Background
An important aspect of nanomaterial (NM) risk assessment is establishing relationships between physicochemical properties and key events governing the toxicological pathway leading to adverse outcomes. The difficulty of NM grouping can be simplified if the most toxicologically relevant dose metric is used to assess the toxicological dose-response.
Here, we thoroughly investigated the relationship between acute and chronic inflammation (based on polymorphonuclear neutrophil influx (% PMN) in lung bronchoalveolar lavage) and the retained surface area in the lung. Inhalation studies were performed in rats with three classes of NMs: titanium dioxides (TiO2) and carbon blacks (CB) as poorly soluble particles of low toxicity (PSLT), and multiwall carbon nanotubes (MWCNTs). We compared our results to published data from nearly 30 rigorously selected articles.
Results
This analysis combined data specially generated for this work on three benchmark materials - TiO2 P25, the CB Printex-90 and the MWCNT MWNT-7 - following subacute (4-week) inhalation with published data relating to acute (1-week) to subchronic (13-week) inhalation exposure to the classes of NMs considered. Short and long post-exposure recovery times (immediately after exposure up to more than 6 months) allowed us to examine both acute and chronic inflammation.
A dose-response relationship across short-term and long-term studies was revealed linking pulmonary retained surface area dose (measured or estimated) and % PMN. This relationship takes the form of sigmoid curves, and is independent of the post-exposure time. Curve fitting equations depended on the class of NM considered, and sometimes on the duration of exposure. Based on retained surface area, long and thick MWCNTs (few hundred nm long with an aspect ratio greater than 25) had a higher inflammatory potency with 5 cm2/g lung sufficient to trigger an inflammatory response (at 6% PMN), whereas retained surfaces greater than 150 cm2/g lung were required for PSLT.
Conclusions
Retained surface area is a useful metric for hazard grouping purposes. This metric would apply to both micrometric and nanometric materials, and could obviate the need for direct measurement in the lung. Indeed, it could alternatively be estimated from dosimetry models using the aerosol parameters (rigorously determined following a well-defined aerosol characterization strategy).
In addition to chemical composition, particle concentration and size are among the main parameters used to characterize exposure to airborne ultrafine or nanoparticles. To assess occupational inhalation exposure, real-time instruments are recommended in recent strategies published. Among portable devices for personal exposure assessment in the workplace, DiSCmini (Matter Aerosol AG, Switzerland) has been identified as a potential candidate with its capacity to measure the airborne nanoparticle concentration and average particle size with good time-resolution. Monodisperse and polydisperse test nanoaerosols of varying compositions and morphologies were produced in the laboratory using the CAIMAN facility. These aerosols covered a range of particle sizes between 15 and 400 nm and number concentrations from 700 to 840,000 cm(-3). The aerosols were used to investigate the behavior of DiSCmini, comparing experimental data to reference data. In spite of a slight tendency to underestimate particle size, all particle diameters, number concentrations and surface area concentrations measured were in the same order of magnitude as reference data. Furthermore, no significant effect due to particle composition or morphology was noted.
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