Page 878 - The Toxicology of Fishes

858 The Toxicology of Fishes

during the time of their greatest exposures to HAHs, a correlation between HAH exposure and thyroid
dysfunction was never established.

Specificity
The criterion of specificity requires investigators to evaluate how specific the biological outcomes are in
relation to the disease-causing agent. In other words, can the observed symptoms of the disease be explained
by other factors or causal agents? More specifically, could blue sac syndrome and stage-specific mortality
observed in Great Lakes lake trout be caused by factors other than HAHs? Further, could the lack of
recruitment observed in populations of lake trout from Lakes Michigan, Huron, and Ontario over the
period of greatest HAH exposure have been specific to the one factor of elevated concentrations of HAHs?
The specificity of dioxin-like symptoms of toxicity in lake trout sac fry following exposure to TCDD-like
AhR agonists is fairly unique among chemical-induced toxicities. From the perspective of contaminant-
induced effects, the specificity criterion is supported by the blue sac syndrome observed in lake trout;
consequently, this supports the hypothesis that HAH-induced sac fry mortality occurred in Great Lakes
lake trout. The specific signs of yolk sac edema, hemorrhage in the vitelline vasculature and trunk,
craniofacial anomalies, lack of swim-bladder inflation, circulatory failure, and stage-specific mortality
between hatch and swim-up are all well known in dioxin-treated salmonines (Helder, 1981; Spitsbergen
et al., 1988, 1991; Tillitt and Wright, 1997; Walker et al., 1991; Wright, 2006). This suite of developmental
toxicity endpoints is also conserved across various families of fish (Elonen et al., 1998; Walker and
Peterson, 1994a). The receptor-mediated mechanisms of HAHs in developing fish embryos that have been
elucidated in the zebrafish are consistent with what is known regarding molecular mechanisms of dioxin-
like toxicity in salmonines. These mechanisms of toxicity are conserved across taxa, as well as within a
taxonomic class such as teleost fishes. Thus, the presence of blue sac disease in Great Lakes lake trout
from the mid-1970s to 1980s was consistent with AhR-related toxicity. Some of the endpoints of toxicity
observed in lake trout swim-up fry from Lake Michigan (Mac and Edsall, 1991) or Lake Ontario (Burdick
et al., 1964, 1972) during this period resembled those associated with DDT (Macek 1968). However, the
embryo-larval signs of DDT toxicity in salmonines are not similar to AhR-induced blue sac syndrome. It
is reasonable to hypothesize that even though the major symptom of toxicity observed in lake trout during
this period were associated with dioxin-like toxicity of PCBs, PCDDs, and PCDFs, simultaneous DDT
contamination of eggs may have influenced survival and subsequently recruitment.
The name blue sac syndrome was first coined to identify a condition observed in hatchery-reared
salmonines (Wolf, 1954). Under hatchery conditions, blue sac syndrome could be triggered by a variety
of different stressors including ammonia, temperature shock, or hypoxia (Balon, 1980; Burkhalter and
Kaya, 1977; Lasee, 1995; Spitsbergen et al., 1991; Wolf, 1969). The suite of symptoms described in the
literature for these hatchery fish resembled AhR-induced toxicity so much that Walker and Peterson
(1994a) adopted the same term, blue sac syndrome, to describe dioxin-related toxicity. The specificity
criterion for establishing cause-and-effect linkages between HAH exposure and stage-specific mortality
in Great Lakes lake trout is not supported by these water quality factors; however, no information
available indicates that ammonia, temperature, or dissolved oxygen was outside of acceptable levels in
the spawning areas for lake trout in the lower Great Lakes (Elrod et al., 1995; Holey et al., 1995). Thus,
the specificity criterion is supported in the fact that there is little likelihood that factors other than HAHs
could have caused the pathologies, blue sac syndrome, and stage-specific mortality observed in Great
Lakes lake trout.
Consistency of Association
This criterion refers to the ability to observe the same cause-and-effect relationship over time, across
geographic regions or locations, in different species at the same locations, and by different researchers
using a variety of approaches. It is sometimes referred to as consistency of replication (Fox, 1991), but
it is hoped that replication of contamination events on this scale will not reoccur. So, in ecoepidemiology
consistency of association must generally refer to the consistency of the observed relationship over space,
time, and species. More specifically, for this case, we must evaluate the consistency of the relationship
between HAH contamination in the aquatic food webs of the Great Lakes and either a lack of recruitment
or symptoms of dioxin-like toxicity in the exposed fish.