Iron oxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

10 mg/m³

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:

10 mg/m³

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

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Starting point

In consideration of the available data no acute or chronic oral or dermal effects of the members of the category are expected. From mutagenicity studies (Bayer, 1982e; Moriya et al., 1983; Bevan and Manger, 1985; Fujita et al., 1994; Bayer 1990, Bayer 2008 a, b, c) and despite the widespread use and ubiquitous occurrence of the category members no carcinogenic potential of the group members is identified (Steinhoff, Mohr, and Hahnemann, 1991).

The only critical exposure pathway to humans is the inhalation of the dust of the compounds of the group members. Therefore it is only necessary to consider this way of exposure as a threshold mode of action for workers and the general population.

Due to the same physicochemical properties and the absence of systemic effects of iron oxides, Fe3O4 has been chosen as a representative substance and the results of the inhalations studies are significant for Fe2O3 and FeO as for the iron oxides.

For Fe3O4 valid subacute and subchronic inhalation studies (according OECD) are available (Bayer, 2006a; Bayer, 2006b).

The NOAECs are 10.1 mg/m³ from the 28 days study (Bayer, 2006b) and 4.7 mg/m³ from the 90 days study ( Bayer, 2006a) with LOAECs of 19.7 mg/m³and 16.6 mg/m³, respectively. In the subchronic inhalation study in rats exposure was 6 hours/day, 5 days/week for 13 weeks.

In the 13 weeks study the rats were exposed to mean actual concentrations (i.e. breathing zone volumes) of highly respirable aerosol of 4.7 +/- 0.6, 16.6 +/- 3.0 and 52.1 +/- 6.4 mg/m³, respectively. The repeated exposure was not associated with any specific clinical signs. Hematology, clinical pathology and urinalysis were unobtrusive. No evidence of extrapulmonary toxicity existed (Bayer, 2006a).

With regard to the most sensitive parameters considered to be adverse, viz. increased counts of cells and especially PMNs in BAL, elevated LDH as marker of cytotoxicity, and ß-NAG as marker of increased lysosomal activities 4.7 mg/m³ constitute an exposure level without evidence of adversity (Bayer, 2006a).

The NOAEC of Fe3O4 as a surrogate for the whole group is 4.7 mg/m³ for respirable dust. Non-specific toxicity consistent with a ‘poorly soluble particle’ and no specific toxicity were observed at higher concentrations at the port of entry (respiratory tract) only (Bayer, 2006a). There is no evidence of systemic toxicity, genotoxicity or carcinogenicity. Therefore the group can be treated as dust without specific toxicity and the general dust limit applies.

Derivation of DNEL:

According to ECHA Guidance Document R.8; Appendix R 8-13 a national Occupational Exposure Limit (OEL) can be used in place of a DNEL under certain circumstances. For general dust in Germany the current binding national Occupational Exposure Limit is 10 mg/m3 for inhalable and 3 mg/m3 for respirable dust (TRGS900; http://www.baua.de/cae/servlet/contentblob/666764/publicationFile/55580/TRGS-900.doc), whereas the German MAK commission has published a value of 4 mg/m3 for inhalable and 1.5 mg/m3 for respirable dust (DFG, 2009).

The use of the official national German value for general dust is in line with the proposal in ECHA Guidance document R8 from May 2008. Here it is stated that the general dust limits of 10 mg/m3 for the inhalable airborne fraction and 3 mg/m3 for the respirable airborne fraction used in setting Occupational Exposure Limits in many countries should be considered in combination with nature of the dust. It is stated in the ECHA Guidance document that for non-soluble inert dusts if the derived DNEL for inhalation is above these dust limits, the general dust limits should apply for exposure scenarios with exposure to dust (see chapter 8.7.1, page 54 of ECHA guidance document R.8 from May 2008).

In the case of the ferrous oxides covered by this assessment based on the data of the 13-week inhalation toxicity study it was demonstrated that the effects after inhalation are attributable to the particle per se rather than a substance specific toxicity; therefore the use of the general dust limit value as DNEL is confirmed by experimental data. The NOAEC for repeated inhalation in the 13 week study for the respirable dust is higher than the respective general dust limit and therefore does not argue against that approach.

Overall, based on

• the substance-specific data on the mode of action of iron oxide after inhalation,

• the available 90 day inhalation toxicity study and

• the ECHA guidance how to select the critical DNEL in case of inert dusts

the current binding national Occupational Exposure Limit in Germany for dust of 10 mg/m3 for inhalable and 3 mg/m3 for respirable dust (TRGS900) will be used as DNEL for long term exposure to iron oxides.

Iron(II)Oxide belongs to the iron oxides family and presents comparable physico chemical properties, leading to similar behaviour for the all members of the iron oxide substances. In particular, based on affinity of the chemical structure, Iron Oxide (Fe3O4) and Iron(III)Oxide (Fe2O3) are selected to support read across for the Iron(II)Oxide dossier. Full justification paper is attached in the current Summary Section.

General Population - Hazard via inhalation route

Systemic 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

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:

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

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

General Population - Hazard via oral route

Systemic 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 for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

The only critical exposure pathway to humans is the inhalation of the dust of the compounds of the group members. Therefore it is only necessary to consider this way of exposure as a threshold mode of action for workers and the general population. However, consumers are not exposed via inhalation as the substance is bound physically in the matrix of an article. Therefore, no relevant exposure via inhalation is expected for consumers.

Iron(II)Oxide belongs to the iron oxides family and presents comparable physico chemical properties, leading to similar behaviour for the all members of the iron oxide substances. In particular, based on affinity of the chemical structure, Iron Oxide (Fe3O4) and Iron(III)Oxide (Fe2O3) are selected to support read across for the Iron(II)Oxide dossier. Full justification paper is attached in the current Summary Section.