Page 864 - The Toxicology of Fishes

844 The Toxicology of Fishes

1997; Toomey et al., 2001; Walker and Peterson, 1994b; Walker et al., 1991; Wright 2006). Brook trout
and rainbow trout are about 3 to 6 times less sensitive than lake trout, whereas the other species are 8
to 38 times less sensitive. The only species that has demonstrated greater sensitivity than lake trout
toward TCDD-induced toxicity is the bull trout (Salvelinus confluentus), also a member of the charr
family (Cook et al., 2000). This latter study indicates that the bull trout has an LD value approximately
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one third that of the LD of lake trout for the early-life-stage toxicity of TCDD.
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The reason for the greater risk posed by TCDD-like PCBs, PCDDs, and PCDFs to early-life-stage
survival of lake trout is not known. Elonen et al. (1998) suggested that the ability of non-salmonine fish
species to tolerate higher egg concentrations of TCDD might be related to their shorter development
time to swim-up. The time from hatch to swim-up and first feeding ranged from 1 to 18 days for the
non-salmonine species compared to 30 to 60 days for rainbow trout and up to 120 days for lake trout,
the longest development time. Comparison of post-swim-up TCDD elimination rates between the non-
salmonine species and lake trout suggests that lake trout with a long development time retain TCDD
longer than species with short development times; however, this might not be the complete explanation.
When induction of CYP1A mRNA is compared between rainbow trout and zebrafish cell cultures in
response to graded concentrations of TCDD (a condition in which species differences in TCDD elimi-
nation rate is less likely to be a factor), TCDD is still less potent in eliciting an AhR-mediated response
in zebrafish cells (Henry et al., 1997). This suggests that the species difference in potency of TCDD in
causing AhR-mediated responses may involve species differences in the AhR signaling pathway (TCDD
binding to AhR, dimerization of AhR with ARNT, DNA binding of TCDD/AhR/ARNT, or transactiva-
tion). Alternatively, the fish species that are most sensitive toward TCDD are also those species that are
more oxygen sensitive. If, indeed, the cardiovascular system is an initial target for TCDD, species that
are more sensitive to disruptions in oxygen homeostasis may be more sensitive to the untoward effects
of dioxin.

Developmental Stages Sensitive to TCDD Toxicity
The lethal potency of TCDD is affected by the developmental stage at which exposure occurs (egg, sac
fry, swim-up fry, or juvenile). In rainbow trout it has been clearly demonstrated that TCDD is most
potent in causing early-life-stage mortality if administered immediately after egg fertilization. When
TCDD is administered later in development, at the eye-up stage, at hatching, at the fry stage, or during
juvenile development, it is progressively less potent in causing mortality. More specifically, the LD in
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rainbow trout exposed to TCDD as fertilized eggs (230 to 488 pg TCDD per g egg) is less than for
TCDD exposure of swim-up fry (21 days post-hatch), where whole-body concentrations of 990 pg TCDD
per g body result in 45% mortality (Mehrle et al., 1988; Walker et al., 1991). Even higher whole body
concentrations (>5000 pg TCDD per g body) are required to produce mortality in juvenile rainbow trout
(Spitsbergen et al., 1988). Thus, the developmental stage of trout, at the time of TCDD exposure, is an
important factor in determining susceptibility to mortality with the sac fry stages being the most sensitive.

Route of TCDD Egg Exposure and Sensitivity to Toxicity

No significant difference was observed in the potency of TCDD to cause lake trout sac fry mortality
when exposure of eggs to TCDD occurred via maternal transfer, waterborne exposure, or egg injection
(Walker et al., 1994). The no-observable-adverse-effect level (NOAEL), lowest-observable-adverse-effect
level (LOAEL), LD , and LD of TCDD were in the same range for all routes of TCDD exposure to
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lake trout eggs (Walker et al., 1994); thus, it was the egg dose of TCDD that determined toxicity, as
opposed to the route of exposure. Dietary exposure of adult female brook trout and zebrafish to sublethal
concentrations of TCDD has also been shown to cause toxicity in their embryos (Johnson et al., 1996;
Wannemacher et al., 1992). In brook trout, the concentration of TCDD in eggs that resulted in dose-
related increases in sac fry mortality was also similar following waterborne exposure and maternal
transfer (Johnson et al., 1998; Walker and Peterson, 1994b).