Case Studies in Nanotoxicology and Particle Toxicology

Antonietta M Gatti, Stefano Montanari

• Publisher: Academic Press
• Year: 2015
• Print ISBN: 9780128012154
• eBook ISBN: 9780128012543
• Topic: Medicine
• Subtopic: Toxicology

Case Studies in Nanotoxicology and Particle Toxicology presents a highly-illustrated analysis of the most prominent cases on the adverse effects of nanoparticles and their impact on humans and the environment. This comprehensive reference demonstrates the possible risks imposed by managing and handling nanoparticles, showing the effects of involuntary inhalation or ingestion during their use and after their incineration. Through the use of numerous examples, readers will discover the possible risks and effects of working with nanoparticles, along with best practices to prevent these effects. The text is an essential reference for anyone working in the risk assessment of nanoparticles, including nanosafety professionals, occupational toxicologists, regulatory toxicologists, and clinicians. - Presents real-life cases showing the potential risks to human health following exposure to nanoparticles - An ideal reference for anyone working in the risk assessment of nanoparticles, including nanosafety professionals, occupational toxicologists, regulatory toxicologists, and clinicians - Provides examples to help assess risks of handling engineered nanomaterials - Advises on the best forms of protection and the safest nanotechnological products

Chapter 1

Introduction

Abstract

The main aim of this book is the description of our studies on human pathologies caused by the interaction between particulate matter, be it of natural or artificial origin, cells, tissues, organs and the whole organism. To date, very little exists on this topic, since virtually all research is limited to in-vitro, laboratory studies. Nanopathology introduces a novel, scientific, interdisciplinary approach and is an important step toward customized medicine. Particles have different origins and carriers and those subjects will be discussed as well.

Keywords

Nanopathology

nanoparticles

microparticles

submicronic

cryptogenic diseases

personalized medicine

environment

Contents

1.1 The history 1

1.2 What is Nanopathology? 2

References 5

1.1. The history

Back in early 2008 we published the book Nanopathology: The Health Impact of Nanoparticles [1]. In those pages we told the circumstances that led us to start our research about how solid, inorganic, and non-biodegradable micro- and nanosized particles, whatever their origin, can interfere with living beings, and described the basic principles we abide by.

But, on a larger scale, that particular dust also has an impact on the environment of which all living beings are inevitably guests and protagonists at the same time, by which they are as inevitably influenced and, in some cases, affected. And that topic was also dealt with in the book mentioned above.

Nanopathology is a word that we invented in 2002, which became the title of a European project that Dr. Gatti directed and coordinated (Nanopathology: The role of micro and nanoparticles in inducing human health effect (FP5-QOL-147-2002-05)). At that time it was not much more than an empty box. Today, after little more than a decade, nanopathology is a new philosophy, a novel approach to medicine.

As happens with many works in progress, particularly when exploring unknown or little-known territories is the aim, much has been done in the last few years and that work is summed up in this new title. In the lapse of time between the two books, Antonietta M. Gatti had a chance to coordinate a further European project and to be part of a few more research projects sponsored by different agencies; the two of us came across more clinical cases (now amounting to more than 2,000), checked more food, drugs and cosmetics, analyzed more samples collected in polluted environments and, altogether, we were lucky enough to learn a great deal. A selection of our cases, some of which will be considered “sentinel” cases, is illustrated in Chapter 4. The technique we used was described in detail in our former book.

Though it is not always possible, here we will try as much as we can to avoid repeating what has already been written and keep referring our readers to Nanopathology: The Health Impact of Nanoparticles for what they will not find in these chapters. The book describes also the methods and protocols used to detect nanoparticles in biological matrices performed by means of an Environmental Scanning Electron Microscope (ESEM) and of Field Emission Gun Environmental Scanning Electron Microscope (FEG-ESEM); the equipment is also described.

1.2. What is nanopathology?

It is understood that the particles discussed here are both engineered, i.e., fabricated in a laboratory, and non-engineered, i.e., incidental. Among the incidental, are those produced by natural phenomena, those coming from high-temperature industrial processes and those generated as by-products of a fair number of activities carried out at low temperature. The others are those intentionally manufactured by nanotechnology industries and, in this case, their fate at their usable-life end will be discussed.

Natural inorganic nanoparticles do exist in nature: sea-water aerosols, some structures of snow and dust erupted by volcanoes are a few of them and with them man has lived all along.

The nanosized by-products are the nanoparticles mostly discussed in this book, since, in our opinion, they are responsible for a non-negligible number of diseases affecting people. They are mostly generated by accidental combustions and are freely dispersed in air, in water and in soil, thus exposing their effects to people who inhale or ingest that particulate matter (PM), sequestering it, at least in part, in their organism.

In general, we take into consideration solid, inorganic and non-biodegradable, i.e., biopersistent, PM.

In this book we do not consider polymeric particles or carbon nanotubes.

Even if the ISO standard [2] defines nanoparticles – but their interest is limited to the engineered ones, those obtained with nanotechnological processes and ranging from just above 0 to 100 nm – in our opinion, for the focus on possible risks to human life, we would rather refer to a functional definition of nanoparticles, i.e., we consider nanoparticles all the particles able to escape the physiological barriers including the cell and its nuclear membrane, so capable of inducing a nanoeffect.

This is a definition made of nanoobjects, but what is nano when biology is what matters? What is the minimum size range of foreign bodies that can induce a nanoeffect, i.e., an effect that the same material, when in bulk form, is unable to induce?

A more specific definition of nanoeffect can be: Whatever damages, changes or causes a modification to a cell that can alter its physiological metabolism. For this reason, we consider “nano” to be what can be internalized by a cell: to give an order of magnitude, that which is below one micron. We know some “bureaucrats” of science will turn up their nose at the way we use the word, but words are nothing more than a means to communicate concepts in the easiest possible way, and we claim the right to use the word nano as it is more convenient for us. The adjective “submicronic” will also be used throughout the book as a synonym, meaning a particle whose size is smaller than one micron.

Until now, there has been no real definition of nanoeffect, but by that term we mean any interaction of nanoparticles with cellular organelles, proteins, enzymes, DNA, etc., interactions that can give origin to stable compounds that are not recognized or only partially recognized by the biological environment where they have been somehow introduced and can no longer participate in the local physiological metabolism. It is a “partial” foreign body that the cell probably tolerates, but this unwanted coexistence can physically alter/condition the normal cellular functions. It must be considered that a foreign body occupies a volume and, at the cell level, can block the in-and-out-flow of nutrients/metabolites or can disturb the chromatin strands during mitosis (see Chapter 10).

But it is not only nanoparticles, whatever their definition, that are responsible for health effects. Particles with a size up to some tens of microns, when they manage to enter the organism, interfere negatively with tissues and organs.

In the last few years many studies have been performed by a great number of authors on engineered nanoparticles matched with cell cultures or organs. In contrast, the reader will find in this book, a focus mostly on human cases, something largely missing in today’s literature and very often seen as premature. But, premature or not, what we found in our research was a very interesting new world.

Micro- and nanoparticles are produced in quantities that are rapidly increasing and, in spite of pointless discussions, man is actually reacting to them in a very visible and, to be sure, worrisome way.

Unfortunately, we may not infer the behavior in humans of particles generated by the multitude of sources characterizing our world from how a cell reacts when matched for a short time and in laboratory conditions with very simple (and, for the time being, very uncommon in the environment) particles made by a technician. Man is far more complicated and, to be honest, we still know very little about his physiology.

The particles we find in real-life conditions are not only complicated but often unpredictable at least as to chemical composition, besides coming in a large variety of shapes, sizes, mixes, and exposure, something strictly personal, is in most cases equally unpredictable.

Particles can enter the organism through a variety of doors, and as much as what we have done allows, the different origins and carriers of those particles will be described.

Nanotechnology, treated in Chapter 11, represents the biggest investment ever made in the history of the industry. As a matter of course, investors in the industry have – or think they have – an interest in making the world believe that no risk is involved in their technologies and in their products. Though unproven, that may be the case, but we think it worth considering how the insurance companies deem nanotech one of the riskiest enterprises as seen from their pragmatic point of view.

The cases discussed in this book are mostly Italian since we live in Italy and the investigations performed need a technical background that ranges from the knowledge of the territory to repeated analyses. Of course, physiology and pathology do not change with geography.

What we describe is based on objective observation and repeatable evidence, never contradicting traditional medicine as taught in universities throughout the world. Nanotechnology’s contribution is to show further content of pathological tissues that, so far, have escaped due consideration. We introduce an added value for medicine: an interdisciplinary approach that includes physics, chemistry and the study of the environment. Only with an integrated approach do some new and/or idiopathic, i.e., as a matter of fact, mysterious, diseases become understandable.

What we propose is a novel tool, i.e., “customized or personalized medicine,” an approach tailored to individual patients that has the drawback of looking more expensive, but has the advantage of being far more effective. Then, all things considered, its being represented as more expensive should probably be reconsidered. In any case, it is obvious that, when the general rules that govern the behavior of particles interacting with living organisms, complex as they are likely to be, are discovered, the economic costs will be greatly reduced.

For the time being, nanopathology is particularly efficacious in finding what the origin is of some pathologies – many of which still considered cryptogenic – provided that the origin is either environmental or comes from the more or less conscious use of nanoparticles or from their presence in food, drugs, cosmetics and other products. That is of the utmost importance, since it gives the patient the chance to avoid or eliminate the exposure, and those responsible for that pollution the possibility to make up for the problem, in addition to putting lawgivers in a position to legislate correctly. Setting aside generic and often vague rules, it is easy to see that in many cases no effective laws exist to protect people against pollution and, when quantitative limits are set, they vary from country to country or groups of countries, being t...

Table of contents

• Cover
• Title page
• Table of Contents
• Copyright
• Dedication
• Foreword
• Preface
• Acknowledgments
• Chapter 1: Introduction
• Chapter 2: A Very Brief History of Particulate Pollution
• Chapter 3: Nanotoxicity
• Chapter 4: Clinical Cases
• Chapter 5: Sentinel Cases
• Chapter 6: Environmental Cases and Nanoecotoxicology
• Chapter 7: War Cases and Terrorist Attacks
• Chapter 8: Food, Drugs and Nanoparticles
• Chapter 9: Occupational Cases
• Chapter 10: Miscellaneous Cases
• Chapter 11: The Future of Nanotechnologies
• Chapter 12: Conclusions
• Index