Assessment of information as regards the toxicity of deoxynivalenol for horses and poultry
2023; Wiley; Volume: 21; Issue: 2 Linguagem: Inglês
10.2903/j.efsa.2023.7806
ISSN1831-4732
AutoresDieter Schrenk, Margherita Bignami, Laurent Bodin, James Kevin Chipman Jesús del Mazo, Bettina Grasl‐Kraupp, Christer Högstrand, Jean‐Charles Leblanc, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Sven Dänicke, Carlo Nebbia, Isabelle P. Oswald, Elena Rovesti, Hans Steinkellner, L.A.P. Hoogenboom,
Tópico(s)Pesticide Residue Analysis and Safety
ResumoEFSA JournalVolume 21, Issue 2 e07806 Scientific OpinionOpen Access Assessment of information as regards the toxicity of deoxynivalenol for horses and poultry EFSA Panel on Contaminants in the Food Chain (CONTAM), Corresponding Author EFSA Panel on Contaminants in the Food Chain (CONTAM) [email protected] Correspondence:[email protected]Search for more papers by this authorDieter Schrenk, Dieter SchrenkSearch for more papers by this authorMargherita Bignami, Margherita BignamiSearch for more papers by this authorLaurent Bodin, Laurent BodinSearch for more papers by this authorJames Kevin Chipman Jesús del Mazo, James Kevin Chipman Jesús del MazoSearch for more papers by this authorBettina Grasl-Kraupp, Bettina Grasl-KrauppSearch for more papers by this authorChrister Hogstrand, Christer HogstrandSearch for more papers by this authorJean-Charles Leblanc, Jean-Charles LeblancSearch for more papers by this authorElsa Nielsen, Elsa NielsenSearch for more papers by this authorEvangelia Ntzani, Evangelia NtzaniSearch for more papers by this authorAnnette Petersen, Annette PetersenSearch for more papers by this authorSalomon Sand, Salomon SandSearch for more papers by this authorTanja Schwerdtle, Tanja SchwerdtleSearch for more papers by this authorChristiane Vleminckx, Christiane VleminckxSearch for more papers by this authorHeather Wallace, Heather WallaceSearch for more papers by this authorSven Dänicke, Sven DänickeSearch for more papers by this authorCarlo Stefano Nebbia, Carlo Stefano NebbiaSearch for more papers by this authorIsabelle P Oswald, Isabelle P OswaldSearch for more papers by this authorElena Rovesti, Elena RovestiSearch for more papers by this authorHans Steinkellner, Hans SteinkellnerSearch for more papers by this authorLaurentius (Ron) Hoogenboom, Laurentius (Ron) HoogenboomSearch for more papers by this author EFSA Panel on Contaminants in the Food Chain (CONTAM), Corresponding Author EFSA Panel on Contaminants in the Food Chain (CONTAM) [email protected] Correspondence:[email protected]Search for more papers by this authorDieter Schrenk, Dieter SchrenkSearch for more papers by this authorMargherita Bignami, Margherita BignamiSearch for more papers by this authorLaurent Bodin, Laurent BodinSearch for more papers by this authorJames Kevin Chipman Jesús del Mazo, James Kevin Chipman Jesús del MazoSearch for more papers by this authorBettina Grasl-Kraupp, Bettina Grasl-KrauppSearch for more papers by this authorChrister Hogstrand, Christer HogstrandSearch for more papers by this authorJean-Charles Leblanc, Jean-Charles LeblancSearch for more papers by this authorElsa Nielsen, Elsa NielsenSearch for more papers by this authorEvangelia Ntzani, Evangelia NtzaniSearch for more papers by this authorAnnette Petersen, Annette PetersenSearch for more papers by this authorSalomon Sand, Salomon SandSearch for more papers by this authorTanja Schwerdtle, Tanja SchwerdtleSearch for more papers by this authorChristiane Vleminckx, Christiane VleminckxSearch for more papers by this authorHeather Wallace, Heather WallaceSearch for more papers by this authorSven Dänicke, Sven DänickeSearch for more papers by this authorCarlo Stefano Nebbia, Carlo Stefano NebbiaSearch for more papers by this authorIsabelle P Oswald, Isabelle P OswaldSearch for more papers by this authorElena Rovesti, Elena RovestiSearch for more papers by this authorHans Steinkellner, Hans SteinkellnerSearch for more papers by this authorLaurentius (Ron) Hoogenboom, Laurentius (Ron) HoogenboomSearch for more papers by this author First published: 02 February 2023 https://doi.org/10.2903/j.efsa.2023.7806 Requestor: European Commission Question number: EFSA-Q-2021-00712 Panel members: Dieter Schrenk, Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl-Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean-Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx and Heather Wallace. Declarations of interest: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact [email protected]. Acknowledgements: The Panel wishes to thank the following for the support provided to this scientific output: Federico Cruciani. Adopted: 15 December 2022 Annex A is available under the Supporting Information section. AboutSectionsPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract In 2017, the EFSA Panel on Contaminants in the Food Chain (CONTAM) adopted a Scientific Opinion on the risks for animal health related to the presence of deoxynivalenol (DON) and its acetylated and modified forms in food and feed. No observed adverse effect levels (NOAELs) and lowest observed adverse effect levels (LOAELs) were derived for different animal species. For horses, an NOAEL of 36 mg DON/kg feed was established, the highest concentration tested and not showing adverse effects. For poultry, an NOAEL of 5 mg DON/kg feed for broiler chickens and laying hens, and an NOAEL of 7 mg DON/kg feed for ducks and turkeys was derived. The European Commission requested EFSA to review the information regarding the toxicity of DON for horses and poultry and to revise, if necessary, the established reference points (RPs). Adverse effect levels of 1.9 and 1.7 mg DON/kg feed for, respectively, broiler chickens and turkeys were derived from reassessment of existing studies and newly available literature, showing that DON causes effects on the intestines, in particular the jejunum, with a decreased villus height but also histological damage. An RP for adverse animal health effects of 0.6 mg/kg feed for broiler chickens and turkeys, respectively, was established. For horses, an adverse effect level of 5.6 mg DON/kg feed was established from studies showing reduced feed intake, with an RP for adverse animal health effects of 3.5 mg/kg feed. For ducks and laying hens, RPs remain unchanged. Based on mean and P95 (UB) exposure estimates performed in the previous Opinion, the risk of adverse health effects of feeds containing DON was considered a potential concern for broiler chickens and turkeys. For horses, the risk for adverse health effects from feed containing DON is low. 1 Introduction Background and terms of reference as provided by the requestor Background In 2017, the EFSA Panel on Contaminants in the Food Chain (CONTAM) adopted a Scientific Opinion on the risks for animal health related to the presence of deoxynivalenol (DON) and its acetylated and modified forms in food and feed. The CONTAM Panel established for DON in horses a No Observed Adverse Effect Level (NOAEL) of 36 mg DON/kg feed and in poultry a NOAEL of 5 mg DON/kg feed for broiler chickens and laying hens and a NOAEL of 7 mg DON/kg feed for ducks and turkeys. Due to limited or no data on adverse effects caused by 3-Ac-DON, 15-Ac-DON and/or DON-3-glucoside, no specific NOAELs/LOAELs could be identified for 3-Ac-DON, 15-Ac-DON and DON-3-glucoside for poultry or horses. Information was more recently provided to the European Commission (EC) concluding that the Reference Points for adverse animal health effects for DON in horses and poultry (other than laying hens) established by EFSA in the abovementioned Opinion should be lower, based on an assessment of available scientific information. The Commission has requested EFSA to assess this information to verify if the Reference Points for adverse animal health effects established for DON in horses and poultry (other than laying hens) can be confirmed or need to be updated. In case the Reference Points for horses and poultry (other than laying hens) are updated, the risks to these farm animals in relation to the presence of DON in feed will be assessed using the exposure assessment included in the EFSA's 2017a opinion (EFSA CONTAM Panel, 2017a). Terms of Reference In accordance with Art. 29 (1) of Regulation (EC) No 178/2002, the EC asked EFSA to assess the information on the adverse animal health effects of deoxynivalenol in horses and poultry other than laying hens, and, if necessary, to update the scientific opinion on the risks to animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed, taking into account: – information submitted to the Commission, and – the exposure assessment included in the previous opinion (EFSA CONTAM Panel, 2017a). The information on adverse effects of DON on animal health submitted by the European Commission are summarised in Table 1 below. Table 1. Selection of research studies to be (re)assessed, as submitted by the European Commission Animal species Studies to be (re)assessed Poultry Antonissen et al., 2014a Yunus et al., 2012a Yunus et al., 2012b Horses Johnson et al., 1997 Khol-Parisini et al., 2012 Raymond et al., 2003 Raymond et al., 2005 Interpretation of the Terms of Reference Although the initial request from the European Commission referred to 'poultry other than laying hens', the CONTAM Panel, based on the observed effects in broilers, deemed it necessary to also assess new and old available evidence for laying hens. Additional information 1.2.1 Chemistry Deoxynivalenol (DON), 3-acetyl deoxynivalenol (3-Ac-DON) and 15-acetyl deoxynivalenol (15-Ac-DON) (see Figure 1) are mycotoxins belonging to the group of trichothecenes, which are produced by Fusarium species. The chemistry of DON is described by EFSA (EFSA CONTAM Panel, 2017a). Trichothecenes, characterised by a tetracyclic sesquiterpenoid 12,13 epoxytrichothec-9-en ring structure, have been classified into four groups (A–D) based on to their chemical structures. Type A and type B trichothecenes are predominant in food and feed. DON, 3-Ac-DON and 15-Ac-DON, being assessed in this Opinion, are type B trichothecenes. DON-3-glucoside, also assessed in this Opinion, is the main plant metabolite of DON and considered as a modified mycotoxin. DON is a relatively thermostable compound and soluble in water and in some polar solvents (e.g. aqueous methanol, acetonitrile and ethyl acetate). The presence of an acetyl moiety in 3-Ac-DON and 15-Ac-DON results in a decrease in the polarity of the molecule compared with the parent toxin while on the other hand, the presence of a glucoside in DON-3-glucoside leads to an increase in polarity compared with DON (EFSA CONTAM Panel, 2017a). 1.2.2 Previous animal health risk assessments In 2004, the EFSA CONTAM Panel published a Scientific Opinion related to the presence of Deoxynivalenol (DON) as undesirable substance in animal feed. Pigs were identified as the most sensitive animal species regarding these adverse effects. Nevertheless, the CONTAM Panel concluded that, due to incomplete data on exposure via feedingstuffs, no safe intake levels for pigs or other animals could be deduced. The Opinion also concluded with the comment on the transfer of DON and its metabolites into edible tissues, milk and eggs as being very low, thus, not contributing significantly to human exposure. In 2013, EFSA published a scientific report on Occurrence and exposure to DON in food and feed. Regarding animal exposure, poultry was identified as the most exposed animal group, followed by pigs, companion animals and fish. In its report, EFSA recommended further harmonisation of the monitoring strategy of DON throughout Europe and improvement of data reporting (EFSA, 2013). In 2017, the EFSA CONTAM Panel developed a Scientific Opinion on the risks for human and animal health related to the presence of DON and its acetylated and modified forms in food and feed (EFSA CONTAM Panel, 2017a). Reference points for adverse animal health effects (termed NOAELs) were derived based on the data shown various species as shown in Table 2. NOAELs were set at 5 mg/kg feed for broiler chickens and laying hens, 7 mg/kg feed for ducks and turkeys and 36 mg/kg feed for horses. The CONTAM Panel concluded that, based on estimated mean dietary concentrations of the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside in feed, adverse effects in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, a potential risk for chronic adverse effects was identified in pigs and fish and for acute adverse effects in cats and farmed mink. Table 2. NOAELs/LOAELs derived for DON in horses and poultry in the EFSA 2017 Opinion (EFSA CONTAM Panel, 2017a) and relevant toxicity studies Species No observed adverse effect level (NOAEL) Lowest observed adverse effect level (LOAEL) Adverse effects observed (type of study) References Horses 36 mg/kg feed – Reduced feed intake Johnson et al. (1997) Broiler chickens 7 mg/kg feed 10.5 mg/kg feed Decreased spleen weight, reduced body weight gain, decreased Newcastle Disease Virus (NDV) vaccine response Dänicke et al. (2003) 5 – Reduced feed intake, reduced body weight, reduced body weight gain during the first 2 weeks Awad et al. (2011) 4.6 – No effects on feed conversion ratio and body weight gain Antonissen et al. (2015) – 12 mg/kg feed Reduced feed intake, reduced body weight gain and alteration of intestinal morphology during the first 3 weeks, no zootechnical effects at the end of the experiment Yunus et al. (2012b) – 10 mg/kg feed Reduced feed intake, reduced body weight gain during the first 2 weeks, reduced total lymphocyte count, decreased Infectious Bronchitis Virus vaccine response Ghareeb et al. (2012, 2014) – 10 mg/kg feed No effects on feed intake or body weight gain or other zootechnical parameters, alteration of intestinal morphology Awad et al. (2004, 2006) Turkeys 6.5 mg/kg feed – Body weight, body weight gain, feed intake or feed conversion ratios Devreese et al. (2014) Ducks 7 mg/kg feed – Activities of glutamate dehydrogenase and gamma-glutamyl-transferase in serum (no zootechnical parameters change) Dänicke et al. (2004) Legislation Directive 2002/32/EC1 on undesirable substances in animal feed, aimed to limit undesirable substances in feed, includes, within Annex I, a list of substances which are tolerated in products intended for animal feed, subject to certain conditions. DON is not included in Annex I. Guidance values for DON concentrations in feed are provided in Commission Recommendation 2016/1319/EC.2 In particular, the Recommendation provides guidance values of DON in a feedingstuff with a moisture content of 12%, being 5 mg/kg for compound feed with the exception of compound feed for pigs (0.9 mg/kg) and calves, lambs, kids and dogs (2 mg/kg). In feed materials, a guidance value of 8 mg/kg is provided for cereals and cereal products and for maize by-products of 12 mg/kg (both relative to a feedingstuff with a moisture content of 12%). 2 Data and methodologies The current assessment was developed applying a structured methodological approach, which implied developing a priori the protocol, or strategy, of the risk assessment and performing each step of the risk assessment in line with the strategy and documenting the process. The protocol in Annex A to this Opinion contains the method that was proposed for all the steps of the assessment process, including any subsequent refinements/changes made, if applicable. Data EFSA commenced the collection of data on DON in 2004, when EFSA received a request of the European Commission, for a scientific opinion on DON as undesirable substance in animal feed (EFSA, 2004). Although EFSA called data for feed samples between 2004 and 2014, no data were reported to EFSA before 2007. In addition, in December 2010, EFSA started collected data on DON, the acetylated derivatives 3-Ac-DON and 15-Ac-DON, and DON-3-glucoside in food and feed with a call for an annual collection of chemical contaminant occurrence data in food and feed. The data set on feed used in the 2017 opinion comprised 10,771 analytical results, including 6,980 results for DON, 1,649 for 3-Ac-DON, 1,210 for 15-Ac-DON and 932 analytical results for DON-3-glucoside, which were used in the estimated dietary exposure. The methodology used in the estimated dietary exposure assessment is briefly summarised in this section. For the full details on data collection, the 2017 Opinion should be consulted (EFSA CONTAM Panel, 2017a). Methodologies 2.2.1 Methodology for data collection and study appraisal In 2021, the CONTAM Panel received from the European Commission the mandate for an assessment of information on the adverse animal health effects for DON in horses and poultry other than laying hens. Several research studies were submitted by the Commission to inform the assessment and potentially derive a lower reference point compared to the previous EFSA Opinion (EFSA CONTAM Panel, 2017a). In addition to the papers provided as part of the mandate, the working group (WG) performed a literature search to obtain further evidence on horses and poultry overall which might have become available since the previous Opinion (EFSA CONTAM Panel, 2017a). Three search strings were designed to identify potentially relevant studies published between 31 July 2016 (based on the year of publication of the EFSA CONTAM Panel, 2017a) and 19 April 2022, the date when the actual search was performed (see Appendix A). After removal of duplicates and applying inclusion/exclusion criteria, potentially relevant references were identified. The total number of publications identified were 512 and 50 for poultry and horses, respectively, while the number of publications identified as potentially relevant were 41 for poultry and 5 for horses. The abstracts considered as potentially relevant were screened by the experts of the WG and were used in the assessment if considered relevant for the scope of the mandate by applying expert judgement. In addition to the literature search and the use of the papers submitted by the European Commission, a 'forward snowballing' approach33 was applied by the WG members in order to potentially obtain further papers published up to 19 April 2022. 2.2.2 Methodology applied for dietary exposure assessment, hazard and risk characterisation In the 2017 Opinion (EFSA CONTAM Panel, 2017a), two approaches were followed. Where information was available, the levels of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside contamination in species-specific compound feeds were used to estimate exposure. Where these data were provided in sufficient numbers (> 60 samples), the mean and 95th percentile dietary concentrations and exposures were calculated using the concentrations reported. For those farm animal categories for which data were insufficient, DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside concentrations of individual feed materials were taken into account, together with example diets, to estimate and the mean and P95th percentile exposure. For the full details on the dietary exposure assessment performed for DON, the 2017 Opinion should be consulted (EFSA CONTAM Panel, 2017a). The CONTAM Panel applied the general principles of the risk assessment process for chemicals in food as described by the WHO/IPCS (2009), which include hazard identification and characterisation, exposure assessment and risk characterisation. In addition to the principles described by the WHO/IPCS (2009). EFSA guidance relevant for the present assessment has been duly considered (see Appendix B for the EFSA guidance applied). 3 Assessment Hazard identification and characterisation 3.1.1 Toxicokinetics The toxicokinetics (TK) of DON in poultry and horses has been summarised by EFSA (EFSA CONTAM Panel, 2017a); a recent review by Sun et al. (2022) covers several species excluding horses. In poultry, DON is rapidly absorbed being characterised by low oral bioavailability (5–20%), wide distribution in most tissues and rapid clearance from the body. Sulfation and de-epoxidation are the main metabolic pathways and lead to the formation of metabolites with a markedly lower toxicity (Schwartz-Zimmermann et al., 2015). In liver and to some extent in the gut, DON undergoes extensive sulfation, DON 3-sulfate (DON-3 S) being the prevalent metabolite. A very efficient de-epoxidation of DON to DOM-1 and DOM-3 is reported to occur in gut microbiota and may explain the comparatively lesser sensitivity of poultry to this mycotoxin; both DOM derivatives also undergo sulfation. As further gut-derived DON metabolites, the sulfonates DONS 1, DONS 2 and DONS 3 have been reported (Schwartz-Zimmermann et al., 2015). There are studies indicating a rapid plasma clearance of DON (t1/2 < 1 h) and DON-3 S; in a recent study, however, no detectable plasma levels of DON and DON-3 S could be detected in plasma from chickens exposed to DON orally at two different doses (0.75 and 2.25 mg/kg bw) (Riahi et al., 2021a). In poultry, DON metabolites are excreted via the bile and urines and only little amounts of unmodified DON is found in the excreta. In broiler chickens, a nearly complete hydrolysis of 3-Ac-DON to DON and a partial hydrolysis of 15-Ac-DON to DON was observed. Limited results indicate that DON-3-glucoside was not hydrolysed to DON in broiler chickens. The oral bioavailability of DON-3-glucoside was low and comparable to that of DON. Little is known about DON TK in horses. In a recent paper, samples of soil and animal excreta collected in a horse stable were found to extensively metabolise DON into DOM-1 (Cai et al., 2022) which, however, is not reflected by the ratio of DON to DOM-1 in blood of DON-exposed horses (Schulz et al., 2015). The predominance of DON in blood of horses suggests that it is probably intensively absorbed in the proximal parts of the intestine where microbial activity is less pronounced compared to colon and caecum. Based on a limited data set, the oral bioavailability of DON remains unclear so far. As in other mammalian species, glucuronidation is the major conjugation reaction and a rapid plasma clearance of DON- and DOM-1 glucuronides was observed. No data were identified for 3-Ac-DON, 15-Ac-DON and DON-3-glucoside in horses. 3.1.2 Mode of action DON, like other trichothecenes, binds to the 60 S subunit of the ribosome. This binding leads to an inhibition of protein synthesis and subsequently an inhibition of RNA and DNA synthesis. DON binding to the ribosome activates different mitogen-activated protein kinases (MAPKs). The binding to the ribosome and the activation of MAPKs induces multiple consequences such as cell death, ribotoxic stress response, inflammation, oxidative stress, cell cycle arrest, endoplasmic reticulum stress (EFSA CONTAM Panel, 2017a). More recently, autophagy has also been described as a consequence of DON exposure (Kowalska et al., 2022). DON is well described to induced anorexia and/or emesis. Two mediators may explain this effect: on the one hand, the secretion of pro-inflammatory cytokines and on the other hand the secretion of satiety hormones, which activate receptors in the abdominal vagus afferent neurons (Lebrun et al., 2015; Terciolo et al., 2018). Since 3-Ac-DON and 15-Ac-DON are largely deacetylated and DON-3-glucoside cleaved in the intestines the same toxic effects as DON can be expected. 3.1.3 Adverse effects in horses and poultry The sections below describe the critical studies from the 2017 Opinion for poultry and horses, as well as newly identified studies, not evaluated in that assessment. Based on the review of the available evidence for broilers, the CONTAM Panel decided to also reassess all poultry, including laying hens. Where reported, the concentrations of 3-Ac-DON, 15-Ac-DON and DON-3-glucoside were added to that of DON to calculate the reference point (RP) for adverse animal health effects. In assessing toxicity of DON in the above-mentioned animal species, the CONTAM Panel noted that the exposure to DON from naturally contaminated materials is of complex interpretation due to impacts on physico-chemical alterations (e.g. in growing chicken, intestinal viscosity increasing effects due to increased proportion of soluble non-starch polysaccharides) caused by Fusarium infection of the plant used as feed material (Dänicke et al., 2007). 3.1.3.1 Poultry In the EFSA 2017 Opinion, the CONTAM Panel concluded that in broiler chickens, DON caused adverse effects such as reduced feed intake, reduced body weight gain, alteration of intestinal morphology and alteration of vaccine response to Newcastle disease (NDV) vaccine response, based on studies from Awad et al. (2004, 2006), Dänicke et al. (2003), Ghareeb et al. (2012, 2014) and Yunus et al. (2012b). The CONTAM Panel concluded that an NOAEL of 5 mg DON/kg feed could be identified. Further detail is included in Section 1.2.2. Several new studies were identified and are described below, as well as studies brought to the attention of the Panel by competent authorities. Broilers Studies to be reassessed Yunus et al. (2012a,b) treated 7-day-old broilers (n = 25 per group) for up to 5 weeks with diets shown to contain 0.27 (considered by the authors as control group), 1.68 or 12.2 mg/kg dry matter (DM), in addition to 3-acetyl-DON (0.01, 0.20 and 1.45 mg/kg DM, respectively) and zearalenone (0.01, 0.15 and 1.09 mg/kg DM, respectively). Part of the animals were slaughtered after 8–10 or 22–24 days of treatment to examine effects on the intestines. The studies showed a decreased body weight at some time points and effects on gut physiology. These studies were considered by the CONTAM Panel previously, but the effects on body weight gain after 3 weeks of exposure were deemed transient; and since the broilers showed a good adaptation to tested concentrations of DON at the end of the exposure period, the concentration of 12.2 mg/kg feed was identified as the LOAEL of the study. Having reassessed the Yunus et al. (2012a,b) papers, the CONTAM Panel noted: The reduced body weight gain was observed at the high DON level after 1 week, at both DON levels after 3 weeks. At the end of the productive cycle (after 5 weeks of treatment), body weights were 2,365 ± 131, 2,231 ± 75 and 2,064 ± 97 g (mean ± SE) for the seven remaining broilers per group, the differences not being statistically significant. There was a significantly reduced feed intake at both feed levels during the third week and for the whole 5-week period for the high level. Differences in unit weight (g/cm) of different intestinal segments were observed at week 4 of treatment (22–24 days of exposure) at both levels but were not dose-dependent; the same applies for the significant decrease in both villus height and crypt depth. Provided that zootechnical performances4 do not seem to be affected in a statistically significant way (but see also point a), it remains to be established whether the described changes may impair animal welfare. An adverse effect concentration of 1.9 mg/kg feed for the sum of DON and 3-Ac-DON was identified, resulting in an RP of 0.6 mg/kg feed, using an uncertainty factor (UF) of 3 since the lowest concentration already showed effects. Antonissen et al. (2014) investigated the effects of a DON contaminated diet (between 2.9 and 4.4 mg DON/kg feed), administered for 14 days to Ross broilers, on the enteric epithelial barrier integrity and morphology. DON-treated animals showed a reduction in villus height and transepithelial electric resistance (TEER) of duodenal segments. New studies Several new studies have been published since the last Opinion (EFSA CONTAM Panel, 2017) and are described below. Grenier et al. (2016) investigated the effects of DON on chickens challenged with Eimeria spp., responsible for coccidiosis. In this study, 1-day-old male broilers (Ross 708) were fed on diets (84 birds/diet) contaminated with DON (1.6 mg/kg) or fumonisins (FUM) (20.5 mg/kg) alone, in combination or without mycotoxins (control diet) for 20 days. The 14th day of the experiment, half of the birds were challenged with Eimeria spp., responsible for coccidiosis, and samples of the intestines were taken after 6 days. A group of 42 birds fed with DON diet remained unchallenged. The performance, clinical signs, gross lesions, gut integrity and inflammation were studied in all birds. Considering the unchallenged birds exposed to DON, no mortality and no changes in body weight and feed intake were observed, as well as no alterations in villus height of the jejunum. Liu et al. (2020) used male Cobb broilers to investigate the impact of DON and FUM on growth, nutrients and digestible energy. Therefore, 320 birds (plus 80 used as control) were fed with corn−soybeans contaminated with DON (1.3, 4.3 mg/kg) for 15 days. Subsequently, half of them were switched to the respective nitrogen-free diets (NFD) (NFD control; NFD DON 1.4 mg/kg and NFD DON 3.7 mg/kg) for the next 6 days. On the last day (21) of the experiments, ileum digesta was sampled to calculate digestible energy. No impact on mortality-adjusted feed conversion ratio and body weight gain (BWG) was observed in DON-fed chicks. DON alone (1.3, 4.3 mg/kg) failed to influence BWG but reduced it significantly when combined with 20 mg FUM/kg diet irrespective of the DON concentration. Regarding digestibility, no significant differences were noticed except from a decreased diges
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