Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Abstract

Deoxynivalenol (DON) is a mycotoxin primarily produced by Fusarium fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3-acetyl-DON (3-Ac-DON), 15-acetyl-DON (15-Ac-DON) and DON-3-glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used. For human exposure, grains and grain-based products were main sources, whereas in farm and companion animals, cereal grains, cereal by-products and forage maize contributed most. DON is rapidly absorbed, distributed, and excreted. 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. The TDI of 1 μg/kg bw per day, that was established for DON based on reduced body weight gain in mice, was therefore used as a group-TDI for the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside. In order to assess acute human health risk, epidemiological data from mycotoxicoses were assessed and a group-ARfD of 8 μg/kg bw per eating occasion was calculated. Estimates of acute dietary exposures were below this dose and did not raise a health concern in humans. The estimated mean chronic dietary exposure was above the group-TDI in infants, toddlers and other children, and at high exposure also in adolescents and adults, indicating a potential health concern. Based on estimated mean dietary concentrations in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, there is a potential risk for chronic adverse effects in pigs and fish and for acute adverse effects in cats and farmed mink.

Keywords: 15‐acetyl‐deoxynivalenol; 3‐acetyl‐deoxynivalenol; Deoxynivalenol; deoxynivalenol‐3‐glucoside; exposure; human and animal risk assessment; toxicity.

Figure 1

Chemical structures of DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside

Figure 2

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside collected from the European countries

1. Results were reported for food, feed and unprocessed grains of undefined end use. AT, Austria; BE, Belgium; BG, Bulgaria; CY, Cyprus; CZ, the Czech Republic; DE, Germany; DK, Denmark; EE, Estonia; ES, Spain; FI, Finland; FR, France; GR, Greece; HU, Hungary; IE, Ireland; IT, Italy; LT, Lithuania; LU, Luxembourg; LV, Latvia; MT, Malta; NL, the Netherlands; NO, Norway; PO, Poland; PT, Portugal; RO, Romania; SE, Sweden; SI, Slovenia; SK, Slovakia; UK, the United Kingdom.

Figure 3

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside over the sampling years

Figure 4

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in food collected from the European countries

1. AT, Austria; BE, Belgium; BG, Bulgaria; CY, Cyprus; CZ, the Czech Republic; DE, Germany; DK, Denmark; EE, Estonia; ES, Spain; FI, Finland; FR, France; GR, Greece; HU, Hungary; IE, Ireland; IT, Italy; LT, Lithuania; LU, Luxembourg; LV, Latvia; MT, Malta; NL, the Netherlands; NO, Norway; PO, Poland; RO, Romania; SE, Sweden; SI, Slovenia; SK, Slovakia; UK, the United Kingdom.

Figure 5

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in food over the sampling years

Figure 6

Distribution of DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside analytical results across food groups

Figure 7

Distribution of the LOQs for (a) DON, (b) 3‐Ac‐DON, (c) 15‐Ac‐DON and (d) DON‐3‐glucoside across food groups

1. (Box‐plot: whiskers at minimum and maximum, box at 25th percentile and 75th percentile with line at 50th percentile). When the median is equal to the lower or upper quartile, the median and the quartile overlap and in the graph a bold single line is displayed. This may occur especially when the number of left‐censored data is high. Moreover, when the maximum (minimum) value is equal to the upper (lower) quartile, whiskers overlap with the box and a bold line is displayed.

Figure 8

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in feed across the European countries

1. BE, Belgium; BG, Bulgaria; CZ, the Czech Republic; DE, Germany; EE, Estonia; ES, Spain; FI, Finland; FR, France; HU, Hungary; LT, Lithuania; LU, Luxembourg; NL, the Netherlands; NO, Norway; PT, Portugal; RO, Romania; SI, Slovenia; SK, Slovakia; UK, the United Kingdom.

Figure 9

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in feed over the sampling years

Figure 10

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in the feed categories

Figure 11

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in the feed categories

Figure 12

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in unprocessed grains of undefined end‐use across the European countries

1. BE, Belgium; BG, Bulgaria; CY, Cyprus; CZ, the Czech Republic; DE, Germany; DK, Denmark; FI, Finland; FR, France; HU, Hungary; IE, Ireland; LT, Lithuania; NL, the Netherlands; RO, Romania; SI, Slovenia; SK, Slovakia; UK, the United Kingdom.

Figure 13

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in unprocessed grains of undefined end‐use over the sampling years

Figure 14

Distribution of analytical results for DON, 3‐Ac‐DON, 15‐Ac‐DON and DON‐3‐glucoside in unprocessed grains across grain groups

Figure G.1

Dose–response curves for the body weight of female and male mice combined (see also Table G.2)

1. Mean body weight is expressed as g and dose as mg/kg bw per day. The red (upper) curve is for male and the black (lower) for female mice data.

Figure G.2

Dose–response curves for the feed intake of female and male mice combined of Iverson et al. (1995) (see Table G.3)

1. Mean feed intake is expressed as g feed per day and dose as mg/kg bw per day. The red curve is for female mice data and the black for male mice data.

Figure G.3

Concentration–response curves for the body weight of female and male mice combined (see also Table G.4)

1. Mean body weight is expressed as g and concentration as mg/kg feed per day. The red (upper) curve is for male and the black (lower) for female mice data.

Figure G.4

Concentration–response curves for feed intake of female and male mice combined (see also Table G.5)

1. Mean feed intake is expressed as g feed per day and concentration as mg/kg feed per day. The red (upper) curve is for male and the black (lower) for female mice data.

Figure G.5

Dose–response curves of body weight for p53+/+ and p53+/− mice combined of Bondy et al. (2016) (see also Table G.7)

1. Means are expressed as body weight (g) and dose as mg/kg bw per day. The blue (upper) curve is for the p53+/+ male mice, the green (lower) for the p53+/− male mice and the red (middle) for the combined mice data.

Figure G.6

Dose–response curve of mean body weight in male rats of Sprando et al. (2005) (see also Table G.8)

1. Mean is expressed as body weight (kg) and dose as mg/kg bw per day.

Figure G.7

Dose–response curve of body weight gain in male rats of Sprando et al. (2005) (see also Table G.8)

1. Mean is expressed as body weight (kg) and dose as mg/kg bw per day.

Figure G.8

Dose–response curve of feed intake in male rats of Sprando et al. (2005) (see also Table G.8)

1. Mean is expressed as body weight (kg) and dose as mg/kg bw per day.

Figure G.9

Dose–response curve of body weight in female rats Collins et al. (2006) (see also Table G.9)

1. Mean is expressed as body weight (kg) and dose as mg/kg bw per day.

Figure G.10

Dose–response curve of body weight gain in female rats Collins et al. (2006) (see also Table G.9)

1. Mean is expressed as body weight (kg) and dose as mg/kg bw per day.

Figure G.11

Dose–response curve of feed intake in female rats Collins et al. (2006) (see also Table G.9)

1. Mean is expressed as body weight (kg) and dose as mg/kg bw per day.

Figure G.12

Concentration–response curve of the incidence of vomiting in pigs reported by Young et al. (1983) (see also Table G.11)

1. The (red) curve is the fitted dose–response curve from the Weibull model and the dotted line curve indicates the 95% lower confidence limit to the calculated BMCL.

Figure G.13

Concentration–response curve of the incidence of vomiting in pigs reported by Williams et al. (1988) (see also Table G.12)

1. The (red) curve is the fitted dose–response curve and the dotted line curve indicates the 95% lower confidence limit to the calculated BMCL.

Figure G.14

Concentration–response curve of the incidence of vomiting in dogs reported by Hughes et al. (1999) (see also Table G.14)

1. The (red) curve is the fitted dose–response curve and the dotted line curve indicates the 95% lower confidence limit to the calculated BMCL.

Figure G.15

Concentration–response curve of the incidence of vomiting in cats reported by Hughes et al. (1999) (see also Table G.15)

1. The (red) curve is the fitted dose–response curve and the dotted line curve indicates the 95% lower confidence limit to the calculated BMCL.

Figure G.16

Dose–response curve of the incidence of vomiting/retching in mink exposed to DON reported by Wu et al. (2013) (see also Table G.17)

1. The (red) curve is the fitted dose–response curve and the dotted line curve indicates the 95% lower confidence limit to the calculated BMDL.

Figure G.17

Dose–response curve of the incidence of vomiting/retching in mink exposed to 3‐Ac‐DON reported by Wu et al. (2013a) (see also Table G.18)

1. The (red) curve is the fitted dose–response curve and the dotted line curve indicates the 95% lower confidence limit to the calculated BMDL.

Figure G.18

Dose–response curve of the incidence of vomiting/retching in mink exposed to 15‐Ac‐DON reported by Wu et al. (2013a) (see also Table G.19)

1. The (red) curve is the fitted dose–response curve and the dotted line curve indicates the 95% lower confidence limit to the calculated BMDL.