2
Basic Toxicological Terminology

Introduction

This chapter explores some of the common toxicological terminology that is useful to understand prior to reading the other chapters of this book.

2.1 The Cell

The cell is the basic building block of all living organisms, and in mammals, the cells typically have a nucleus and cytoplasm, which contains various cellular organelles and a cell membrane (Figure 2.1). They can, however, differ in terms of shape, size, and function. For example, epithelial cells line both internal and external surfaces and are generally cuboidal in shape, whereas nerve cells (neurons) are long structures that transmit messages by means of an electrical impulse (Figure 2.2).

Figure 2.1 Cell structure.

Source: © Vladmir Ischuk/Shutterstock.com.

Figure 2.2 Different cell types.

Source: © Alila Media Medical/Shutterstock.com.

2.1.1 Stem Cells, Somatic Cells, and Germ Cells

As will be seen in later chapters, cells can be categorized as stem cells, somatic cells, and germ cells. Stem cells are nondifferentiated cells that can proliferate to produce more stem cells or differentiate into specific cell types. For example, the stem cells present in the bone marrow can differentiate into different blood-cell types. Somatic cells are all the nonreproductive cells of the body; they include the epithelial and nerve cells mentioned earlier. Germ cells or gametes are the sex cells, and in males these are sperm, and in females the ovum or egg. Tissues are groups of similar cells, all with a specialized function and structure. There are four main types of tissue: muscular, epithelial, nervous, and connective tissue. Different types of tissue make up organs, which have a common function and shape. Examples include the liver, kidneys, and the heart. Toxicologists are particularly interested in chemically induced harm to different organs or organ systems. This is known as "target organ toxicity" and is covered in more detail in Chapter 8.

2.2 Homeostasis

The internal environment of the body is constantly changing not only in response to the external environment but also because of changes in activity. However, the maintenance of a stable internal environment is essential for all the cells of the body to ensure that they can maintain both function and viability. For example, changes in body temperature can have a significant impact on the functioning of enzymes, which are needed for metabolism. Also, concentrations of blood glucose, pH, and specific ions need to be maintained within a narrow range of physiological parameters (Tortora and Grabowski 1996). This process of maintaining optimum conditions and making the relevant adjustments by means of feedback loops is called homeostasis. As will be seen in Chapter 8, both the nervous system and endocrine system are closely involved in homeostasis, albeit in different ways.

2.3 Adaptation and Cell Injury

Homeostasis occurs because of the cells and tissues of the body being able to continually adapt to their ever-changing environment, which enables them to maintain both function and viability.

An adaptive response is a reversible process by which the organism manages an increase in demand or compensates for injury or disease. Once the increased demand or injury has resolved, everything usually returns to normal. For example, in the absence of any hepatocellular injury, chemical induced liver enlargement, which is commonly observed in repeated dose toxicity studies, is generally considered to be an adaptive response. However, if the capacity for an adaptive response is exceeded, this may result in cell injury. At the cellular level, the main adaptive responses are hypertrophy, atrophy, hyperplasia (Figure 2.3), and metaplasia, all of which are summarized in Table 2.1.

Figure 2.3 Image showing normal cells, hyperplasia, hypertrophy, and a combination of both.

Source: © Designua/Shutterstock.com.

Table 2.1 Common adaptive responses at the cellular level.

Source: Adapted from Malarkey et al. (2013) and Glaister (1986).

2.4 Cellular Responses to Injury

In some cases, the cell injury will, upon cessation of exposure, be reversible. However, should the exposure be sufficiently high or prolonged, then this could give rise to irreversible injury and cell death (i.e. necrosis).

Pathology is the study of disease. It is an important aspect of toxicology reports.

2.5 Mode of Action and Mechanism of Action

According to Bogert et al. (2004, p. 87), the mechanism of action "denotes the molecular sequence of events leading from the absorption of an effective dose of a chemical to the production of a specific biological response in the target organ" (see box opposite). The mode of action is a more generalized description and "refers to the type of response produced in an exposed organism or to only the critical steps or features of the mechanism required for production of the particular biological response" (Bogert et al. 2004, p. 87).

For example, organophosphates inhibit the action of acetylcholinesterase within the nervous system (see Chapter 8).

2.6 Adverse Effects

According to ECETOC (2002), an adverse effect is "a biochemical behavioural, morphological, or physiological change (in response to a stimulus) that either singly or in combination adversely affects the performance of the whole organism or reduces the organism's ability to respond to an additional environmental challenge." The International Program on Chemical Safety (IPCS, 2004) defines adverse effect as a "change in the morphology, physiology, growth, development, reproduction, or life span of an organism, system, or (sub)population that results in an impairment of functional capacity, an impairment of the capacity to compensate for additional stress, or an increase in susceptibility to other influences." (IPCS, 2004). In other words, an adverse effect is something that is harmful to the organism.

According to ECETOC (2002),

"An effect is less likely to be adverse if:

1. There is no alteration in the general function of the test organism or of the organ/tissue affected;
2. It is secondary to other adverse effect(s);
3. It is an adaptive response;
4. It is transient;
5. Severity is limited e.g. below thresholds of concern;
6. Effect is isolated or independent, i.e. changes in other parameters usually associated with the effect of concern are not observed;
7. Effect is not a precursor, i.e. the effect is not part of a continuum of changes known to progress with time to an established adverse effect;
8. It is a consequence of the experimental model."

A nonadverse effect is defined as "those biological effects that do not cause biochemical behavioural morphological or physiological changes that affect the general well-being, growth, development or life span of an animal" (ECETOC 2002).

2.7 Biological and Statistical Significance

According to ECETOC (2002), a biologically significant effect is "a response (to a stimulus) in an organism or other biological system that is considered to have substantial or noteworthy effect (positive or negative) on the well-being of the biological system." Some biologically significant effects often arise from normal homeostatic responses to a change, such as sweating in a hot climate or liver adaptation. The development of tumors or severe hepatoxicity, however, would not be considered "normal". Instead they would be considered to be adverse effects. It is...