Contact Us    Contact Us     |     Feedback
MOBILE VIEW  | 

DIARRHEIC SHELLFISH POISONING

Export To Excel

Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Diarrheic shellfish poisoning occurs following the consumption of shellfish that have been feeding on marine phytoplankton that contain the diarrheic toxins.
    B) The marine dinoflagellates of the Dinophysis and Prorocentrum genera are the primary sources of the polyether toxins (ie, okadaic acid and the dinophysis toxins (DTXs 1-4).

Specific Substances

    A) SYNONYMS ASSOCIATED WITH ILLNESS
    1) DSP
    2) Diarrheic shellfish toxins
    3) DST
    4) Shellfish poisoning, Diarrheic
    5) Shellfish, Diarrheic Poisoning
    DINOFLAGELLATES ASSOCIATED WITH DIARRHEIC SHELLFISH POISONING.
    1) Dinophysis acuta
    2) Dinophysis acuminata
    3) Dinophysis caudata
    4) Dinophysis fortii
    5) Dinophysis hastate
    6) Dinophysis mitra
    7) Dinophysis norvegica
    8) Dinophysis rotundata
    9) Dinophysis tripos
    10) Prorocentrum belizeanum
    11) Prorocentrum concavum
    12) Prorocentrum hoffmianum
    13) Prorocentrum lima
    14) Prorocentrum maculosum
    15) Prorocentrum redfieldi
    BIOTOXINS-ASSOCIATED WITH DIARRHEIC SHELLFISH OUTBREAKS
    1) Okadaic acid (OA)
    2) Okadaic acid group
    3) Dinophysistoxins
    4) DTXs
    5) Dinophysistoxin-1
    6) Dinophysistoxin-2
    7) Dinophysistoxin-3
    8) Dinophysistoxin-4
    9) DTX-1
    10) DTX-2
    11) DTX-3
    12) DTX-4
    13) Pectenotoxins
    14) Pectenotoxin group
    15) PTXs
    16) Yessotoxin
    17) YTXs

Available Forms Sources

    A) FORMS
    1) TOXINS PRODUCING ILLNESS
    a) TOXIN TYPE: In European outbreaks the primary toxin has been okadaic acid (OA) (Kumagai et al, 1986; Vernoux et al, 1994). In Ireland, however, the dinophysistoxin-2, an isomer of OA, was found most often during diarrhetic shellfish poisoning (DSP)(Carmody et al, 1996). In Asia, Japanese outbreaks have been dominated by dinophysistoxin-1 and -3 toxins (Ragelis, 1986).
    B) SOURCES
    1) Various shellfish, such as the blue mussel (Mytilus edulis) are known to contain the toxin. Edebo et al (1988) tested various portions of the prepared mussel for activity and found that in contaminated mussels the hepatopancreas and the liquid used for steaming the mussel had the greatest activity. Other body parts had minimal or no activity (Edebo et al, 1988).
    2) By using fractionation and isolation methods prepared from Dinophysis-contaminated mussels, it was observed that the digestive gland had the highest toxin concentration of okadaic acid with minute amounts of toxin observed in the remaining meat (Vernoux et al, 1994). Toxin concentration remained high in the digestive gland in both raw and cooked samples.
    3) Diarrheic shellfish toxins may be found in fish as well. In one experiment DTX-1 and okadaic acid (OA) contaminated mussels were fed to cod. The fish accumulated OA, but not DTX-1 (Edebo et al, 1992).
    4) In the summer of 2002, approximately 200 people became ill after eating brown crabs (Cancer pagurus) from shallow waters on the south coast of Norway. The symptoms were similar to diarrhetic shellfish poisoning, but less severe and had a delayed onset. In the same region, a toxin producing Dinophysis acuta appeared earlier than usual and okadaic acid (OA) and its derivative levels in blue mussels reached up to 4000 mcg/kg. Analysis of the crabs revealed very little free okadaic acid; however, after alkaline hydrolysis of the crab material, okadaic acid concentrations above the toxic level were obtained. It was suggested that the crabs became toxic from consumption of contaminated blue mussels, with accumulation of the fatty acid esters of okadaic acid in the crab flesh (Torgersen et al, 2005).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdcd.gov.
    b) ACUTE SYMPTOMS
    1) Symptoms may include: GI: Nausea, vomiting, diarrhea, and abdominal pain. OTHER: Chills, headache, and fever. Symptoms are usually mild and self limiting.
    c) CHRONIC SYMPTOMS
    1) Unknown. Animal data indicates that Okadaic acid an Dinophysistoxin 1 are potential tumor promoters.
    d) FATALITY RATE
    1) No deaths have been reported.
    e) TIME TO ONSET OF SYMPTOMS
    1) Less than 24 hours (typically 30 minutes to 12 hours)
    f) DURATION
    1) Recovery is usually complete within 72 hours
    g) CAUSATIVE ORGANISM
    1) Dinoflagellates: Dinophysis spp. (including D. acuta, D. fortii, D. acuminate, D. norvegica, D. mitrao, D. caudata) and Prorocentrum spp.
    h) TOXINS
    1) Okadaic acid (OA)
    2) Dinophysistoxin (DTXs) - at least 6 congeners have been identified
    3) Pectenotoxin group (PTX) - a polyether lactone that is lipid soluble; at least 10 congeners have been identified.
    i) ROUTE OF EXPOSURE
    1) Eating contaminated shellfish
    j) VECTOR
    1) Contaminated bivalve shellfish including scallops, mussels, clams, and oysters
    k) MECHANISM
    1) Phosphorylase phosphatase inhibitor
    2) PTX group target liver and intestines
    3) Possible tumor promoters, carcinogen or cytotoxic
    l) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Essentially worldwide, especially Europe and Japan
    m) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisonings (e.g. azaspiracid, neurotoxic and paralytic shellfish poisoning), ciguatera fish poisoning, pesticide poisoning, cholinesterase inhibitor poisoning, microbial food poisonings and food allergies may present with similar symptoms.
    n) DIAGNOSIS
    1) Clinical presentation. Shellfish tissue analysis using ELISA, mouse bioassay or HPLC. Tests kits are commercially available.
    o) SUSPECT CASE
    1) History of consuming shellfish and diarrhea (possibly other GI symptoms) occurring within 24 hours of exposure.
    p) CONFIRMED CASE
    1) Suspect case and laboratory confirmation of toxin in meal remnants.
    q) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)

Laboratory Monitoring

    A) If fluid loss is extensive, monitor fluid and electrolyte status.
    B) Both biologic and HPLC tests are available for measuring these toxins, but are generally not done on patient samples. Confirmatory tests are done on the mussels eaten.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Treatment is symptomatic and supportive. Onset of symptoms and the degree of illness are based on the amount of toxin ingested and can vary from 30 minutes to 2 to 3 hours. Symptoms usually resolve within 3 to 4 days. There is no specific antidote.
    B) Decontamination is not likely to be useful; patients generally do not present for medical care until after the onset of symptoms
    C) Monitor fluid and electrolyte status. Initiate oral or intravenous hydration and administer antiemetics as necessary.

Range Of Toxicity

    A) TOXICITY: Only small amounts of the toxin are needed to cause symptoms. The concentration per shellfish is not constant, so the number of shellfish required to produce symptoms will vary depending on the concentration. Illness has been reported after consuming 10 mussels (approximately 2 g) containing 20 to 30 micrograms of okadaic acid/100 g shellfish.

Clinical Effects

Summary Of Exposure

    A) WITH POISONING/EXPOSURE
    1) CDC CASE DEFINITIONS
    a) BACKGROUND
    1) Harmful algal blooms are fast growing algae that are found worldwide, which can have a negative impact on the environment, as well as the health and safety of humans and animals. As part of the ongoing efforts by the Centers for Disease Control and Prevention (CDC), the Harmful Algal Bloom-related Illness Surveillance System (HABISS) collects data on the effects to human and animal health due to the potential environmental impact of HABs. It has developed case definitions for harmful algal bloom (HABs) toxin-related diseases as part of their national surveillance efforts to support public health decision-making. The following has been created to identify pertinent information related to a potential exposure to HABs. For further information regarding the reporting of suspected human illness due to HABs, please contact: Lorraine C. Backer, PhD, MPH, Senior Scientist and Team Lead, National Center for Environmental Health, CDC, Atlanta, GA at lfb9@cdc.gov or Rebecca LePrell, MPH, HABISS Coordinator, National Center for Environmental Health, CDC, at gla7@cdcd.gov.
    b) ACUTE SYMPTOMS
    1) Symptoms may include: GI: Nausea, vomiting, diarrhea, and abdominal pain. OTHER: Chills, headache, and fever. Symptoms are usually mild and self limiting.
    c) CHRONIC SYMPTOMS
    1) Unknown. Animal data indicates that Okadaic acid an Dinophysistoxin 1 are potential tumor promoters.
    d) FATALITY RATE
    1) No deaths have been reported.
    e) TIME TO ONSET OF SYMPTOMS
    1) Less than 24 hours (typically 30 minutes to 12 hours)
    f) DURATION
    1) Recovery is usually complete within 72 hours
    g) CAUSATIVE ORGANISM
    1) Dinoflagellates: Dinophysis spp. (including D. acuta, D. fortii, D. acuminate, D. norvegica, D. mitrao, D. caudata) and Prorocentrum spp.
    h) TOXINS
    1) Okadaic acid (OA)
    2) Dinophysistoxin (DTXs) - at least 6 congeners have been identified
    3) Pectenotoxin group (PTX) - a polyether lactone that is lipid soluble; at least 10 congeners have been identified.
    i) ROUTE OF EXPOSURE
    1) Eating contaminated shellfish
    j) VECTOR
    1) Contaminated bivalve shellfish including scallops, mussels, clams, and oysters
    k) MECHANISM
    1) Phosphorylase phosphatase inhibitor
    2) PTX group target liver and intestines
    3) Possible tumor promoters, carcinogen or cytotoxic
    l) LIKELY GEOGRAPHIC DISTRIBUTION
    1) Essentially worldwide, especially Europe and Japan
    m) DIFFERENTIAL DIAGNOSIS
    1) Other marine toxin poisonings (e.g. azaspiracid, neurotoxic and paralytic shellfish poisoning), ciguatera fish poisoning, pesticide poisoning, cholinesterase inhibitor poisoning, microbial food poisonings and food allergies may present with similar symptoms.
    n) DIAGNOSIS
    1) Clinical presentation. Shellfish tissue analysis using ELISA, mouse bioassay or HPLC. Tests kits are commercially available.
    o) SUSPECT CASE
    1) History of consuming shellfish and diarrhea (possibly other GI symptoms) occurring within 24 hours of exposure.
    p) CONFIRMED CASE
    1) Suspect case and laboratory confirmation of toxin in meal remnants.
    q) REFERENCE
    1) (HABISS Work-Group et al, Jan 12, 2009)

Vital Signs

    3.3.3) TEMPERATURE
    A) Chills and fever have been observed in some patients (DeSchrijver et al, 2002).
    B) INCIDENCE - Chills are experienced by about 10% of individuals with DSP (Edebo et al, 1988).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache may occur with DSP exposure (DeSchrijver et al, 2002).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) Nausea, vomiting, abdominal pain, and diarrhea can occur. Onset of symptoms can vary from 30 minutes to 2 to 3 hours; complete recovery generally occurs within 72 hours (DeSchrijver et al, 2002).
    B) DIARRHEA
    1) Diarrhea is the cardinal symptom following exposure to these toxins (Scoging & Bahl, 1998).
    2) INCIDENCE - Approximately 92% of patients with DSP experience diarrhea (Edebo et al, 1988).
    C) ABDOMINAL PAIN
    1) ABDOMINAL PAIN - is relatively common symptoms of DSP (Scoging & Bahl, 1998).
    2) INCIDENCE - About 53% of patients with DSP experience abdominal pain (Edebo et al, 1988).
    D) NAUSEA
    1) Nausea is a frequent symptom of DSP (Scoging & Bahl, 1998).
    2) INCIDENCE - About 80% of patients with DSP experience nausea (Edebo et al, 1988).
    E) VOMITING
    1) Vomiting is a frequent symptom of DSP (Scoging & Bahl, 1998).
    2) INCIDENCE - About 79% of patients with DSP experience vomiting (Edebo et al, 1988).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) GASTROINTESTINAL DISORDER
    a) When either okadaic acid, dinophysistoxin-1 or dinophysistoxin-3 were fed to MICE, excessive fluid accumulation was found in the intestine (Ragelis, 1986). The effect was similar to that seen with cholera toxin, the E. coli enterotoxins LT and ST, or the enterotoxin from Clostridium difficile.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) If fluid loss is extensive, monitor fluid and electrolyte status.
    B) Both biologic and HPLC tests are available for measuring these toxins, but are generally not done on patient samples. Confirmatory tests are done on the mussels eaten.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) If fluid loss is extensive due to vomiting and diarrhea, monitor fluid and electrolyte status.

Methods

    A) BIOASSAY
    1) RATS - Rats are fed the hepatopancreas of mussels in their normal food. They are then observed for the amount of food eaten and feces consistency (Kat, 1983a).
    2) MICE - Homogenized hepatopancreas is extracted with acetone and ether. The extract is injected intraperitoneally into adult mice to determine an LD5O or given to infant mice in a test similar to E. coli enterotoxin testing (Hamano et al, 1986; Ragelis, 1986; Dean et al, 1972).
    B) HPLC/LC-MS
    1) HPLC and liquid chromatography-mass spectrometry have been used to identify the specific toxin(s) associated with shellfish poisoning (DeSchrijver et al, 2002). The biotoxins okadaic acid and dinophysistoxin-1 have been identify following several outbreaks of shellfish contamination (Luckas, 1992; Marr et al, 1992; Lee et al, 1987; Kat, 1983).
    2) Due to decomposition of reagents and impurities in samples, poor results may be obtained using the HPLC method. Stabell et al (1991) and Gonzalez et al (1998), however, have developed cleaning processes that improve the resolution of HPLC (Gonzalez et al, 1998; Stabell et al, 1991).
    C) ELISA
    1) In Mutsu Bay, Japan, ELISA (specific enzyme-linked immunosorbent assay) was used to analyze diarrheic shellfish poisoning in small-sized plankton fraction using a mouse monoclonal anti-okadaic acid antibody which can recognize okadaic acid, dinophysistoxin-1 and dinophysistoxin-3. It was proposed that ELISA monitoring could detect diarrheic shellfish toxins up to two weeks before contamination was found in scallops. It was further suggested that monitoring of plankton toxicity, in particular small-sized fraction which are possible foods of mixotrophic Dinophysis, can be used as a tool for detecting and predicting DSPs in coastal waterways with bivalve aquaculture (Imai et al, 2003).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Hospitalization is usually not required. Symptoms can generally be managed at home. Intravenous fluids and/or electrolyte replacement may be needed in severe cases (Sobel & Painter, 2005).

Monitoring

    A) If fluid loss is extensive, monitor fluid and electrolyte status.
    B) Both biologic and HPLC tests are available for measuring these toxins, but are generally not done on patient samples. Confirmatory tests are done on the mussels eaten.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) Decontamination is not likely to be useful; patients generally do not present for medical care until after the onset of symptoms.
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Decontamination is not likely to be useful; patients generally do not present for medical care until after the onset of symptoms
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive. Onset of symptoms and the degree of illness are based on the amount of toxin ingested and can vary from 30 minutes to 2 to 3 hours. Symptoms usually resolve within 3 to 4 days. There is no specific antidote.
    2) Fluid and electrolyte replacement (oral or intravenous) may be necessary if gastrointestinal loss is significant (eg, diarrhea, vomiting). Antiemetics may be useful.

Range Of Toxicity

Summary

    A) TOXICITY: Only small amounts of the toxin are needed to cause symptoms. The concentration per shellfish is not constant, so the number of shellfish required to produce symptoms will vary depending on the concentration. Illness has been reported after consuming 10 mussels (approximately 2 g) containing 20 to 30 micrograms of okadaic acid/100 g shellfish.

Maximum Tolerated Exposure

    A) SPECIFIC SUBSTANCE
    1) SHELLFISH
    a) Only small amounts of the toxin are needed. The concentration/shellfish is not constant, so the number of shellfish required to produce symptoms will vary, depending on the concentration.
    b) Mussels and scallops may become toxic to humans at concentrations of D. fortii of 200 cells/liter (Luckas, 1992).
    2) OKADAIC ACID
    a) The upper limit of okadaic acid/100 grams mussel meat is set at 60 micrograms by the Swedish Food Authority (1987) (Edebo et al, 1988a).
    b) CASE SERIES - In an outbreak of contaminated mussels in the United Kingdom, 49 individuals developed symptoms of diarrheic shellfish poisoning; okadaic acid concentrations were 25.3 and 36.7 micrograms/100 grams shellfish. The authors noted that concentrations of 40 micrograms (or more) for okadaic acid were previously thought to be required to produce diarrhea symptoms (Scoging & Bahl, 1998).
    c) CASE REPORTS - In another exposure in the UK, two patients became ill after consuming 10 mussels (approximately 200 g) containing 20 to 30 micrograms of okadaic acid per 100 g shellfish (Scoging & Bahl, 1998).
    d) DECONTAMINATION
    1) BOILING - Toxin concentration is NOT significantly reduced by boiling and/or cooking. It was observed that drying did reduce the amount of toxin found in the meat by as much as 30% (Vernoux et al, 1994).

Pharmacology Toxicology

Toxicologic Mechanism

    A) Diarrheic shellfish poisoning (DSP) is produced by the ingestion of shellfish contaminated with toxins from blooms of toxic algae. The toxins are produced by marine dinoflagellates that belong to Dinophysis species (ie, D. fortii, D. acuta, D. acuminata, D. caudate, D. hastate, D. mitra, D. rotundata, and D. tripos) and Prorocentrum species (P. lima, P. maculosum, P. concavum, and P. hoffmianum) (Economou et al, 2007; None Listed, 1997; Edebo et al, 1988; Luckas, 1992). In general, bivalve molluscs become toxic after ingesting these dinoflagellates. Humans can become ill after eating shellfish, because the algal toxins concentrate in the digestive glands of mussels and other filter feeding bivalve molluscs (None Listed, 1997).
    B) The toxins that produce DSP belong to a group of fat-soluble polyether compounds and include:
    1) OKADAIC ACID - a liphophilic toxin produced by dinoflagellates (DeSchrijver et al, 2002; Ragelis, 1986). In vivo bioassay results suggest that OA diol-ester is a lipid-soluble, uncharged molecule which can be hydrolyzed to OA (Windust et al, 1997). This process may aid in the transfer of OA across cell walls and membranes. Although further study is required, it is postulated that OA diol ester may be an effective transport of DSP toxins across cell membranes, which could be a significant factor in activation of the toxin.
    a) In humans, okadaic acid can cause acute gastroenteritis (ie, nausea, vomiting and diarrhea), because the toxin is a potent inhibitor of protein phosphatase 1, and likely stimulates phosphorylation that controls sodium secretion by intestinal cells (DeSchrijver et al, 2002; Economou et al, 2007; Torgersen et al, 2005; Scoging & Bahl, 1998). It has also been suggested that chronic exposure to okadaic acid can promote tumour formation in the digestive system (Economou et al, 2007).
    2) DINOPHYSISTOXINS (DTX) - Dinophysis toxins have been identified as DTXs (1 - 4) and are an analogue of okadaic acid which can be found in molluscs and phytoplankton. These biotoxins are detected mainly in phytoplankton belonging to the genus Dinophysis, and in bivalve molluscs that have been feeding on Dinophysis (Torgersen et al, 2005). The toxins are lipophilic and can accumulate in the fatty tissue of shellfish.
    3) PECTENOTOXINS (PTXs) - named after the scallop from which the toxin was extracted.
    4) YESSOTOXIN (YTXs) - has been identified in the digestive glands of scallops, but human toxicity has not been established (Luckas, 1992).
    C) In general, the highest levels of DSP toxins found in molluscs are as follows (Torgersen et al, 2005):
    1) Blue mussels (Mytilus edulis)
    2) Scallops
    3) Oysters
    4) Clams, cockles and crabs

Physicochemical

Physical Characteristics

    A) There is no characteristic taste while the toxin is in the mussel. A toxic mussel may not be differentiated from a non-toxic by taste.
    B) These DSP toxins are polyether agents which are stable to heat (Edebo et al, 1988a).

Molecular Weight

    A) Not applicable

References

General Bibliography

    1) Carmody EP, James KJ, & Kelly SS: Dinophysistoxin-2: The predominant diarrhoetic shellfish toxin in Ireland. Toxicon 1996; 34:351-359.
    2) DeSchrijver K, Maes I, DeMan L, et al: An outbreak of diarrhoeic shellfish poisoning in Antwerp, Belgium. Euro Surveill 2002; 7(10):138-141.
    3) Dean AG, Ching YC, & Williams RG: Test for Escherichia coli enterotoxin using infant mice: Application in a study of diarrhea in children in Honolulu. J Infect Dis 1972; 125:407-411.
    4) Economou V, Papadopoulou C, Brett M, et al: Diarrheic shellfish poisoning due to toxic mussel consumption: the first recorded outbreak in Greece. Food Addit.Contam. 2007; 24(3):297-305.
    5) Edebo L, Hovgaard P, & Hu Y: On the presence of diarrheic shellfish toxins in fish. Planta Med 1992; 58(Suppl 1):A583-A584.
    6) Edebo L, LI XP, & Allenmark S: Seasonal, geographic and individual variation of okadaic acid content in cultivated mussels in Sweden. APMIS 1988a; 96:1036-1042.
    7) Edebo L, Lange S, & Li XP: Toxic mussels and okadaic acid induce rapid hypersecretion in the rat small intestine. APMIS 1988; 96:1029-1035.
    8) Gago-Martinez A, Rodriguez-Vazquez JA, & Thibault P: Simultaneous occurrence of diarrhetic and paralytic shellfish poisoning toxins in Spanish mussels in 1993. Natural Toxins 1996; 4:72-79.
    9) Gonzalez JC, Vieytes MR, & Vieites JM: Improvement on sample clean-up for high-performance liquid chromatographic-fluorimetric determination of diarrhetic shellfish toxins using 1-bromoacetylpyrene. J Chromatograph 1998; 793:63-70.
    10) HABISS Work-Group & Backer, L: Harmful algal bloom-related illness surveillance system (HABISS) case definitions . Centers for Disease Control and Prevention, Health Studies Branch, National Center for Environmental Health , Jan 12, 2009.
    11) Hamano Y, Kinoshita Y, & Yasumoto T: Enteropathogenicity of diarrhetic shellfish toxins in intestinal models. Studies on diarrhetic shellfish toxins I. J Food Hyg Soc JPN 1986; 27:375-379.
    12) Heredia-Tapia A, Arredondo-Vega BO, Nunez-Vazquez EJ, et al: Isolation of Prorocentrum lima (Syn. Exuviaella lima) and diarrhetic shellfish poisoning (DSP) risk assessment in the Gulf of California, Mexico. Toxicon 2002; 40(8):1121-1127.
    13) Imai I, Sugioka H, Nishitani G, et al: Monitoring of DSP toxins in small-sized plankton fraction of seawater collected in Mutsu Bay, Japan, by ELISA method: relation with toxin contamination of scallop. Mar Pollut Bull 2003; 47(1-6):114-117.
    14) Kat M: Diarrhetic mussel poisoning in the Netherlands related to the dinoflagellate Dinophysis acuminata. Ant Van Leeuwenhoek 1983a; 49:417-427.
    15) Kat M: Diarrhetic mussel poisoning in the Netherlands related to the dinoflagellate Dinophysis acuminata. Antonie Van Leeuwenhoek 1983; 49(4-5):417-427.
    16) Krogh P, Edler L, & Graneli E: Outbreak of diarrheic shellfish poisoning on the west coast of Sweden. 3rd Internatl Congr on Toxic Dinoflagellates, St Andrews, New Bruswick, Canada, 1985, pp 501-503.
    17) Kumagai M, Yanagi T, & Murata M: Okadaic acid as the causative toxin of diarrhetic shellfish poisoning in Europe. Agric Biol Chem 1986; 50:2853-2857.
    18) Lee JS, Yanagi T, & Kenma R: Fluorometric determination of diarrhetic shellfish toxins by high pressure liquid chromatography. Agric Biol Chem 1987; 51:877-881.
    19) Luckas B: Phycotoxins in seafood - toxicological and chromatographic aspects. J Chromatogr 1992; 624:439-456.
    20) Marr JC, Hu T, & Pleasance S: Detection of new 7-O-acyl derivatives of diarrhetic shellfish poisoning toxins by liquid chromatography-mass spectrometry. Toxicon 1992; 30:1621-1630.
    21) None Listed: Algae Bloom Prompts DSHS to Close 3 Bays to Shellfish Harvesting, Issue Recall. Food and Drug Administration. Rockville, MD. 2008. Available from URL: http://www.fda.gov/oc/po/firmrecalls/shellfish03_08.html.
    22) None Listed: An outbreak of diarrhetic shellfish poisoning. Commun Dis Rep CDR.Wkly 1997; 7(28):247.
    23) Paz B, Daranas AH, Cruz PG, et al: Identification of 19-epi-okadaic acid, a new diarrhetic shellfish poisoning toxin, by liquid chromatography with mass spectrometry detection. Marine drugs 2008; 6(3):489-495.
    24) Ragelis E: Seafood toxins. J Assoc Off Anal Chem 1986; 69:250-253.
    25) Scoging A & Bahl M: Diarrhetic shellfish poisoning in the UK (letter). Lancet 1998; 352:117.
    26) Sobel J & Painter J: Illnesses caused by marine toxins. Clin Infect Dis 2005; 41(9):1290-1296.
    27) Stabell OB, Hormazabal V, & Steffenak I: Diarrhetic shellfish toxins: improvement of sample clean-up for HPLC determination. Toxicon 1991; 29:21-29.
    28) Torgersen T, Aasen J, & Aune T: Diarrhetic shellfish poisoning by okadaic acid esters from Brown crabs (Cancer pagurus) in Norway. Toxicon 2005; 46:572-578.
    29) Vernoux JP, Bansard S, & Simon JF: Cooked mussels contaminated by dinophysis sp.: A source of okadaic acid. Natural Toxins 1994; 2:184-188.
    30) Windust AJ, Quilliam MA, & Wright JLC: Comparative toxicity of the diarrhetic shellfish poisons, okadaic acid, okadaic acid diol-ester and dinophysistoxin-4, to the diatom thalassiosira weissflogii. Toxicon 1997; 35:1591-1603.