Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.8 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):
50
Modified dose descriptor starting point:
LOAEC
Value:
91 mg/m³
Explanation for the modification of the dose descriptor starting point:

Systemic effects

AF for dose response relationship:
1
Justification:
the LOAEL was 150 mg/kg bw
AF for differences in duration of exposure:
2
Justification:
subchronic (3 months) study
AF for interspecies differences (allometric scaling):
1
Justification:
has already been done at the correction in sRV
AF for other interspecies differences:
2.5
Justification:
remaining differences in case of systemic effects
AF for intraspecies differences:
5
Justification:
standard assessment factor
AF for the quality of the whole database:
1
Justification:
many studies available
AF for remaining uncertainties:
2
Justification:
from LOAEL to NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
3 750 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):
200
Modified dose descriptor starting point:
LOAEL
Value:
750 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Systemic effects

AF for dose response relationship:
1
Justification:
The LOAEL was 150 mg/kg bw
AF for differences in duration of exposure:
2
Justification:
Subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Standard for allometric scaling
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Standard for worker
AF for the quality of the whole database:
1
Justification:
Many studies available
AF for remaining uncertainties:
2
Justification:
From LOAEL to NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

See at justification and comments

Note 1: because EDTA-CuK2 is hardly absorbed from the gut and is not metabolized no significant differences in toxicokinetics are expected and as such the assessment factor of 2.5 (in case of systemic effects) would not be warranted. However, in view of possible differences in absorption of copper in individuals it was proposed to use this assessment factor.

Note 2: in several European countries the occupational exposure limit for copper (dust) is 1 mg/m3; in some other European countries this limit is 0.2 or 0.1 mg/m3. These limits for copper would correspond to 430/63.5 (MW EDTA-CuK2 / MW Cu) x 1, 0.2 or 0.1, or 6.8, 1.35 or 0.68 mg EDTA-CuK2/m3, respectively. The calculated DNEL of 1.8 mg/m3 is slightly higher than 0.68 mg/m3 or 1.35 mg/m3 (but lower than 6.8 mg/m3). However, copper-ions are strongly bound by EDTA, they will presumably not be deliberated easily and the unchanged EDTA-copper-complex will be rapidly excreted.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.45 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):
100
Modified dose descriptor starting point:
LOAEC
Value:
45 mg/m³
Explanation for the modification of the dose descriptor starting point:

systemic effects

AF for dose response relationship:
1
Justification:
LOAEL is 150 mg/kg bw
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
1
Justification:
has already been done at the correction in sRV
AF for other interspecies differences:
2.5
Justification:
remaining differences in case of systemic effects
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
many studies available
AF for remaining uncertainties:
2
Justification:
LOAEL to NOAEL
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
1 875 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):
400
Modified dose descriptor starting point:
LOAEL
Value:
750 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

systemic effects

AF for dose response relationship:
1
Justification:
LOAEL was 150 mg/kg
AF for differences in duration of exposure:
2
Justification:
Subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Standard for allometric scaling
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
10
Justification:
Standard for general population
AF for the quality of the whole database:
1
Justification:
Many studies available
AF for remaining uncertainties:
2
Justification:
From LOAEL to NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.375 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):
400
Modified dose descriptor starting point:
LOAEL
Value:
150 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

systemic effects

AF for dose response relationship:
1
Justification:
LOAEL 150 mg/kg bw
AF for differences in duration of exposure:
2
Justification:
subchronic study
AF for interspecies differences (allometric scaling):
4
Justification:
allometric scaling
AF for other interspecies differences:
2.5
Justification:
remaining differences in case of systemic effects
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
many studies available
AF for remaining uncertainties:
2
Justification:
LOAEL to NOAEL
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

See at justification and comments

Note: because EDTA-CuK2 is hardly absorbed from the gut and is not metabolized no significant differences in toxicokinetics are expected and as such the assessment factor of 2.5 (in case of systemic effects) would not be warranted. However, in view of possible differences in absorption of copper in individuals it was proposed to use this assessment factor.