Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
12 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
304 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation data available. The oral NOAEL of 57 mg/kg bw/d (Fe) is equivalent to 246 mg/kg bw/d iron trinitrate. Correction for breathing rate (/0.38) and actviity level (*6.7/10) and the extent of oral absorption (70%) and inhalation absorption (100% assumed) results in an inhalation NOAEC of 304 mg/m3.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required - already accounted for
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
default value: reliable database
AF for remaining uncertainties:
1
Justification:
default value: no other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 722 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Data for repeated dermal exposure are not available. The oral NOAEL of 57 mg/kg bw/d (Fe) is equivalent to 246 mg/kg bw/d iron trinitrate. Correction for the extent of oral absorption (70%) and dermal absorption (10%) gives a dermal NOAEL of 1722 mg/kg bw/d.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
extrapolation from a sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
standard value (rat study)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value: workers
AF for the quality of the whole database:
1
Justification:
default value: reliable database
AF for remaining uncertainties:
1
Justification:
default value: no other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

The relevant starting point for the derivation of systemic DNEL values is the oral NOAEL of 57 mg/kg bw/d (Fe) from a 90 -day oral toxicity study with ferric chloride.

The oral NOAEL of 57 mg/kg bw/d (Fe) is equivalent to 246 mg/kg bw/d iron trinitrate. Correction for breathing rate (/0.38) and activity level (*6.7/10) and the extent of oral absorption (70%) and inhalation absorption (100% assumed) results in an inhalation NOAEC of 304 mg/m3. A long-term systemic inhalation DNEL for workers of 12 mg/m3 is derived following the application of an overall assessment factor of 25, according to REACH guidance.

A short-term systemic inhalation DNEL for workers is not derived in the absence of any identified acute systemic hazard.

Local inhalation DNEL values for workers are not derived. The substance is of low pH and is therefore considered to be a potential respiratory irritant. Inhalation exposure should be controlled through the use of appropriate RMMs (engineering controls and/or RPE) where significant exposure is possible.

Correction of the oral NOAEL of 246 mg/kg bw/d for the extent of oral absorption (70%) and dermal absorption (10%) gives a dermal NOAEL of 1722 mg/kg bw/d. Application of an overall assessment factor of 100, according to REACH guidance gives a long-term systemic dermal DNEL for workers of 17 mg/kg bw/d.

A short-term systemic dermal DNEL for workers is not derived in the absence of any identified acute systemic hazard.

Local dermal DNEL values for workers are not derived. Skin corrosivity is assumed based on the low pH of the substance. Dermal exposure should therefore be minimised.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 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:
NOAEC
DNEL value:
150 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalation data available. The oral NOAEL of 57 mg/kg bw/d (Fe) is equivalent to 246 mg/kg bw/d iron trinitrate. Correction for breathing rate (/1.15) and the extent of oral absorption (70%) and inhalation absorption (100% assumed) results in an inhalation NOAEC of 150 mg/m3.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value: extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
not required: already accounted for
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value: general population
AF for the quality of the whole database:
1
Justification:
default value: reliable database
AF for remaining uncertainties:
1
Justification:
default: value no other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.6 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:
NOAEL
DNEL value:
1 722 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Data for repeated dermal exposure are not available. The oral NOAEL of 57 mg/kg bw/d (Fe) is equivalent to 246 mg/kg bw/d iron trinitrate. Correction for the extent of oral absorption (70%) and dermal absorption (10%) gives a dermal NOAEL of 1722 mg/kg bw/d.
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value: extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
standard factor: rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value: general population
AF for the quality of the whole database:
1
Justification:
default value: reliable database
AF for remaining uncertainties:
1
Justification:
default value: no other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
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:
1.2 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:
NOAEL
DNEL value:
246 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value: extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
standard factor: rat study
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
10
Justification:
default value: general population
AF for the quality of the whole database:
1
Justification:
default value: reliable database
AF for remaining uncertainties:
1
Justification:
default value: no other uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
repeated dose toxicity
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

The relevant starting point for the derivation of systemic DNEL values is the oral NOAEL of 57 mg/kg bw/d (Fe) from a 90 -day oral toxicity study with ferric chloride.

The oral NOAEL of 57 mg/kg bw/d (Fe) is equivalent to 246 mg/kg bw/d iron trinitrate. Correction for breathing rate (/1.15) and the extent of oral absorption (70%) and inhalation absorption (100% assumed) results in an inhalation NOAEC of 150 mg/m3. A long-term systemic inhalation DNEL for the general population of 3 mg/m3 is derived following the application of an overall assessment factor of 50, according to REACH guidance.

A short-term systemic inhalation DNEL for the general population is not derived in the absence of any identified acute systemic hazard.

Local inhalation DNEL values for the general population are not derived. The substance is of low pH and is therefore considered to be a potential respiratory irritant. Inhalation exposure to high concentrations should be minimised.

Correction of the oral NOAEL of 246 mg/kg bw/d for the extent of oral absorption (70%) and dermal absorption (10%) gives a dermal NOAEL of 1722 mg/kg bw/d. Application of an overall assessment factor of 200, according to REACH guidance gives a long-term systemic dermal DNEL for the general population of 8.6 mg/kg bw/d.

A short-term systemic dermal DNEL for the general population is not derived in the absence of any identified acute systemic hazard.

Local dermal DNEL values for the general population are not derived. Skin corrosivity is assumed based on the low pH of the substance. Dermal exposure to high concentrations of the substance should be avoided.

Application of an overall assessment factor of 200, according to REACH guidance gives a long-term systemic oral DNEL for the general population of 1.2 mg/kg bw/d.

A short-term systemic oral DNEL for the general population is not derived in the absence of any identified acute systemic hazard