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FOOD 525 > Seafood Toxins > Flashcards

Seafood Toxins Flashcards

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1
Q

Compare seafood allergies with seafood poisoning.

A
  • Allergies: including fish, shrimp, lobster, crab, mussels, and clams - represent frequent causes
  • Poisoning: reactions to natural toxins are not infrequent; also described in the medical literature and general press
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2
Q

Describe the origin of marine toxins.

A
  • Animals produce toxins as an offense, or a defense system (e.g., capturing and digesting prey or protection against predators)
  • Toxins may be a by-product, or product of animal metabolism, or a chemical that is passed along the food chain (bio-magnification), eventually coming to humans

Problematic and hard to predit; necessitates consistent monitoring.

bioaccumulation a.k.a. biomagnification

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3
Q

What is scomboid poisoning?

A

Histamine release

All these fish convert histamine from histidine in their muscle tissue. Some of these fish eat the others, so bioaccumulation occurs. Smaller fish are safer for that reason.
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4
Q

Describe the scheme to determine risk to marine toxin exposure.

A
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5
Q

Name the toxin.

PSP-Paralytic shellfish poisoning

The toxicity

A

Saxitoxin

Worldwide occurence - most common example of a seafood toxin.

The toxin - many metabolites and isomers of saxitoxin that also exist, but have different toxicity levels.

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6
Q

Name the toxin.

DSP-Diarrheic shellfish poisoning

The toxicity

A

Okadaic acid dinophysis toxin

Worldwide occurrance

The toxin

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7
Q

Name the toxin.

NSP- Neurotoxic shellfish poisoning

The toxicity

A

Brevetoxins

Occurrance: USA, Caribbean, New Zealand

The toxins

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8
Q

Name the toxin.

ASP- Amnesic shellfish poisoning

The toxicity

A

Domoic acid

Occurrance: North America

The toxin

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9
Q

Name the toxin.

Ciguatera fish poisoning

The toxicity

A

Ciguatoxin (CTX)

Tropical & subtropical occurrance

The toxin

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10
Q

Name the toxin.

Puffer fish poisoning

The toxicity

A

Tetrodotoxin (TTX)

Occurrance: Japan, South Pacific

The toxin

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11
Q

Name the toxicity.

Saxitoxin

Worldwide occurence

The toxin

A

PSP-Paralytic shellfish poisoning

The toxicity

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12
Q

Name the toxicity.

Okadaic acid dinophysis toxin

Worldwide occurrance

The toxin

A

DSP-Diarrheic shellfish poisoning

The toxicity

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13
Q

Name the toxicity.

Brevetoxins

Occurrance: USA, Caribbean, New Zealand

The toxins

A

NSP- Neurotoxic shellfish poisoning

The toxicity

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14
Q

Name the toxicity.

Domoic acid

Occurrance: North America

The toxin

A

ASP- Amnesic shellfish poisoning

The toxicity

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15
Q

Name the toxicity.

Ciguatoxin (CTX)

Tropical & subtropical occurrance

The toxin

A

Ciguatera fish poisoning

e.g., barracuda

The toxicity

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16
Q

Name the toxicity.

Tetrodotoxin (TTX)

Occurrance: Japan, South Pacific

The toxin

A

Puffer fish (tetrodotoxin) poisoning

The toxicity

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17
Q

Paralytic shellfish toxin

A

Saxitoxin

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18
Q

Amnesic shellfish toxin

A

Domoic acid

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19
Q

Puffer fish toxin

A

Tetrodotoxin

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20
Q

Ciguatera toxin

A

Ciguatoxin

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21
Q

Saxitoxin

A

Paralytic shellfish toxin

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22
Q

Domoic acid

A

Amnesic shellfish toxin

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23
Q

Tetrodotoxin

A

Puffer fish toxin

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24
Q

Ciguatoxin

A

Ciguatera toxin

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25
Q

For paralytic shellfish poisoning, name:

  • Region
  • Seafood source
  • Symptoms
  • Toxin
A
  • Region: Worldwide
  • Seafood source: Bivalves
  • Symptoms: Tingling/numbness; respiratory paralysis
  • Toxin: Saxitoxin
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26
Q

For neurotoxic shellfish poisoning, name:

  • Region
  • Seafood source
  • Symptoms
  • Toxin
A
  • Region: Gulf of Mexico; Florida; Atlantic; Greece; Japan; New Zealand
  • Seafood source: Bivalves; Oysters; Clams; Mussels
  • Symptoms: Paraesthesia; reversal of hot and cold sensation; uncoordinated movements
  • Toxin: Brevetoxins
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27
Q

For amnesic shellfish poisoning, name:

  • Region
  • Seafood source
  • Symptoms
  • Toxin
A
  • Region: East Coast Canada; West Coast USA
  • Seafood source: Razer clams; crabs
  • Symptoms: Abdominal cramps; vomiting; disorientation; seizures; memory loss
  • Toxin: Domoic acid
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28
Q

Paralytic shellfish toxins (e.g., saxitoxin, neosaxitoxin, gonyautoxin) are produced by: [3]

A
  • Dinoflagellate algae
  • Aquatic cyanobacteria
  • Eubacteria

Paralytic shellfish toxins can accumulate in marine organisms such as clams, mussels, oysters, scallops, and others that feed on the algae

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29
Q

What is the toxicity and regulatory tolerance of paralytic shellfish toxins?

A
Method of analysis: mouse bioassay
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30
Q

What is red tide?

A
  • Toxin-producing algal cells have a red pigmentation and the bloom event is known as ‘red tide’
Not all red tides are this severe and often cannot be visually identified.

Paralytic shellfish poisoning and saxitoxins.

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31
Q

Describe the distribution of toxin gonyaulacoid species.

A
The letters denote different dinoflagellates species that produce toxins.
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32
Q

Describe the structure of the principle toxin in paralytic shellfish poisoning.

A

Saxitoxin: hydroxy & sulfate derivatives on a tetrahydroxypuridine structure

Group of non-protein neurotoxins. The amino groups (circled) are responsible for associating with sodium-channels and blocking them, which can eventually lead to respiratory failure and death.

Minimal fluorescence and too small to measure on its own.

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33
Q

Describe the rate of accumulation and loss in shellfish contaminated with saxitoxin.

Paralytic shellfish poisoning

A
  • Depends on marine species
    • Mussels - lose toxicity within weeks
    • Clams - lose toxicity in 2 years
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34
Q

Which paralytic shellfish toxin is the most toxic?

A
  • Non-protein neurotoxins
  • Saxitoxin is the most toxic - 0.5-1.0 mg is fatal
Saxitoxin may be present in shellfish as different (less toxic) isoforms. Therefore, it is important to be able to measure the full spectrum of saxitoxins and its isomers. PSP can be quantified using HPLC.
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35
Q

Paralytic shellfish toxins are heat stable, so cooking or steaming of shellfish will not destroy toxin.

True or False?

A

True.

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36
Q

Paralytic shellfish toxins are heat labile, so cooking or steaming of shellfish will destroy the toxin.

True or False?

A

False.
These toxins are heat stable!

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37
Q

In paralytic shellfish poisoning, diagnosis is based on:

A

Patient history and symptoms

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38
Q

In paralytic shellfish poisoning, what is linked to improved survival rates?

A
  • Early airway management
  • Adherence to public health guidelines on harvesting, processing, and consumption of shellfish

Activated charcoal has been used to filter water (charcoal is ionic so the toxin will bind it and be unavailable), but it did not work very well in practice to reduce risk of shellfish poisoning.

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39
Q

What are the clinical symptoms of paralytic shellfish poisoning? [7]

A
  • Symptoms develop within 30 minutes to 2 hours after ingestion
  • Mortality range is 3 - 24%
  • Paresthesia of the mouth, lips, face, and overall
  • Numbness
  • Nausea, vomiting, and diarrhea
  • Muscular paralysis
  • Respiratory failure that can lead to death
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40
Q

List the available bioassays for paralytic shellfish poisoning.

A
  • Mouse lethality test - official method of measuring shellfish toxicity
  • Chemical-fluorometric
  • Electrophoresis
  • Toxin analyser
  • HPLC
  • Radioimmunoassay
  • ELISA-Biomarkers

Aside from the mouse assay these tests are all chemically based and are limited. (e.g., electrophoresis cannot detect non-protein toxins). None of these methods indicate anything about lethality, which is why the mouse lethality test is still used today.

41
Q

Describe the official method of measuring shellfish toxicity.

A
  • Mouse bioassay gives meaningful lethality information
  • Measures total toxicity of shellfish sample
    • Swiss, male, 18-22 g mice, 10-12 mice/sample
    • Intraperitoneal injection of crude acid homogenate
    • Measures survival time (min) to give mouse units
A downside of this assay is variations within the mice.

Mouse unit = amount of poison that will kill 20 gram mouse in 15 minutes with symptoms of paralysis or respiratory failure.

42
Q

Human paralytic shellfish poisoning is reported at […]

A

600 MU/100 g shellfish

43
Q

Shellfish quarantines are in place with […]

A

400 MU/ 100 g shellfish

44
Q

In MU, human death of paralytic shellfish poisoning can occur at […]

A

3000 MU/ 100 g shellfish

45
Q

Calculate the paralytic shellfish toxicity, given:

  • Reference saxitoxin standard = 5500 MU/mg (1 MU = 0.18 ug STX)
  • Shellfish sample = 100 g in 200 mL
  • Average mouse weight = 24.97 g
  • Death time = 4.27 minutes
A
  • Average mouse weight = 24.97 g = 1.11 MU
  • Death time = 4.27 minutes = 2.32 MU
  • Corrected MU = 1.11 x 2.32 = 2.58
  • Toxicity = 2.58x 0.18ugSTX poison equiv.
    = 0.4644 ug PSP x df(200)
    = 92.7 ug PSP/100 g meat

This amount is considered unfit for human consumption because the limit is 80 ug PSP / 100 g tissue.

46
Q

Calculate the paralytic shellfish toxicity, given:

  • Reference saxitoxin standard = 5500 MU/mg (1 MU = 0.18 ug STX)
  • Shellfish sample = 100 g in 200 mL
  • Average mouse weight = 24.30 g
  • Death time = 1.82 minutes
A
  • Average mouse weight = 24.30 g = 1.10 MU
  • Death time = 1.82 minutes = 9.50 MU
  • Corrected MU = 1.10 x 9.50 = 10.45 MU
  • Toxicity = 10.45 x 0.18 ug STX poison equiv.
    = 1.88 ug PSP x df(200)
    = 376.2 ug PSP/100 g meat

This amount is considered unfit for human consumption because the limit is 80 ug PSP / 100 g tissue. This amount is far above the safe human consumption limit and would result in beach closures.

47
Q

What factors influence the accuracy of the mouse assay? [5]

A
  • Gender of the mouse
  • Body weight must be within 20-22 g
  • Not reliable estimates when of the shellfish extract pH > 4 (this is because the toxin is more likely to be in free form when in acid conditions and is more likely to associate with proteins or other compounds at higher pH)
  • Not reliable estimates when sodium ions are present above 0.1 M
  • Storage of samples for more than 4 weeks at pH 6 can decrease toxicity by half
48
Q

Describe the HPLC results of shellfish toxins in different shellfish species.

A
  • Whatever the dinoflagellate produces the shellfish will store.
  • Challenge: quantify toxicity of shellfish unless you do the mouse bioassay
  • Mouse bioassay does not tell you about isomers present
Typically HPLC will be used to identify which isomers are there, and then follow up with mouse bioassay if there are indications of high levels.
49
Q

Describe the relationship between HPLC toxicity and the mouse bioassay.

A
The mouse assay and HPLC do correlate!

Current methods include mass spectrometry that can detect even smaller quantities.

50
Q

Describe the correlation between ELISA and mouse bioassay results.

A

Too specific and doesn’t give enough information, and do not correlate to mouse assay results, which is why HPLC is used and other methods like ELISA are not.

S = saxitoxin; N = neosaxitoxin
51
Q

What is the toxicity and regulatory tolerance of tetrodotoxin?

Puffer fish poisoning
A
Method of analysis: mouse bioassay
52
Q

Tetrodotoxin is found in […]

A
  • About 90 species of puffer fish, which include: blowfish, porcupine fish, toadfish, fugu, and molas.

The fish is considered a delicacy, but its consumption can result in a tingling sensation.

53
Q

Tetrodotoxin is the product of […]

A
  • Certain bacteria such as Pseudoalteromonas tetraodonis and certain species of Pseudomonas and Vibrio
  • The toxin is produced by bacteria within blue-ringed octopi, and it is believed that pufferfish acquire the toxin through their diet
A neurotoxin; MW = 319; like saxitoxin, binds to sodium-channels, effectively blocking them.
54
Q

Describe the puffer fish poisoning toxin.

A
  • Tetrodotoxin
    • Water soluble
    • Heterocyclic guanidine
    • Similar, but more intense action compared to saxitoxin
55
Q

Tetrodotoxin is stable to boiling temperatures unless […]

A

Made alkaline

56
Q

Tetrodotoxin is heat labile, so cooking puffer fish before consumption will destroy the toxin.
True or False?

A

False.
Tetrodotoxin is stable to boiling temperatures unless made alakaline.

57
Q

Tetrodotoxin is heat stable, so cooking puffer fish before consumption will not destroy the toxin.
True or False?

A

True.
Tetrodotoxin is stable to boiling temperatures, unless made alkaline.

58
Q

When are pufferfish most toxic?

A
  • Reproductive cycle of the fish has influence on toxicity; peak occurs around spawning season
  • Its major concentration is found in the liver, then ovaries, intestine, and skin

Proper preparation is required to avoid poisoning

59
Q

What is the mechanism of action of tetrodotoxin?

A
  • Tetrodotoxin has effects both on action potential generation and impulse conduction.
  • The toxin blocks the fast Na+ current in human myocytes (the contractile cells of the muscles), thereby inhibiting their contraction.
  • The poisoned individual therefore dies not because the electrical activity of the heart is compromised, but because the muscles are effectively paralyzed.
60
Q

Describe the clinical symptoms of tetrodotoxin poisoning.

A
  • Symptoms appear usually in 10 to 45 min after ingestion.
  • For toxic fish, 10 g is fatal.
  • Initial tingling sensation can be followed by malaise, dizziness, numbness of extremities, lips and tongue, subcutaneous hemorrhage, respiratory distress, incoordination, muscle paralysis, cyanosis, convulsions, and death (40-60%).
  • Prognosis is good if patient survives 24 hr.
61
Q

What is the toxicity and regulatory tolerance for domoic acid?

Amnesic shellfish poisoning

A
Method of analysis: HPLC

Mouse assay is not necessary to detect domoic acid as there is only one isoform and it is easy to quantify.

62
Q

What is the active agent in amnesic shellfish poisoning?

A

Domoic acid, a neuroexcitatory amino acid

Domoic acid is a heat stable neurotoxin related to neurotransmitter glutamate. Its binding affinity for the kainate type of glutamate receptor is 3X that of kainic acid. This causes neural hyperexcitation that can cause seizures.

63
Q

What are sources of amnesic shellfish poisoning? [2]

A

Razor clams and crab

64
Q

What are the symptoms of amnesic shellfish poisoning?

A
  • Headache, short term memory loss.
  • Onset from ingestion 15min to 38 hrs. (medium= 5.5 h)
  • Older age male gender, and quantity of mussels consumed important factors
  • Domoic acid is heat stable neurotoxin related to neurotransmitter glutamate. Its binding affinity for the kainate type of glutamate receptor is 3X that of kainic acid.
    • Neural hyperexitation leading to seizures.
65
Q

Discuss the different isomers of domoic acid.

A
66
Q

Discuss the correlation between ELISA and HPLC analysis for domoic acid.

Amnesic shellfish poisoning

A

ELISA is possible for domoic acid detection but it is not used because it has not gained regulatory approval.

ELISA correlates with HPLC results in the case of domoic acid.

Much easier to quantify ASP compared to PSP because PSP has many isomers.

67
Q

Compare the reported symptoms of paralytic shellfish poisoning and amnesic shellfish poisoning.

A

PSP: Tingling, prickling sensation of lips and mouth (5-30 min); numbness spreads from mouth to arms, legs and neck; ataxia, loss of coordination; impaired speech; impaired respiration; coma; death

ASP: Nausea, cramps, diarrhea; headache; seizures; memory loss; coma; death

68
Q

What is the cause of ciguatera poisoning?

A
  • Caused by eating fish contaminated with ciguatoxin
  • Ciguatoxin is produced by a dinoflagellate (below)
69
Q

What are the fish sources of ciguatoxin?

A
  • Reef fish (from warm tropical water
    • E.g., barracuda; amberjack; mackerel; red snapper; moray eel; parrotfish; grouper
70
Q

Describe ciguatoxin.

A
  • A neurotoxin
  • Very heat-resistant
  • Mainly found in the liver then head, gonads, and viscera of the contaminated fish.
  • Two types: Pacific and Caribbean
    • Pacific is 10X more toxic than Caribbean
Large molecular weight toxins will be metabolized by phase 1 and 2 enzymes and produce free radicals.
71
Q

Pacific ciguatoxin-1 is 10x more toxic than Caribbean ciguatoxin-1.
True or False?

A

True.

72
Q

Caribbean ciguatoxin-1 is 10x more toxic than Pacific ciguatoxin-1.
True or False?

A

False.
Pacific ciguatoxin-1 is 10x more toxic than Caribbean ciguatoxin-1.

73
Q

Describe the mechanism of action of ciguatoxin.

A
  • It binds receptor sites on the Na+ channels
  • Activates voltage-sensitive Na+ channels at nanomolar and picomolar concentrations
  • This results in hyper-excitability (enhanced activation and firing), decreased conduction, and prolonged refractory periods.
74
Q

Describe the clinical symptoms of ciguatoxin poisoning.

A
  • Onset of symptoms is highly variable
  • Symptoms can appear from 1 to 48 hrs after ingestion.
  • Characterized by moderate to severe:
    • Gastrointestinal symptoms (vomiting, diarrhea)
    • Neurological signs (myalgia, paraesthesia, ataxia)
    • Itching, mood disorders, bradycardia.
75
Q

Describe the toxicity and regulatory tolerance of neurotoxic shellfish poisoning.

A
Method of analysis: mouse assay
76
Q

The distribution of NSP is more restricted than PSP.
True or False?

A

True.

77
Q

The distribution of PSP is more restricted than NSP.
True or False?

A

False.
The distribution of NSP is more restricted than PSP.

78
Q

What causes neurotoxic shellfish poisoning?

A
  • Caused by the marine dinoflagellate Gymnodinium Brevis that filter feeding fish eat
79
Q

Describe brevetoxin.

Neurotoxic shellfish poisoning

A
  • Lipid soluble polyether toxin
  • Neuroexcitatory effects
80
Q

Using brevetoxin as an example, describe Phase I and Phase II reactions.

A
  • Shellfish toxins can be converted to oxidized products that damage tissues, which can be more damaging in the long run than the acute symptoms of seafood illness.
  • This occurs when there is an imbalance between phase 1 and 2 enzymes.
81
Q

What are 4 main categories for future research regarding marine sea food toxins?

A
  • Surveillance activities
  • Human toxicology and epidemiology
  • Outreach and education
  • Establish preventive measures to reduce incidence of seafood poisoning
82
Q

How can surveillance activities be improved? [4]

A
  • Further development/ evaluation into new ELISA- MSFT detection methods as potential replacement of the mouse bioassay for screening.
  • Increase and improve public health disease surveillance of marine toxins for better estimates of disease incidence.
  • Provide timely alerts to public health epidemiologists during an outbreak to improve detection of shellfish associated illness.
  • Improve surveillance; obtain better estimates of national incidence of MSFT-related illness and to develop appropriate prevention strategies.
83
Q

How can human toxicology and epidemiology improve our understanding of marine seafood toxins?

A
  • Improve understanding of MSFT (and metabolites) toxicity:
    • minimal doses for adverse effects,
    • dose response curves, with emphasis on human exposures.
  • Evaluate efficacy of antidote (e.g., mannitol or brevenal for treatment of NSP).
  • Follow confirmed MSFT cases over a longer period of time to determine whether there are long term adverse effects or chronic sequela to exposures.
84
Q

Describe outreach and education for reduction of marine seafood toxin poisoning.

A
  • Develop easily available user friendly websites/apps and related materials for the general public including transient populations like tourists and part time residents.
  • Improve the dissemination of information on shellfish harvesting beds and regulations including harvesting openings and closings
85
Q

What general preventive measures can be used to reduce the incidence of seafood poisoning?

A
  • Avoid/ be careful of eating raw seafood
  • Do not partially cook (e.g. steam for 1 min to just open shell) mollusks.
  • Adhere to state, local or federal guidelines regarding safe locations to harvest shellfish
  • Avoid eating unusually implicated species of ciguatera poisoning (e.g. barracuda)
  • Prompt reporting of suspected outbreaks of seafood poisoning to local health departments.
  • Produce targeted educational campaign on signs, symptoms and diagnosis of NSP for first responders, emergency department physicians, and other healthcare providers, particularly in high-risk areas.
86
Q

Tetrodotoxin is water soluble.
True or False?

A

True.

87
Q

Tetrodotoxin is lipid soluble.
True or False?

A

False.
It is water soluble.

88
Q

Domoic acid is water soluble.
True or False?

A

True.

89
Q

Domoic acid is lipid soluble.
True or False?

A

False.
It is water soluble.

90
Q

Saxitoxin is lipid soluble.
True or False?

A

False.
It is water soluble.

91
Q

Saxitoxin is water soluble.
True or False?

A

True.

92
Q

Brevetoxins are lipid soluble.
True or False?

A

True.

93
Q

Brevetoxins are water soluble.
True or False?

A

False.
They are lipid soluble polyether neurotoxins.

94
Q

Ciguatoxin is water soluble.
True or False?

A

False.
It is lipid soluble.

95
Q

Ciguatoxin is lipid soluble.
True or False?

A

True.

96
Q

Why is the mouse assay not necessary for detection of domoic acid?

A

Mouse assay is not necessary to detect domoic acid as there is only one toxic isoform and it is easy to quantify via HPLC.

97
Q

What is the seafood source of saxitoxin? [1]

A

Bivalves

98
Q

What are the seafood sources of brevetoxin? [4]

A

Bivalves
Oysters
Clams
Mussels

99
Q

Compare the action of the seafood toxins.

A

Tetrodotoxin and saxitoxin block sodium channels, while ciguatoxin and brevetoxin opens them.

Domoic acid stimulates excitatory amino acids at the NMDA receptors (greater binding affinity than kainic acid)

FOOD 525 (10 decks)

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