319
Chapter fourteen: Toxicology and poisons
feeding anchovy (Lefebvre et al. 1999; Scholin et al. 2000). Domoic acid is structurally
analogous to glutamate, a neurotransmitter, which is an excitatory amino acid (Pulido
2008). Domoic acid activates ionotropic glutamate receptors which overstimulates the
neuron by allowing high levels of calcium to enter the cell and also prevents rapid desensitization in a mechanism consistent with excitotoxicity (Jeffery et al. 2004; Ramsdell and
Stafstrom 2009).
Intriguingly, although several isomers of domoic acid have been identified it appears
that deleterious effects are caused by a single toxic species, the same chemical species that
is found accumulating in high concentrations in shellfish (Iverson et al. 1989). This would
appear to suggest that the absorbed molecule does not undergo any biotransformation
processes, as opposed to other compounds such as gambiertoxin/ciguatoxin. Furthermore,
Suzuki and Hierlihy (1993) found that in rats nearly 100% of administered domoic acid was
recovered in the urine, suggesting that biotransformation and other forms of elimination
play little to no role in the toxicodynamics of domoic acid in mammals.
Concentrations of domoic acid of 96.8 μg/g in feces were found in California sea
lions exhibiting acute signs of neurotoxicity including seizures, erratic head movements,
and ataxia (Gulland et al. 2002; Bargu et al. 2012). Though catastrophic neurologic effects
have been well documented, vexing results in rats suggest that the blood–brain barrier is
effective in limiting the distribution of the toxin into the brain (Preston and Hynie 1991).
However, the excitatory nature of domoic acid is consistent with the idea that acute neurologic effects can be induced by relatively small concentrations in the brain tissue. Recent
evidence has suggested a host of deleterious effects on a variety of tissues, including myocardial lesions in California sea lions (Zalophus californianus) which may explain rapid
lethality following acute exposure (Gulland et al. 2002; Pulido 2008).
Linking disease of stranded California sea lions to blooms of a toxic diatom can be
difficult, especially considering confounding considerations such as the patchiness of
diatom blooms, wind or current transport of blooms as well as lag time associated with
disease progression (Goldstein et al. 2008). For instance, Goldstein et al. (2008) found clinical signs of both chronic and acute domoic acid toxicity associated with abnormal epileptiform discharges, but high incidence of chronic neurologic cases lagged behind cases of
acute toxicity by 4 months. It is conceivable that the observed lag time in chronic toxicity
is caused by the progression of toxicosis due to low level exposure, however, another more
feasible explanation is that signs of chronic toxicity are merely a progression of an acute
sub-lethal toxic response.
There are a several interesting observations that arise from studying stranding data
from California sea lions from the last 15 years (Goldstein et al. 2008; Bargu et al. 2012).
Strandings associated with acute and chronic domoic acid toxicity were reported in every
year from 1998 to 2006 except 1999 (Bejarano et al. 2008). This may be explained by an
increased stranding response effort or improved diagnostics and surveillance, or both.
However, there is also evidence that blooms of Pseudo-nitzschia have co-occurred during
periods of increased domoic acid poisoning frequency (Scholin et al. 2000; Bejarano et al.
2008). The majority of strandings associated with domoic acid appear to be adult females
(68%) as opposed to non-domoic acid cases which are dominated by pups (59%) (Bejarano
et al. 2008). While this difference could be associated with sex-based differences in toxicodynamics or activity of domoic acid, it seems a more plausible explanation is differences
in exposure related to foraging ecology. For instance, the breeding season for California
sea lions occurs during the summer months in California (May–August), which generally coincides with blooms of Pseudo-nitzschia. Adult females spend a large portion of the
breeding season foraging at sea, while the adult males are generally hauled out defending
Chapter fourteen: Toxicology and poisons
feeding anchovy (Lefebvre et al. 1999; Scholin et al. 2000). Domoic acid is structurally
analogous to glutamate, a neurotransmitter, which is an excitatory amino acid (Pulido
2008). Domoic acid activates ionotropic glutamate receptors which overstimulates the
neuron by allowing high levels of calcium to enter the cell and also prevents rapid desensitization in a mechanism consistent with excitotoxicity (Jeffery et al. 2004; Ramsdell and
Stafstrom 2009).
Intriguingly, although several isomers of domoic acid have been identified it appears
that deleterious effects are caused by a single toxic species, the same chemical species that
is found accumulating in high concentrations in shellfish (Iverson et al. 1989). This would
appear to suggest that the absorbed molecule does not undergo any biotransformation
processes, as opposed to other compounds such as gambiertoxin/ciguatoxin. Furthermore,
Suzuki and Hierlihy (1993) found that in rats nearly 100% of administered domoic acid was
recovered in the urine, suggesting that biotransformation and other forms of elimination
play little to no role in the toxicodynamics of domoic acid in mammals.
Concentrations of domoic acid of 96.8 μg/g in feces were found in California sea
lions exhibiting acute signs of neurotoxicity including seizures, erratic head movements,
and ataxia (Gulland et al. 2002; Bargu et al. 2012). Though catastrophic neurologic effects
have been well documented, vexing results in rats suggest that the blood–brain barrier is
effective in limiting the distribution of the toxin into the brain (Preston and Hynie 1991).
However, the excitatory nature of domoic acid is consistent with the idea that acute neurologic effects can be induced by relatively small concentrations in the brain tissue. Recent
evidence has suggested a host of deleterious effects on a variety of tissues, including myocardial lesions in California sea lions (Zalophus californianus) which may explain rapid
lethality following acute exposure (Gulland et al. 2002; Pulido 2008).
Linking disease of stranded California sea lions to blooms of a toxic diatom can be
difficult, especially considering confounding considerations such as the patchiness of
diatom blooms, wind or current transport of blooms as well as lag time associated with
disease progression (Goldstein et al. 2008). For instance, Goldstein et al. (2008) found clinical signs of both chronic and acute domoic acid toxicity associated with abnormal epileptiform discharges, but high incidence of chronic neurologic cases lagged behind cases of
acute toxicity by 4 months. It is conceivable that the observed lag time in chronic toxicity
is caused by the progression of toxicosis due to low level exposure, however, another more
feasible explanation is that signs of chronic toxicity are merely a progression of an acute
sub-lethal toxic response.
There are a several interesting observations that arise from studying stranding data
from California sea lions from the last 15 years (Goldstein et al. 2008; Bargu et al. 2012).
Strandings associated with acute and chronic domoic acid toxicity were reported in every
year from 1998 to 2006 except 1999 (Bejarano et al. 2008). This may be explained by an
increased stranding response effort or improved diagnostics and surveillance, or both.
However, there is also evidence that blooms of Pseudo-nitzschia have co-occurred during
periods of increased domoic acid poisoning frequency (Scholin et al. 2000; Bejarano et al.
2008). The majority of strandings associated with domoic acid appear to be adult females
(68%) as opposed to non-domoic acid cases which are dominated by pups (59%) (Bejarano
et al. 2008). While this difference could be associated with sex-based differences in toxicodynamics or activity of domoic acid, it seems a more plausible explanation is differences
in exposure related to foraging ecology. For instance, the breeding season for California
sea lions occurs during the summer months in California (May–August), which generally coincides with blooms of Pseudo-nitzschia. Adult females spend a large portion of the
breeding season foraging at sea, while the adult males are generally hauled out defending