Page 234 - The Toxicology of Fishes

214 The Toxicology of Fishes

Anionic Esteratic

OH
O
CH 3 +
NCH CH O CCH 3 Acetylcholine
2
2
CH 3 CH 3
OCH CH 3
2
NO 2 O P Paroxon
OCH CH 3
2
O
CH
3
OCH 3
~ +
S O P Fenthion sulfoxide
OCH 3
CH 3 O S
CH 3
~ +
CH S–CCH=NO–CNHCH 3 Aldicarb sulfoxide
3
OCH 3 O

FIGURE 4.25 Inhibition of acetylcholinesterase by aldicarb sulfoxide demonstrating partial positive-charge interactions
with enzyme.

Studies in channel catfish have examined the relative differences between dearylation and desulfuration
of parathion as well as chlorpyrifos and the role of specific CYP isoforms in these processes (Straus et
®
al., 2000). Pretreatment of fish with Arochlor 1254 failed to alter either reaction in chlorpyrifos or
parathion, indicating CYP1A was not involved in dearylation or desulfuration of either compound.
Diazinon is another insecticide in which in vitro and in vivo biotransformations have been well documented
in fish (Keizer et al., 1991, 1993). In fact, differences in oxidative desulfuration have been shown to be
responsible for toxicity differences between fish species and developmental stages (Hamm et al., 1998).
Oxidative desulfuration is not the only transformation enhancing the inhibitory potency of cholinest-
erase-inhibiting xenobiotics. Sulfoxidation of xenobiotics anterior to the phosphorothionate moiety has
also been shown to enhance the binding of the xenobiotic to the cationic site of cholinesterase (Figure
4.25). Recent studies in goldfish have shown that fenthion undergoes transformation to the sulfoxide
and separately desulfuration to the oxon in vivo (Kitamura et al., 2000). In vitro studies using hepato-
pancreas microsomes from goldfish demonstrated conversion of fenthion to the sulfoxide, which was
inhibited by SKF-525A and partially by alpha-naphthylthiourea, thus suggesting roles of CYP and FMO
in the transformation (Kitamura et al., 1999). Studies with hepatopancreas cytosol indicated reduction
of the sulfoxide to the sulfide through aldehyde oxidase (Kitamura et al., 1999). Fenthion sulfoxide was
also observed in bioaccumulation studies using medaka treated with fenthion, but neither the sulfone
nor oxon was observed (Tsuda et al., 1996).
Although aldicarb is a carbamate insecticide, oxygenation of the sulfur anterior to the carbamyl moiety
significantly elevates the toxicity of this compound 40 to 150 times depending on the species (El-Alfy
and Schlenk, 2002; El-Alfy et al., 2001; Perkins et al., 1999). S-Oxygenation of aldicarb has been
observed in rainbow trout, Japanese medaka (Oryzias latipes), hybrid striped bass (Morone saxatilis ×
chrysops), channel catfish (Ictalurus punctatus), and rainbow trout (Oncorhynchus mykiss) (El-Alfy and
Schlenk, 1998; Perkins and Schlenk, 2000; Perkins et al., 1999; Schlenk and Buhler, 1991; Wang et al.,
2001). In each species except catfish, FMOs contributed to the S-oxygenation. As channel catfish and
other predominantly freshwater fish do not have active FMOs (Schlenk et al., 1993), cytochrome P450