1601f A new risk grouping concept for high aspect ratio materials – the shaker dustiness test

Abstract

Introduction Because of their unique physico-chemical properties, CNTs have attracted a great deal of research interest and have many promising industrial applications. However, this also increases the exposure potential for workers, raising the need to understand their hazard for an effective occupational health and safety management. CNTs can induce lung inflammation, granuloma formation, fibrosis and cancer in rodents; in particular, MWCNTs are known to induce in vitro markers of remodelling and fibrosis. CNTs greatly vary in length, thickness, rigidity, aspect ratio, surface defects and reactivity, with a remarkable contribution of synthesis methods and posttreatments. Thus, CNTs are not a single substance, but a heterogeneous family of materials that elicit different biological responses and, thus, are associated with different hazard levels not simply ascribable to the fibre paradigm. Methods Cell models representative of the airway barrier were challenged with MWCNT preparations endowed with different physico-chemical properties, evaluating endpoints such as viability, expression of pro-inflammatory markers, nitric oxide production, epithelial barrier competence, clonogenic activity, genotoxicity. Epithelial-mesenchymal transition (EMT) was also assessed as an early event leading to fibrosis and, possibly, involved in neoplastic transformation. Results Only long MWCNTs promoted EMT and caused frustrated phagocytosis. On the other hand, MWCNT agglomeration led to contact-mediated focal epithelial damage and impaired barrier functionality in vitro. Functionalization with carboxyl or amino groups modified the quantity and type of proteins adsorbed and, hence, the interaction with cells. Discussion These findings may contribute to safe-by design manufacturing of MWCNT. Importantly, all the endpoints evaluated represent MIEs than can be combined to construct putative AOPs, associated with disease onset and progression. It is therefore concluded that the knowledge of the physicochemical properties associated to the MIEs of different adverse outcomes is a prerequisite for the toxicological profile of a MWCNT preparation.

A Practicable Measurement Strategy for Compliance Checking Number Concentrations of Airborne Nano- and Microscale Fibers

“…test results on nanofibers of known diameter and composition are available for multi-walled carbon nanotubes (MWCNTs) Figure 7.2 in Ref. [8]. Rittinghausen et al reported a positive, fiber-like i.p.…”

“…Carbon nanotubes (CNTs) became famous for being very high modulus materials compared to other nano-and microscale fibers Table 7.3 in Ref. [8]. However, depending on the synthesis method and the measurement technique, MWCNT can show a rather broad variation of elastic modulus values of 1200-20 GPa Table 1 in [30].…”

“…For MWCNTs, Broßell et al proposed a first estimate of the critical rigidity of about R crit = 0.5•10 −19 N•m 2 , based on 37-44 nm (mean 40 nm) diameter and 36-1000 GPa (mean 550 GPa) elastic modulus [8]. Even if the i.p.-tested MWCNTs with a mean diameter of 37nm had a very low modulus of 50 GPa, the resulting rigidity of about R = 5•10 −21 N•m 2 would correspond to that of nanofibers of just D = 20 nm and a modulus of about E f = 550 GPa, cf.…”

“…However, asbestos-like toxicity has also been reported for biodurable fibers thinner than 200 nm [5][6][7][8], including nanofibers below 100 nm [9,10]. For comparable exposure concentrations, it is mandatory to explicitly specify the minimum diameter of the fibers that were actually included in a count result [11].…”

“…With the aim of reducing the analysis effort to a practicable amount, we propose using the so-called fiber rigidity hypothesis [6,8,30,31]. It toxicologically motivates ignoring a specific fraction of thin fibers and thus permits reducing the resolution of image acquisition.…”