Abstract
BackgroundAn 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.ResultsThis 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.ConclusionsRetained 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).
Highlights
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
This metric would apply to both micrometric and nanometric materials, and could obviate the need for direct measurement in the lung. It could alternatively be estimated from dosimetry models using the aerosol parameters
Particles deposited in the lung remain either for only a short duration, as they are gradually eliminated over time due to various clearance mechanisms, or persist long-term, in which case they can induce chronic inflammation leading to pathologies such as chronic obstructive pulmonary disease (COPD), emphysema, lung fibrosis, or cancer [5, 6]
Summary
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 recently completed EU-funded Smartnanotox project (www.smartnanotox.eu) leveraged data from in vivo, in vitro and in silico studies, and proposed pulmonary AO pathways (AOPs) for inhaled NMs, presenting their associated molecular initiating events or key events (KEs). This structured AOP-based approach for hazard grouping is considered a relevant tool to assess the risks associated with inhaled materials, for NMs [1, 2]. Both inflammation and oxidative stress are central mechanisms driving NM-induced adverse effects [3]. Particles deposited in the lung remain either for only a short duration (acute), as they are gradually eliminated over time due to various clearance mechanisms, or persist long-term, in which case they can induce chronic inflammation leading to pathologies such as chronic obstructive pulmonary disease (COPD), emphysema, lung fibrosis, or cancer [5, 6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
