Registration Dossier

Administrative data

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 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.

Acute toxicity: oral

The acute oral toxicity was low with an LD50 value exceeding 5000 mg/kg bw in rats (cut-off value) according to OECD TG 423 (Schuengel, 2006a). At a test dose of 2000 mg/kg bw no animal died and no clinical signs were observed during the 14-day post observation period.

Acute toxicity: dermal

The acute dermal toxicity is low with LD50 values exceeding 2000 mg/kg bw in rats with no clinical signs noted (OECD TG 402, Schüngel, 2006b).

Acute toxicity: inhalation 

Rats (40 males/dose group) were exposed to 11 or 241 mg MWCNT/m³ of respirable, solid aerosol for 6-hours on a single day which was followed by a maximum postexposure period of 3 months (Pauluhn 2008a,b). Micronization of MWCNT was applied to increase the dustiness of the test material without destroying the assemblage structure of MWCNT. This was verified by characterization the MWCNT before and after micronization. The aerosolized MWCNT was also confirmed to share essentially identical composition and morphology with the non-dispersed/non-micronized MWCNT.

Rats similary exposed to air, carbon black (229 mg/m³) or crystalline quartz (248 mg/m³) served as control and reference groups. The study was conducted in accordance with OECD TG 403 and expanded to include the determination of inflammatory endpoints in bronchoalveolar lavage, gene expression analysis of eight selected genes with potential role in fibrosis, determination of cobald (lungs, lung-associated lymph nodes, brain, kidneys, testes and liver) and histopathological examination of the lungs.

No specific clinical signs or consistent changes in body weights were observed at 10 mgMWCNT/m³ while the rats exposed to 250 mg MWCNT/m³ revealed transient clinical signs (irregular and labored breathing patterns up to postexposure day 2) and reduced body weights. Mortality did not occur in any group. Therefore the LC50 for MWCNT is described to be > 241 mg/m³, as this is the maximum technically attainable concentration of MWCNT.

Irreversible pulmonary inflammatory response (i.e. influx of polymorphonuclear cells (PMNs), which was more pronounced at 241 mg/m³, was observed at all reading points (7, 28, 90 days after exposure) with peak concentrations shortly after exposure (day 7).

The determination of cobalt as trace impurity of inhaled MWCNT yielded a concentration-dependent increase of cobalt in lungs.

A dose-dependent induction of gene expression 90 days after MWCNT exposure was restricted to the gene encoding SPP1 (= OPN = Osteopontin). During necropsy discolorations of the lungs were detected in rats exposed to 11 mg MWCNT/m³ at the day 7 sacrifice, whilst no changes were seen thereafter. Discolorations of the lungs and enlargement/discolorations of lung-associated lymph nodes (LALNs) were apparent at all sacrifices at 241 mg MWCNT/m³.

Histopathology at recovery days 28 and 90 revealed an accumulation of enlarged and/or foamy marcrophages with dark cytoplasmatic spots in the 11 and 241 mg/m³-groups. Bronchiolo-alveolar hypercellularity, focal septal thickening and focally increased septal collagen were restricted to the 241 mg/m³-dose group. Distinct time-dependent differences between recovery days 28 and 90 were not apparent.

Acute toxicity: other routes

Several studies (Muller, 2004, 2005, 2008 and Nemmar, 2007) have investigated pulmonary effects subsequent to intratracheal instillation and pharyngeal aspiration. Both administration routes are not physiological routes of exposure for humans but have been used in mice and rats to investigate potential pulmonary toxicity of high concentration. In general intratracheal instillation resulted in more severe effects than observed after inhalation because large bolus doses can overwhelm the clearance mechanism. Therefore these results from bolus-type dose delivery are not used for purposes of risk assessment. For definitive information on risk assessment of airborne particles data should be based on inhalation exposure. Preliminary information and comparative data may however be obtained using instillation studies.

Justification for classification or non-classification

No classification is required for acute oral, dermal and inhalation toxicity according to EU-Directive 67/548/EEC, Annex VI and Regulation (EC) No 1272/2008, Annex I for the test substances meeting the form described in section 4.5 of the IUCLID dossier.