Nanomaterials Versus Ambient Ultrafine Particles: An Opportunity to Exchange Toxicology Knowledge

Abstract

Background: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models.

Objectives: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP.

Methods: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas.

Discussion: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously.

Conclusion: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. https://doi.org/10.1289/EHP424.

Figure 1.

Time line showing the increased interest in particulate matter (PM) and nanomaterials (NMs) over the last three decades, highlighting key studies and research trends in both areas. Number of references per year (noncumulative) based on Pubmed (https://www.ncbi.nlm.nih.gov/pubmed/) search without further limits applied.

Figure 2.

Schematic providing an example of the complex composition of ultrafine particles (UFPs) [e.g., urban particulate matter (PM) or particles in vehicle exhaust], which in urban air often have a carbon core coated with a diverse range of chemical species including reactive transition metals and organic hydrocarbons. Detail is not to scale.

Figure 3.

Schematic illustrating some of the key mechanisms through which inhaled ultrafine particles (UFPs) may influence secondary organs and systemic tissues, with emphasis on the means through which inhaled particles may cause cardiovascular events. Note that there are three main pathways linking the pulmonary and cardiovascular systems (grey arrows, left to right): autonomic regulation, passage of inflammatory mediators, and particle translocation. The arrows between these three pathways highlight the degree of interaction between mechanistic pathways and the challenges involved in broad categorization of the wide-ranging biological actions of inhaled UFPs. Added to these pathways is the potential for desorbed components to exert effects.

Figure 4.

A range of health effects and biological indicators of disease that can be used to identify relevant end points for study design.

Figure 5.

Exposure to nanomaterials (NMs) via the lungs results in rapid transport into the epithelium and interstitial spaces and long-term retention as a result of substantial endocytosis by epithelial cells (Type I and Type II) and limited initial phagocytosis by alveolar macrophages. Pathways exist for the transport of inhaled NMs into the alveolar epithelium and interstitium of rodent lung and further across the endothelial vascular membrane of blood circulation as well as into the lymphatic drainage system. Some evidence suggests that a predominant route of clearance from the lung tissue is then via reentrainment back onto the alveolar epithelial surface (via an unknown mechanism) for long-term macrophage-mediated transport toward ciliated airways and the larynx. Nanosized NMs may cross the epithelium, whereas larger aggregates/agglomerates are likely to be phagocytosed by alveolar macrophages.