Part F | 33.5
800 Part F Marine Derived Metabolites
ins are heat-stable and water-soluble nonproteinaceous
toxins. The basic structures of PSP toxins are 3,4propinoperhydropurine tricyclic systems. STX and its
analogs can be divided into three categories: the carbamate compounds, which include STX, neosaxitoxin,
and gonyautoxins 14; the N-sulfo-carbamoyl compounds, which include the C and B toxins; and finally
the decarbamoyl compounds with respect to the presence or absence of 1-N-hydroxyl, 11-hydroxysulfate,
and 21-N-sulfocarbamoyl substitutions, as well as
epimerization at the C-11 position. In the past few
decades at least 24 structurally related imidazoline
guanidinium PSP derivatives have been identified and
characterized from dinoflagellate species [33.88, 89].
STX and its analogs are very dangerous compounds,
with possible military potential and have been listed
by the Organization for the Prohibition of Chemical
Weapons (OPCW) as a Schedule 1 chemical intoxicant, the manufacture, use, transfer, and reuse of which
are now strictly regulated by the OPCW (Chemical
Weapons Convention, September 1998, The Hague,
The Netherlands).
Action Mechanism
The pharmacological action of the PSP toxins strongly
resembles that of TTX. STX and several other PSP toxins block the voltage-gated sodium channel with great
potency, thus slowing or abolishing the propagation of
the action potential. However, they leave the potassium
channel unaffected.
Lethal Dose
The lethal dose for humans is 0:11 mg. It is estimated that 0:51 mg can be fatal to humans [33.90].
There is evidence that children are more susceptible
to STX than adults. The pathogenic dose for humans
0:12 mg. The lethal oral dose in humans is 14 mg
(500020 000 mouseunits), depending on the gender
and physiological condition of the patient [33.91].
Regulatory Tolerances by FDA
The FDA regulatory tolerance is 0:8 ppm STX equivalent (80 g/100 g tissue) in all fish.
Incubation Period
Symptoms may occur within a few minutes and up to
10 h after ingestion.
Symptoms
The symptoms of PSP include a tickling sensation
of the lips, mouth and tongue, numbness of the extremities, gastrointestinal problems, difficulty in breathing, and a sense of dissociation followed by complete paralysis [33.92]. In the case of serious intoxication, PSP leads to a variety of neurological
symptoms culminating in respiratory arrest and cardiovascular shock or death. Paralysis is foremost
here.
Mortality
Based on mortality figures from recent outbreaks, children appear to be more sensitive to the STXs of PSP
than adults. The case-fatality ratio averages 6%. The
death rate may be particularly high in children. If a patient survives the first 1218 h, the prognosis is good.
Muscle weakness can persist for days to weeks. In
cases of severe poisoning, muscle paralysis and respiratory failure occur, and in these cases death may
occur in 225 h. Its high mortality rate in some areas
is caused by poor access to advanced life support capabilities. In an epidemic in Guatemala, the mortality
rate was 26/187, whereby young children of < 6 years
had a mortality rate of 50% and adults of > 18 years
of 7%.
Treatment
No specific treatment exists. Victims require supportive care that may include mechanical ventilation. It is symptomatic and supportive. Since respiratory depression can develop surreptitiously, extreme
vigilance should be exercised to monitor and support patients, especially during the first 12 h. The
use of monoclonal neutralizing antibodies has been
proposed. Endotracheal intubation and artificial respiration may be necessary for a period of several
days.
Neurotoxic Shellfish Poisoning (NSP)
NSP shellfish poisoning is caused by the unarmored dinoflagellates Gymnodinium breve (Ptychodiscus breve,
also called Karenia brevis) producing brevetoxins. The
polyether brevetoxins are toxic to fish, marine mammals, birds, and humans, but not to shellfish. An unusual feature of Gymnodinium breve is the formation
by wave action of toxic aerosols, which can lead to
asthma-like symptoms in humans. Until 1992/1993,
NSP was considered to be endemic to the Gulf of
Mexico and the east coast of Florida, where red tides
had been reported as early as 1844. NSP is the least
common of the shellfish poisonings. The illness is selflimiting and resolves within several days with no lasting
effects.
800 Part F Marine Derived Metabolites
ins are heat-stable and water-soluble nonproteinaceous
toxins. The basic structures of PSP toxins are 3,4propinoperhydropurine tricyclic systems. STX and its
analogs can be divided into three categories: the carbamate compounds, which include STX, neosaxitoxin,
and gonyautoxins 14; the N-sulfo-carbamoyl compounds, which include the C and B toxins; and finally
the decarbamoyl compounds with respect to the presence or absence of 1-N-hydroxyl, 11-hydroxysulfate,
and 21-N-sulfocarbamoyl substitutions, as well as
epimerization at the C-11 position. In the past few
decades at least 24 structurally related imidazoline
guanidinium PSP derivatives have been identified and
characterized from dinoflagellate species [33.88, 89].
STX and its analogs are very dangerous compounds,
with possible military potential and have been listed
by the Organization for the Prohibition of Chemical
Weapons (OPCW) as a Schedule 1 chemical intoxicant, the manufacture, use, transfer, and reuse of which
are now strictly regulated by the OPCW (Chemical
Weapons Convention, September 1998, The Hague,
The Netherlands).
Action Mechanism
The pharmacological action of the PSP toxins strongly
resembles that of TTX. STX and several other PSP toxins block the voltage-gated sodium channel with great
potency, thus slowing or abolishing the propagation of
the action potential. However, they leave the potassium
channel unaffected.
Lethal Dose
The lethal dose for humans is 0:11 mg. It is estimated that 0:51 mg can be fatal to humans [33.90].
There is evidence that children are more susceptible
to STX than adults. The pathogenic dose for humans
0:12 mg. The lethal oral dose in humans is 14 mg
(500020 000 mouseunits), depending on the gender
and physiological condition of the patient [33.91].
Regulatory Tolerances by FDA
The FDA regulatory tolerance is 0:8 ppm STX equivalent (80 g/100 g tissue) in all fish.
Incubation Period
Symptoms may occur within a few minutes and up to
10 h after ingestion.
Symptoms
The symptoms of PSP include a tickling sensation
of the lips, mouth and tongue, numbness of the extremities, gastrointestinal problems, difficulty in breathing, and a sense of dissociation followed by complete paralysis [33.92]. In the case of serious intoxication, PSP leads to a variety of neurological
symptoms culminating in respiratory arrest and cardiovascular shock or death. Paralysis is foremost
here.
Mortality
Based on mortality figures from recent outbreaks, children appear to be more sensitive to the STXs of PSP
than adults. The case-fatality ratio averages 6%. The
death rate may be particularly high in children. If a patient survives the first 1218 h, the prognosis is good.
Muscle weakness can persist for days to weeks. In
cases of severe poisoning, muscle paralysis and respiratory failure occur, and in these cases death may
occur in 225 h. Its high mortality rate in some areas
is caused by poor access to advanced life support capabilities. In an epidemic in Guatemala, the mortality
rate was 26/187, whereby young children of < 6 years
had a mortality rate of 50% and adults of > 18 years
of 7%.
Treatment
No specific treatment exists. Victims require supportive care that may include mechanical ventilation. It is symptomatic and supportive. Since respiratory depression can develop surreptitiously, extreme
vigilance should be exercised to monitor and support patients, especially during the first 12 h. The
use of monoclonal neutralizing antibodies has been
proposed. Endotracheal intubation and artificial respiration may be necessary for a period of several
days.
Neurotoxic Shellfish Poisoning (NSP)
NSP shellfish poisoning is caused by the unarmored dinoflagellates Gymnodinium breve (Ptychodiscus breve,
also called Karenia brevis) producing brevetoxins. The
polyether brevetoxins are toxic to fish, marine mammals, birds, and humans, but not to shellfish. An unusual feature of Gymnodinium breve is the formation
by wave action of toxic aerosols, which can lead to
asthma-like symptoms in humans. Until 1992/1993,
NSP was considered to be endemic to the Gulf of
Mexico and the east coast of Florida, where red tides
had been reported as early as 1844. NSP is the least
common of the shellfish poisonings. The illness is selflimiting and resolves within several days with no lasting
effects.