Calculated Risks: Understanding the Toxicity of Chemicals in our Environment
So what is this book about? The introductory remarks below from the preface provide part of the answer:
“A word about organization of topics […] First, it is important to understand what we mean when we talk about ‘chemicals’. Many people think the term refers only to generally noxious materials that are manufactored in industrial swamps, frequently for no good purpose. The existence of such an image impedes understanding of toxicology and needs to be corrected. Moreover, because the molecular architecture of chemicals is a determinant of their behaviour in biological systems, it is important to create a little understanding of the principles of chemical structure and behavior. For these reasons, we begin with a brief review of some fundamentals of chemistry.
The two ultimate sources of chemicals – nature and industrial and laboratory synthesis – are then briefly described. This review sets the stage for a discussion of how human beings become exposed to chemicals. The conditions of human exposure are a critical determinant of whether and how a chemical will produce injury or disease, so the discussion of chemical sources and exposures naturally leads to the major subject of the book – the science of toxicology.
The major subjects of the last third of this volume are risk assessment […] and risk control, or management, and the associated topic of public perceptions of risk in relation to the judgments of experts.”
What can I say? – it made sense to read a toxicology textbook in between the Christie novels… The book was written in the 90s, but there are a lot of key principles and -concepts covered here that probably don’t have a much better description now than they did when the book was written. I wanted the overview and the book has delivered so far – I like it. Here’s some more stuff from the first half of the book:
“the greatest sources of chemicals to which we are regularly and directly exposed are the natural components of the plants and animals we consume as foods. In terms of both numbers and structural variations, no other chemical sources matches food. We have no firm estimate of the number of such chemicals we are exposed to through food, but it is surely immense. A cup of coffee contains, for example, nearly 200 different organic chemicals – natural components of the coffee bean that are extracted into water. Some impart color, some taste, some aroma, others none of the above. The simple potato has about 100 different natural components …” […]
“These facts bring out one of the most important concepts in toxicology: all chemicals are toxic under some conditions of exposure. What the toxicologist would like to know are those conditions. Once they are known, measures can be taken to limit human exposures so that toxicity can be avoided.” […]
The route of exposure refers to the way the chemical moves from the exposure medium into the body. For chemicals in the environment the three major routes are ingestion (the oral route), inhalation, and skin contact (or dermal contact). […]
The typical dose units are […] milligram of chemical per kilogram of body weight per day (mg/kg b.w./day). […] For the same intake […] the lighter person receives the greater dose. […] Duration of exposure as well as the dose received […] needs to be included in the equation […] dose and its duration are the critical determinants of the potential for toxicity. Exposure creates the dose.” […]
Analytical chemistry has undergone extraordinary advances over the past two to three decades. Chemists are able to measure many chemicals at the part-per-billion level which in the 1960s could be measured only at the part-per-million level […] or even the part-per-thousand level. […] These advances in detection capabilities have revealed that industrial chemicals are more widespread in the environment than might have been guessed 10 or 20 years ago, simply because chemists are now capable of measuring concentrations that could not be detected with analytical technology available in the 1960s. This trend will no doubt continue …” […]
“The nature of toxic damage produced by a chemical, the part of the body where that damage occurs, the severity of the damage, and the likelihood that the damage can be reversed, all depend upon the processes of absorption, distribution, metabolism and excretion, ADME for short. The combined effects of these processes determine the concentration a particular chemical […] will achieve in various tissues and cells of the body and the duration of time it spends there. Chemical form, concentration, and duration in turn determine the nature and extent of injury produced. Injury produced after absorption is referred to as systemic toxicity, to contrast it with local toxicity.” […]
“Care must be taken to distinguish subchronic or chronic exposures from subchronic or chronic effects. By the latter, toxicologists generally refer to some adverse effect that does not appear immediately after exposure begins but only after a delay; sometimes the effect may not be observed until near the end of a lifetime, even when exposure begins early in life (cancers, for example, are generally in this category of chronic effects). But the production of chronic effects may or may not require chronic exposure. For some chemicals acute or subchronic exposures may be all that is needed to produce a chronic toxicity; the effect is a delayed one. For others chronic exposure may be required to create chronic toxicity.” […]
“In the final analysis we are interested not in toxicity, but rather in risk. By risk is meant the likelihood, or probability, that the toxic properties of a chemical will be produced in populations of individuals under their actual conditions of exposure. To evaluate the risk of toxicity occurring for a specific chemical at least three types of information are requred:
1) The types of toxicity the chemical can produce (its targets and the forms of injury they incur).
2) The conditions of exposure (dose and duration) under which the chemical’s toxicity can be produced.
3) The conditions (dose, timing and duration) under which the population of people whose risk is being evaluated is or could be exposed to the chemical.
It is not sufficient to understand any one or two of these; no useful statement about risk can be made unless all three are understood.” […]
“It is rare that any single epidemiology study provides sufficiently definitive information to allow scientists to conclude that a cause-effect relationship exists between a chemical exposure and a human disease. Instead epidemiologists search for certain patterns. Does there seem to be a consistent association between the occurence of excess rates of a certain condition (lung cancer, for example) and certain exposures (e.g. to cigarette smoke) in several epidemiology studies involving different populations of people? If a consistent pattern of associations is seen, and other criteria are satisfied, causality can be established with reasonable certainty. […] Epidemiology studies are, of course, only useful after exposure has occurred. For certain classes of toxic agents, carcinogens being the most notable, exposure may have to take place for several decades before the effect, if it exists, is observable […] The obvious point is that epidemiology studies can not be used to identify toxic properties prior to the introduction of the chemical into commerce. This is one reason toxicologists turn to the laboratory. […] “The ‘nuts and bolts’ of animal testing, and the problems of test interpretation and extrapolation of results to human beings, comprise one of the central areas of controversy in the field of chemical risk assessment.” […]
Toxicologists classify hepatic toxicants according to the type of injuries they produce. Some cause accumulation of excessive and potentially dangerous amounts of lipids (fats). Others can kill liver cells; they cause cell necrosis. Cholestasis, which is decreased secretion of bile leading to jaundice […] can be produced as side effects of several therapeutic agents. Cirrhosis, a chronic change characterized by the deposition of connective tissue fibers, can be brought about after chronic exposure to several substances. […] ‘hepatotoxicity’ is not a very helpful term, because it fails to convey the fact that several quite distinct types of hepatic injury can be induced by chemical exposures and that, for each, different underlying mechanisms are at work. In fact, this situation exists for all targets, not only the liver.”