Page 526 - The Toxicology of Fishes

506 The Toxicology of Fishes

type I pyrethroids, permethrin. Since its synthesis in 1973, permethrin has gained in popularity due to
its photostability, low mammalian and avian toxicity, and relatively short environmental half-life (i.e.,
a half-life of 28 days in soil and 14 days in seawater exposed to sunlight) (Rebach, 1999). Unfortunately,
even though permethrin appears to degrade rapidly in water, it tends to bioconcentrate in fish (Wei et
al., 1995). In fact, the major contraindication to permethrin use is its relatively high toxicity to non-
target organisms, including macro-invertebrates (ranging from 0.02 to 0.73 ppb in species tested) and
estuarine fishes (ranging from 2.2 to 12 ppb in species tested).
In addition to acute toxicity (Hohreiter et al., 1991; Holcombe et al., 1982; Rebach, 1999) and
neurological effects (i.e., restlessness, loss of coordination, systemic tremors, and paralysis) (Eells et
al., 1993; Rebach, 1999), several studies have shown that exposure of fish to permethrin also modulates
immune function (Sopinska and Guz, 1998; Zelikoff et al., 1997). Exposure of carp (Cyprinus carpio)
for example, for 96 hours to the synthetic pyrethroid Ambusz 25EC (at a concentration of 0.03 or 1.1
ppb) induced leukopenia, neutrocytosis, and reduced the percentage of kidney cells active in phagocytosis
(Sopinska and Guz, 1998). Given that shorter and longer exposure times failed to produce similar effects,
however, the results of these studies are questionable. Zelikoff et al. (1998) examined the immunomod-
ulating effects of permethrin at concentrations ranging from 0.01 to 2.0 ppb on Japanese medaka (Oryzias
latipes). Although no effects were observed on body or immune organ weight, kidney and spleen cell
viability, or hematocrit and leukocrit levels, permethrin concentrations ≥0.5 ppb tended to reduce plasma
Ig levels and kidney and spleen cellularity after 7 days (compared to solvent-exposed controls); thymic
cellularity was reduced by about 30% in fish exposed to the highest permethrin concentration. Alterna-
tively, exposure to permethrin for 48 hours tended to increase the proliferative response of splenic
lymphocytes. Probably the most dramatic effect of permethrin exposure in this study was on host survival
following bacterial challenge. Exposure of medaka to either 0.05 or 0.01 ppb permethrin for 2 or 7 days,
respectively, increased host mortality by about 30% in response to Yersinia ruckeri infection (compared
to unexposed, bacterially challenged fish). Results in medaka resemble those produced in BALBc mice
exposed to permethrin by oral gavage (Blaylock et al., 1995). In the latter case, exposure to 1.0, 0.1, or
0.01% permethrin for 10 days had no effect on body and spleen weight or mitogen-stimulated lymphocyte
proliferation. Alternatively, those responses in mice requiring specific antigen recognition or effector
function (i.e., MLR, CTL, or NK activity) were depressed by permethrin exposure.

Organochlorine Insecticides
The organochlorines (OCs), popular for their potent insecticidal activity and cost efficiency, consist of
three major families of compounds: (1) those related to DDT, including dicofol and methoxychlor; (2)
cyclodienes, such as aldrin and dieldrin; and (3) hexachlorocyclohexanes, such as lindane. To varying
degrees, OCs are all characterized by low water solubility and high chemical stability that contribute to
their persistence in the environment. The highly lipophilic nature of these compounds makes them subject
to bioaccumulation such that organisms of sequentially higher trophic levels concentrate the pesticides
from surrounding soil and water or through the consumption of organisms in lower trophic levels. In
mammals, the most commonly observed non-immune effects of OC pesticides relate to hepatotoxicity
and neurotoxicity with some difference in the actual symptoms produced by a given agent or isomer of
that agent (Barnett and Rodgers, 1994).

Lindane—Five isomers of 1,2,3,4,5,6-hexachlorocyclohexane (HCH)—alpha (α), beta (β), gamma (γ),
delta (δ), and epsilon (ε)—were originally contained in a commercial preparation of HCH known as
benzene hexachloride. This compound has not been marketed since 1978, but OC γ-HCH is commercially
available as the insecticide lindane. Lindane is used as an insecticide treatment for crop protection and
in human and veterinary medicine against ectoparasites. Excessive lindane can be persistent in food
chains and readily accumulated by most animal species; fish can absorb lindane directly from the water
or by ingestion of contaminated food, and it can bioaccumulate in fish at ratios of 500- to 1200-fold
(Betoulle et al., 2000). In addition to reported effects on hematological parameters (Ferrando and Andreu-
Moliner, 1991), ATPase activity (Hanke et al., 1983), and nervous system function (Joy, 1982), a number
of studies have demonstrated the immunomodulatory effects of lindane in fish (Betoulle et al., 2000;
Ferrando and Andreu-Moliner, 1991; Hart et al., 1997; Svensson et al., 1994; Sweet et al., 1998). Early