Frédéric Cosnier1, Carole Seidel2, Sarah Valentino2, Otmar Schmid3,4, Sébastien Bau2, Ulla Vogel5,6, Jérôme Devoy2, Laurent Gaté2. 1. Institut National de Recherche et de Sécurité, 1 Rue du Morvan, CS 60027, 54519, Vandœuvre-les-Nancy Cedex, France. frederic.cosnier@inrs.fr. 2. Institut National de Recherche et de Sécurité, 1 Rue du Morvan, CS 60027, 54519, Vandœuvre-les-Nancy Cedex, France. 3. Institute of Lung Biology and Disease, Helmholtz Zentrum München, 85764, Neuherberg, Germany. 4. Comprehensive Pneumology Center, Munich (CPC-M) - Member of the German Center for Lung Research (DZL), 81377, Munich, Germany. 5. National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100, Copenhagen, Denmark. 6. Department of Health Technology by DTU Food, Technical University of Denmark, DK-2800, Kgs. Lyngby, Denmark.
Abstract
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).
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).
Authors: S H van Rijt; D A Bölükbas; C Argyo; K Wipplinger; M Naureen; S Datz; O Eickelberg; S Meiners; T Bein; O Schmid; T Stoeger Journal: Nanoscale Date: 2016-04-21 Impact factor: 7.790
Authors: Sarah S Poulsen; Petra Jackson; Kirsten Kling; Kristina B Knudsen; Vidar Skaug; Zdenka O Kyjovska; Birthe L Thomsen; Per Axel Clausen; Rambabu Atluri; Trine Berthing; Stefan Bengtson; Henrik Wolff; Keld A Jensen; Håkan Wallin; Ulla Vogel Journal: Nanotoxicology Date: 2016-07-07 Impact factor: 5.913