Chemistry Reference
In-Depth Information
starvation or disease can lead to rapid release of the stored xenobiotic and to delayed
toxic effects. In one well-documented case in the Netherlands (see Chapter 5),
wild female eider ducks (
Somateria mollissima
) experienced delayed neurotoxic-
ity caused by dieldrin. The ducks had laid down large reserves of depot fat before
breeding, and these reserves were run down during the course of egg laying. Dieldrin
concentrations quickly rose to lethal levels in the brain. Male eider ducks did not
lay down and mobilize body fat in this way and did not show delayed neurotoxicity
due to dieldrin.
Binding to proteins can also represent storage. In the first place, highly lipophilic
compounds, such as organochlorine insecticides, associate with lipoproteins and are
circulated in blood in this state. Indeed, their water solubility is so low that only
an extremely small proportion of the total concentration present in body fluids is
in true solution. Their association with lipoproteins is due, at least in part, to the
hydrophobic effect of water. They are excluded from water by the mutual attraction
of water molecules and are pushed into association with the lipoproteins and other
hydrophobic domains of the body, including lipoproteins. Apart from “dissolving”
in mobile lipid depots, they can bind to hydrophobic proteins as a consequence of
van der Waals interactions between the compounds and the surfaces of the proteins.
More polar compounds (including ionic compounds) also interact with proteins, but
in different ways. The formation of ionic bonds or hydrogen bonds leads to the bind-
ing of more polar xenobiotics to functional groups of certain proteins. Albumin, for
example, is abundant in mammalian plasma and can bind a number of relatively
polar xenobiotics. Hydroxy-metabolites of PCBs can bind to certain plasma proteins.
One particular case, the binding of 3.3′,4,4′ tetrachloro-biphenyl to transthyretin, has
been closely studied because it is associated with toxicity rather than storage (see
Chapter 6, Section 6.2 and Brouwer et al. 1990).
Storage of lipophilic pollutants in the eggs of invertebrates, birds, amphibians,
and reptiles is of importance in ecotoxicology. Organochlorine insecticides are
transported by lipoproteins from females to eggs. At first, they are stored within the
yolk of birds eggs. When the eggs develop, they are mobilized and can cause delayed
toxicity in the developing embryo. Such effects have been observed with dieldrin
and DDT.
2.3.4 e
x c r e T i o n
As explained in Chapter 1, there is strong evidence for the rapid evolution of enzyme
systems concerned with the metabolism of xenobiotics coinciding in time with the
movement of animals from water to land. Thus, radiation of the CYP2 family of
P450s corresponds closely with the colonization of land at the start of the Devonian
period circa 400 million years ago. The CYP2 family is particularly concerned with
the metabolism of xenobiotics and is represented by a considerable number of differ-
ent forms in terrestrial mammals (see Section 2.3.2.2). On the other hand, this fam-
ily of P450s, and indeed xenobiotic metabolizing enzymes more generally, are less
well developed in fish, as will be explained later. Fish can “excrete” many lipophilic
xenobiotics by diffusion across the gills into ambient water. This excretion mecha-
nism is not, however, available to terrestrial animals. They depend on the conversion
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