ENCYCLOPEDIA OF ENVIRONMENTAL SCIENCE AND ENGINEERING - POLLUTION EFFECTS ON FISH potx

1010
POLLUTION EFFECTS ON FISH
INTRODUCTION
During the past twenty-five years, man has subjected the
earth to an ever increasing variety of chemical substances
never before encountered by living organisms. Many of
these foreign substances, which originated from industrial,
agricultural and municipal sources, are seriously threaten-
ing the natural environmental conditions established over
geologic time by evolutionary processes. Organisms, includ-
ing man, are finding it more and more difficult to escape
the consequences of exposure to these compounds, many of
which are known to interfere with life sustaining biochemi-
cal and reproductive mechanisms. Little is known, however,
concerning the effects the vast majority of these pollutants
will have on plants and animals that inhabit this planet.
The aquatic environment is the ultimate destination of most
of these contaminants as a result of rainfall and runoff from the
lands. The establishment of water quality requirements for the
protection of fish life must, therefore, become an item of first
priority. The task is complicated, however, by the fact that dif-
ferent species of fish as well as different developmental states
of the same or different species exhibit wide variations in their
sensitivity or tolerance to foreign materials. In addition, the
basic biochemical and physiological information needed to
evaluate the harmful effects foreign substances have on organ-
isms is severely lacking for fish and other aquatic organisms.
It is the purpose of this chapter to briefly discuss the
current state of knowledge in regard to the response of fishes
to environmental contaminants. Because of the serious lack
of information in the area of fish toxicology,

†
it is not pos-
sible, nor is it within the scope of this discussion, to pre sent
even an outline of the toxic effects of the many foreign sub-
stances which fish encounter. Instead, representative com-
pounds have been selected to illustrate the principles that
are believed to play a major role in determining how fish
respond to environmental contaminants. Unfortunately,
these principles are based almost entirely on research per-
formed over the last several decades dealing with the toxi-
cologic responses of mammalian species, including man,
to drugs and foreign compounds. Until equivalent research
is performed on fishes, we will be forced to rely on these
mammalian principles when attempting to evaluate the
effects foreign compounds have on fish species.
MECHANISMS OF TOXICITY
Foreign substances can injure organisms through a vari-
ety of mechanism but these can generally be grouped into
two categories: specific and non-specific injury. Chemicals
that produce non-specific injury usually do so at the site of
exposure, such as skin, respiratory membranes, oral mucosa,
and intestinal mucosa. Frequently, such injury is the result
of the caustic or corrosive nature of the chemical with the
cellular responses being directly related to the concentration
of toxicant within the cell or tissue involved. Agents pro-
ducing this type of injury are commonly referred to as “pri-
mary irritants” because they induce local, minor to severe
inflammatory responses and occasionally extensive necrosis
(death) of cells. Excellent examples of these chemicals are
acids, bases and aldehydes, all of which are strong irritants

to mucous and gill membranes.
Other compounds, unlike the non-specific action of the
primary irritants, can have a high degree of specificity and
act at low dose levels at certain receptor sites to produce
pathological change in specific cells with subsequent altera-
tion of the function of organ systems. The degree of injury is
dependent on the efficiency of the repair mechanisms for the
tissue involved. If a cell is not irreversibly damaged, func-
tional and structural characteristics may return to normal.
Cells that are permanently injured at usually replaced by
fibrous (scar) tissue. Fibrosis can seriously impair the func-
tional capability of the tissue or organ involved.
Examples of substances that exhibit specific toxicologi-
cal actions are those that produce mutations by interfering
with the genetic machinery of germ cells. Mutation of a
dominant gene may express itself immediately and produce
fatal abnormalities (teratogenic effects) or early fetal death.
Other mutations may not express themselves for several gen-
erations and then suddenly appear creating serious abnor-
malities for that individual and its offspring. Chemicals may
be carcinogenic (e.g. diethylnitrosamine and aflatoxin) and
initiate the growth of malignant tumors in fish and mammals
(Stanton, 1965; Ashley et al. , 1964). Many toxicants directly
or indirectly affect reproductive mechanism, gonadal growth
and development, spawning behavior, and fry survival by
specific toxicological actions. This can frequently result in a
depletion or extinction of a susceptible species.
†
Toxicology is the scientific discipline that deals with the quantita-
tion of injurious effects on living systems resulting from chemi-

cal and physical agents that bring about alterations in cell or organ
structure and function.
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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
Excretion
Absorption
Free
Toxicant
Tissue Depots
Bound

Free
Biotransformation
FIGURE 1
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1012 POLLUTION EFFECTS ON FISH
they have much less plasma protein. Compounds that have
a high tendency to bind to plasma proteins may compete
or displace one another from binding sites when they exist
together in the blood. This may be the mechanism of danger-
ous toxic interactions because plasma protein binding sites
become so saturated that a greater percentage of unbound
toxicant exists in the blood than would normally be present
with only one toxicant. When the degree of plasma binding
is high and the rate of release is low, plasma proteins can act
as a storage depot for the bound substances. Storage depots
also frequently result from a particular affinity a toxicant
may possess for certain organs or tissues. Examples of this
are the chlorinated hydrocarbon pesticides which are stores
in body fat and heavy metals such as copper and mercury
which are stored in the liver and kidney of fish (Life, 1969).
Many foreign compounds are capable of producing a
specific effect, that is, are selectivity toxic, on a specific bio-
logical system or systems. These systems are said to be the
site of locus of action of the chemical. The site may be con-
fined to one anatomic location within the animal, or may be
diffusely located throughout the animal. Two fundamental
types of mechanisms are responsible for the selective action
of chemicals on cells or cellular mechanisms.
The first type is a result of factors that increase the con-

centration of the toxicant at specific cell or tissue sites. This
is accomplished in the organisms by mechanisms of selec-
tive translocation and biotransformation. One good example
is the renal tubular (kidney cell) injury produced in fish
exposed to copper. Because copper is excreted by the kidney
it accumulates at tubular cells. As the concentration rises
injurious levels are reached and these cells are damaged or
destroyed (Life, 1969).
A second mechanism in the selective toxicity of chemicals
on cells involves the presence of specific targets or receptor
systems in exposed cells. In this case, the concentration of
the toxicant is the same for all cells, but only certain cells are
affected. This is due to the specificity of action of the toxi-
cant on receptors that are normally occupied by endogenous
hormonal or neurohormonal substances. Organophosphorus
compounds such as parathion and malathion are good exam-
ples of selectively toxic agents that act in this way. These
cholinesterase inhibitors act to inhibit the enzyme respon-
sible for hydrolysis of the neurotransmitter, acetylcholine. In
this example cholinesterase is considered to be the receptor.
Prevention of the hydrolysis of acetylcholine results in the
continuous stimulation of post-synaptic sites throughout the
central and peripheral nervous systems and rapid death due
to respiratory paralysis is the usual outcome.
Biotransformation and Excretion of the Toxicant
The duration and intensity of injurious action of many for-
eign compounds are largely determined by the degree and
speed at which an organism can eliminate these compounds
(Conney, 1967). The kidneys of both marine and fresh water
fishes have been shown to share with mammalian kidneys

the primary role of ridding an animal of potentially toxic
compounds (Forster, 1961, 1967).
The excretion of substances by the kidney is largely
determined by lipid solubility characteristics of the com-
pounds as they enter renal tubules. Molecules with a high
degree of lipid solubility are readily re-absorbed from the
renal tubule through lipoidal membranes back into the cir-
culating blood and consequently are not excreted. It is only
through certain specific biochemical transformations of these
foreign compounds by the organism itself that lipid solubili-
ties are altered and tubular excretion is successful (Brodie
and Erdos, 1962). These reactions or transformations can be
classified as oxidations, reductions, hydrolyses and synthe-
ses (conjugation).
Most animals, including fish, transform (metabolize)
foreign compounds in two successive phases, the first phase
consisting of a variety of oxidations, reductions, and hydro-
lyses and the second phase of a limited number of synthe-
ses or conjugations (Williams, 1967). Phase I reactions can
result in:
1) The inactivation of a toxic compound;
2) The conversion of an initially inactive compound
into a toxic compound; and
3) The conversion of a toxic compound into another
toxic compound.
The second phase of biotransformation, consisting of
synthetic reactions, most often results in the conversion of
toxic compounds into inactive excretory products. This con-
cept of the metabolism of foreign compounds can be repre-
sented as in Figure 2 (Williams, 1967).

Biochemical reactions of both phases of metabolism
are catalyzed by enzymes located in various organ systems,
and it is from the study of the qualitative and quantitative
variations in these enzymes that an evaluation of detoxifying
capacities can be made for an organism (Williams, 1967).
Phase I reactions are carried out by enzymes of normal
metabolic routes and by enzymes which occur in the smooth
endoplasmic reticulum of liver cells. When these cells are
ruptured in the laboratory by homogenization the endoplas-
mic reticulum undergoes fragmentation. High-speed cen-
trifugation separates these fragments from the remaining
cell constituents. These fragments are referred to as micro-
somes and it is the microsomal enzymes that are involved
in the metabolism of many drugs and foreign compounds.
Microsomal enzymes do not generally act on lipid-insoluble
compounds but rather convert lipid-soluble materials by oxi-
dative and reductive processes to less lipid-soluble metabo-
lites, which are more polar substances and, therefore, readily
Phase I
Drug
Activation or
inactivation
Oxidation
reduction
and/or
Hydrolysis
products
Phase II
Inactivation
Synthetic o

r
conjugation
products
FIGURE 2
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POLLUTION EFFECTS ON FISH 1013
excretable by the kidney. Without these biotransformations,
the effects of some foreign substances on organisms would
last for months (Brodie et al., 1965). Excretion of these lipid-
insoluble metabolites can be achieved by active secretion at
the tubules of the kidney or by passive transport across the
glomerular membrane into the renal tubule (Forster, 1961,
1967). Since the metabolite has been transformed to a less
lipid-soluble derivative, it will not diffuse back into the
plasma for recirculation subsequent to passing through the
glomerulus into the tubule.
The microsomal enzymes were, until recently, thought
to be concerned only with the metabolism of compounds
which are normally regarded as foreign to the body. Conney
(1967) has recently shown that steroid hormones and other
normal body constituents are also substrates of the drug-
metabolizing enzymes in liver microsomes and he suggests
that this enzyme system may play a significant role in their
regulation and physiological action. These enzyme systems
are thought to operate by a mixed function oxidase mecha-
nism whereby NADPH reduces a component in microsomes
which reacts with molecular oxygen to form an “active
oxygen” intermediate. The “active oxygen” is then trans-
ferred to the drug or toxicant (Gillette, 1963). Key enzymes

in the overall reaction are NADP-cytochrome c reductase,
the flavin enzyme involved in the oxidation of NADP, cyto-
chrome P-450, and NADPH cyctochrome P-450 reductase,
which acts to reduce oxidized cytochrome P-450 (Gillette
and Sasame, 1966).
Many foreign compounds can alter these key enzymes
and enhance or impair the ability of liver microsomal
enzymes to metabolize other foreign compounds and ste-
roids (Conney, 1967). Halogenated hydrocarbon insecti-
cides have long been known to be potent stimulators of
mammalian drug-metabolizing enzymes (Hart and Fouts,
1963; Hart, Shultice and Fouts, 1963). Buhler (1966)
selectively induced drug-metabolizing enzymes in rain-
bow trout by exposing these animals to DDT or phenyl-
butazone. Organophosphate insecticides are unlike the
halogenated hydrocarbons in that they inhibit, rather than
stimulate, the metabolism of drugs and steroids by liver
microsomes, when given chronically to rats (Rosenberg
and Coon, 1958; Welch et al., 1967). Some heavy metals
(Fe
ϩϩ
, Cu
ϩϩ
, Zn
ϩϩ
and Co
ϩϩ
) have also been shown to be
inhibitory to drug metabolism in mice and rats (Peters
and Fouts, 1970). Alterations in microsomal enzyme

metabolizing capacities can substantially alter an animal’s
response to foreign compounds as well as its ability to
hydroxylate steroid hormones and other normal body con-
stituents (Conney, 1967). Altered steroid metabolism can
directly affect the animal’s ability to cope with environ-
mental stresses as well as seriously impair reproductive
mechanisms.
Other than Buhler’s (1966) work on rainbow trout,
little is known about the effects foreign compounds have
on the microsomal drug metabolizing capacities of fishes.
In addition, the current state of knowledge dealing with
metabolism of foreign compounds in fishes is, at best,
scanty (Adamson, 1967).
THE TOXICITY OF COMPLEX EFFLUENTS
Most industrial effluents contain mixtures of two or more
substances. These complex effluents present special prob-
lems in evaluating their toxicities to fish and other organisms.
In some cases two agents with similar pharmacologic actions
can produce a response that is equal to the summation of the
effects of the individual agents or greater than the summa-
tion of the independent effects of the two agents. The latter
response is called “potentiation” and represents the condition
whereby one compound is made more toxic in the presence of
another compound which alone may produce minimal or no
pharmacologic effect. Potentiation poses a special problem
for the aquatic environment as well as the terrestrial environ-
ment for it is possible that a certain combination of relatively
harmless substances may result in an unpredictable high level
of toxicity that would seriously threaten the existence of one
or many species. Usually, however, the effect of two agents

is the summation of responses to each agent. Occasionally,
the effect of a toxic substance is reduced on the addition of
another substance, a phenomenon referred to as antagonism.
In some cases the antagonistic substance may or may not be
toxic when present by itself.
Synergism (potentiation and summation) and antagonism
are poorly understood phenomena and greatly confuse the
understanding and prediction of the toxic effects of industrial
effluents. The majority of toxicological studies conducted in
this and other countries on both mammals and fish deal with
the effects of single substances on organisms; only a few stud-
ies are currently investigating the responses of organisms to
complex mixtures of substances. Synergism and antagonism
are worthy of further investigation, for little is known about
the basic mechanisms governing these processes.
RESISTANCE OF FISH TO TOXICANTS
Resistance of animals to chemicals has been known to exist
for some time now and has posed serious obstacles in the
control of insects and bacteria. While the mechanisms of
resistance remain thus far a mystery, we know that they are
genetically based. Most susceptible populations of animals
have an occasional individual which exhibits resistance and
it is this member that provides the genetic material for selec-
tion pressures to act upon.
Resistance has best been demonstrated with various
pesticides in several natural populations of fishes (Ferguson
et al., 1964, 1966), but these findings have attracted little
attention. Many biologists have, in fact, believed this phe-
nomenon to be beneficial to these animals, especially since
they are useful to man.

Recently, some disturbing evidence has emerged sug-
gesting that pesticide-resistant vertebrates pose a major
hazard in natural ecosystems and that they may be creating
serious toxicological problems for man (Ferguson, 1967).
The reason for this is some resistant animals carry massive
residues of unaltered pesticides in their tissues and aggra-
vate the already serious problem of biological magnification.
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1014 POLLUTION EFFECTS ON FISH
Animals whose resistance is due to enhanced abilities to
metabolize toxic substances to inactive metabolites do not,
however, contribute to biological magnification.
Biological magnification results when a foreign sub-
stance enters plants and small animals and is then passed
rapidly along food chains to larger animals. As this happens
the substance becomes more and more concentrated until it
reaches dangerous levels in the large predacious fish, many
of which are consumed by birds and mammals including
man. Clearly, the more resistance a fish has for the particu-
lar toxicant in its tissues the greater the likelihood it will
be consumed by animals living on the land. Unfortunately,
these animals may not have equivalent levels of resistance
and may be unable to adequately deal with these toxicants.
CURRENT METHODS OF EVALUATING
TOXICITY IN FISHES
The establishment of water quality standards for concentra-
tions of toxic pollutants that will be safe for fish has recently
become a major concern of Federal and State Governments
in pollution control (Water Quality Criteria, 1968). Efforts in

this regard have centered around determining lethal limits of
toxicants by establishing a TLm (tolerance limit, median) of
various species exposed to toxicants for periods of time up
to 96 hr (Sprague, 1969).
These short term studies have been valuable in defin-
ing the upper limits of toxicity but have not considered the
subtle deleterious effects of foreign compounds which may
not be evident for weeks, months, or longer (Water Quality
Criteria, 1963). These responses to toxicity may manifest
themselves in appetite changes, metabolic alterations, dis-
orders of the nervous system, reproductive changes, behav-
ioral abnormalities, or alteration of vital functions which are
not immediately lethal. For this reason, investigations have
only recently been conducted to measure toxicity in terms of
survival, growth, and reproductive alterations resulting from
long-term exposure to sublethal levels of pollutants (Water
Quality Criteria, 1968). The concept of a “maximum accept-
able toxicant concentration (MATC)” has originated from
these studies and is defined as the highest continuous con-
centration of a toxicant that does not significantly decrease
the laboratory fish production index; an index developed by
Mount and Stephen (1967) which takes into account sur-
vival, growth, reproduction, spawning behavior, viability of
eggs, and growth of fry.
Because the toxicity of most pollutants varies with water
characteristics and fish species, Mount and Stephen (1967)
proposed the use of an “application factor,” (calculated by
dividing the MATC of the 96-hr TLm value), to determine
safe concentrations of toxic pollutants which, when deter-
mined for one species of fish in one type of water, may be

applicable to other waters and other species. Studies are
currently underway to test the practicality of this approach
(Mount, 1968; Mount and Stephen, 1969).
The “application factor” approach may improve upon
present methods of estimating safe concentrations of toxicants.
At best, however, this approach requires considerable time for
collection and evaluation of data and measures only the end
result of a multitude of biochemical, physiological, metabolic,
pharmacological and pathological responses to toxicants. Little
definitive information is gained concerning the mechanism
which produces the gross changes upon which the “application
factor” is based.
Because of the virtual impossibility of thoroughly assess-
ing the individual, cumulative, synergistic and antagonistic
effects of the numerous substances continually being intro-
duced into our environment, it is imperative that we know
the basic metabolic, physiologic and toxicologic responses
of fish to compounds representative of broad categories of
foreign substances. Only then will we be in a position to
predict intelligently the biological effects of toxicants and
regulate their concentrations to assure protection of this very
important biological resource. If fish toxicologists continue
to consider only the effect of a substance on the labora-
tory fish production index without understanding causative
mechanisms, they will severely limit the amount of informa-
tion available for making meaningful decisions so desper-
ately needed in water pollution control programs.
Investigations of the disposition of foreign compounds
in fish will shed valuable information on the evolution of
enzymes that metabolize drugs, on drug metabolic pathways

and excretion, and on factors affecting the biological half-
life of foreign compounds in their lower species as well as
higher vertebrates including man (Adamson, 1967). The edi-
the collection of fishes with fin erosion or other deformities.
A few concentrated on fresh water streams (Reash and Berra,
1989; Sindermann, 1979) whereas a preponderance focused
on marine or estuarine environments with and without pol-
example. Reash and Berra found that the incidence of fish
erosion was significantly greater at polluted stream sites
compared to unpolluted sites.
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tors refer the reader to numerous studies which have noted
POLLUTION EFFECTS ON FISH 1015
Goodman, L.S. and A. Glman (1970) The Pharmacological Basis of Thera-
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JOHN E. BARDACH
University of Michigan
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