Chemistry Reference
In-Depth Information
2.3 toxIcokInetIcS
From a toxicological point of view, the critical issue is how much of the toxic form
of the chemical reaches the site of action. This will be determined by the interplay
of the processes of uptake, distribution, metabolism, storage, and excretion. These
processes will now be discussed in a little more detail.
2.3.1
u p T a k e a n d d i s T r i b u T i o n
The major routes of uptake of xenobiotics by animals and plants are discussed in
Chapter 4, Section 4.1. With animals, there is an important distinction between ter-
restrial species, on the one hand, and aquatic invertebrates and fish on the other.
The latter readily absorb many xenobiotics directly from ambient water or sediment
across permeable respiratory surfaces (e.g., gills). Some amphibia (e.g., frogs) read-
ily absorb such compounds across permeable skin. By contrast, many aquatic ver-
tebrates, such as whales and seabirds, absorb little by this route. In lung-breathing
organisms, direct absorption from water across exposed respiratory membranes is
not an important route of uptake.
Once compounds have entered organisms, they are transported in blood and
lymph (vertebrates), in hemolymph (invertebrates), and in the phloem or xylem of
plants, eventually moving into organs and tissues. During transport, polar com-
pounds will be dissolved in water or associated with charged groups on proteins such
as albumin, whereas nonpolar lipophilic compounds tend to be associated with lipo-
protein complexes or fat droplets. Eventually, the ingested pollutants will move into
cells and tissues, to be distributed between the various subcellular compartments
(endoplasmic reticulum, mitochondria, nucleus, etc.). In vertebrates, movement from
circulating blood into tissues may be due to simple diffusion across membranes, or to
transportation by macromolecules, which are absorbed into cells. This latter process
occurs when, for example, lipoprotein fragments are absorbed intact into liver cells
(hepatocytes). The processes of distribution are less well understood in invertebrates
and plants than they are in vertebrates.
An important factor in determining the course of uptake, transport, and distribu-
tion of xenobiotics is their polarity. Compounds of low polarity tend to be lipophilic
and of low water solubility. Compounds of high polarity tend to be hydrophilic and
of low fat solubility. The balance between the lipophilicity and hydrophilicity of any
compound is indicated by its octanol-water partition coefficient ( K ow ), a value deter-
mined when equilibrium is reached between the two adjoining phases:
K ow = Concentrationofcompound in octanol
Concentrationofcompound in water
Compounds with high K ow values are of low polarity and are described as being
lipophilic and hydrophobic. Compounds with high K ow values are of high polarity
and are hydrophilic. Although the partition coefficient between octanol and water is
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