Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

Abal, Paula; Louzao, M. Carmen; Antelo, Álvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luís M.

doi:10.3390/toxins9030075

Cited by 54 publications

(73 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…: time to intake TTX not available. (a): Modified from Leung et al (2011). and the LOQ was 1 ng/mL (Abal et al, 2017). More details on the study are presented in Section 3.2.2, Toxicity.…”

Section: Methods Advantages Disadvantagesmentioning

confidence: 99%

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

Self Cite

View full text Add to dashboard Cite

Tetrodotoxin (TTX) and its analogues are produced by marine bacteria and have been detected in marine bivalves and gastropods from European waters. The European Commission asked EFSA for a scientific opinion on the risks to public health related to the presence of TTX and TTX analogues in marine bivalves and gastropods. The Panel on Contaminants in the Food Chain reviewed the available literature but did not find support for the minimum lethal dose for humans of 2 mg, mentioned in various reviews. Some human case reports describe serious effects at a dose of 0.2 mg, corresponding to 4 lg/kg body weight (bw). However, the uncertainties on the actual exposure in the studies preclude their use for derivation of an acute reference dose (ARfD). Instead, a group ARfD of 0.25 lg/kg bw, applying to TTX and its analogues, was derived based on a TTX dose of 25 lg/kg bw at which no apathy was observed in an acute oral study with mice, applying a standard uncertainty factor of 100. Estimated relative potencies for analogues are lower than that of TTX but are associated with a high degree of uncertainty. Based on the occurrence data submitted to EFSA and reported consumption days only, average and P95 exposures of 0.00-0.09 and 0.00-0.03 lg/kg bw, respectively, were calculated. Using a large portion size of 400 g bivalves and P95 occurrence levels of TTX, with exception of oysters, the exposure was below the group ARfD in all consumer groups. A concentration below 44 lg TTX equivalents/kg shellfish meat, based on a large portion size of 400 g, was considered not to result in adverse effects in humans. Liquid chromatography with tandem mass spectroscopy (LC-MS/MS) methods are the most suitable for identification and quantification of TTX and its analogues, with LOQs between 1 and 25 lg/kg.

show abstract

“…: time to intake TTX not available. (a): Modified from Leung et al (2011). and the LOQ was 1 ng/mL (Abal et al, 2017). More details on the study are presented in Section 3.2.2, Toxicity.…”

Section: Methods Advantages Disadvantagesmentioning

confidence: 99%

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

Self Cite

View full text Add to dashboard Cite

show abstract

“…Plasma/serum concentrations of TTX fall rapidly and may be undetectable after 6–24 h [ 137 ]. No data are available regarding the distribution and metabolism of TTX in humans, and little is known in animals [ 138 ].…”

Section: Tetrodotoxinsmentioning

confidence: 99%

“…ARfD of 0.25 µg/kg b.w. was derived from a TTX dose of 25 µg/kg b.w., at which no adverse effects were observed in an acute oral study with mice, applying a standard uncertainty factor of 100 [ 138 ]. This ARfD (0.25 µg/kg b.w.)…”

Section: Tetrodotoxinsmentioning

confidence: 99%

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

Self Cite

113

View full text Add to dashboard Cite

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.

show abstract

“…In recent years, the rapid development of aptamer OA is a kind of phycotoxin mainly produced by algaes including Dinophysis and Prorocentrum, which can be enriched in shellfish because of its feature of lipophilicity and heat-stablity [46], OA is one of the most widely distributed marine toxins that causes the highest incidence of events. LD 50 (intravenous injection of mice) of OA was 166 µg/kg (body weight) [47]. The toxic mechanism of OA is complex.…”

Section: Introductionmentioning

confidence: 99%

“…It acts rapidly on nerve endings and nerve centers after absorption, and can block sodium channels on nerve excitation membranes with high selectivity and affinity, thus causing nerve conduction blocking and resulting in nerve paralysis and death [49]. The acute oral toxicity of TTX was determined, and the LD 50 of TTX towards mice by oral means was 10 µg/kg (body weight) [50]. PTX, a toxic polypeptide from Anemonia sulcata, can cause nerve and heart poisoning, and inhibit the activity of proteolytic enzymes.…”

Section: Introductionmentioning

confidence: 99%

Marine Toxins Detection by Biosensors Based on Aptamers

Wei

Liu

Zhang

et al. 2019

Toxins

View full text Add to dashboard Cite

Marine toxins cause great harm to human health through seafood, therefore, it is urgent to exploit new marine toxins detection methods with the merits of high sensitivity and specificity, low detection limit, convenience, and high efficiency. Aptasensors have emerged to replace classical detection methods for marine toxins detection. The rapid development of molecular biological approaches, sequencing technology, material science, electronics and chemical science boost the preparation and application of aptasensors. Taken together, the aptamer-based biosensors would be the best candidate for detection of the marine toxins with the merits of high sensitivity and specificity, convenience, time-saving, relatively low cost, extremely low detection limit, and high throughput, which have reduced the detection limit of marine toxins from nM to fM. This article reviews the detection of marine toxins by aptamer-based biosensors, as well as the selection approach for the systematic evolution of ligands by exponential enrichment (SELEX), the aptamer sequences. Moreover, the newest aptasensors and the future prospective are also discussed, which would provide thereotical basis for the future development of marine toxins detection by aptasensors.Key Contribution: This article reviews systematically the toxicity of marine toxins, the development of aptarmer-based biosensors, and progress in the marine toxin detection by aptasensors.Toxins 2020, 12, 1 2 of 22 selection technology and biosensor fabrication technology offer a new solution for the detection of marine toxins with high efficiency and sensitivity [13][14][15][16][17].Marine toxins are a class of small molecular compounds mainly produced by red tide algae. In recent years, with the aggravation of environmental pollution, human deaths due to accidental ingestion of toxic shellfish are also often reported [18][19][20][21]. At present, the main methods for the detection of marine toxins include mouse bioassay (MBA) [22], enzyme-linked immunosorbent assay (ELISA) [23][24][25], high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS/MS), etc. [26][27][28]. However, these traditional methods have some drawbacks including the requirement of a technician, poor repeatability, expensive equipment, and issues related to animal ethics [22]. As a new detection technology, the biosensor is a kind of analysis systems using cell molecules and other bio-materials as sensitive elements, combined with a secondary sensor to detect a variety of chemicals by cascade amplified signal [29]. Because of their advantages of simple operation, high speed, high sensitivity, miniaturization, and easy automation, biosensors have been widely used in different fields including cell physiology [30], drug screening [31,32], food safety detection [33], disease diagnosis [34], etc.Aptamer, meaning "to fit", is a kind of oligonucleotide which can bind to target molecules with high selectivity and affinity. On account of the existence of aptamers in nature and the po...

show abstract

Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

Cited by 54 publications

References 19 publications

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Risks for public health related to the presence of tetrodotoxin (TTX) and TTX analogues in marine bivalves and gastropods

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Marine Toxins Detection by Biosensors Based on Aptamers

Contact Info

Product

Resources

About