Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
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:
no hazard identified
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

Additional information - workers

Further elucidation of the justifications above is provided in the various endpoint summaries that are presented in this chapter, in particular the endpoint summary of IUCLID Section 7.1 and 7.5.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.5 mg/m³
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
2
AF for intraspecies differences:
2
Justification:
Metallic-iron particles behave as poorly soluble particles (inert dust in the parlance of the REACH guidance) and should be regulated as such. Occupational DNELs of 3 mg/m3 and 10 mg/m3 are prescribed for respirable inert dust and inhalable inert dust, respectively. Taking into account the larger intraspecies variation in the general population compared to occupationally exposed people, DNELs of 1.5 mg/m3 and 5 mg/m3 are derived for respirable dust and inhalable dust, respectively. According to ECHA’s Guidance document (Table R.8-6 Default assessment factors, pp. 38), the default assessment factors for intraspecies differences for systemic effects are: 5 for the workers and 10 for the general population, which ultimately leads to a factor of 2, when extrapolating from a DNEL for workers to a DNEL for the general population.
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:
no hazard identified
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:
0.71 mg/kg bw/day
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The establishement of a DNEL for long term oral exposure of the general population is discussed below.

No extrapolation from animal studies is possible, because experimental animals, in particular rats, differ strongly in the regulation of iron homeostasis and, as a result, are much more prone to become overloaded. Overload-related adverse effects in humans after oral exposure are only observed in relation to pathological conditions.

A number of human studies were concerned with the iron status. Several indicators of iron homeostasis were followed during a period of iron supplementation. It is hard to interpret these studies in terms of oral iron hazard assessment. Important questions are: Are the endpoints reflecting adverse effects, or do they just indicate the adaptation of iron status to the changing intake levels? How reliable is serum ferritin as an indicator of total amount of stored iron? How are the results affected by the nutritional and pathological history of the subjects?

It is clear that an additional 10 mg of absorbable iron (iron(II)sulphate) per day over a long period in iron replete subjects has no effect on serum ferritin. One study shows that 50 mg of absorbable iron had hardly any effect on serum ferritin, while another study did not yield hepatotoxicity and hematotoxicity after 21 days of 1.8 g of carbonyl iron per day in iron deplete women.

The amount of iron absorbed from metallic iron, in particular when the particles are large, will be lower than the amount absorbed from soluble substances like iron(II)sulphate. It was demonstrated in one study that 1.8 grams of iron carbonyl resulted in the absorption of only in 1.5 times the amount absorbed from the 0.180 g of iron(II)sulphate. This difference in absorption rate is confirmed in other studies. A review states that the "average relative bioavailability" of carbonyl iron in humans compared to iron(II)sulphate is 5 -20%. A much lower absorption of iron from carbonyl iron than fron iron(II)sulphate is demonstrated in a study that used radiolabelled iron.

These results show that the earlier mentioned value of 10 mg/day for absorbable iron can be multiplied by a factor of at least 5 for metallic iron. Thus it is concluded that a long-term oral dose of 50 mg carbonyl iron represents a worst-case, and should be used as a DNEL. Assuming a body weight of 70 kg, this value equals 0.71 mg/kg bw/day.