Marine Dinoflagellate-Associated Human Poisoning 33.5 Toxigenic Dinoflagellate-Associated Human Poisoning 797
Part F | 33.5
MTX-3 have been identified from Gambierdiscus toxicus [33.71]. MTX has been proved to be the most potent
toxin identified on a weight basis: the lethal dose 50
(LD 50 ) of MTX in mice is less than 0:2 g kg
1 (intraperitoneally) and it is at least fivefold more toxic than
tetrodotoxin. These precursors are biotransformed to
ciguatoxins by herbivorous fish and invertebrates grazing on Gambierdiscus toxicus and then accumulated in
higher trophic levels [33.72]. In ciguatera poisoning,
the poisonous ingredient is ciguatoxin.
Ciguatoxin was originally isolated in Hawaii in 1967.
The toxins form a family of very closely related structures with a molecular weight of 9411117 Da. There
are a number of variants, depending on whether or not
certain chemical groups (H, CH 3 , etc.) are present.
The ciguatoxins are a family of heat-stable, lipid-soluble,
highly oxygenated, cyclic polyether molecules with
a structural framework reminiscent of the brevetoxins [33.73–75], and more than 20 toxins may be involved
in CFP [33.76]. Scaritoxin was isolated in 1976 in Tahiti
from a parrotfish (Scarus gibbus). It is a metabolite of
ciguatoxin, but dinoflagellates are also said to be able to
produce the poison in in vitro culture.
Action Mechanism
Ciguatoxin and the closely-related MTX both cause
symptoms by interfering with ion channels on cell
membranes. Ciguatoxin opens sodium channels and
MTX opens calcium channels, disrupting the signaling
between nerves and muscles.
Lethal Dose
In mice, ciguatoxin is lethal at 0:45 g kg
1 ip, and
MTX at a dose of 0:15 g kg
1 ip. Oral intake of as little as 0:1 g ciguatoxin can cause illness in the human
adult. The pathogenic dose for humans is 23230 g.
Regulatory Tolerances by the Food and Drug
Administration (FDA)
The FDA safety levels of CFP – 0:01 ppb P-CTX-1
equivalents for Pacific ciguatoxin and 0:1 ppb C-CTX-1
equivalent for Caribbean ciguatoxin.
Incubation Period
Ciguatoxin usually causes symptoms within a few minutes to 30 h after consumption of contaminated fish, and
occasionally it may take up to 6 h.
Symptoms
Since more than 20 toxins are involved they produce
more than 175 ciguateric symptoms, classified into four
categories: gastrointestinal, neurological, cardiovascular, and general symptoms [33.77, 78]. It should be emphasized that the symptoms of ciguatera vary in different oceans: in the Pacific Ocean neurological symptoms
predominate, while in the Caribbean Sea gastrointestinal symptoms dominate due to the difference in toxin
composition. The onset of GI and neurologic symptoms after the consumption of fish are the hallmarks
of ciguatera poisoning. Symptoms are usually evident
within 26 h after ingestion and usually resolve within
24 h, although a late-presenting and extended course is
not uncommon. Gastrointestinal (GI) symptoms generally consist of diaphoresis, abdominal cramps, nausea,
vomiting, profuse watery diarrhea, and dysuria. GI
symptoms are usually reported to occur prior to neurological symptoms. Interesting, however, is that the
predominance of GI or neurologic symptoms seems to
vary according to regions, with GI-predominant illness
seen in the Caribbean, while neurologic symptoms predominate in the Indo-Pacific region.
Neurologic symptoms tend to occur later (up to
72 h) and may persist for months. These are predominantly paresthesias, but a myriad of other sometimes
bizarre neurologic symptoms may also be observed, including pruritus; the sensation of loose painful teeth;
tingling in the lips, tongue, throat, and perioral tissues;
metallic taste; reversal of temperature sensation; and
the sensation of heat in the superficial tissues of the
extremities with concomitant sensation of cold in the
deeper tissues. Further neurologic symptoms can include vertigo, ataxia, visual changes, and seizures. In
more severe poisoning, bradycardia with hypotension
and cardiovascular collapse may occur.
Common, nonspecific symptoms include nausea, vomiting, diarrhea, cramps, excessive sweating,
headache, and muscle aches. The sensation of burning
or pins-and-needles, weakness, itching, and dizziness
can occur. Patients may experience reversal of temperature sensation in their mouth (hot surfaces feeling
cold and cold surfaces hot), unusual taste sensations,
nightmares, or hallucinations. Symptoms of exposure
include eye and respiratory irritation, headache, and
gastrointestinal complaints, skin irritation, and difficulties with learning and memory [33.79].
Mortality
Ciguatera poisoning is rarely fatal. The overall death
rate from ciguatera poisoning is approximately 0:1%,
but varies according to the toxin dose and availability
of medical care to deal with complications. Death from
CFP is rare (< 1% worldwide).
Part F | 33.5
MTX-3 have been identified from Gambierdiscus toxicus [33.71]. MTX has been proved to be the most potent
toxin identified on a weight basis: the lethal dose 50
(LD 50 ) of MTX in mice is less than 0:2 g kg
1 (intraperitoneally) and it is at least fivefold more toxic than
tetrodotoxin. These precursors are biotransformed to
ciguatoxins by herbivorous fish and invertebrates grazing on Gambierdiscus toxicus and then accumulated in
higher trophic levels [33.72]. In ciguatera poisoning,
the poisonous ingredient is ciguatoxin.
Ciguatoxin was originally isolated in Hawaii in 1967.
The toxins form a family of very closely related structures with a molecular weight of 9411117 Da. There
are a number of variants, depending on whether or not
certain chemical groups (H, CH 3 , etc.) are present.
The ciguatoxins are a family of heat-stable, lipid-soluble,
highly oxygenated, cyclic polyether molecules with
a structural framework reminiscent of the brevetoxins [33.73–75], and more than 20 toxins may be involved
in CFP [33.76]. Scaritoxin was isolated in 1976 in Tahiti
from a parrotfish (Scarus gibbus). It is a metabolite of
ciguatoxin, but dinoflagellates are also said to be able to
produce the poison in in vitro culture.
Action Mechanism
Ciguatoxin and the closely-related MTX both cause
symptoms by interfering with ion channels on cell
membranes. Ciguatoxin opens sodium channels and
MTX opens calcium channels, disrupting the signaling
between nerves and muscles.
Lethal Dose
In mice, ciguatoxin is lethal at 0:45 g kg
1 ip, and
MTX at a dose of 0:15 g kg
1 ip. Oral intake of as little as 0:1 g ciguatoxin can cause illness in the human
adult. The pathogenic dose for humans is 23230 g.
Regulatory Tolerances by the Food and Drug
Administration (FDA)
The FDA safety levels of CFP – 0:01 ppb P-CTX-1
equivalents for Pacific ciguatoxin and 0:1 ppb C-CTX-1
equivalent for Caribbean ciguatoxin.
Incubation Period
Ciguatoxin usually causes symptoms within a few minutes to 30 h after consumption of contaminated fish, and
occasionally it may take up to 6 h.
Symptoms
Since more than 20 toxins are involved they produce
more than 175 ciguateric symptoms, classified into four
categories: gastrointestinal, neurological, cardiovascular, and general symptoms [33.77, 78]. It should be emphasized that the symptoms of ciguatera vary in different oceans: in the Pacific Ocean neurological symptoms
predominate, while in the Caribbean Sea gastrointestinal symptoms dominate due to the difference in toxin
composition. The onset of GI and neurologic symptoms after the consumption of fish are the hallmarks
of ciguatera poisoning. Symptoms are usually evident
within 26 h after ingestion and usually resolve within
24 h, although a late-presenting and extended course is
not uncommon. Gastrointestinal (GI) symptoms generally consist of diaphoresis, abdominal cramps, nausea,
vomiting, profuse watery diarrhea, and dysuria. GI
symptoms are usually reported to occur prior to neurological symptoms. Interesting, however, is that the
predominance of GI or neurologic symptoms seems to
vary according to regions, with GI-predominant illness
seen in the Caribbean, while neurologic symptoms predominate in the Indo-Pacific region.
Neurologic symptoms tend to occur later (up to
72 h) and may persist for months. These are predominantly paresthesias, but a myriad of other sometimes
bizarre neurologic symptoms may also be observed, including pruritus; the sensation of loose painful teeth;
tingling in the lips, tongue, throat, and perioral tissues;
metallic taste; reversal of temperature sensation; and
the sensation of heat in the superficial tissues of the
extremities with concomitant sensation of cold in the
deeper tissues. Further neurologic symptoms can include vertigo, ataxia, visual changes, and seizures. In
more severe poisoning, bradycardia with hypotension
and cardiovascular collapse may occur.
Common, nonspecific symptoms include nausea, vomiting, diarrhea, cramps, excessive sweating,
headache, and muscle aches. The sensation of burning
or pins-and-needles, weakness, itching, and dizziness
can occur. Patients may experience reversal of temperature sensation in their mouth (hot surfaces feeling
cold and cold surfaces hot), unusual taste sensations,
nightmares, or hallucinations. Symptoms of exposure
include eye and respiratory irritation, headache, and
gastrointestinal complaints, skin irritation, and difficulties with learning and memory [33.79].
Mortality
Ciguatera poisoning is rarely fatal. The overall death
rate from ciguatera poisoning is approximately 0:1%,
but varies according to the toxin dose and availability
of medical care to deal with complications. Death from
CFP is rare (< 1% worldwide).