Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
50 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:
830 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 bis[12-hydroxyoctadecanoate]

It is assumed that after intake zinc bis[12-hydroxyoctadecanoate] 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. 12-hydroxystearate, 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 bis[12-hydroxyoctadecanoate] is a zinc salt of a fatty acid containing 18 C-atoms. Thus, read-across of data available for zinc salts of shorter-chained (C8,12) and similar chained (C16 -18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of zinc bis[12-hydroxyoctadecanoate].

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 with similar chain length (C16-18) and shorter chain length (C8, C12)) 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 bis[12-hydroxyoctadecanoate] (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 bis[12-hydroxyoctadecanoate] were derived based on the DNEL values for slightly soluble/ insoluble zinc compounds (as described below) assuming an average zinc content of zinc bis[12-hydroxyoctadecanoate] of 10%.

Workers
DNEL-Dermal:               83 mg/ kg bw/d zinc      -->830 mg/kg bw/d zinc bis[12-hydroxyoctadecanoate]

DNEL-Inhalation:          5 mg/m3zinc                   -->50 mg/m3 zinc bis[12-hydroxyoctadecanoate]

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:

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

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, http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db).

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., 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)

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., NOAELsyst= 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%;

NOAELinhal sol. Zn= 10 mg Zn/day / 40% = 25 mg Zn/day

NOAELinhal 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

NOAELinhal insol. Zn= 50 mg Zn/day / 10m3/day = 5 mg/m3

Corrected dose descriptor for consumers considering a breathing volume of 20m3per day NOAELinhal sol. Zn= 25 mg Zn/day / 20m3/day = 1.25 mg/m3

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:

DNELinhal sol Zn (worker)= 2.5 mg/m3;

DNELinhal insol Zn (worker)= 5 mg Zn/m3;

DNELinhal sol Zn (consumer)= 1.25 mg/m3;

DNELinhal 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/m3

1

2.5 mg Zn/m3

Slightly soluble/ insoluble

50 mg Zn/day (0.83 mg/kg bw/day)

5 mg Zn/ m3

1

 

5 mg Zn/ m3

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/m3

1

1.3 mg Zn/m3

Slightly soluble/ insoluble

50 mg Zn/day (0.83 mg/kg bw/day)

2.5 mg Zn/ m3

1

 

2.5 mg Zn/ m3

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

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

DNELoral insol Zn= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);

Dermal

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);

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, 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

DNELinhal soluble Zn (worker)= 1 mg Zn/m3;

DNELinhal insoluble Zn (worker)= 5 mg Zn/m3;

Inhalation – Consumer

DNELinhal soluble Zn (consumer)= 1.3 mg Zn/m3;

DNELinhal 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:
25 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:
830 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:
8.3 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 bis[12-hydroxyoctadecanoate]

It is assumed that zinc bis[12-hydroxyoctadecanoate] is changed after intake (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. 12-hydroxystearate, 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 bis[12-hydroxyoctadecanoate] is a zinc salt of a fatty acid containing 18 C-atoms. Thus, read-across of data available for zinc salts of shorter-chained (C8,12) and similar chained (C16 -18) fatty acids based on structural similarity, water solubility and zinc content in a conservative, worst-case approach is assumed to adequately describe the toxicological potential of zinc bis[12-hydroxyoctadecanoate].

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 with similar chain length (C16-18) and shorter chain length (C8, C12)) 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 bis[12-hydroxyoctadecanoate] (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 bis[12-hydroxyoctadecanoate] were derived based on the DNEL values for slightly soluble/ insoluble zinc compounds (as described below) assuming an average zinc content of zinc bis[12-hydroxyoctadecanoate] of 10%.

General Population

DNEL-Dermal: 83 mg/kg bw/d zinc      -->830mg/kg bw/d zinc bis[12-hydroxyoctadecanoate]

DNEL-Inhalation: 2.5 mg/m3zinc         --> 25 mg/m3 zinc bis[12-hydroxyoctadecanoate]

DNEL-Oral: 0.83 mg/ kg bw/d zinc       -->8.3 mg/kg bw/d zinc bis[12-hydroxyoctadecanoate]

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:

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

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, 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., 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)

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., NOAELsyst= 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%;

NOAELinhal sol. Zn= 10 mg Zn/day / 40% = 25 mg Zn/day

NOAELinhal 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

NOAELinhal insol. Zn= 50 mg Zn/day / 10m3/day = 5 mg/m3

Corrected dose descriptor for consumers considering a breathing volume of 20m3per day NOAELinhal sol. Zn= 25 mg Zn/day / 20m3/day = 1.25 mg/m3

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:

DNELinhal sol Zn (worker)= 2.5 mg/m3;

DNELinhal insol Zn (worker)= 5 mg Zn/m3;

DNELinhal sol Zn (consumer)= 1.25 mg/m3;

DNELinhal 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/m3

1

2.5 mg Zn/m3

Slightly soluble/ insoluble

50 mg Zn/day (0.83 mg/kg bw/day)

5 mg Zn/ m3

1

 

5 mg Zn/ m3

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/m3

1

1.3 mg Zn/m3

Slightly soluble/ insoluble

50 mg Zn/day (0.83 mg/kg bw/day)

2.5 mg Zn/ m3

1

 

2.5 mg Zn/ m3

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

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

DNELoral insol Zn= 50 mg Zn/day (i.e., 0.83 mg Zn/kg bw/day);

Dermal

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);

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, 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

DNELinhal soluble Zn (worker)= 1 mg Zn/m3;

DNELinhal insoluble Zn (worker)= 5 mg Zn/m3;

Inhalation – Consumer

DNELinhal soluble Zn (consumer)= 1.3 mg Zn/m3;

DNELinhal 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)]