Page 832 - The Toxicology of Fishes

812 The Toxicology of Fishes

Elimination
The experiments conducted on the toxicokinetics of fenvalerate indicated that the elimination rate in
rainbow trout was much slower than in birds or mammals. After the uptake across the gill membrane,
80 to 90% of the dose taken up was still in the body at time periods of 8 hours to 48 hours after the
exposure was stopped. In contrast, research on quail (Bradbury, 1982; Mumtaz and Menzer, 1986) and
rats (Ohkawa et al., 1979) found 90 to 100% elimination occurred within 48 hours of administration of
a dose. The 10 to 20% of the fenvalerate found in the trout bile between 8 and 48 hours was all present
as the glucuronide conjugate of 4′-hydroxy fenvalerate. Any deficiency that fish show in detoxifying or
eliminating pyrethroid insecticides could lead to higher concentrations of the parent molecule in their
brain. Distribution within the fish body results in relatively small percentages of the parent compound
reaching the central nervous system, so any factor that contributes to slower detoxification or excretion
of these potent neurotoxicants can enhance the potency in the nervous system by facilitating a small
increment in concentration at the site of toxic action. One other question that has to be considered is
that of potentially high bioconcentration factors (BCFs) of synthetic pyrethroids in fish. Although the
elimination rate is relatively slow, the uptake rate has also been shown to be slow, and sufficient oxidative
biotransformation has been observed to preclude grouping these lipophilic, relatively stable synthetic
pyrethroids with the older chlorinated hydrocarbons that accumulated to extremely high levels, especially
through food chains. Several studies have reported BCFs of 400 to 4000 for fish, which are several
orders of magnitude lower than those reported for DDT, dieldrin, chlordane, heptachlor, and endrin. A
discussion of the results of several studies is presented in Bradbury and Coats (1989a). The bioconcen-
tration factors for the pyrethroids are not notably higher than those for other, much less toxic, insecticides,
including organophosphates and carbamates; the pyrethroid bioconcentration factors probably do not
contribute greatly to their extreme potency to fish.
In summary, the toxicokinetics of photostable synthetic pyrethroid insecticides in fishes is substantially
different from their toxicokinetics fate in mammals and birds. Some of the differences, especially the
lack of hydrolytic detoxification capability and the slow elimination, are consistent with greater toxicity
of the pyrethroids in fish.

Toxicodynamics

The effects of synthetic pyrethroids on the nervous system have been studied for decades, but the
comparative toxicodynamics have primarily focused on the differences between type I and type II
pyrethroids in the mammalian central nervous system and the function and number of sodium gates in
the nervous systems of resistant vs. susceptible insects. Additionally, researchers have been curious about
the negative temperature coefficient of insects, although it has been documented in other species as well.
It is important that a comparative study of fish susceptibility relative to avian and mammalian suscep-
tibility include some consideration of possible differences in toxicokinetics that could contribute to
differential susceptibilities. Other questions that may be significant include the following:

• Is the stereoselective toxicity of pyrethroid isomers different for fish than for birds and mammals?
• Do secondary toxic mechanisms of action contribute to the ultra-susceptibility of fish to
pyrethroids?
• Are fish nervous systems more susceptible to neurotoxicological effects of pyrethroids com-
pared to avian and mammalian nervous systems?

Stereoselective Toxicity
Insect toxicity is dramatically different for individual diastereomers of pyrethroid insecticides, with some
isomers demonstrating incredible potency and their mirror-image isomers showing virtually no toxicity.
A similar pattern has been recorded for mammalian LD values, but little information was available for
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fish. Some of the limited data in fish depend on the stability of the individual isomers in the water and