Risk Assessment of Deoxynivalenol by Revisiting Its Bioavailability in Pig and Rat Models to Establish Which Is More Suitable

Saint-Cyr, Manuel Jimmy; Perrin-Guyomard, Agnès; Manceau, J. N.; Houée, Paméla; Delmas, Jean-Michel; Rolland, Jean-Guy; Laurentie, Michel

doi:10.3390/toxins7124873

Cited by 13 publications

(11 citation statements)

References 40 publications

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“…a) Swine DON, (Saint-Cyr et al, 2015) b) Swine DON, (Paulick et al, 2015) c) Chicken DON, d) Chicken ZEN, (Buranatragool et al, 2015) e) Chicken T2, (Sun et al, 2015) f) Chicken NIV, (Kongkapan et al, 2015) g) Chicken ENNB ENNB1 (Fraeyman et al, 2016) -PIGS + DON All the chemical properties of mycotoxins for internal dose modelling were recovered and are available online on the MYCHIF repository and EFSA knowledge junction (10.5281/zenodo.3615174).…”

Section: Toxicokinetics (In Vivo) Database: Internal Dose Calculationmentioning

confidence: 99%

“…Toxicokinetic model 1-cmpt, output and comparison with data reported by (Saint-Cyr et al, 2015) DON-swine oral administration.Data reported by(Saint-Cyr et al, 2015) are used for model initialization.…”

mentioning

confidence: 99%

“…ZEN-chicken intravenous and oral administration.Data reported by(Saint-Cyr et al, 2015) are used for model initialization.MYCHIF www.efsa.europa.eu/publications 78 EFSA Supporting publication 2020:EN-1757 ZEN-chicken intravenous and oral administration.Data reported by(Saint-Cyr et al, 2015) are used for model initialization.MYCHIF www.efsa.europa.eu/publications 78 EFSA Supporting publication 2020:EN-1757…”

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confidence: 99%

See 2 more Smart Citations

Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Battilani¹,

Palumbo²,

Giorni³

et al. 2020

EFS3

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Mycotoxins are toxic compounds mainly produced by fungi of the genera Aspergillus, Penicillium and Fusarium. They are present, often as mixtures, in many feed and food commodities including cereals, fruits and vegetables. Their ubiquitous presence represents a major challenge to the health and well being of humans and animals. Hundreds of compounds are listed as possible mycotoxins occurring in raw and processed materials destined for human food and animal feed. In this study, mycotoxins of major toxicological relevance to humans and target animal species were investigated in a range of crops of interest (and their derived products). Extensive Literature Searches (ELSs) were undertaken for data collection on: (i) ecology and interaction with host plants of mycotoxin producing fungi, mycotoxin production, recent developments in mitigation actions of mycotoxins in crop chains (maize, small grains, rice, sorghum, grapes, spices and nuts), (ii) analytical methods for native, modified and co-occurring mycotoxins (iii) toxicity, toxicokinetics, toxicodynamics and biomarkers relevant to humans and animals (poultry, suidae (pig, wild boar), bovidae (sheep, goat, cow, buffalo), rodents (rats, mice) and others (horses, dogs), (iv) modelling approaches and key reference values for exposure, hazard and risk modelling. Comprehensive databases were created using EFSA templates and were stored in the MYCHIF platform. A range of approaches were implemented to explore the modelling of external and internal exposure as well as dose-response of mycotoxins in chicken and pigs. In vitro toxicokinetic and in vivo toxicity databases were exploited, both for single compounds and mixtures. However, large data gaps were identified particularly with regards to absence of common statistical and study designs within the literature and constitute an obstacle for the harmonisation of internal exposure and dose-response modelling. Finally, risk characterisation was also performed for humans as well as for two animal species (i.e. pigs and chicken) using available tools for the modelling of internal dose and a component-based approach for selected mycotoxins mixtures.© European Food Safety Authority, 2020 MYCHIF www.efsa.europa.eu/publications 2 EFSA Supporting publication 2020: EN-1757

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Section: Toxicokinetics (In Vivo) Database: Internal Dose Calculationmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Battilani¹,

Palumbo²,

Giorni³

et al. 2020

EFS3

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“…42.5 µg/kg bw/day). Calculating with the average feed intake of 30 g/animal/day and the absorption ratio of the toxins as 3.5% (Martinez-Larranaga et al, 1999), 47% (Saint-Cyr et al, 2015) and 28% (Mallis, Sarkahian, Harris, Zhang, & McConnell, 2003), respectively, the intraperitoneal (i.p.) administration represented the following dietary exposures: approximately.…”

Section: Animals and Feedingmentioning

confidence: 99%

Interaction between the three frequently co‐occurringFusariummycotoxins in rats

Szabó-Fodor

Szabó

Kócsó

et al. 2018

Animal Physiology Nutrition

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To test the complex, acute biochemical effects of combined, naturally co‐occurring fusariotoxins, a 5‐day rat study was performed. Mycotoxin treatment was invented by intraperitoneal injection: FB1 (F): 9 µg/animal/day (approx. 30 µg/kg bw/day), DON (D): 16.5 µg/animal/day (approx. 55 µg/kg bw/day) and ZEN (Z): 12.75 µg/animal/day (approx. 42.5 µg/kg bw/day). The binary groups (FB1 and DON [FD], FB1 and ZEN [FZ] and DON and ZEN [DZ]) as well as the ternary (FB1, DON and ZEN [FDZ]) group were dosed at the same combined level as the individual mycotoxins. Body weight, feed intake and mortality were not affected by any of the treatments. FB1 and DON in combination (FD) increased the plasma aspartate aminotransferase activity synergistically (compared to the individual FB1 and DON). In the liver, both the total glutathione (GSH) and the glutathione peroxidase (GPx) activity were increased (p < 0.05) by the binary FB1 and ZEN (FZ) and the DON and ZEN (DZ) groups as well as the ternary FB1, DON and ZEA group (FDZ) compared to the control. The GSH level of the ternary group was significantly increased compared to the FB1 group, whereas the GPx activity of the ternary group was significantly increased compared to all three the individual mycotoxin groups. The Bliss independence method revealed synergism between DON and ZEN (DZ), as well as FB1 and DON (FD) on liver GPx activity. None of the toxins alone or in combination exerted strong genotoxicity on lymphocytes, neither on the gross histopathological characteristics. However, even at these low levels acute exposure of more than one of these mycotoxins (FB1, DON and ZEN) affected metabolic and detoxification changes.

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“…In pigs, both ADONs are completely absorbed following oral administration, while the oral bioavailability of DON and acetylated derivatives is rather low in broiler chickens (Broekaert et al 2015b). For DON, it has been demonstrated multiple factors might influence the oral bioavailability of DON such as the prandial state (fed versus fasted), the administration of a bolus versus the administration of contaminated feed, feed composition, and breed (Broekaert et al 2015b;Eriksen and Pettersson 2004;Goyarts and Dänicke 2006;Prelusky et al 1988;Saint-Cyr et al 2015). Taking into account the substantial to complete presystemic hydrolysis of both ADONs, in broiler chickens and pigs, these acetylated forms can be regarded as potent as DON itself with regard to systemic toxicity (Broekaert et al 2015b).…”

Section: Introductionmentioning

confidence: 99%

The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics

et al. 2018

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A clinical case in Belgium demonstrated that feeding a feed concentrate containing considerable levels of deoxynivalenol (DON, 1.13 mg/kg feed) induced severe liver failure in 2-to 3-month-old beef calves. Symptoms disappeared by replacing the highly contaminated corn and by stimulating ruminal development via roughage administration. A multi-mycotoxin contamination was demonstrated in feed samples collected at 15 different veal farms in Belgium. DON was most prevalent, contaminating 80% of the roughage samples (mixed straw and maize silage; average concentration in positives: 637 ± 621 µg/ kg, max. 1818 µg/kg), and all feed concentrate samples (411 ± 156 µg/kg, max. 693 µg/kg). In order to evaluate the impact of roughage provision and its associated ruminal development on the gastro-intestinal absorption and biodegradation of DON and its acetylated derivatives (3-and 15-ADON) in calves, a toxicokinetic study was performed with two ruminating and two non-ruminating male calves. Animals received in succession a bolus of DON (120 µg/kg bodyweight (BW)), 15-ADON (50 µg/kg BW), and 3-ADON (25 µg/kg) by intravenous (IV) injection or per os (PO) in a cross-over design. The absolute oral bioavailability of DON was much higher in non-ruminating calves (50.7 ± 33.0%) compared to ruminating calves (4.1 ± 4.5%). Immediately following exposure, 3-and 15-ADON were hydrolysed to DON in ruminating calves. DON and its acetylated metabolites were mainly metabolized to DON-3-glucuronide, however, also small amounts of DON-15-glucuronide were detected in urine. DON degradation to deepoxy-DON (DOM-1) was only observed to a relevant extent in ruminating calves. Consequently, toxicity of DON in calves is closely related to roughage provision and the associated stage of ruminal development.Keywords Biodegradation · Calf · Deoxynivalenol · 3-and 15-Acetyldeoxynivalenol · Mycotoxin · Toxicokinetics Bonnie Valgaeren and Léonard Théron contributed equally to this work.Alfons Callebaut: Deceased. Electronic supplementary materialThe online version of this article (https ://doi.

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Risk Assessment of Deoxynivalenol by Revisiting Its Bioavailability in Pig and Rat Models to Establish Which Is More Suitable

Cited by 13 publications

References 40 publications

Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach:

Interaction between the three frequently co‐occurringFusariummycotoxins in rats

The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics

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