dataesr/scientific-paragraphs-categorization huggingface dataset:
Occurrence data Within the continuous data collection of EFSA, a total of 21,916, 4,000 and 1,621 analytical results of DON in food, feed and unprocessed grains of undefined end-use, respectively, fulfilled the required quality criteria. For 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, fewer analytical results, which fulfilled the criteria, were submitted to EFSA. The numbers of results ranged from 430 for 15-Ac-DON in unprocessed grains of undefined end-use to 11,944 for 3-Ac-DON in food. For 'Grains and grain-based products', which was the food category with the majority of analytical results, the proportion of left-censored data (results below the limit of detection (LOD) or limit of quantification (LOQ)) was 52% for DON and 59% for DON-3-glucoside, but above 95% for both acetylated forms. 'Cereal grains' was the category with the majority of analytical results for feed and had only 47% of left-censored data for DON, 80% for 15-Ac-DON, and about 95% for DON-3-glucoside and 3-Ac-DON.
The proportions of left-censored data for unprocessed grains of undefined end-use ranged from 45% for DON to 96% for the other three forms. The highest mean concentrations of DON and the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside were recorded for the categories 'Products for special nutritional use' and 'Grains and grain-based products' for food, 'Cereal straw' for feed and 'Grains as crops' for unprocessed grains of undefined end-use. Because DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside are mostly attached to the outer hull of the grain, cleaning, sorting, sieving and dehulling of grains lead to marked increases in concentrations of these toxins in cereal by-products, e. g. bran. During baking and cooking, DON appears to be relatively stable but the results for 3-Ac-DON and 15-Ac-DON were inconclusive and studies on DON-3glucoside showed inconsistent and varying results.
Relevant increases of concentrations were observed during fermentation stages, while relevant reductions occurred during baking. Malting and brewing do not seem to lead to losses of DON and DON-3-glucoside and no increased concentrations were observed in by-products of brewing. However, the ratio between DON and DON-3-glucoside concentrations changed during the process due to a notable increase of the concentrations of DON-3glucoside as compared to DON. Studies on the fate of 3-Ac-DON and 15-Ac-DON during malting and brewing were too limited to draw conclusions. The data on feed processing were limited but since many of the processes applied to cereal grains for food production are also applied to grains used for animal feeds, the findings for food should also apply to feed. The CONTAM Panel estimated the relative ratios of concentrations of 3-Ac-DON, 15-Ac-DON and DON-3-glucoside to DON as 10%, 15% and 20%, respectively, and noted that they concurred with observations in feed and unprocessed grains of undefined end-use, except for 'Alcoholic beverages' ('Beer and beer-like beverage') where the ratio of DON-3-glucoside to DON was estimated as 80%.
In porcine and human intestinal cells, the cytotoxic potency ranked in the order of 15-Ac-DON > DON > 3-Ac-DON and that was similar for barrier function, MAPK activation and expression of tight junction, and histological alterations. DON-3glucoside was considerably less toxic than DON in both in vitro and in vivo studies. The available database on effects of combined exposure to DON and other mycotoxins was weak and insufficient for establishing the nature of combined effects. In addition, no in vivo studies on the combined effects of 3-Ac-DON, 15-Ac-DON or DON-3-glucoside with other mycotoxins were identified. Accounting all toxicokinetic and toxicity information available, the CONTAM Panel noted that 3-Ac-DON and 15-Ac-DON were largely deacetylated to DON prior to systemic distribution, such that they might induce the same acute and chronic effects as DON.
In addition, the available human biomarker data were exploited as supporting information. Based on adverse gastrointestinal effects identified from the human outbreak data in China and noting that vomiting occurred within 30 min after an eating occasion, the CONTAM Panel calculated a NOAEL of 26 lg DON/kg bw for a single eating occasion. By applying a default uncertainty factor of 3. 16 for toxicodynamic kinetic differences in the intra-human population variability, a group ARfD of 8 lg/kg bw per eating occasion was determined. The CONTAM Panel concluded that the dose range calculated from the human biomarker data supported this reference dose. In the absence of data on chronic effects in humans, the CONTAM Panel identified reduced body weight gain in experimental animals as the critical chronic effect for human risk assessment.
Risk characterisation for farm and companion animals For the farm and companion animals, the CONTAM Panel characterised the chronic animal health risk for the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside using the dietary concentration estimates at the UB mean and UB 95th percentile based on feed composition and the available occurrence data on feeds and compared them with the identified NOAELs. For characterising the acute animal health risk, the calculated UB 95th percentile dietary concentrations (dietary exposure in case of farmed mink) were used and compared with the respective NOAEL or BMDL/BMCL 10 for pigs, farmed mink, dogs and cats, for whom vomiting was reported. The dietary concentrations of the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside for ruminants and horses were clearly below the identified NOAELs for chronic adverse effects and are therefore considered unlikely to be a health concern, while for poultry and farmed rabbits the estimated dietary concentrations indicated that the risk of chronic adverse health effects from the feed containing DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside is low.
, 1999). Five toxicological studies (four on mice and one on swine) were examined for deriving a NOAEL. The 2-year feeding study in mice by  Iverson et al. (1995)  was used to derive a provisional TDI. An uncertainty factor of 100 (10 for interspecies and 10 for interindividual uncertainty) and a more accurate round-up approach than in other assessments mentioned above were applied and, therefore, the TDI was reported as 1. 1 lg/kg bw per day. The Health Council of the Netherlands also conducted a risk assessment on DON  (HCN, 2001). The Council used the data from the same 2-year feeding study  (Iverson et al. , 1995)  with an uncertainty factor of 210 to establish a TDI of 0. 5 lg/kg bw per day. The uncertainty factor comprised the subfactors of 10 for intra-and 3 for interspecies differences, and a factor of 7 for differences in energy use and differences in metabolism, possibly affecting body weight changes, between humans and mice.
, 2008a). The samples were purified with IAC and analysed by HPLC-MS using an internal standard ( 13 C-DON). The method was validated using the UK Adult National Diet and Nutrition Survey (ANDNS) data and individual 24-h urine samples (see  Turner et al. , 2008a Turner et al. , , 2010a)). Fast advances in LC-MS technology have allowed multiple mycotoxins to be analysed simultaneously. This technique was applied to multiple mycotoxin biomarker development and several methods have been reported recently. For LODs/LOQs of the multi-biomarker methods see Table  53. Solfrizzo et al. (2011)  developed a multi-biomarker method using UPLC-MS/MS for detection of DON, DOM-1 and six other mycotoxins and their metabolites following a combined IAC and SPE purification. b-Glucuronidase/sulfatase were added to deconjugate DON prior to extraction.
In summary, based on limited available information the data from the literature on comparative occurrence of DON in organically and conventionally produced cereal grains (used for food and feed) and grain products generally confirmed the pattern as derived from the data on occurrence of DON in food, feed and unprocessed grains of undefined end-use submitted to EFSA. DON concentrations were either generally at the same level or marginally lower in organically produced grains (and food and feed products) as compared to conventionally produced grains (and food and feed products). 4. 2. 7. Currently reported co-occurrence of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside in food, feed and unprocessed grains of undefined end-use The occurrence data submitted to EFSA, where analytical results on DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside in all possible combinations (singletons, pairs, triplets or quadruplets) were reported for the same samples, were extracted from the EFSA database.
There were a total of 142, 168 and 83 samples with quantified ratios of 3-Ac-DON, 15-Ac-DON and DON-3-glucoside to DON, respectively, for the group of 'Grains and grain-based products'. The CONTAM Panel noted that these ratios represented only a very small proportion of the entire database of occurrence in food (see Tables  12 13 14 15 16 17 ). The mean ratios were 1. 6 for 3-Ac-DON to DON, 0. 7 for 15-Ac-DON to DON and 1. 9 for DON-3-glucoside to DON for the food group of 'Grains and grain-based products'. For 'Alcoholic beverages' the number of quantified ratios was too small to draw any conclusions (Table  31 ). The CONTAM Panel noted that the ratios in 'Grain and grain-based products' for 3-Ac-DON, 15-Ac-DON, and DON-3-glucoside to DON (i. e. 3. 0, 1. 2 and 2. 1, respectively) were higher for one MS compared to other countries where the ratios were 0.
It was concluded that the method performance of the two laboratories was similar and gave comparable results for DON, 3-Ac-DON, 15-Ac-DON and DON-3glucoside for this set of samples. However, since no samples of 'Grain and grain-based products' were available where DON concentrations were lower than the other DON forms (i. e. ratio > 1) this ad hoc study could not confirm the higher concentrations of 3-Ac-DON, 15-Ac-DON and DON-3-glucoside compared to DON reported by the one MS shown in Table  31. For feed, there were 44, 69 and 50 samples with quantified ratios of 3-Ac-DON, 15-Ac-DON and DON-3-glucoside to DON, respectively, all for complete feed, the largest category of samples of feed. As for food, the CONTAM Panel noted that these ratios represented only a very small proportion of the entire database of occurrence in feed.
The mean ratios were 0. 3 for 3-Ac-DON to DON, 0. 3 for 15-Ac-DON to DON and 0. 4 DON-3-glucoside to DON. For grains of undefined end-use in grain and grain-based products, there were 94, 125 and 175 samples with quantified information for the ratios of 3-Ac-DON, 15-Ac-DON and DON-3-glucoside to DON, respectively, again only a small proportion of the entire database. The mean ratios were 0. 2 for 3-Ac-DON to DON, 0. 3 for 15-Ac-DON to DON and 0. 4 for DON-3-glucoside to DON. A comparison of the three ratios of 3-Ac-DON, 15-Ac-DON and DON-3-glucoside to DON as derived from the EFSA database with those found in the literature was difficult to make since the ratios derived from data in the EFSA database were means of the ratios, while it was not possible to derive these from the literature data (see Section 4.
2. 7 for samples for the food groups 'Grains and grain-based products' and 'Alcoholic beverages' for which analysis results with a numerical values were reported. The data from these food groups were considered the most relevant due to the high number of overall reported results and the sufficient number of quantified results. Noting that the pairs of samples with such quantified co-occurrence results were only a small proportion of the entire occurrence database, the CONTAM Panel decided to supplement these ratios by ratios calculated from the available literature data for food and feed (see  Section 4. 1. 4). Excluding the data of the one MS (see Section 4. 2. 7 and Table  31 ), the ratios for 3-Ac-DON and 15-Ac-DON to DON for 'Grains and grain-based products' were approximately 0. 1 and 0.
3 respectively. Accounting furthermore for the ratios reported in the literature (see Section 4. 1), the CONTAM Panel concluded that a %-ratio of 10% for 3-Ac-DON to DON was well supported by literature data. In contrast, a %-ratio of 30% for 15-Ac-DON to DON was not at all supported by the ratios reported in the literature, which were ranging from 0. 05 to 0. 3. Therefore, a %-ratio of 15% for 15-Ac-DON to DON appeared to be a plausible estimate. For the estimation of a %-ratio for DON-3-glucoside to DON, the CONTAM Panel decided to use only literature data because the amount of samples with quantified co-occurrence results available to calculate the ratio of DON-3-glucoside to DON was much smaller in the EFSA database than in the available literature (see Section 4. 1). From the ratios of DON-3-glucoside to DON calculated based on available literature data on 'Grains intended for food consumption' (see Section 4.
Although the data on the concentration ratios on cereal grains for feed were scarce in both the available literature and the EFSA database (see  Sections 4. 1. 4 and 4. 2. 7) , the available calculated concentration ratios for cereal grains for feed were not inconsistent with those calculated for food. Therefore the CONTAM Panel assumed that using the %-ratios derived for food would also be plausible for feed and unprocessed grains of undefined end-use. The CONTAM Panel also explored whether the non-analysed concentrations of 3-Ac-DON and/or 15-Ac-DON and/or DON-3-glucoside in the food sample could be estimated by the mean concentration of the respective DON-form of the same food category. Such an approach would then also apply for the non-analysed concentrations of feed or the concentrations of unprocessed grains of undefined end-use.
2) which reported all four DON forms and at least one of the other Fusarium toxins in the same sample were extracted from the EFSA database. Co-occurrence of DON, 3-Ac-DON, 15-Ac-DON or DON-3-glucoside with zearalenone, a/b-zearalenols, nivalenol, sum of T-2 and HT-2 toxins or fumonisins (mainly B1) were calculated considering 266,686 samples both with quantified and detected results reported for food, feed and unprocessed grains of undefined end-use. The highest co-occurrence with the other Fusarium toxins was observed for DON (58% of the samples) with one of the other Fusarium toxins. The highest co-occurrence was for DON and nivalenol (63% of the samples) and the second highest for fumonisins (56% of the samples). Co-occurrence of approximately 50% was observed for DON with zearalenone and for DON with the sum of T-2 and HT-2 toxins, whereas 20% of the samples for DON and a/b-zearalenols co-occurred at approximately 20% only.
Food consumption Since 2010, the EFSA Comprehensive European Food Consumption Database (Comprehensive Database) has been populated with national data from national information on food consumption at a detailed level. Competent authorities in the European countries provide EFSA with food consumption data at the level of the individual consumer from the most recent national dietary survey in their country (cf. Guidance of EFSA 'Use of the EFSA Comprehensive European Food Consumption Database in Exposure Assessment' (EFSA, 2011a)). New consumption surveys added in 2015 in the Comprehensive Database 30  were also taken into account in this assessment. 31 ood consumption data included in the Comprehensive Database were collected through different methodologies, and thus direct country-to-country comparisons should be interpreted with caution.
Depending on the food category and the level of detail used in the exposure calculations, uncertainties can be introduced because of possible subjects' underreporting and/or misreporting of the consumption amounts. Nevertheless, the food consumption data gathered at EFSA in the Comprehensive Database are the most complete and detailed data currently available in Europe. Competent authorities in the European countries provided EFSA with data from the most recent national dietary survey in their country at the level of consumption by the individual consumer. This included food consumption data concerning infants (6 surveys from 6 countries), toddlers (11 surveys from 10 countries), children (20 surveys from 17 countries), adolescents (20 surveys from 17 countries), adults (24 surveys from 22 countries), elderly (16 surveys from 15 countries) and very elderly (14 surveys from 14 countries) for a total of 41 different dietary surveys carried out in 23 different countries covering more than 78,400 individuals.
Wheat was the major contributor (56-100%) to DON exposure in the majority of the regions (FAO/WHO, 2011). Acute DON exposure was assessed using the highest mean occurrence data and the 97. 5th percentile consumption data for the sum of DON, 3-Ac-DON and 15-Ac-DON using the GEMS/Food database. For the acute exposure calculation, bread was taken as the representative food type due to the frequent daily consumption (typically 9 g/kg bw per day). Based on the concentration of 1 mg DON/kg, the estimated acute dietary exposure was 9 lg/kg bw per day (FAO/WHO, 2011). c)  0. 36, 1. 00 (c) 0. 08, 0. 13 (c) 0. 14 (c)  0. 18 (c)  0. 50 (c)  0. 48 (c) 0. 37 (c)  0. 29, 0. 66 (c) 0. 25, 1. 26 (c) 0. 17, 0. 21 (c) 0. 14, 0. 25 (c)   SCOOP (  2003 ) 0. 01-0. 02 0. 17 (a)  0. 36 (a)   FSCJ (  2010   and DON-3-glucoside (see Sections 4.
Current mean and 95th percentile acute dietary exposure The acute dietary exposure to the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside and the exposure to DON (Appendix F, Table  F. 2) was calculated on a per day basis, since individual meals are recorded for only a few countries in the consumption database. The preferred option is, therefore, to use individual consuming days. Consuming days offer a conservative estimate of the exposure, since it will sum the contribution of all meals during the same day. Acute exposure was assessed for each reporting day by multiplying the total consumption amount for each food category by an occurrence level randomly drawn among individual results available for that food category. Respective intakes of the foods consumed that day were summed and finally divided by the individual's body weight.
Current mean and 95th percentile chronic dietary exposure For assessing the chronic dietary exposure to the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3glucoside and DON alone, food consumption and body weight data at the individual level were accessed in the Comprehensive Database. Occurrence data and consumption data were linked at the lowest FoodEx code possible. Exposure estimates were calculated per dietary survey and age class for each of the 35 different dietary surveys carried out in 19 different European countries (see Section 5. 1). However, it should be noted that not all countries provided consumption information for all age groups of interest or in some cases the same country provided more than one consumption survey. The mean and the 95th percentile chronic dietary exposure to the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside and to DON alone were calculated separately for each dietary survey using consumption data recorded at the individual level.
3. In accordance with the specifications of the EFSA Guidance on the use of the Comprehensive database (EFSA, 2011b), the 95th percentile estimates for dietary surveys/age classes with less than 60 observations may not be statistically robust and therefore they were not considered in the exposure assessment. Given the high number of occurrence data reported for DON alone and the high percentage of leftcensored data for 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, the CONTAM Panel calculated that the % of the contribution 38 of the chronic exposure to DON alone (Appendix F) to the chronic exposure of the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside was between 60% and 85% across different age groups and concluded that the overall dietary exposure was driven by DON.
Dietary exposure to the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside for vegetarian diets include more cereal and cereal-based products and therefore it was considered that the exposure to the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside in this consumer group could be higher. The Comprehensive Database contains only limited data on food consumption of vegetarians. Dietary exposure was calculated and compared to the exposure of all subjects included in the respective dietary study. Generally, for acute exposure, higher mean and 95th percentile exposures were not observed compared to the general population, with the exception of toddlers, other children and adults who appeared to have marginally higher exposures (Table  38 ). Similarly, for chronic exposure higher mean and 95th percentile exposures were not generally observed in vegetarians compared to the total population within the same dietary survey (Table  39 ).
Thus, the limited data on vegetarians do not indicate a substantial difference in the dietary exposure to the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside between the vegetarians and the general population. This finding was supported by the estimated exposure based on the database in the EFSA biomarker study  (Brera et al. , 2015)  (see also Section 7. 5. 2).
The first section below focuses on studies performed in vivo (ingestion of contaminated diet) on experimental animals and assessing immune functions. In vitro experiments performed on human immune cells are also described since they may be relevant for hazard characterisation. Due to the large database on in vivo and in vitro studies on immunotoxicity of DON, the CONTAM Panel decided to base the description of the immunotoxicity of DON mainly on review papers  (Rotter et al. , 1996; Pestka, 2003 Pestka, , 2010b;; Pestka et al. , 2004; Antonissen et al 2014; Wu et al. , 2014c; Payros et al. , 2016). The evidence database was far smaller for the 3-Ac-DON, 15-Ac-DON and DON-3-glucoside and for these compounds the CONTAM Panel reviewed all the identified studies. As reported by the SCF (1999), studies with experimental animals demonstrated effects on the immune system notably effects on IgA.
Ruminants A number of studies have reviewed the health effects of DON in cattle  (DiConstanzo and Murphy, 1994; Yiannikouris and Jouany, 2002; Pestka, 2007 Pestka, , 2010b;; Fink-Gremmels, 2008; Whitlow et al. , 2010). As described in the toxicokinetic section (see  Section 7. 1. 5. 1) , DON is converted into the less toxic de-epoxidised metabolite DOM-1 by the ruminal flora. Therefore from the studies available in the literature, only those performed using the largest number of animals and the highest DON concentrations in feed combined with the longest periods of time were selected for this opinion. However, young ruminants, in which the rumen is not fully developed, could be less active in de-epoxidation and might therefore be more sensitive than adult ruminants when exposed to DON. For small ruminants (sheep and goats) the database on adverse effects of DON, 3-Ac-DON, 15-Ac-DON and/or DON-3-glucoside was very limited or lacking.
Reduced feed intake and weight gain reduction were identified as the critical chronic adverse effects of DON in pigs and wide ranges of NOAEL and LOAEL values were identified by the CONTAM Panel. The overall NOAEL for reduced feed intake and weight gain was 0. 7 mg DON/kg feed and the overall LOAEL 0. 35 mg DON/kg feed. The CONTAM Panel noted that the LOAELs in some studies on pigs were lower than the NOAELs in other studies and depending on the observation period NOAELs were equal to the LOAELs in some studies, which was likely due to adaptation of the pigs to the DON exposure. However, reiterating EFSA (  2004 ), the CONTAM Panel noted that the reduction in body weight gain observed during the first period was not fully compensated by the time when the pigs reached slaughter weight. Due to the limited or lack of data on adverse effects in pigs caused by 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, no specific NOAELs/LOAELs could be identified for these forms.