Toxicity equivalence factors for regulated and non-regulated marine toxins

Louzao, M. Carmen; Abal, Paula; Vilariño, Natalia

doi:10.1016/j.cofs.2017.11.008

Cited by 5 publications

(8 citation statements)

References 53 publications

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“…HPLC with UV detection is the official method to monitor DA in shellfish in the European Union [ 22 ]. To estimate the total toxicity of seafood samples there is a need to know the relative toxicity of regulated DA analogues [ 60 ]. This requires the determination of toxicity equivalency factors (TEFs) defined as the ratio between the toxicity of each analogue and that of the reference compound within the same toxin group [ 20 ].…”

Section: Domoic Acidmentioning

confidence: 99%

“…established to TTX could be applied to TTX analogues detected in marine bivalves and gastropods (TTX, 11-oxoTTX, 4-epi-TTX, 4,9-anhydro-TTX, 5,6,11-tri-deoxy-TTX and 11-norTTX-6-ol). Nevertheless, more data obtained after oral exposure are needed to estimate relative potencies of TTX analogues [ 60 ].…”

Section: Tetrodotoxinsmentioning

confidence: 99%

“…toxicity, EFSA established the following TEF values: OA = 1, DTX1 = 1, DTX2 = 0.6 [ 157 ]. Since DTX3 can be hydrolyzed in the gut, TEF values for this toxin can be considered equal to those of the corresponding unesterified toxins (OA, DTX1 and DTX2) [ 60 ]. However, DSP is due to ingestion of shellfish contaminated by OA and analogues; therefore, TEF should be established on the basis of their acute oral toxicity [ 170 ].…”

Section: Okadaic Acid Groupmentioning

confidence: 99%

See 2 more Smart Citations

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

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114

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Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by ingestion of contaminated seafood, although other exposure routes like inhalation or contact have also been reported and may cause serious illness. This review shows the current data regarding the symptoms of acute intoxication for several toxin classes, including paralytic toxins, amnesic toxins, ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and palytoxins. The information available about chronic toxicity and relative potency of different analogs within a toxin class are also reported. The gaps of toxicological knowledge that should be studied to improve human health protection are discussed. In general, gathering of epidemiological data in humans, chronic toxicity studies and exploring relative potency by oral administration are critical to minimize human health risks related to these toxin classes in the near future.

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Section: Domoic Acidmentioning

confidence: 99%

Section: Tetrodotoxinsmentioning

confidence: 99%

Section: Okadaic Acid Groupmentioning

confidence: 99%

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Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

Self Cite

114

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“…Considering OA as the reference compound, the oral toxicity equivalency factors (TEFs) derived from LD 50 values are: OA = 1.0, DTX1 = 1.5 and DTX2 = 0.3 different from the current TEF values established by EFSA: OA = 1.0, DTX1 = 1.0 and DTX2 = 0.6 [20]. Therefore, to evaluate the toxicity of a shellfish sample regardless of the DSP toxins present, oral TEFs proposed in the present study are more appropriate to protect human health than TEF based on i.p toxicity [18]. Symptoms reported after OA or DTX1 administration were similar to those previously described [24,29].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, to estimate the total toxicity of seafood samples there is a need to know the relative toxicity of OA regulated analogues [18]. This requires determination of Toxicity Equivalency Factors (TEFs) defined as the ratio between the toxicity of each analogue and that of the reference compound within the same toxin group [19].…”

Section: Introductionmentioning

confidence: 99%

Toxic Action Reevaluation of Okadaic Acid, Dinophysistoxin-1 and Dinophysistoxin-2: Toxicity Equivalency Factors Based on the Oral Toxicity Study

Abal

Louzao

Suzuki

et al. 2018

Cell Physiol Biochem

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Background/Aims: Okadaic acid (OA) and the structurally related compounds dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2) are marine phycotoxins that cause diarrheic shellfish poisoning (DSP) in humans due to ingestion of contaminated shellfish. In order to guarantee consumer protection, the regulatory authorities have defined the maximum level of DSP toxins as 160 µg OA equivalent kg^-1 shellfish meat. For risk assessment and overall toxicity determination, knowledge of the relative toxicities of each analogue is required. In absence of enough information from human intoxications, oral toxicity in mice is the most reliable data for establishing Toxicity Equivalence Factors (TEFs). Methods: Toxins were administered to mice by gavage, after that the symptomatology and mice mortality was registered over a period of 24 h. Organ damage data were collected at necropsy and transmission electron microscopy (TEM) was used for ultrastructural studies. Toxins in urine, feces and blood were analyzed by HPLC-MS/MS. The evaluation of in vitro potencies of OA, DTX1 and DTX2 was performed by the protein phosphatase 2A (PP2A) inhibition assay. Results: Mice that received DSP toxins by gavage showed diarrhea as the main symptom. Those toxins caused similar gastrointestinal alterations as well as intestine ultrastructural changes. However, DSP toxins did not modify tight junctions to trigger diarrhea. They had different toxicokinetics and toxic potency. The lethal dose 50 (LD₅₀) was 487 µg kg^-1 bw for DTX1, 760 µg kg^-1 bw for OA and 2262 µg kg^-1 bw for DTX2. Therefore, the oral TEF values are: OA = 1, DTX1 = 1.5 and DTX2 = 0.3. Conclusion: This is the first comparative study of DSP toxins performed with accurate well-characterized standards and based on acute toxicity data. Results confirmed that DTX1 is more toxic than OA by oral route while DTX2 is less toxic. Hence, the current TEFs based on intraperitoneal toxicity should be modified. Also, the generally accepted toxic mode of action of this group of toxins needs to be reevaluated.

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