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[PMID]: | 29107028 |
[Au] Autor: | Pelin M; Kilcoyne J; Nulty C; Crain S; Hess P; Tubaro A; Sosa S |
[Ad] Endereço: | Department of Life Sciences, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy. |
[Ti] Título: | Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, -2 and -3 in mice. |
[So] Source: | Toxicol Lett;282:136-146, 2018 Jan 05. | [Is] ISSN: | 1879-3169 |
[Cp] País de publicação: | Netherlands |
[La] Idioma: | eng |
[Ab] Resumo: | Azaspiracids (AZAs) are marine algal toxins that can be accumulated by edible shellfish to cause a foodborne gastrointestinal poisoning in humans. In the European Union, only AZA1, -2 and -3 are currently regulated and their concentration in shellfish is determined through their toxic equivalency factors (TEFs) derived from the intraperitoneal lethal potency in mice. Nevertheless, considering the potential human exposure by oral route, AZAs TEFs should be calculated by comparative oral toxicity data. Thus, the acute oral toxicity of AZA1, -2 and -3 was investigated in female CD-1 mice treated with different doses (AZA1: 135-1100µg/kg; AZA2 and AZA3: 300-1100µg/kg) and sacrificed after 24h or 14days. TEFs derived from the median lethal doses (LD ) were 1.0, 0.7 and 0.5, respectively for AZA1, -2 and -3. In fact, after 24h from gavage administration, LD were 443µg/kg (AZA1; 95% CL: 350-561µg/kg), 626µg/kg (AZA2; 95% CL: 430-911µg/kg) and 875µg/kg (AZA3; 95% CL: 757-1010µg/kg). Mice dead more than 5h after the treatment or those sacrificed after 24h (doses: ≥175µg AZA1/kg, ≥500µg AZA2/kg and ≥600µg AZA3/kg) showed enlarged pale liver, while increased serum markers of liver alteration were recorded even at the lowest doses. Blood chemistry revealed significantly increased serum levels of K ions (≥500mg/kg), whereas light microscopy showed tissue changes in the gastrointestinal tract, liver and spleen. No lethality, macroscopic, tissue or haematological changes were recorded two weeks post exposure, indicating reversible toxic effects. LC-MS/MS analysis of the main organs showed a dose-dependency in gastrointestinal absorption of these toxins: at 24h, the highest levels were detected in the stomach and, in descending order, in the intestinal content, liver, small intestine, kidneys, lungs, large intestine, heart as well as detectable traces in the brain. After 14days, AZA1 and AZA2 were still detectable in almost all the organs and intestinal content. |
[Mh] Termos MeSH primário: |
Furanos/toxicidade Toxinas Marinhas/toxicidade Piranos/toxicidade Compostos de Espiro/toxicidade
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[Mh] Termos MeSH secundário: |
Administração Oral Animais Relação Dose-Resposta a Droga Feminino Furanos/farmacocinética Dose Letal Mediana Toxinas Marinhas/farmacocinética Camundongos Endogâmicos Mytilus edulis/química Especificidade de Órgãos Piranos/farmacocinética Compostos de Espiro/farmacocinética Distribuição Tecidual Testes de Toxicidade Aguda
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Furans); 0 (Marine Toxins); 0 (Pyrans); 0 (Spiro Compounds); 0 (azaspiracid); 0 (azaspiracid-2); 0 (azaspiracid-3) |
[Em] Mês de entrada: | 1712 |
[Cu] Atualização por classe: | 171201 |
[Lr] Data última revisão:
| 171201 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171107 |
[St] Status: | MEDLINE |
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