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Description of key information

Key value for chemical safety assessment

Additional information

All relevant and available information on intrinsic properties of MWCNT are cited in chapter 7 of the IUCLID. Although a large number of studies on the toxicity of MWCNTs have recently been published, clear characterization of the test materials including sample preparation which are quite essential for ensuring reproducibility and reliability in the toxicity test using suspension, in vivo and in vitro methods, is often missing. Importantly, modifications of some specific characteristics of the MWCNT tested such as variations in particle size distribution or length might give rise to differences in the toxicological profile. 

Toxic effects of different MWCNTs seem to depend on the form (length) and physico-chemical properties (metal content, aggregation/agglomeration, surface chemistry, and functionalisation). Thus for the time being, a case-by-case approach would be appropriate and the hazard assessment for MWCNT meeting the form described in section 4.5 of the IUCLID dossier based solely on the information collected with this MWCNT. That is the reason why a comprehensive documentation in the IUCLID dossier and the chemical safety report involved automatically is restricted to all available and relevant data on the MWCNT meeting the form described in section 4.5 of the IUCLID dossier. That means on the other hand that the values used for the risk assessment exercise should not be used in general for all MWCNTs or CNTs, as the results obtained with one particular type of MWCNTs may not necessarily be relevant for other CNTs with other dimensions and properties

In addition the information on MWCNT not meeting the form described in section 4.5 of the IUCLID dossier (the differences can be tracked back to the original papers or because in others the characterization of the materials was unclear or inclomplete) is also included in the IUCLID dossier but the entries are restricted to the information on data source to give a quick overview of all available data.

Subsequent to pulmonary exposure Pauluhn (single inhalation) and Muller (single i.t. instillation) demonstrated that test substance meeting the form described in section 4.5 of the IUCLID dossier remained within the lungs (Co causally linked to exposure) for up to several months. Pauluhn (2010) described in a longterm inhalation study (90 days) a concentration dependent increase of test substance in the lung verified by quantification of the tracer Co. Kinetic analyses appear to suggest a markedly delayed clearance from lungs at overload condition. Translocation into lungs associated lymph nodes (LALNs) occurred concentration dependent and required at least 13 weeks of exposure to become detectable. Rolin et al. (2008a) suggested oral absorption as following single or repeated oral exposure granulomatous changes were observed to occur in the liver of rats and after repeated exposure MWCNT were detected in the urine of rats by TEM analysis, although no MWCNT were documented during the microscopic examination of liver and kidneys. However no permeability was detected in a validated Caco-2 cell assay which gives evidence that the test substance meeting the form described in section 4.5 does not cross intestinal epithelium and does not enter the systemic blood circulation. Therefore the data are inconsistent and further investigations are necessary to verify the results of Rolin et al. (2008a) and to clarify whether MWCNT meeting the form described in section 4.5 of the IUCLID dossier can penetrate the GIT epithelial barrier in vivo, and thereby gain access to the circulation.

Discussion on absorption rate:

All relevant and available information on intrinsic properties of MWCNT are cited in chapter 7 of the IUCLID. Although a large number of studies on the toxicity of MWCNTs have recently been published, clear characterization of the test materials including sample preparation which are quite essential for ensuring reproducibility and reliability in the toxicity test using suspension, in vivo and in vitro methods, is often missing. Importantly, modifications of some specific characteristics of the MWCNT tested such as variations in particle size distribution or length might give rise to differences in the toxicological profile. 

Toxic effects of different MWCNTs seem to depend on the form (length) and physico-chemical properties (metal content, aggregation/agglomeration, surface chemistry, and functionalisation). Thus for the time being, a case-by-case approach would be appropriate and the hazard assessment for MWCNT meeting the form described in section 4.5 of the IUCLID dossier is based solely on the information collected with this MWCNT. That is the reason why a comprehensive documentation in the IUCLID dossier and the chemical safety report involved automatically is restricted to all available and relevant data on the MWCNT meeting the form described in section 4.5 of the IUCLID dossier. That means on the other hand that the values used for the risk assessment exercise should not be used in general for all MWCNTs or CNTs, as the results obtained with one particular type of MWCNTs may not necessarily be relevant for other CNTs with other dimensions and properties

In addition the information on MWCNT not meeting the form described in section 4.5 of the IUCLID dossier (the differences can be tracked back to the original papers or because in others the characterization of the materials was unclear or inclomplete) is also included in the IUCLID dossier but the entries are restricted to the information on data source to give a quick overview of all available data.

In vivo assessment of dermal absorption is based on the acute dermal study (Schüngel, 2006b) and the skin sensitisation study (Vohr, 2007) with the test substance meeting the form described in section 4.5 of the IUCLID dossier, which show no adverse effects and thus there is no evidence for systemic availability after dermal exposure (for detailed information see section 7.2.3 and 7.4.1 of the IUCLID dossier).

In an in-vitro study Vankoningsloo et al. (2010) showed that the test substance meeting the form described in section 4.5 of the IUCLID dossier does not disconnect the tight intercellular junctions in reconstructed human epidermis (RHE) epidermis. Lack of cytotoxicity in this skin cellular model suggests that the test substance meeting the form described in section 4.5 of the IUCLID dossier is not able to enter epidermis through the corn barrier within the incubation time and with amounts applied.