Page 859 - The Toxicology of Fishes

Reproductive Impairment of Great Lakes Lake Trout by Dioxin-Like Chemicals 839

trout embryos co-exposed to TCDD and PCB 77 or PCB 126 (Zabel et al., 1995b). Depending on the
egg dose ratio of PCB 126 or PCB 77 to TCDD, cumulative mortality induced by the pair of congeners
injected into the eggs is altered. PCB 126 is synergistic with TCDD at a dose ratio of 400:1; that is, the
percentage of rainbow trout sac fry that died from co-exposure to PCB 126 and TCDD was greater than
expected by summing the TEQs contributed by both compounds. PCB 77 was also found to be synergistic
with TCDD at a dose ratio of 3500:1 and 4500:1 but antagonistic at a ratio of 1250:1. Bol et al. (1989)
also found a synergistic relationship between PCB 77 and TCDD, or between PCB 77 and 2,3,4,7,8-
PCDF, toward sac fry mortality in rainbow trout after waterborne exposure of rainbow trout sac fry.
Synergistic activity between PCB 77 and TCDD was reported in rainbow trout for induction of hepatic
AHH activity (Janz and Metcalfe, 1991) and for increased hepatic CYP1A protein levels and EROD
activity in rainbow trout (Newsted et al., 1995). Thus, at certain egg concentrations there is a tendency
for PCB 126 and TCDD and for PCB 77 and TCDD to interact synergistically in causing early-life-
stage mortality in trout. In contrast, other congener pairs appear to interact additively or show no
consistent pattern of synergism or antagonism. This difference, although slight, may have to be considered
in ecological risk assessments for trout exposed to PCDDs, PCDFs, and PCBs where PCBs are the major
contributor to the total TEQ concentration in eggs (Cook et al., 1997).

Toxicity of Mixture of PCBs, PCDDs, and PCDFs Toward Trout Early Life Stages

The complex interactions that might occur with mixtures of AhR agonist and non-AhR agonists have
been investigated through a variety of techniques under controlled laboratory conditions. To understand
the early-life-stage toxic effects of complex mixtures of PCDDs, PCDFs, and PCBs present in Lake
Michigan salmonines, investigators have prepared mixtures of these compounds or extracted these
compounds from feral fish and exposed rainbow trout or lake trout embryos to them. Additionally, Edsall
(unpublished data, cited in Mac and Edsall, 1991) conducted a study with adult lake trout in which
hatchery broodstock were fed a diet supplemented with a complex organic extract obtained from lake
trout collected in 1984 from southeastern Lake Michigan. Egg hatchability and fry survival were
significantly reduced in eggs from lake trout that had been fed and exposed in water to a high concen-
tration of the extract. Unfortunately, no information on the total PCDDs, PCDFs, or planar PCB
concentration in the lake trout eggs was provided, as this study predated routine analysis for these AhR
agonists.
Direct injection of mixtures of HAHs into freshly fertilized trout eggs has also provided important
information on the toxicity toward early life stages in salmonines. Wilson and Tillitt (1996) conducted
a study in which a complex organic extract (containing TCDD-like PCBs, PCDDs, and PCDFs) was
prepared from lake trout captured from Lake Michigan in 1988. In this study, fertilized rainbow trout
eggs were injected with extracts containing 8.8 to 8800 ng/g total PCBs. The sublethal effects and
mortality observed were consistent with TCDD-like toxicity. PCBs, PCDDs, and PCDFs contributed
about one third each to the total TEQ concentration of the lake trout tissue extract (Wright and Tillitt,
1999). The same extract was also examined for its toxicity toward lake trout early life stages (Figure
21.5) (Tillitt and Wright, 1997). The toxicity of the extract was found to be additive in lake trout for
lethality (Tillitt and Wright, 1997), as well as for sublethal endpoints of hemorrhage, edema, and
craniofacial anomalies (Wright, 2006).
Lake trout and rainbow trout were exposed as eggs to either TCDD alone or a mixture of PCDD,
PCDF, and PCB congeners at mass ratios mimicking those found in Lake Michigan lake trout eggs to
study additivity (Walker et al., 1996). PCDD and PCDF congeners contributed approximately 45% to
the total TEQ concentration of the dosing solution while the planar PCBs (77, 126, and 169) contributed
54%. Di-ortho-substituted PCBs (e.g., PCB 153) accounted for 98% of the congener mass of the dosing
solution but were assumed not to contribute to the total TEQ concentration because PCB 153 does not
produce signs of TCDD-like toxicity in trout (Walker and Peterson, 1991; Zabel et al., 1995a). Exposure
of fertilized eggs to graded doses of the above simulated Lake Michigan lake trout egg PCDD, PCDF,
and PCB mixture produced the same signs of early-life-stage toxicity, sac fry stage-specific mortality,
and slope of the dose–response curve for mortality as TCDD (Walker et al., 1996). The LD values for
50
the mixture—362 pg TEQ per g rainbow trout egg and 97 pg TEQ per g lake trout egg (calculated using