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Toxicological information

Carcinogenicity

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Description of key information

Long term inhalation, oral and dermal carcinogenicity studies are not available. Seven different types of iron oxides were examined for carcinogenic properties after intratracheal instillation and intraperitoneal injection tests in rats, which represent particularly sensitive methods for local carcinogenic effects of particles/fibres. The total doses lay in the range of maximum tolerance. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In the key studies seven different types of iron oxides were examined for carcinogenic properties after intratracheal instillation and intraperitoneal injection tests in rats, which represent particularly sensitive methods for local carcinogenic effects of particles/fibres. The total doses lay in the range of maximum tolerance. No carcinogenic effect was observed. Overall, based on a weight-of-evidence consideration there is no evidence of a carcinogenic potential of iron oxides from animal data. From epidemiological studies there is no evidence for carcinogenicity after exposure to zinc or its compounds through relevant routes of exposure. No valid studies are available for Mn3O4. There are no epidemiological data showing that excess manganese will cause cancer in human beings. Based on the physico-chemical properties, the negative genotoxicity data as well as the lack of specific long term local effects in the most valid studies with intraperitoneal (i.p.) administration there is no evidence of any specific toxicity. This is confirmed by the result of the subchronic inhalation study with Fe3O4 that revealed findings consistent with a 'poorly soluble particle' and no specific toxicity. No analytical or toxicological evidence existed that free, biosoluble iron was liberated from the inhaled particle dust to any appreciable extent. Also no evidence of extrapulmonary toxicity existed. Haematology, clinical pathology and urinalysis were unobtrusive and no specific clinical signs were observed during the study.

A human study is available with the objective to study the possible association between iron oxide exposures and lung cancer risk among workers employed in a French carbon steel-producing factory. A historical cohort was set up of all workers ever employed for at least one year between 1959 and 1997. The cohort was followed up for mortality from January 1968 to December 1998. Causes of death were ascertained from death certificates. Job histories in the factory and smoking habits were available. Occupational exposures were assessed by a factory-specific job-exposure matrix (JEM) developed by a panel of 8 experts and validated with atmospheric measurements. Standardized Mortality Ratios (SMRs) were computed using local death rates (external references). Poisson regressions were used to estimate the Relative Risks (RRs) for occupational exposures (internal references), adjusted on potential confounding factors (Bourgkard et al., 2008).

The cohort comprised 16,742 males and 959 females. Among males, the observed mortality was lower than expected for lung cancer when compared to the local population (233 deaths, SMR 0.89, 95%CI 0.78-1.01) and higher than expected when compared to the French population (SMR 1.30, 95%CI 1.15-1.48). No lung cancer excess was observed for exposure to iron oxides (RR 0.80, 95%CI 0.55-1.17) and no dose-response relationship was found with intensity, duration of exposure, and cumulative index. A significant bladder cancer excess was observed among workers exposed to oil mist, increasing significantly with intensity, duration of exposure, and cumulative index. The authors concluded: “This study did not detect any relationship between exposure to iron oxides and lung cancer mortality.” (Bourgkard et al., 2008).

Justification for classification or non-classification

Based on the available data (see discussion) a classification is not justified