Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.82 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):
75
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
661.18 mg/m³
Explanation for the modification of the dose descriptor starting point:

Key oral combined repeated dose toxicity/reproductive and developmental toxicity study available; no repeated dose inhalation toxicity study available. In absence of kinetic data, inhalation absorption is considered 2x oral absorption as conservative approach.

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default (subacute study)
AF for interspecies differences (allometric scaling):
1
Justification:
Factor already taken into account in route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.5 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):
300
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Key oral combined repeated dose toxicity/reproductive and developmental toxicity study available; no

repeated dose inhalation toxicity study available. In absence of kinetic data, inhalation absorption is

considered 2x oral absorption as conservative approach

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default (subacute study)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
5
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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

Source information for the DNELs:

A key combined repeated dose/reproductive & developmental toxicity study for subacute oral toxicity in rats

was available for read across substance iron dichloride, showing NOAEL values of 125 and 250 mg/kg bw

for males and females, respectively. Identified target organs were the liver, stomach and adrenal gland.

Read across with iron dichloride is justified, although a factor 6 was considered in benefit of iron sulfide,

which would bring the NOAEL to 750 mg/kg bw. The relevance of the stomach as target organ for iron sulfide

is questioned, as it has no corrosive proporties. A 90-day study was waived based on the availability of a

carcinogenicity study. A key 24-month carcinogenicity study was available in rats for ferric chloride by drink

water administration at concentrations of 0.25 and 0.5%, corresponding with mean dose levels of 170 and

320 mg/kg bw in males and 188 and 336 mg/kg bw in females. NOAEL for systemic toxicity was 170/188 mg/kg

in males/females, whereas NOAEL for carcinogenicity was 320/336 mg/kg bw in males/females.For iron sulfide,

similar NOAEL values are assumed.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.17 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):
150
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
326.09 mg/m³
Explanation for the modification of the dose descriptor starting point:

Key oral combined repeated dose toxicity/reproductive and developmental toxicity study available; no

repeated dose inhalation toxicity study available. In absence of kinetic data, inhalation absorption is

considered 2x oral absorption as conservative approach.

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default (subacute study)
AF for interspecies differences (allometric scaling):
1
Justification:
Factor already taken into account in route to route extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 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):
600
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Key 28-day oral toxicity study available; no repeated dose dermal toxicity study available. In absence of

kinetic data, dermal absorption is considered equal to oral absorption as conservative approach.

AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default (subacute study)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
1.25 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):
600
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable
AF for dose response relationship:
1
Justification:
ECHA default
AF for differences in duration of exposure:
6
Justification:
ECHA default (subacute study)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
10
Justification:
ECHA default
AF for the quality of the whole database:
1
Justification:
Based on high reliability study
AF for remaining uncertainties:
1
Justification:
No indication that another factor is needed
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

Source information for the DNELs:

A key combined repeated dose/reproductive & developmental toxicity study for subacute oral toxicity in rats

was available for read across substance iron dichloride, showing NOAEL values of 125 and 250 mg/kg bw

for males and females, respectively. Identified target organs were the liver, stomach and adrenal gland.

Read across with iron dichloride is justified, although a factor 6 was considered in benefit of iron sulfide,

which would bring the NOAEL to 750 mg/kg bw. The relevance of the stomach as target organ for iron

sulfide is questioned, as it has no corrosive proporties. A 90-day study was waived based on the availability

of a carcinogenicity study. A key 24-month carcinogenicity study was available in rats for ferric chloride by

drink water administration at concentrations of 0.25 and 0.5%, corresponding with mean dose levels of

170 and 320 mg/kg bw in males and 188 and 336 mg/kg bw in females. NOAEL for systemic toxicity was

170/188 mg/kg in males/females, whereas NOAEL for carcinogenicity was 320/336 mg/kg bw in

males/females. For iron sulfide, similar NOAEL values are assumed.