Retained particle surface area dose drives inflammation in rat lungs following acute, subacute, and subchronic inhalation of nanomaterials

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).

Particles Emission from an Industrial Spray Coating Process Using Nano-Materials

“…Toxicological studies have shown that LDSA correlates with negative health effects [ 26 ]. In our experimental conditions, LDSA values were lower than 50 µm 2 /cm 3 in all tests (see Figure 6 ) both at the NF and FF positions, and much lower than the peak value emitted by a burning candle (about 250 µm 2 /cm 3 ) and comparable with urban background sites in Los Angeles and in Cassino [ 27 ].…”

Approach toward In Vitro-Based Human Toxicity Effect Factors for the Life Cycle Impact Assessment of Inhaled Low-Solubility Particles

“…The parameters used for both models are reported in the Supporting Information. Whenever possible, the retained dose was preferred to the deposited dose as it has been shown to better correlate with the effects measured in the animal . Both in vitro and in vivo deposited/retained doses were normalized by the surface area of the cell culture well or the animal alveoli, respectively.…”

Agglomeration State of Titanium-Dioxide (TiO2) Nanomaterials Influences the Dose Deposition and Cytotoxic Responses in Human Bronchial Epithelial Cells at the Air-Liquid Interface

“…Toxicological evaluations of TiO 2 NMs are often performed using in vivo models such as mice and rats. Short and long term exposure to TiO 2 NMs via inhalation induced pulmonary inflammation, fibrosis and tumours [6,[13][14][15]. A significant increase in cytotoxicity, inflammation, oxidative stress, and DNA damage was observed in mice exposed to high doses (10 mg/kg [16] and ~4 mg/kg [17]) of TiO 2 NMs.…”