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additional toxicological information
Type of information:
other: Review of the literature on the risks of nanoparticles; based on 172 references.
Adequacy of study:
supporting study
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Review of a large number of publications. Due to the concise form in which the information in these publications is presented it is not possible to evaluate their reliability. Neither does a review paper of this sort allows for a evaluation of its reliability.

Data source

Reference Type:
review article or handbook
The potential risks of nanomaterials: a review carried out for ECETOC.
Paul JA Borm, David Robbins, Stephan Haubold, Thomas Kuhlbusch, Heinz Fissan, Ken Donaldson, Roel Schins, Vicki Stone, Wolfgang Kreyling, Jurgen Lademann, Jean Krutmann, David Warheit and Eva Oberdorster.
Bibliographic source:
Particle and Fibre Toxicology 2006; 3: 11.

Materials and methods

Type of study / information:
7.2.2 Acute inhalation; 7.5.2 Repeated dose toxicity: inhalation;
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
It is not customary to refer to GLP in reviews of scientific literature. Moreover, GLP applies typically to experimental studies.

Test material

Details on test material:
The review is on particle toxicology in general; it does not specifically address iron-containing materials.

Results and discussion

Any other information on results incl. tables

See executive summary.

Applicant's summary and conclusion

The review presents a detailed overview of the possible adverse effects of nanoparticles and the mechanisms involved in these effets as well as the toxicokinetics of the particles. Although the iron-oxide containing substance for which the present IUCLI 5 file has been compiled do not contain nanoparticles and thus do not necessary cause the adverse effects of nanoparticles, the review also contains information on large particles. Moreover, it helps to distinguish between the particles in the substance under consideration and the effects caused by nanoparticles. Sometimes, effects described are not strictly limited to nanoparticles, but may be caused by larger particles as well, in which case they might be relevant to the substance under consideration. Taken together, a valuable document when the effects of the substance have to be considered when it occurs in the form of smaller particles, even if it only demonstrates that these particles cannot cause effects restricted to the nanoscale and ultrafine scale. For instance because translocation cannot occur for particles larger than ultrafine.
Executive summary:

What follows is the summary of the original publication, which suffices as an executive summary in the present context.

During the last few years, research on toxicologically relevant properties of engineered nanoparticles has increased tremendously. A number of international research projects and additional activities are ongoing in the EU and the US, nourishing the expectation that more relevant technical and toxicological data will be published. Their widespread use allows for potential exposure to engineered nanoparticles during the whole lifecycle of a variety of products. When looking at possible exposure routes for manufactured Nanoparticles, inhalation, dermal and oral exposure are the most obvious, depending on the type of product in which Nanoparticles are used. This review shows that:

(1) Nanoparticles can deposit in the respiratory tract after inhalation. For a number of nanoparticles, oxidative stress-related inflammatory reactions have been observed. Tumour-related effects have only been observed in rats, and might be related to overload conditions. There are also a few reports that indicate uptake of nanoparticles in the brain via the olfactory epithelium. Nanoparticle translocation into the systemic circulation may occur after inhalation but conflicting evidence is present on the extent of translocation. These findings urge the need for additional studies to further elucidate these findings and to characterize the physiological impact.

(2) There is currently little evidence from skin penetration studies that dermal applications of metal oxide nanoparticles used in sunscreens lead to systemic exposure. However, the question has been raised whether the usual testing with healthy, intact skin will be sufficient.

(3) Uptake of nanoparticles in the gastrointestinal tract after oral uptake is a known phenomenon, of which use is intentionally made in the design of food and pharmacological components.

Finally, this review indicates that only few specific nanoparticles have been investigated in a limited number of test systems and extrapolation of this data to other materials is not possible. Air pollution studies have generated indirect evidence for the role of combustion derived nanoparticles (CDNP) in driving adverse health effects in susceptible groups. Experimental studies with some bulk nanoparticles (carbon black, titanium dioxide, iron oxides) that have been used for decades suggest various adverse effects. However, engineered nanomaterials with new chemical and physical properties are being produced constantly and the toxicity of these is unknown. Therefore, despite the existing database on nanoparticles, no blanket statements about human toxicity can be given at this time. In addition, limited ecotoxicological data for nanomaterials precludes a systematic assessment of the impact of Nanoparticles on ecosystems.