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Table 7 CARBON-study; analysis of raw material

From: How to achieve safe, high-quality clinical studies with non-Medicinal Investigational Products? A practical guideline by using intra-bronchial carbon nanoparticles as case study

Carbon black pigments are the product of incomplete combustion of hydrocarbons. Depending on the specific manufacturing process a wide range of different carbon blacks are available, differing in primary particle size, structure, surface area, and surface chemistry. As these products are not intended for human use, limited information was available. We, therefore, extensively tested several commercially available products for their characteristics by transmission electron microscopy, nanoparticle tracking analysis, dynamic light scattering, and asymmetric-flow field-flow fractionation. Figure 2 shows a Transmission Electron Micrograph (TEM) of Printex-U with a cluster of particles with a primary particle size < 50 nm. Elemental analysis was performed by transmission electron microscope energy dispersive X-ray spectroscopy (TEM-EDX). The copper signal (Cu) is caused by background radiation hitting the copper sample holder grid on which the particles are deposited for measurement in the TEM. Unlike the other products, Printex-U nanoparticles had a circular shape and onion-like arrangement of atom layers comparable to that of carbon nanoparticles in diesel soot. Finally, we also tested whether our samples were contaminated with endotoxins by limulus amebocyte lysate test, which showed a contamination of < 0.01 Eu/ml [14].

Toxicological studies in literature: In vitro analysis of the raw material showed no direct mutagenic effects, but this could be secondary to other mechanisms such as oxidative stress or by triggering the inflammatory processes [22]. For these effects there was a threshold of 1 mg/m3 [23].

In vivo exposure to rats showed mutations in genes of the epithelial cells caused by oxidative stress. Also, in situations of impaired lung clearance (“overload”) and inflammation, some rats developed lung tumours. Mice and hamsters did not develop tumours. Various cohort and case-control studies in the U.S. did not show any increases in lung cancer among carbon black production workers [23].