Encyclopedia of Environmental Science and Engineering, Volume I and II

POLLUTION EFFECTS ON FISH 1011

FACTORS THAT INFLUENCE TOXICITY

Several biological, physical and chemical factors play a part

in determining the ultimate toxicological consequences of

a foreign compound on an organism. To produce injurious

effects, a toxicant must achieve an adequate concentration

at its sites of action. The concentration attained at these sites

in the animal obviously depends on the amount of foreign

compound present in the animal’s environment. Equally

important, however, are the extent and rate of the toxicant’s

absorption, distribution, binding or localization in tissues,

inactivation, and excretion. These factors are depicted in

Figure 1 (Goodman and Gilman, 1970).

The following sections discuss each of these aspects that

play the major role in the response of organisms to foreign

compounds.

Absorption of the Toxicant

Generally speaking, a compound with specific toxicologi-

cal actions must first be absorbed and distributed (biological

translocation) in an organism before it can reach its specific

site of action and exert its toxic effect. The ease with which

foreign substances are absorbed, therefore, is a significant

factor in determining the toxicity of foreign compounds.

Absorption of substances by fish occurs through the skin,

oral mucosa, intestinal mucosa, and gills. Because it is nec-

essary that gill surfaces be exposed to large volumes of water

for the maintenance of adequate blood levels of CO 2 and O 2 ,

this organ is an especially vulnerable site for the absorp-

tion of foreign materials. Fish are, therefore, exceptionally

susceptible to toxicants that readily cross the gill epithe-

lium. In addition, fish acquire many foreign substances from

their diet by absorption across the gastrointestinal mucosa.

It should be mentioned, however, that studies are severely

lacking about this and other mechanisms of translocation of

foreign substances in fishes.

The biochemical and physicalchemical properties of

a compound determine both its ability to cross biological

membranes and its distribution within an organism. In gen-

eral, the non-ionized, non-polar forms of compounds are

significantly soluble in fat, i.e. lipid soluble, and are there-

fore readily transported across the lipidal components which

characterize animal-cell membranes (Whittaker, 1968). The

chemical structure of a foreign compound also determines

its ability to react with biological molecules as well as its

susceptibility to biotransformation (metabolism) by organ-

isms. The ability of an animal to metabolize foreign com-

pounds is important to that organism because the products

(metabolites) formed usually are less toxic (but occasionally

greater) than the parent compound. A more detailed discus-

sion of biotransformation mechanisms appears later in this

chapter.

Distribution of the Toxicant

Once the toxicant is absorbed and has entered an organism’s

blood or lymphatic system, it is readily transported and dis-

tributed to sites of action, centers of metabolic breakdown or

detoxication, storage, and excretion.

Most toxicants are transported reversibly bound to

blood proteins with only a small portion existing in the free

or unbound state. Compounds must usually exist in this

unbound state to react with biological molecules (receptors)

and interfere with biochemical mechanisms. Therefore, the

total amount of plasma protein available for the binding and

transport of toxic substances plays an important role in the

toxicological consequences of these compounds (Petermann,

1961). It is interesting to note that fish, when compared to

mammals, have a distinct disadvantage in this regard since

Locus of Action

Receptor

Free

Toxicant

Bound

Toxicant

Plasma

Bound

Toxicant

Metabolites

Absorption Excretion

Free

Toxicant

Tissue Depots

Bound Free Biotransformation

FIGURE 1

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