Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, −2 and −3 in mice

Pelin, Marco; Kilcoyne, Jane; Nulty, Cíara; Crain, Sheila; Heß, Philipp; Tubaro, Aurelia; Sosa, Silvio

doi:10.1016/j.toxlet.2017.10.016

Cited by 15 publications

(31 citation statements)

References 46 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order for a 60 kg adult to not exceed the ARfD, a 400 g portion of shellfish should not contain more than 12 μg AZA eq, i.e., 30 μg AZA eq/kg shellfish meat [ 39 ], much higher than the amount found in the present study. In 2018, more proper TEFs from oral LD 50 results (in mice) were proposed, resulting in 1.0, 0.7, and 0.5 for AZA-1, AZA-2, and AZA-3 respectively [ 40 ]. These TEFs seems more adequate since considering the potential human exposure by oral route, AZAs TEFs should be calculated by comparative oral toxicity data [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…In 2018, more proper TEFs from oral LD 50 results (in mice) were proposed, resulting in 1.0, 0.7, and 0.5 for AZA-1, AZA-2, and AZA-3 respectively [ 40 ]. These TEFs seems more adequate since considering the potential human exposure by oral route, AZAs TEFs should be calculated by comparative oral toxicity data [ 40 ]. Considering these new TEFs, the amount of total AZA in T. gayi is lower than 3 µg eq AZA/kg.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis

Otero

Vale

Boente-Juncal

et al. 2020

Toxins

View full text Add to dashboard Cite

Seafood represents a significant part of the human staple diet. In the recent years, the identification of emerging lipophilic marine toxins has increased, leading to the potential for consumers to be intoxicated by these toxins. In the present work, we investigate the presence of lipophilic marine toxins (both regulated and emerging) in commercial seafood products from non-European locations, including mussels Mytilus chilensis from Chile, clams Tawerea gayi and Metetrix lyrate from the Southeast Pacific and Vietnam, and food supplements based on mussels formulations of Perna canaliculus from New Zealand. All these products were purchased from European Union markets and they were analyzed by UPLC-MS/MS. Results showed the presence of the emerging pinnatoxin-G in mussels Mytilus chilensis at levels up to 5.2 µg/kg and azaspiracid-2 and pectenotoxin-2 in clams Tawera gayi up to 4.33 µg/kg and 10.88 µg/kg, respectively. This study confirms the presence of pinnatoxins in Chile, one of the major mussel producers worldwide. Chromatograms showed the presence of 13-desmethyl spirolide C in dietary supplements in the range of 33.2–97.9 µg/kg after an extraction with water and methanol from 0.39 g of the green lipped mussels powder. As far as we know, this constitutes the first time that an emerging cyclic imine toxin in dietary supplements is reported. Identifying new matrix, locations, and understanding emerging toxin distribution area are important for preventing the risks of spreading and contamination linked to these compounds.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis

Otero

Vale

Boente-Juncal

et al. 2020

Toxins

View full text Add to dashboard Cite

show abstract

“…LD 50 of these three molecules, with values of 1.0, 1.8 and 1.4 for AZA1, AZA2 and AZA3, respectively; AZA1 being the reference compound [ 192 ]. Very recently, more relevant TEFs have been proposed from oral LD 50 results in mice in a joint FAO/WHO technical paper [ 27 , 207 ]. The oral (gavage) toxicity-based TEFs would be 1.0, 0.7 and 0.5 for AZA1, AZA2 and AZA3 respectively.…”

Section: Azaspiracidsmentioning

confidence: 99%

“…In addition, cardiotoxicity was detected after i.p. administration, and, although there is evidence of AZAs absorption after oral administration [ 207 ], the cardiotoxic effect should be confirmed by the oral route. In general, chronic/subacute effects should be tested also in other species, considering the differences found between humans and rodents regarding toxic symptoms.…”

Section: Azaspiracidsmentioning

confidence: 99%

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

114

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 addition, a toxicokinetic study in mice after the acute oral administration of sub-lethal doses of AZA1 (100–300 μg/kg), detected the highest amount of toxin in the liver, followed by kidneys, lungs, spleen, and heart, even though significant tissue damage was only observed at the intestinal level [18]. Recently, a comparative acute oral toxicity study in mice on AZA1, -2, and -3 confirmed the hepatotoxic effects of these toxins, as revealed by the enlarged pale liver, hepatocytes necrosis, and increased serum markers of hepatic alteration [19]. Therefore, when considering the liver as one of the target organs of AZAs, an in vitro study was carried out to investigate the effects of AZA1, -2, and -3 on human hepatocytes, using the IHH non-tumor cell line.…”

Section: Introductionmentioning

confidence: 99%

Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions

et al. 2019

View full text Add to dashboard Cite

Background: Azaspiracids (AZAs) are marine toxins that are produced by Azadinium and Amphidoma dinoflagellates that can contaminate edible shellfish inducing a foodborne poisoning in humans, which is characterized by gastrointestinal symptoms. Among these, AZA1, -2, and -3 are regulated in the European Union, being the most important in terms of occurrence and toxicity. In vivo studies in mice showed that, in addition to gastrointestinal effects, AZA1 induces liver alterations that are visible as a swollen organ, with the presence of hepatocellular fat droplets and vacuoles. Hence, an in vitro study was carried out to investigate the effects of AZA1, -2, and -3 on liver cells, using human non-tumor IHH hepatocytes. Results: The exposure of IHH cells to AZA1, -2, or -3 (5 × 10−12–1 × 10−7 M) for 24 h did not affect the cell viability and proliferation (Sulforhodamine B assay and 3H-Thymidine incorporation assay), but they induced a significant concentration-dependent increase of mitochondrial dehydrogenases activity (MTT reduction assay). This effect depends on the activity of mitochondrial electron transport chain complex I and II, being counteracted by rotenone and tenoyl trifluoroacetone, respectively. Furthermore, AZAs-increased mitochondrial dehydrogenase activity was almost totally suppressed in the K+-, Cl−-, and Na+-free media and sensitive to the specific inhibitors of KATP and hERG potassium channels, Na+/K+, ATPase, and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. Conclusions: These results suggest that AZA mitochondrial effects in hepatocytes derive from an imbalance of intracellular levels of K+ and, in particular, Cl− ions, as demonstrated by the selective reduction of toxin effects by CFTR chloride channel inhibition.

show abstract

Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, −2 and −3 in mice

Cited by 15 publications

References 46 publications

Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis

Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions

Contact Info

Product

Resources

About