Physico-Chemical Properties of Nanomaterials

Richard C. Pleus, Vladimir Murashov

• Publisher: Jenny Stanford Publishing
• Year: 2018
• Print ISBN: 9789814774802
• eBook ISBN: 9781351168588
• Edition: 1
• Topic: Medicine
• Subtopic: Pharmacology

Throughout human history, we have long encountered the combination of promise, risk, and uncertainty that accompanies emerging technologies. Nanotechnology is a recent example of an emerging technology that promises to drastically improve existing products as well as allow for creative development of new goods and services. This new technology also has its potential downsides. Industry, academia, and regulatory agencies are all working overtime to assess risks accurately while keeping up with the pace of development.

Subtle changes in the physicochemical properties of engineered nanomaterials (ENMs) can influence their toxicity and behavior in the environment and so can be used to help control potential ENM risks. This book attempts to encompass the state of the science regarding physicochemical characterization of ENMs. It illuminates the effort to understand these properties and how they may be used to ensure safe ENM deployment in existing or future materials and products.

Chapter 1

Introduction

Richard C. Pleus^a,* and Vladimir Murashov^b

^aIntertax, Inc. Seattle, WA 98121, USA

^bNational Institute for Occupational Safety and Health [NIOSH], Washington, DC, 20201, USA

[email protected], [email protected]

Throughout human history, our society has long encountered the combination of promise, risk, and uncertainty that accompanies emerging technologies. Nanotechnology is a recent example of an emerging technology which brought about engineered nanomaterials (ENMs) offering the potential to improve existing products or to develop new products that are technically superior to existing ones. As we all are well informed, this new technology has its potential downsides as well. Based on where we are today, ENMs are “new” and complex. This book is an attempt to encompass the state of the science regarding physicochemical characterization of ENMs. We believe subtle changes in physicochemical properties can influence ENM toxicity and behavior in the environment, and so can be used to help control potential ENM risks. This book aims to illuminate the effort to understand these properties and how they may affect ENM deployment in existing or future materials and products.

With this book, we aim to further push (i) researchers, journal editors, and grant reviewers to ensure that adequate “research level” physicochemical characterization is an integral part of any scientific study and reporting and (ii) standards-developing organizations to finalize the development of “risk assessment level” physicochemical characterization methods so that new ENMs are manufactured and utilized safely.

We are interested in physicochemical properties because science has shown that those properties are key to how chemical agents can affect the health, both positively and negatively, of humans and the environment. As Toews et al. state in Chapter 2, “… Paul Ehrlich made the prophetic statement, in Latin, that ‘corpora non agunt nisis fixate’ – ‘entities do not act unless attached’.”

Physicochemical properties of nanomaterials are critical determinants of their biological activity, including adverse health effects in people and the environment. Their adequate characterization in toxicity studies and risk assessments continue to draw attention and criticism even now after almost 20 years since governments around the world initiated national programs aimed at commercializing nanotechnology and nanomaterials. This book presents the state of the science in this critical field.

With the advent of commercial interest in nanotechnology, there was a strong incentive in the health science community to learn from the past in bringing new chemicals on the market and develop guidance on best practices or standards for nanomaterials. The theme was "let’s get it right the first time.” That has led to industry, government, and nongovernmental organizations all working together to provide scientific guidance and standardization to this field.

The International Organization for Standardization (ISO) started the Technical Committee 229 Nanotechnologies (TC 229), perhaps the first international standard setting organization for nanotechnology, in 2005. Other organizations, including the Organisation for Economic Co-operation and Development (OECD) and ASTM International, worked diligently to assist in developing standards to protect human and environmental health.

The focus of ISO/TC 229 is to develop standards in the field of nanotechnologies that includes either or both of the following [1]:

• Understanding and control of matter and processes at the nanoscale, typically, but not exclusively, below 100 nm in one or more dimensions where the onset of size-dependent phenomena usually enables novel applications

• Utilizing the properties of nanoscale materials that differ from the properties of individual atoms, molecules, and bulk matter in order to create improved materials, devices, and systems that exploit these new properties

The various subgroups of ISO/TC 229 focus on developing standards for terminology and nomenclature; metrology and instrumentation, including specifications for reference materials; test methodologies; modeling and simulations; and science-based health, safety, and environmental practices. The first standard that this committee developed defines different basic categories of nanomaterials starting with the nano-object, which is a discrete piece of material with one, two, or three external dimensions in the nanoscale (see Table 1.1).

Pharmacology has perhaps the longest history of interest in physicochemical properties. For a drug to be effective it must hit a specific and intended target. Pharmacologists use physicochemical properties to design drugs to bind, interconnect, activate, and deactivate specific biomolecules on and in cells. The physicochemical properties of the drug were and are critical and fundamental to its action on tissue, cells, and cellular molecules. Toxicologists have followed in the footsteps of pharmacologists and have begun to investigate how the harmful actions of contaminants, industrial chemicals, or illicit drugs can be characterized by physicochemical properties.

What are some of the unique physicochemical characteristics of nano-objects? Unlike larger particles, like atoms and molecules, nano-objects exhibit discrete electronic energy levels rather than continuous bands of energies. Changes in electronic energies lead, for example, to unique optical properties, material strength, electrical conductivity, magnetic behavior, and chemical reactivity.

Table 1.1 Core definitions for nanomaterials based on ISO/TS 80004

Nanoscale	Length range approximately from 1 nm to 100 nm
Nanomaterial	Material with any external dimension in the nanoscale or having internal structure or surface structure in the nanoscale
Nano-object	Discrete piece of material with one, two, or, three external dimensions in the nanoscale
Nanoparticle	Nano-object with all external dimensions in the nanoscale where the lengths of the longest and shortest axes of the nano-object do not differ significantly
Nanoplate	Nano-object with one external dimension in the nanoscale and the two other external dimensions significantly larger
Nanofiber	Nano-object with two external dimensions in the nanoscale and the third dimension significantly larger
Engineered nanomaterial	Nanomaterial designed for specific purpose or function
Nanotechnology	Application of scientific knowledge to manipulate and control matter predominantly in the nanoscale to make use of size- and structure-dependent properties and phenomena distinct from those associated with individual atoms or molecules, or extrapolation from larger sizes of the same material

Nanoparticles, a subset of nano-objects comprising roughly spherical particles with nanoscale diameter, are in the same size range as critical elements of biological systems such as proteins and nucleic acids. For example, the size of botulinum toxin type c, a protein, is 7.4 nm. Nanoparticles also overlap in size with viruses, as average viruses are 50 to 300 nm in diameter. Thus, the science of pharmaceuticals, pharmacology, has been studying nanoscale interactions since this scientific discipline was established.

Within ISO/TC 229, Working Group (WG) 3 focuses on the health, safety, and environmental aspects of nanotechnologies. Members of this group have introduced technical documents covering ecological, occupational, and human health. It is this mission in particular that is of the greatest interest to both editors of this book. In keeping with this focus, the purpose of this text is to allow readers to engage in this mission by providing them with scientific expertise regarding how physicochemical properties affect key components of the environmental, health, and safety of nanomaterials.

We led the development of one of the first guidance documents developed by ISO/TC 229 WG 3: ISO/TR 13014, Guidance on Physicochemical Characterization of Engineered Nanoscale Materials for Toxicologic Assessment; this was published in 2012. In addition to being perhaps the first international guidance document on physicochemical characterization of nanomaterials in toxicity studies, this document also introduced an important abbreviation encompassing categories of nanomaterials, which have the most potential to cause adverse health effects, NOAA (nano-objects and their aggregates and agglomerates greater than 100 nm). This abbreviation has since become widely used in nanomaterial safety and health literature and guidance. The term was developed by ISO TC229 WG3 in November 2011 during a project group meeting for another nanomaterials safety and health document (ISO TS 12901-2:2014, Occupational Risk Management Applied to Engineered Nanomaterials: Part 2; Use of the Control Banding Approach). However, Guidance on Physicochemical Characterization of Engineered Nanoscale Materials for Toxicologic Assessment was the first ISO document where this abbreviation appeared in public and, therefore, is the primary source for this abbreviation.

It has been five years since Guidance on Physicochemical Characterization of Engineered Nanoscale Materials for Toxicologic Assessment was published, but an adequate physicochemical characterization of nanomaterials remains a high priority for enabling science-based risk assessments and risk mitigations. The collection of papers in this book by various authors is a fuller extension and exploration of that initial guidance document.

There are many ways one can categorize according to the concept of physicochemical properties. The first approach is to divide according to the two key historical categories of environmental assessment: bulk and nanoscale objects. Looking backward in time and prior to the emergence of nanotechnology into commerce, the main focus of physicochemical characterization was on what we call bulk materials. Environmental scientists did not pay much attention to the size of the molecule (not necessarily the size of a particle, such as PM_2.5) and generally prioritized assessing bulk materials. Examples include industrial chemicals, pharmaceutical agents, and their precursors. In retrospect, some large chemical molecules of historical interest are in fact nanoscale.

Material characterization in the scientific literature is a key concern for human and environmental health testing. How are we, as scientists, going to be able to compare results from one study to the next, or trust that the research of today can be applied to research 20 years from now? The most logical approach is to carefully characterize any tested material. Chapter 4 discusses the current lists of toxicologically relevant characteristics for nano-objects. There was an initial push to have publishers and editors require adequate characterization of nanomaterials for the publication of peer reviewed manuscripts. However, the energy behind that sail was short-lived, and now publishers are back to relying primarily on peer reviewers. We encourage our community to continue requiring this for many good scientific reasons.

Since in the nanoscale size range, the fundamental physical and chemical properties of materials change and become distinct from those of larger particles and those of atoms or molecules of the same substance, new methods for characterizing physicochemical properties of nanomaterials are necessary.

Like larger particles (also referred to as bulk materials) and unlike atoms and molecules, nanoparticles have a static physical particle shape and have a core and a surface. About half of all atoms in a 1 nm particle are at the surface. This number drops off to under 1% for particles larger than 100 nm. Since interactions between particles and biological systems take place at the surface, the significant fraction of surface atoms in nanoparticles translates into their increased biological activity on a per mass basis compared to larger particles. This higher fraction of surface atoms also leads to an increased “stickiness” of nanoparticles, which manifests in the tendency of nanoparticles to clump together or agglomerate, to absorb other chemicals, and to stick to the surfaces of larger objects.

The static physical shape of nanoparticles can lead to biological interactions that are not observed for traditional chemicals. For example, the long-fiber paradigm in toxicology is based on the inability of macrophages (a type of white blood cell that engulfs and digests foreign objects, cell debris, and cancer cells) to engulf long fibers such as asbestos fibers, which leads to macrophages’ death and starts a chain of reactions causing adverse health effects. Similar toxicological effects were observed for long, rigid nanofibers.

As noted by Toews et al., the history of molecular interaction is long with many tales of success. Chapter 2 provides the underlying foundation of physicochemical properties. Toews et al. define classical pharmacology (and toxicology), where much work has been accomplished with bulk chemicals, in this case pharmaceutical agents. They discuss how pharmacologists think of drugs acting on biomolecules with “selectivity” and “specificity,” terms that are based on the molecular formula of the chemical agent.

Chapter 3 drills down into the fundamental analysis of chemical-to-chemical interactions. Brown provides an excellent review of fundamental chemical interactions, including chemical properties of molecules (e.g., molecular weight, Henry’s law) and chemical properties of particles (e.g., density, dissolution rate), and identifies the need for physicochemical characterization (e.g., for inhalation exposure, dermal exposure).

Lists of physicochemical properties of nanomaterials necessary for risk assessments in different application areas, suc...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Table of Contents
• Preface
• Acknowledgments
• 1. Introduction
• 2. How Physical and Chemical Information Predicts the Action of Molecules: A Historical Overview
• 3. Physicochemical Characterization: From Molecules to Particles
• 4. Common Physicochemical Properties
• 5. Physicochemical Properties of Engineered Nanomaterials and Their Importance in Assessing Relevant Metrics of Inhalation Exposures in Occupational Settings
• 6. Physicochemical Properties and Their Importance in the Environment: Current Trends in Nanomaterial Exposure
• 7. Categorizing Nanomaterials for Health and Environmental Risk Assessment
• 8. The Regulatory Use of Physicochemical Properties by Environmental Agencies
• 9. Physicochemical Properties of Nanomaterials Relevant to Medical Products
• Index