A Textbook of Modern Toxicology

As illustrated in the previous chapter, the human body can be exposed to a variety of toxicants that may be present in various environmental media such as air, soil, water, or food. However, just simply being exposed to these hazardous chemicals does not necessarily translate into a toxicological response. The mammalian body has several inherent defense mechanisms and membrane barriers that tend to prevent the entry or absorption and distribution of these toxicants once an exposure event has occurred. However, if the toxicant is readily absorbed into the body, there are still other anatomical and physiological barriers that may prevent distribution to the target tissue to elicit a toxic response. As the toxicological response is often related to the exposed dose, interactions between the toxicant and the body’s barriers and defense mechanisms will have an effect on toxicant movement in the body, and ultimately modulate the rate and extent of toxicant absorption and distribution to the target tissue. The skin represents the largest organ in the human body, and one of its primary functions can be seen as a physical barrier to absorption of toxicants. The other major routes of toxicant entry into the body are through the respiratory and gastrointestinal tract, which can be seen to offer less resistance to toxicant absorption than the skin. In general, the respiratory tract offers the most rapid route of entry, and the dermal the least rapid. One reason for this major difference is primarily because membrane thickness, which is really the physical distance between the external environment (skin surface, air in the lung, or lumen of the gut) and the blood capillaries, varies across these portals of entry. The overall entry depends on both the amount present and the saturability of the transport processes involved. Liver metabolism will have the most significant effect on toxicant bioavailability following gastrointestinal absorption, but microbial activity and various enzymes in the gastrointestinal tract and the skin can play a significant role in oral and dermal absorption, respectively. Physicochemical characteristics of the toxicant such as the chemical form can be a useful indicator of whether the toxicant will be absorbed and distributed in the body. In this regard toxicant molecular weight, ionization (pKa), and octanol/water partition coefficient (logP ) are useful indexes of predicting chemical