.2 to 7.4, including acute toxicity endpoints as well as sensitisation, irritation and corrosion are addressed with substance-specific information and/or data read-across from relevant zinc soaps (zinc salts of shorter-chained (C8) and longer-chained (C16-18) fatty acids) as well as supporting information from slightly soluble/insoluble zinc compounds.

3. Chronic endpoints, including 7.5 to 7.8 are addressed with data read-across from relevant slightly soluble/insoluble zinc compounds. A full read-across of data and conclusions based on a molecular weight correction and the solubility of zinc dilaurate (being slightly soluble/insoluble) is considered, see the hazard assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in Appendix 1 of the CSR and cited in excerpts below. The DNEL values for zinc dilaurate were derived based on the DNEL values for slightly soluble/ insoluble zinc compounds (as described below) assuming an average zinc content of zinc dilaurate of 14%.

General Population

DNEL-Dermal: 83 mg/ kg bw/ d zinc       --> 593 mg/kg bw/d zinc dilaurate

DNEL-Inhalation: 2.5 mg/m³ zinc           --> 17.9 mg/m³ zinc dilaurate

DNEL-Oral: 0.83 mg/ kg bw/d zinc         --> 5.93 mg/kg bw/d zinc dilaurate

ZINC:

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, the assessment factors to be used for zinc compounds are relatively small. The following table provides an overview of the assessment factors under consideration for zinc compounds

Table - Assessment factors (AF) for zinc compounds

Uncertainties	Assessment Factor	Justification
Interspecies	1	No AF required; NOAEL has been derived from human experience through food supplementation
Intraspecies -worker	1	No AF required; NOAEL has been derived from human experience through food supplementation
Intraspecies –general population	1	No AF required; NOAEL has been derived from human experience through food supplementation
Exposure duration	1	No AF required; NOAEL has been derived from human experience through food supplementation
Dose response and endpoint specific/severity issues	1	No specifc AF required; NOAEL is considered to be reliable.
Quality of database	1	No specific AF required; limitations of all available studies have been identified and accounted for.

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 sol Zn}= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day)

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, http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1).

Derivation of the dermal DNEL (workers, 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 sol Zn}=10 mg Zn/day / 2% = 500 mg Zn/day

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 sol Zn}= 500 mg Zn/day (i.e., 8.3 mg Zn/kg bw/day)

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 inhalatory DNEL (workers, 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 inhalatory 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 inhalatory 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 inhalatory exposure – 40%; bioavailability of slightly soluble/insoluble zinc compounds following inhalatory 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 workers considering a breathing volume of 10m³per 8hr shift

NOAEL_{inhal 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

Corrected dose descriptor for consumers considering a breathing volume of 20m³per day NOAEL_{inhal 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:

DNEL_{inhal sol Zn (worker)}= 2.5 mg/m³;

DNEL_{inhal insol Zn (worker)}= 5 mg Zn/m³;

DNEL_{inhal sol Zn (consumer)}= 1.25 mg/m³;

DNEL_{inhal insol Zn (consumer)}= 2.5 mg Zn/m³;

The following two tables summarize DNELs that have been calculated for worker and consumer exposure to soluble and slightly soluble/insoluble zinc compounds according to the ECHA guidance methodology.

Table - Corrected dose descriptor(s) per endpoint and endpoint-specific DNELs for workers

Endpoint		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)
Repeated dose toxicity	Oral	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	Not required	1	50 mg Zn/day (0.83 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	500 mg Zn/day (8.3mg/kg bw/day)	1	500 mg Zn/day (8.3 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	2.5 mg Zn/m^3	1	2.5 mg Zn/m^3
		Slightly soluble/ insoluble	50 mg Zn/day (0.83 mg/kg bw/day)	5 mg Zn/ m^3	1	5 mg Zn/ m^3

Table- Corrected dose descriptor(s) per endpoint and endpoint-specific DNELs for consumers

Endpoint		Zinc compound category	Most relevant quantitative dose descriptor for systemic exposure	Corrected dose descriptor for systemic exposure	Overall Assessment factor	Endpoint-specific DNEL (external dose)
Repeated dose toxicity	Oral	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	Not required	1	50 mg Zn/day (0.83 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	500 mg Zn/day (8.3mg/kg bw/day)	1	500 mg Zn/day (8.3 mg/kg bw/day)
		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	Soluble	50 mg Zn/day (0.83 mg/kg bw/day)	1.3 mg Zn/m^3	1	1.3 mg Zn/m^3
		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

Selection of the critical DNEL(s) for critical health effects

In line with the rationale provided in section 5.11.2 of the CSR, 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 sol Zn}= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);

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

Dermal

DNEL_{dermal sol Zn}= 500 mg Zn/day (i.e., 8.3 mg Zn/kg bw/day);

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 inhalatory 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 in chapter 5.11.2 of the CSR 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 chapter 5.11.2 of the CSR, existing data from human supplementary studies results in worker DNELs of 2.5 or 5 mg Zn/m³for soluble and slightly soluble/insoluble zinc compounds respectively and consumer DNELs of 1.3 or 2.5 mg Zn/m³.

The hazard assessment of "Zinc" within the framework of Regulation (EC) No 1907/2006 in Appendix 1 of the CSR provides an overview of existing OELs for soluble zinc compounds represented by zinc chloride (i.e., CSR Zinc, Table "OELs for zinc chloride") as well as slightly soluble/insoluble zinc compounds represented by zinc oxide (i.e., CSR Zinc, Table "OELs for zinc oxide"). While a detailed scientific justification for the OELs is not available, these values have ensureds workers safety for decades which correlates with the DNELs derived from the human volunteer studies. Taking a conservative approach it is proposed that for inhalatory exposure to soluble and slightly soluble/ insoluble zinc compounds, the existing OEL 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 soluble Zn (worker)}= 1 mg Zn/m³;

DNEL_{inhal insoluble Zn (worker)}= 5 mg Zn/m³;

Inhalation – Consumer

DNEL_{inhal soluble Zn (consumer)}= 1.3 mg Zn/m³;

DNEL_{inhal insoluble Zn (consumer)}= 2.5 mg Zn/m³;

[EU RAR Zinc distearate (CAS-No.: 557-05-1 & 91051-01-3 EINECS-No.: 209-151-9 & 293-049-4) Part II - Human Health (Final report, May 2008; http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1)]