Page 833 - The Toxicology of Fishes

Toxicology of Synthetic Pyrethroid Insecticides in Fish: A Case Study 813

TABLE 20.1
Acute Lethality of Fenvalerate and Its Constituent Isomers to Bluegill
48-hr i.p. LD 50 (mg/kg)
Isomer (95% Confidence Interval) Relative Potency

2R,S,αR,S (technical) 0.67 (0.52–0.86) 1.0
2S,αS 0.12 (0.10–0.14) 5.6
2S,αR 11.6 (3.8–35) 0.06
2R,αS >212 <0.003
2R,αR >260 <0.003

their potential differential uptake, distribution, detoxification, etc., which makes it somewhat difficult to
make definitive statements about their differential toxicity. One investigation was initiated to ascertain
more directly the differential toxicity of the diastereomers of fenvalerate (2S,αS, 2S,αR, 2R,αS, and
2R,αR) (Bradbury et al., 1987a). It is possible that the stereoselective toxicity of diastereomers might
differ in fish, compared to other species. The 2S pair of isomers (the 2S,αS and the 2S,αR) was shown
to be 3.3 times more toxic to fathead minnow than the technical mixture (all four isomers). Table 20.1
provides a comparison of stereoselective toxicities. For reference, the 2 chiral center is the benzylic
carbon in the chlorophenyl isovaleric acid portion of the molecule; the α chiral center is the cyano
benzylic carbon of the phenoxybenzyl alcohol portion of this ester molecule. When the four optically
pure isomers were used to treat water, each was isomerized at the α chiral center, to produce a racemic
mixture in the treated water; for example, the 2S,αS isomer racemized to a mixture of the S,S and S,R
isomers. This type of racemization also occurred in other protic solvents (e.g., alcohols, DMF, DMSO);
therefore, it was necessary to inject the optically pure isomers intraperitoneally into the fingerling bluegill
to compare directly their toxicities in that species. The resultant i.p. 48-hour LD values yielded the
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data shown in Table 20.1. The LD for the technical material (mixture of the four isomers) was 0.67
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mg/kg; for the S,S isomer, it was 0.12 mg/kg; and for the S,R isomer, it was 11.6 mg/kg. The LD values
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for each of the two individual 2R isomers were in excess of 212 mg/kg. The pattern of relative potencies
for fenvalerate isomers was determined to be approximately the same as for insects and mammals. The
conclusion was drawn that stereoselective toxicity of pyrethroid isomers does not contribute to their
highly potent toxicity to fish.

Secondary Mechanisms of Action
Numerous studies have shown deleterious effects of synthetic pyrethroids on Ca-ATPases and other
ATPases in vertebrates and invertebrates. Because certain ATPases are involved in ion regulation, research
was initiated to ascertain whether or not pyrethroids exert a toxic effect via disruption of osmoregulation.
If such an osmoregulatory toxic mechanism is in play, it could be a contributing factor enhancing the
toxicity of pyrethroids to fish. Acute toxicity testing of fenvalerate on juvenile bluegill was carried out
at different hardnesses and salinities of the treatment water. Dyer et al. (1989) demonstrated that
fenvalerate was least toxic in very soft water (6 mg/L CaCO hardness), compared to greater hardnesses.
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The tissue residues were analyzed and found to be similar for all four hardnesses tested, allowing the
authors to conclude that the toxicity differences were not due to variations in uptake rates. Four salinity
levels were tested as well. Fenvalerate was most toxic at a salinity of 33% of seawater, which is
approximately isotonic with fish blood. It was hypothesized that less enzyme induction (ATPases) may
have been necessary at physiological salinity, thus requiring less fenvalerate to inhibit/disrupt a significant
amount of the regulatory enzymes. Residue analysis of the fish indicated that most uptake rates were
similar, but the uptake rate was significantly slower at the lowest salinity level tested (12.5% of seawater).
Another project focused on the effects of fenvalerate on regulation of specific ions in fathead minnow
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and bluegill (Symonik et al., 1989). The three radiotracer isotopes utilized in these studies were Na,
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45 Ca, and Cl. They were used to study uptake and depuration of those important electrolytes in
pyrethroid-exposed fish. Fenvalerate caused some significant perturbations in ion regulation in both
species of fish, in a concentration–response manner; however, individual relationships were not easily