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Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
other: review of the scientific literature
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: review (literature evaluation)
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
2010

Materials and methods

Type of study / information:
literature evaluation of human studies on siderosis and pulmonary fibrosis and evaluation of animal studies on effects of iron and iron oxides
Endpoint addressed:
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
This paper evaluates the scientific literature on the effects of prolonged inhalation of iron or iron compounds
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
iron oxide(s)
IUPAC Name:
iron oxide(s)
Constituent 2
Reference substance name:
Iron oxide(s)
IUPAC Name:
Iron oxide(s)
Test material form:
not specified
Details on test material:
test material not specified

Method

Details on study design:
This paper evaluates the scientific literature on the effects of prolonged inhalation of iron or iron compounds and, specifically, any association between these exposures and the development of siderosis or pulmonary fibrosis. It considers whether these two conditions require iron and iron compounds to be classified as causing specific target organ toxicity (STOT) – repeated exposure under the CLP regulation criteria.
Exposure assessment:
not specified

Results and discussion

Results:
The review using a weight of evidence approach to this human and animal literature leads to conclude that:
• The prolonged inhalation of high concentrations of pure iron and iron compounds can produce a benign pneumoconiosis without impairment of lung morphology, function or symptoms;
• Pulmonary siderosis secondary to the inhalation of complex mixtures containing iron or iron compounds, such as welding fumes, is a benign pneumoconiosis without impairment of lung function or symptoms;
• Pulmonary fibrosis (“siderofibrosis”) and loss of lung function may occur after the pronged inhalation of high level of welding fumes ;
• The lung changes of siderosis may regress on cessation of exposure.
The authors conclude that the conditions occurring after prolonged inhalation of high levels of iron or iron compounds do not meet the criteria for classification.

Any other information on results incl. tables

ANIMAL STUDIES ON EFFECTS OF IRON AND IRON OXIDES

A number of authors studied the effects of inhalation and instillation of iron oxide particles in experimental animals. An Inhalation study reported a transient inflammatory response of Syrian hamsters when exposed to 274 mg iron oxide/m3 for 3 hours but failed to demonstrate any fibrogenic potential (Kavet 1978). Similar results were found in instillation studies. Instillation of 3 mg iron oxide particles in Syrian hamsters leads to a mild inflammatory response characterized by transient influx of alveolar macrophages (Keenan 1989). However, Das et al. found no evidence for irreversible changes in the lungs of guinea pigs even after repeated instillations of large amounts of iron oxide up to 50 mg per dose (Das 1983). Naeslund found no evidence of fibrosis produced in lung tissue of rabbits and guinea pigs after intratracheal injection or inhalation of iron oxide mixed with less than 5% silica (Naeslund 1940). The effects of inhalation of welding fume in experimental animals have also been studied. Inhalation and installation studies have demonstrated dose-dependent increases in inflammatory cytokines in bronchio-alveolar washings; these cytokines including tumour necrosis factor and Interleukin -1 beta (Antonini et al 1996, 1997). Hicks et al (1984) found fibrotic changes in the rat lung after single intra-tracheal installation of high doses of welding fumes (10 and 50 mg per rat).

Applicant's summary and conclusion

Conclusions:
Our review using a weight of evidence approach to this human and animal literature leads us to conclude that:
• The prolonged inhalation of high concentrations of pure iron and iron compounds can produce a benign pneumoconiosis without impairment of lung morphology, function or symptoms;
• Pulmonary siderosis secondary to the inhalation of complex mixtures containing iron or iron compounds, such as welding fumes, is a benign pneumoconiosis without impairment of lung function or symptoms;
• Pulmonary fibrosis (“siderofibrosis”) and loss of lung function may occur after the pronged inhalation of high level of welding fumes ;
• The lung changes of siderosis may regress on cessation of exposure.
We conclude that the conditions occurring after prolonged inhalation of high levels of iron or iron compounds do not meet the criteria for classification.
Executive summary:

This paper evaluates the scientific literature on the effects of prolonged inhalation of iron or iron compounds and, specifically, any association between these exposures and the development of siderosis or pulmonary fibrosis. It considers whether these two conditions require iron and iron compounds to be classified as causing specific target organ toxicity (STOT) – repeated exposure under the CLP regulation criteria. The only group of workers exposed to pure iron or iron oxides appear to be silver polishers who are exposed to pure ferric oxide. They have been shown to accumulate iron in their lungs without health consequences. The animal data on inhalation and instillation of iron oxide also demonstrates that iron does not produce lung fibrosis. Most publications and reviews of these conditions discuss the consequences of prolonged high exposures to mixed dust or to welding fumes, a complex mixture of iron and other metal particles and a variety of gases derived from the process. Prolonged inhalation of high levels of these mixed dusts and fumes may cause siderosis (a benign pneumoconiosis) but also may cause pulmonary fibrosis, sometimes called siderofibrosis, which may lead to restriction in lung capacity. It is not known specifically which components of the complex mix of gases and fumes are responsible for the development of fibrosis. Using a weight of evidence approach to this human and animal literature we conclude that the prolonged inhalation of pure iron and iron compounds may produce a benign pneumoconiosis without impairment of lung morphology, function or symptoms. Therefore the conditions occurring after the prolonged inhalation high levels of iron or iron compounds as placed on the market do not meet the criteria for classification under either REACH or CLP.