Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.25 mg/m³
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:
NOAEC
Value:
9.25 mg/m³
Explanation for the modification of the dose descriptor starting point:

For a detailed explanation please refer to "additional information – workers".

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
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30.8 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:
30.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For a detailed explanation please see box "additional information - workers".

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:
medium hazard (no threshold derived)

Additional information - workers

Lactic acid is a ubiquitous and essential molecule of life; natural concentrations in vivo can and will vary widely. Lactate is non-toxic, any (local) effects are due to pH effects only; long-term DNELs are therefore considered not relevant. Therefore, the DNELs for zinc lactate were based solely on the toxicity of zinc.

The NOAEL of 50 mg Zn2+/day (0.83 mg/kg bw/day based on a woman’s body weight of 60 kg) derived from a 10-week oral study with human volunteers was used as a starting point for the risk characterisation for repeated dose toxicity (the value is taken as suggested in the submitted dossier for zinc chloride). The oral NOAEL for zinc lactate was calculated by scaling based on the molecular weight of the substance: 50 × 3.7 = 185 mg zinc lactate/day (3 mg/kg bw/day based on a woman’s body weight of 60 kg). As this NOAEL is based on human data, no additional assessment factors are required, i.e. to overall assessment factor is 1.

Oral

Oral DNELzinc lactate = 3 mg zinc lactate/kg bw/d

Table 1 : Assessment factors (AF) for zinc lactate

Uncertainties

Assessment Factor

Justification

Interspecies

1

No AF required; NOAEL derived from human experience through food supplementation

Intraspecies -worker

1

No AF required; NOAEL derived from human experience through food supplementation

Intraspecies –general population

1

No AF required; NOAEL derived from human experience through food supplementation

Exposure duration

1

No AF required; NOAEL 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.

 

This setting of the DNEL is fully in line with the approach from the EU Risk Assessment – part II Human Health (EU RAR 2004).

Derivation of the systemic exposure reflecting the oral NOAEL was done considering the bioavailability of soluble zinc compounds used in human volunteer studies: NOAELsyst = 50 mg Zn/d × 20 % = 10 mg Zn/d. This internal dose was used as a starting point in determining the dermal and inhalatory DNELs, by route-to-route extrapolation.

Dermal

The bioavailability of soluble zinc compounds following dermal exposure was considered to be 2 % (value as suggested in the submitted zinc chloride dossier).

dermal NOAELZn = 10 mg Zn/d/2 % = 500 mg Zn/d

dermal NOAELzinc lactate= (500 × 3.7)/60 = 30.8 mg zinc lactate/kg bw/d

No assessment factor is considered to be required as the original dose descriptor was derived from appropriate human volunteer studies.

Dermal DNELzinc lactate (worker, consumer) = 30.8 mg zinc lactate/kg bw/d

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

Inhalatory

Derivation of the inhalatory DNEL is also based on the internal dose calculated based on the oral NOAEL. The bioavailability of soluble zinc compounds, including zinc lactate, following inhalatory exposure was considered to be 40 % (value as suggested in the submitted zinc chloride dossier).

NOAELZn = 10 mg Zn/d /40 % = 25 mg Zn/d

NOAELzinc lactate = 25 × 3.7 = 92.5 mg zinc lactate/d

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

Inhalatory NOAECzinc lactate = 92.5 mg/10 m³/d = 9.25 mg/m³

Corrected dose descriptor for consumers considering a breathing volume of 20 m³ per day inhalatory NOAEL = 92.5 mg/20 m³/d = 4.63 mg/m³

No assessment factor is considered to be required as the original dose descriptor was derived from appropriate human volunteer studies; hence the DNELs are as follows:

Inhalatory DNELzinc lactate worker = 9.25 mg/m³

Inhalatory DNELzinc lactate consumer = 4.63 mg/m³

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.63 mg/m³
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:
NOAEC
Value:
4.63 mg/m³
Explanation for the modification of the dose descriptor starting point:

For a detailed explanation please refer to "additional information - workers".

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
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
30.8 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:
30.8 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For a detailed explanation please refer to "additional information - workers".

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:
3 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:
3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For detailed information please refer to "additional information - workers".

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:
low hazard (no threshold derived)
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

For detailed explanation please refer to "additional information - workers".