Page 827 - The Toxicology of Fishes

Toxicology of Synthetic Pyrethroid Insecticides in Fish: A Case Study 807

Environmental concerns eventually resulted in banning or restricting most of the persistent bioaccumu-
lating chlorinated hydrocarbons.
The replacement pesticides were primarily organophosphates and carbamates, which are very degrad-
able and are especially susceptible to pH-dependent hydrolysis in aquatic systems. Water solubilities of
these compounds are generally 3 to 6 orders of magnitude higher, and LC values are more commonly
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in the milligram-per-kilogram range. Although occasional fish kills still occur, the acute and chronic
impacts on fish populations have been greatly diminished since these degradable cholinesterase inhibitors
have replaced the chlorinated hydrocarbons. In the last 20 years, the organophosphates and carbamates
have been scrutinized more and more closely due to acute and chronic toxicity problems in birds and
mammals, including humans. The Food Quality Protection Act is hastening their phase out; for example,
chlorpyrifos and diazinon have been banned for certain uses in homes, gardens, and lawns.
The emergence of synthetic pyrethroids as the primary replacements for the acutely toxic organophos-
phates and carbamates brought valid new concerns about fish toxicity. Pyrethrin-type molecules have
an innate toxicity to fish, and the synthetic pyrethroids represent analogs that have much longer persis-
tence and extreme lipophilicity. Initial toxicity testing revealed LC values that were as low as those
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for many chlorinated hydrocarbons against numerous species and stages of fish. The symptoms of toxicity
are distinctive, and death is violent. Questions of acute and chronic effects, as well as potential bioac-
cumulation, raised concern as the pyrethroids became the predominant class of insecticide employed in
all of agriculture. Researchers have now addressed many of the questions regarding toxicity, uptake, and
tissue residues; this chapter presents the current state of our knowledge of the toxicology of synthetic
pyrethroids in fishes, and it provides a putative answer to the question of why pyrethroids are so much
more toxic to fish than to birds and mammals.

Toxicity

Synthetic pyrethroids are generally extremely toxic to fish in the standard laboratory 96-hour LC tests
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or in 48-hour bioassays, both of which are considered acute toxicity bioassays. As might be expected,
numerous factors can modulate the toxicity, including formulation, water parameters, time, temperature,
and properties of the chemical being tested. Many synthetic pyrethroids have 96-hour LC values of
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less than 1 µg/L, while chronic toxicity can be recorded at one to two orders of magnitude lower than
that (Bradbury and Coats, 1989b). It is important to note that fish toxicity studies vary widely in their
methodology (e.g., static conditions vs. flow-through exposures; nominal concentrations added to the
water vs. measured concentrations). The quality of the test conditions, including exposure, governs to
a great extent the validity of the results.

Toxic Mode of Action
The principal mode of action for pyrethroid insecticides in fish is assumed to be the same as the toxic
action in insects (Holan et al., 1984) and in mammals. In nerve axons, the sodium gates open briefly to
facilitate depolarization of the membrane, which constitutes an action potential that is propagated down
the neuron. The pyrethroid insecticide binds to a receptor at the sodium gate of the neuron and prevents
it from closing fully (Figure 20.2). The resulting steady leakage of sodium ions into the neuron creates
a less stable resting state, and the neuron is susceptible to repetitive firing of the nerve, which leads to
hyperactivity, tremors, and tetany (Motomura and Narahashi, 2000; Narahashi et al., 1998). DDT also
acts at the sodium gate, but at a different site. Similarities and differences in modes of action and
quantitative structure–activity relationships have been addressed (Coats, 1990). Alternative or secondary
modes of action have also been put forth for pyrethroids. Calcium channels have been shown to be affected
adversely (Clark, 1986; Clark and Brooks, 1989), and the inhibition of calcium and calcium/magnesium
ATPase enzymes has also been considered to be a potential toxic effect of pyrethroids (Clark and
Matsumura, 1982). GABA-gated chloride channels have also been studied (Bloomquist and Soderlund,
1985; Seifert and Casida, 1985) for the malfunctions that result from exposure to pyrethroid insecticides.
The two classes of pyrethroids, type I and type II, are distinguished by their differences in symptomology.