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Luis M Botana - One of the best experts on this subject based on the ideXlab platform.

  • in vivo evaluation of the chronic oral toxicity of the marine toxin palytoxin
    Toxins, 2020
    Co-Authors: Andrea Boentejuncal, Carmen Vale, Carmen M Louzao, Sandra Raposogarcia, Paz Otero, Luis M Botana
    Abstract:

    Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a Lethal Dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.

  • Reevaluation of the acute toxicity of palytoxin in mice: Determination of Lethal Dose 50 (LD50) and No-observed-adverse-effect level (NOAEL).
    Toxicon : official journal of the International Society on Toxinology, 2020
    Co-Authors: Andrea Boente-juncal, Mercedes R. Vieytes, Carmen Vale, Mercedes Camiña, J. Manuel Cifuentes, Luis M Botana
    Abstract:

    Abstract Palytoxin is an emergent toxin in Europe and one of the most toxic substances know to date. The toxin disrupts the physiological functioning of the Na+/K+-ATPase converting the enzyme in a permeant cation channel. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Several reports have previously investigated the oral and intraperitoneal toxicity of PLTX in mice. However, in all cases short observation periods (24 and 48 h) after toxin administration were evaluated. In this work, single oral or intraperitoneal Doses of PLTX were administered to healthy mice and surviving animals were followed up for 96 h. The data obtained here allowed us to calculate the oral and intraperitoneal Lethal Doses 50 (LD50) which were in the range of the values previously described. Surprisingly, the oral NOAEL for PLTX was more than 10 times lower than that previously described, a fact that indicates the need for the reevaluation of the levels of the toxin in edible fishery products.

  • Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity
    'MDPI AG', 2019
    Co-Authors: Andrea Boente-juncal, Carmen Vale, Mercedes Camiña, Paz Otero, Manuel Cifuentes, Mercedes Rodriguez-vieytes, Luis M Botana
    Abstract:

    Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. Initially TTX was associated with human food intoxications in Japan, but nowadays, concerns about the human health risks posed by TTX have increased in Europe after the identification of the toxin in fish, marine gastropods, and bivalves captured in European waters. Even when TTX monitoring is not currently performed in Europe, an acute oral no observable effect level (NOAEL) of 75 μg/kg has been recently established but, to date, no studies evaluating the chronic oral toxicity of TTX have been released, even when EFSA has highlighted the need for them. Thus, in this work, the chronic effects of low oral TTX Doses (below the acute Lethal Dose 50) were evaluated following internationally adopted guidelines. The results presented here demonstrate that low oral Doses of TTX have deleterious effects on renal and cardiac tissues. Moreover, alterations in blood biochemistry parameters, urine production, and urinalysis data were already detected at the oral Dose of 75 µg/kg after the 28 days exposure. Thus, the data presented here constitute an initial approach for the chronic evaluation of the in vivo toxicity of tetrodotoxin after its ingestion through contaminated fishery products

  • acute oral toxicity of tetrodotoxin in mice determination of Lethal Dose 50 ld50 and no observed adverse effect level noael
    Toxins, 2017
    Co-Authors: Paula Abal, Eva Cagide, Natalia Vilariño, M. Carmen Louzao, Mercedes R. Vieytes, Mercedes Alvarez, Alvaro Antelo, Luis M Botana
    Abstract:

    Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral Lethal Dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard.

De Proft Michel - One of the best experts on this subject based on the ideXlab platform.

  • Toxicity of several fungicides for orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae)
    2015
    Co-Authors: Chavalle Sandrine, Jansen Jean-pierre, San Martin Gomez Y Gilles, De Proft Michel
    Abstract:

    audience: researcher, professional, studentThe orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), can cause severe losses in wheat grain yield and quality. This pest is known to be susceptible to many insecticides, but various field observations have suggested that some fungicides could also significantly affect S. mosellana. In order to confirm these field observations, the effect on adult midges of several fungicides commonly applied to wheat crops was investigated in the laboratory and in small plots in the field. In each experiment, the fungicides were compared with a positive (insecticide) and a negative control (water). Four fungicides were assessed in the laboratory, each with five Doses based on basis of a tenfold dilution starting at the field-recommended Dose. The mortality rate was evaluated after 24 hours and the Lethal Dose 50% (LD50) was determined for each product. In the field, six fungicides were tested at the recommended Dose. The effect of each product was compared on the basis of the number of S. mosellana adults caught alive with an insect vacuum sampler (Vortis®) on the morning after the treatments. Both experiments showed a significant effect of several fungicides tested on S. mosellana adults. Chlorothalonil was not toxic for S. mosellana, but tebuconazole, fluxapyroxad and azoxystrobin all induced significant mortality rates

  • Toxicity of several fungicides for orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae)
    2015
    Co-Authors: Chavalle Sandrine, Jansen Jean-pierre, San Martin Gomez Y Gilles, De Proft Michel
    Abstract:

    The orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), can cause severe losses in wheat grain yield and quality. This pest is known to be susceptible to many insecticides, but various field observations have suggested that some fungicides could also significantly affect S. mosellana. In order to confirm these field observations, the effect on adult midges of several fungicides commonly applied to wheat crops was investigated in the laboratory and in small plots in the field. In each experiment, the fungicides were compared with a positive (insecticide) and a negative control (water). Four fungicides were assessed in the laboratory, each with five Doses based on basis of a tenfold dilution starting at the field-recommended Dose. The mortality rate was evaluated after 24 hours and the Lethal Dose 50% (LD50) was determined for each product. In the field, six fungicides were tested at the recommended Dose. The effect of each product was compared on the basis of the number of S. mosellana adults caught alive with an insect vacuum sampler (Vortis®) on the morning after the treatments. Both experiments showed a significant effect of several fungicides tested on S. mosellana adults. Chlorothalonil was not toxic for S. mosellana, but tebuconazole, fluxapyroxad and azoxystrobin all induced significant mortality rates

Everton Fagonde Da Silva - One of the best experts on this subject based on the ideXlab platform.

  • highly virulent leptospira borgpetersenii strain characterized in the hamster model
    American Journal of Tropical Medicine and Hygiene, 2011
    Co-Authors: Juliana Alcoforado Diniz, Samuel Rodrigues Felix, Josiane Bonelraposo, Amilton Clair Pinto Seixas Neto, Flavia Aleixo Vasconcellos, Andre Alex Grassmann, Odir Antonio Dellagostin, Jose Antonio Guimaraes Aleixo, Everton Fagonde Da Silva
    Abstract:

    Abstract. A recent study by our group reported the isolation and partial serological and molecular characterization of four Leptospira borgpetersenii serogroup Ballum strains. Here, we reproduced experimental leptospirosis in golden Syrian hamsters (Mesocricetus auratus) and carried out standardization of Lethal Dose 50% (LD50) of one of these strains (4E). Clinical disease features and histopathologic analyses of tissue lesions were also observed. As results, strain 4E induced Lethality in the hamster model with inocula lower than 10 leptospires, and histopathological examination of animals showed typical lesions found in severe leptospirosis. Gross pathological findings were peculiar; animals that died early had more chance of presenting severe jaundice and less chance of presenting pulmonary hemorrhages (P < 0.01). L. borgpetersenii serogroup Ballum has had a considerable growth in human leptospirosis cases in recent years. This strain has now been thoroughly characterized and can be used in more studies, especially evaluations of vaccine candidates.

  • short report highly virulent leptospira borgpetersenii strain characterized in the hamster model
    2011
    Co-Authors: Juliana Alcoforado Diniz, Samuel Rodrigues Felix, Josiane Bonelraposo, Flavia Aleixo Vasconcellos, Andre Alex Grassmann, Odir Antonio Dellagostin, Jose Antonio Guimaraes Aleixo, Everton Fagonde Da Silva
    Abstract:

    Both man and animal become accidental hosts through exposure to chroni- cally infected animals, mostly rodents, that shed leptospires in their urine. 2 This zoonosis is characterized by a broad spec- trum of clinical manifestations, ranging from subclinical infec- tion to Weil's syndrome 3 and severe pulmonary hemorrhage syndrome. 4 Abstract. A recent study by our group reported the isolation and partial serological and molecular characterization of four Leptospira borgpetersenii serogroup Ballum strains. Here, we reproduced experimental leptospirosis in golden Syrian hamsters ( Mesocricetus auratus ) and carried out standardization of Lethal Dose 50% (LD50) of one of these strains (4E). Clinical disease features and histopathologic analyses of tissue lesions were also observed. As results, strain 4E induced Lethality in the hamster model with inocula lower than 10 leptospires, and histopathological examination of ani- mals showed typical lesions found in severe leptospirosis. Gross pathological findings were peculiar; animals that died early had more chance of presenting severe jaundice and less chance of presenting pulmonary hemorrhages ( P < 0.01). L. borgpetersenii serogroup Ballum has had a considerable growth in human leptospirosis cases in recent years. This strain has now been thoroughly characterized and can be used in more studies, especially evaluations of vaccine candidates.

  • characterization of virulence of leptospira isolates in a hamster model
    Vaccine, 2008
    Co-Authors: Everton Fagonde Da Silva, Cleiton S. Santos, Daniel A. Athanazio, Mitermayer G. Reis, Nubia Seyffert, Fabiana Kommling Seixas, Gustavo C Cerqueira, Michel Quevedo Fagundes, Claudiomar Soares Brod, Odir Antonio Dellagostin
    Abstract:

    Effort has been made to identify protective antigens in order to develop a recombinant vaccine against leptospirosis. Several attempts failed to conclusively demonstrate efficacy of vaccine candidates due to the lack of an appropriate model of Lethal leptospirosis. The purposes of our study were: (i) to test the virulence of leptospiral isolates from Brazil, which are representative of important serogroups that cause disease in humans and animals; and (ii) to standardize the Lethal Dose 50% (LD(50)) for each of the virulent strains using a hamster (Mesocricetus auratus) model. Five of seven Brazilian isolates induced Lethality in a hamster model, with inocula lower than 200 leptospires. Histopathological examination of infected animals showed typical lesions found in both natural and experimental leptospirosis. Results described here demonstrated the potential use of Brazilian isolates as highly virulent strains in challenge experiments using hamster as an appropriate animal model for leptospirosis. Furthermore these strains may be useful in heterologous challenge studies which aim to evaluate cross-protective responses induced by sub-unit vaccine candidates.

Chavalle Sandrine - One of the best experts on this subject based on the ideXlab platform.

  • Toxicity of several fungicides for orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae)
    2015
    Co-Authors: Chavalle Sandrine, Jansen Jean-pierre, San Martin Gomez Y Gilles, De Proft Michel
    Abstract:

    audience: researcher, professional, studentThe orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), can cause severe losses in wheat grain yield and quality. This pest is known to be susceptible to many insecticides, but various field observations have suggested that some fungicides could also significantly affect S. mosellana. In order to confirm these field observations, the effect on adult midges of several fungicides commonly applied to wheat crops was investigated in the laboratory and in small plots in the field. In each experiment, the fungicides were compared with a positive (insecticide) and a negative control (water). Four fungicides were assessed in the laboratory, each with five Doses based on basis of a tenfold dilution starting at the field-recommended Dose. The mortality rate was evaluated after 24 hours and the Lethal Dose 50% (LD50) was determined for each product. In the field, six fungicides were tested at the recommended Dose. The effect of each product was compared on the basis of the number of S. mosellana adults caught alive with an insect vacuum sampler (Vortis®) on the morning after the treatments. Both experiments showed a significant effect of several fungicides tested on S. mosellana adults. Chlorothalonil was not toxic for S. mosellana, but tebuconazole, fluxapyroxad and azoxystrobin all induced significant mortality rates

  • Toxicity of several fungicides for orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae)
    2015
    Co-Authors: Chavalle Sandrine, Jansen Jean-pierre, San Martin Gomez Y Gilles, De Proft Michel
    Abstract:

    The orange wheat blossom midge, Sitodiplosis mosellana (Géhin) (Diptera: Cecidomyiidae), can cause severe losses in wheat grain yield and quality. This pest is known to be susceptible to many insecticides, but various field observations have suggested that some fungicides could also significantly affect S. mosellana. In order to confirm these field observations, the effect on adult midges of several fungicides commonly applied to wheat crops was investigated in the laboratory and in small plots in the field. In each experiment, the fungicides were compared with a positive (insecticide) and a negative control (water). Four fungicides were assessed in the laboratory, each with five Doses based on basis of a tenfold dilution starting at the field-recommended Dose. The mortality rate was evaluated after 24 hours and the Lethal Dose 50% (LD50) was determined for each product. In the field, six fungicides were tested at the recommended Dose. The effect of each product was compared on the basis of the number of S. mosellana adults caught alive with an insect vacuum sampler (Vortis®) on the morning after the treatments. Both experiments showed a significant effect of several fungicides tested on S. mosellana adults. Chlorothalonil was not toxic for S. mosellana, but tebuconazole, fluxapyroxad and azoxystrobin all induced significant mortality rates

Richard H. Adamson - One of the best experts on this subject based on the ideXlab platform.

  • The acute Lethal Dose 50 (LD50) of caffeine in albino rats.
    Regulatory toxicology and pharmacology : RTP, 2016
    Co-Authors: Richard H. Adamson
    Abstract:

    An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single Dose and the animals observed for a specified time period. Although conducting routine acute toxicity testing in rodents has been criticized, it can serve useful functions and also have practical implications. Material safety data sheets (MSDS) will reflect the acute toxicity of a substance and may require workers to wear protective gear, if appropriate, based on the LD50. There is no information in the scientific published literature which calculates a mean LD50 and standard deviation for caffeine administered orally to rats, using studies performed under good laboratory practice (GLP) or equivalent. This report does that and should be useful to manufacturers, packagers, transporters and regulators of this material. Using data from studies that are reproducible and reliable, the most accurate estimate of the acute LD50 of caffeine administered orally in male albino rats is hereby reported to be 367/mg/kg.