Page 858 - The Toxicology of Fishes

838 The Toxicology of Fishes

a mixture of chemicals that directly reflected the mixture of hydrophobic chemicals present in Great
Lakes lake trout at the time of collection. Subsequently, lake trout and rainbow trout eggs were exposed
to graded doses of the extracts, and the dose-related mortality followed an additive model of toxicity
(Tillitt and Wright, 1997; Wright and Tillitt, 1999). Other toxic effects of PCBs observed in mammals
such as carcinogenesis, neurotoxicity, or endocrine disruption are, for certain mono-ortho- and di-ortho-
substituted PCB congeners, not AhR-mediated (Safe, 1994); thus, non-AhR-mediated toxicity attribut-
able to PCBs is not assessed by the TEF approach.

Early-Life-Stage Toxicity of PCBs in Trout

Laboratory toxicity studies with PCBs, PCDDs, and PCDFs (AhR agonists) have demonstrated the
adverse effects of these compounds to early life stages of salmonines and support the interpretation that
such toxicity is AhR mediated (Cook et al., 1997; Walker and Peterson, 1991, 1994a; Zabel et al., 1995a).
Studies with PCBs have included early-life-stage toxicity characterizations based on the TEF approach.
Zabel et al. (1995a) determined rainbow trout-specific REPs for PCBs that can be used in assessing
risks to early-life-stage survival of lake trout. Of the 15 PCB congeners tested, only the non-ortho-
substituted PCB congeners were toxic to early life stages of rainbow trout (in the order of potency of
126 > 81 > 77 > 169). Ortho-substituted PCB congeners, including 4, 28, 52, 105, 118, 126, 128, 138,
153, 156, and 170, were essentially inactive in causing signs of early-life-stage toxicity. This was true
even at concentrations in the dosing solution that were approaching the solubility limit for these PCBs.
Although early-life-stage toxicity in rainbow trout of the remaining 194 potential PCB congeners has
yet to be tested, knowledge of the structure–activity relationship for such toxicity between the non-ortho-
, mono-ortho, and di-ortho-substituted PCB congeners already tested suggests that the planar PCB
congeners (PCB 77, 81, 126, and 169) will be the most significant contributors to TCDD-like develop-
mental toxicity from exposure of lake trout eggs to complex mixtures of PCBs where non-AhR agonist
PCB congeners are also present (Cook et al., 1997; Walker et al., 1996; Wright and Tillitt, 1999; Zabel
et al., 1995a).
Some evidence suggests that certain PCB congeners that are not AhR agonists and are prevalent in
lake trout eggs in the Great Lakes (such as PCB 153) are toxic to the early life stages of lake trout;
however, the signs of early-life-stage toxicity are completely different from those produced by TCDD,
and the egg concentration of PCB 153 required to elicit the response is greater than the egg concentration
of this PCB congener in lake trout in the Great Lakes. More specifically, Broyles and Novek (1979)
found that PCB 153, despite its lack of AhR agonist activity in fish (Vodicnik et al., 1981), caused early-
life-stage mortality in Chinook salmon (Oncorhynchus tshawytscha) and lake trout at mean concentra-
tions of 3,700,000 and 8,700,000 pg per g in the sac fry of each respective species. Importantly, the
mortality observed by Broyles and Novek (1979) was not associated with blue sac disease, a sac fry
toxicity syndrome that is the hallmark sign of toxicity of TCDD-like PCBs, PCDDs, and PCDFs (pers.
commun., cited in Walker and Peterson, 1992). Hence, other PCB 153-related di-ortho-chlorinated
congeners have the potential to produce early-life-stage toxicity in fish, albeit at egg concentrations
much greater than those required for AhR agonists and possibly so high that they may not be environ-
mentally relevant. PCB 126 is the most potent PCB AhR agonist in fish. As with TCDD, species
differences exist with regard to its potency in causing early-life-stage mortality. Rainbow trout are less
sensitive than lake trout, as evidenced by the LD for PCB 126 in rainbow trout (74,000 pg/g egg) being
50
greater than in lake trout (29,000 pg/g egg) (Walker et al., 1991; Zabel, 1995a,c).

Additive, Synergistic, or Antagonistic Interactions of Congener Pairs
The major interaction between pairs of congeners to produce early-life-stage mortality in salmonines is
additive interactions. Interactions between PCDDs, PCDFs, and PCBs and polybrominated dibenzo-p-
dioxins (PBDDs), dibenzofurans (PBDFs), and biphenyls (PBBs) in producing rainbow trout and lake
trout early-life-stage mortality have been investigated. As assessed by isobolographic analysis, the
majority of congener pairs tested acted additively in causing mortality (Hornung et al., 1996; Zabel et
al., 1995b); however, deviations from additivity (synergism or antagonism) have been detected in rainbow