Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
16.9 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):
5
Modified dose descriptor starting point:
NOAEC
DNEL value:
84.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

A corrected inhalatory NOAEC rat was calculated on the basis of the oral NOAEL rat (48 mg/kg bw/day) by using a default respiratory volume for the rat corresponding to the daily duration of human exposure (sRVrat; see ECHA Guidance R.8. 2008).

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
1
Justification:
Default assessment factor for interspecies local/systemic effects by inhalation
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance (R.8, 2008), worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: VCI, Verband der Chemischen Industrie e.V. (2010): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität
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:
48 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):
10
Modified dose descriptor starting point:
NOAEL
DNEL value:
480 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
2
Justification:
The mode of action is physicochemical (complexation of metals) and should be irrespective of species. Therefore the proposed assessment factor for interspecies differences is only 2.
AF for other interspecies differences:
1
AF for intraspecies differences:
5
Justification:
ECHA REACH Guidance (R.8, 2008), worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.2 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):
10
Modified dose descriptor starting point:
NOAEC
DNEL value:
41.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

A corrected inhalatory NOAEC rat was calculated on the basis of the oral NOAEL rat (48 mg/kg bw/day) by using a default respiratory volume for the rat corresponding to the daily duration of human exposure (sRVrat; see ECHA Guidance R.8. 2008).

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
1
Justification:
Default assessment factor for interspecies local/systemic effects by inhalation
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance (R.8, 2008), consumer
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: VCI, Verband der Chemischen Industrie e.V. (2010): Ableitung von DNEL für lokal reizende Stoffe mit guter Datenlage zur systemischen Toxizität, aber limitierter Datenlage zur Inhalationstoxizität
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:
24 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):
20
Modified dose descriptor starting point:
NOAEL
DNEL value:
480 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For oral exposure, an absorption of 5% was assumed (see chapter toxicokinetics). For dermal exposure, an absorption of 0.5% was assumed (see chapter toxicokinetics).

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
2
Justification:
The mode of action is physicochemical (complexation of metals) and should be irrespective of species. Therefore the proposed assessment factor for interspecies differences is only 2.
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance (R.8, 2008), consumer
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.4 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):
20
Modified dose descriptor starting point:
NOAEL
DNEL value:
48 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation (oral study). The NOAEL for HEDP-2Na (41 mg/kg bw/d) is equivalent to 48 mg HEDP-4Na/kg bw/d.

AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic oral study
AF for interspecies differences (allometric scaling):
2
Justification:
The mode of action is physicochemical (complexation of metals) and should be irrespective of species. Therefore the proposed assessment factor for interspecies differences is only 2.
AF for other interspecies differences:
1
AF for intraspecies differences:
10
Justification:
ECHA REACH Guidance (R.8, 2008), consumer
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population