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A review of the mycotoxin adsorbing agents, with an emphasis on their

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Food and Chemical Toxicology 114 (2018) 246–259

Contents lists available at ScienceDirect

Food and Chemical Toxicology


journal homepage: www.elsevier.com/locate/foodchemtox

Review

A review of the mycotoxin adsorbing agents, with an emphasis on their T


multi-binding capacity, for animal feed decontamination
P. Vila-Donat, S. Marín, V. Sanchis, A.J. Ramos∗
Applied Mycology Unit, Food Technology Department, UTPV-XaRTA, Agrotecnio Center, University of Lleida, Av. Rovira Roure 191, 25198, Lleida, Spain

A R T I C L E I N F O A B S T R A C T

Keywords: Contamination of animal feed with mycotoxins still occurs very often, despite great efforts in preventing it.
Mycotoxins Animal feeds are contaminated, at low levels, with several mycotoxins, particularly with those produced by
Animal feed Aspergillus and Fusarium genera (Aflatoxin B1, Ochratoxin A, Zearalenone, Deoxynivalenol and Fumonisina B1).
Adsorbents In animal feed, to date, only Aflatoxin B1 is limited through EU regulation. Consequently, mycotoxins cause
Multi-binding
serious disorders and diseases in farm animals. In 2009, the European Union (386/2009/EC) approved the use of
Decontamination
mycotoxin-detoxifying agents, as feed additives, to prevent mycotoxicoses in farm animals. The present review
gives an overview of the problem of multi-mycotoxin contamination of feed, and aims to classify mycotoxin
adsorbing agents (minerals, organic, and synthetic) for feed decontamination, focusing on adsorbents with the
ability to bind to multiple mycotoxins, which should have a more effective application in farms but they are still
little studied in scientific literature.

1. Introduction temperatures, high moisture levels, and insect damage, cause stress and
predispose plants in the field to mould growth and mycotoxin con-
1.1. Overview of mycotoxins in animal feed tamination (Medina et al., 2015). Moreover, poor harvesting practices,
improper drying, handling, packaging, and transport conditions con-
Mycotoxins are low molecular weight (MW) secondary metabolites tribute to increasing the risk of mycotoxin production (Bhat et al.,
produced by filamentous fungi that have adverse effects at low levels on 2010).
humans and animals. They have a significant impact on economies and The economic consequences of mycotoxin contamination are very
international trade. Fungi producing mycotoxins are known as myco- significant, and often crops with large amounts of mycotoxin have to be
toxigenic. Some of them are capable of producing more than one my- destroyed. The most susceptible crops to contamination with myco-
cotoxin and some mycotoxins are produced by more than one fungal toxins are cereals such as wheat, maize, barley, rye and oat (Cano-
species. The most relevant groups of mycotoxins found in animal feed Sancho et al., 2010; Rodríguez-Carrasco et al., 2013; Vidal et al., 2013).
are produced by three genera of fungi: Aspergillus (aflatoxins (AFs) and Cereals constitute a major part of the daily diet of animals and they are
ochratoxin A (OTA)), Penicillium (OTA), and Fusarium species (tri- important ingredients in animal compound feed (Pinotti et al., 2016). A
chothecenes, fumonisins (FBs), and zearalenone (ZEN)) (Fig. 1; Table 1) high percentage of feed samples have been reported to be contaminated
(Marin et al., 2013). They appear in the feed chain because of fungal with mycotoxins, and what is more, most of them have been reported to
infection of crops, and due to the use of mouldy grains and forage as be contaminated with more than one mycotoxin (Kosicki et al., 2016;
components of animal feed. Fungi can invade and produce mycotoxins Streit et al., 2012; Zachariasova et al., 2014). In most cases, the con-
on the growing plants before harvesting (pre-harvest toxins), or pro- centrations were low enough to ensure compliance with the EU gui-
duce toxins after harvest and during crop storage and transportation dance values or Maximum Permitted Levels (MPLs) (Tables 2 and 3).
(postharvest toxins). In general, environmental conditions, such as high However, farm animals have shown to exhibit symptoms of chronic

Abbreviations: 15-Ac-DON, 15-acetyldeoxynivalenol; 3-Ac-DON, 3-acetyldeoxynivalenol; AC, Activated Carbon; AA, Adsorbing Agents; AF, Aflatoxin; AFB1, Aflatoxin B1; AFB2,
Aflatoxin B2; AFM1, Aflatoxin M1; AFs, Aflatoxins; AOH, Alternariol; BA, Biotransforming Agents; BW, Body Weight; DON, Deoxynivalenol; EAs, Ergot Alkaloids; EGM, Esterified
Glucomannans; EC, European Comission; EFSA, European Food Safety Authority; EU, European Union; FAO, Food and Agriculture Organization of the United Nations; FI, Feed Intake;
FB1, Fumonisin B1; FB2, Fumonisin B2; FBs, Fumonisins; FA, Fusaric Acid; GI, Gastrointestinal; GAP, Good Agricultural Practices; GM, Glucomannans; HSCAS, Hydrated Sodium Calcium
Aluminosilicate; IARC, International Agency for Research on Cancer; MPLs, Maximum Permitted Levels; MW, Molecular Weight; NIV, Nivalenol; OTA, Ochratoxin A; YCW, Yeast Cell
Wall; WG, Weight Gain; ZEN, Zearalenone

Corresponding author.
E-mail address: [email protected] (A.J. Ramos).

https://doi.org/10.1016/j.fct.2018.02.044
Received 22 December 2017; Received in revised form 1 February 2018; Accepted 19 February 2018
Available online 21 February 2018
0278-6915/ © 2018 Elsevier Ltd. All rights reserved.
P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

Fig. 1. Chemical structures of major mycotoxins in animal feed.

Table 1
Overview of the most relevant mycotoxins in animal farms.

Major classes of Most relevant Mycotoxin-producing Main effects observed in animals References
mycotoxins representatives in animal fungi
feed

Aflatoxins AFB1, AFB2, Aspergillus flavus, Liver disease (hepatotoxic), carcinogenic and teratogenic Magnoli et al., 2011; Rawal
AFG1, AFG2 Aspergillus parasiticus effects. et al., 2010; Streit et al.,
2012.
Trichothecenes DON, 3- or 15-Ac-DON, Fusarium graminearum, Immunologic effects, haematological changes, digestive Awad et al., 2006; Bryden,
NIV (type B) Fusarium sporotrichioides, disorders (diarrhoea, reduced FI) dermatitis, oral lesions, 2012; Pinton et al., 2012.
T-2, HT-2 (type A) Fusarium poae, haemorrhages of intestinal tissues, edema.
Fusarium equiseti
Zearalenone ZEN Fusarium graminearum Estrogenic effects (edema of vulva, enlargement of uterus), Wozny et al., 2013; Zinedine
atrophy of ovaries and testicles, abortion. et al., 2007.
Ochratoxins OTA Aspergillus ochraceus, Nephrotoxicity, porcine nephropathy, mild liver damage, Boudergue et al., 2009; Pfohl-
Penicillium verrucosum, immune suppression. Leszkowicz et al., 2015.
Penicillium viridicatum
Fumonisins FB1, FB2 Fusarium verticillioide, PPE (porcine pulmonary edema), ELEM (equine Bouhet and Oswald, 2007;
Fusarium proliferatum leukoencephalomalacia), nephrotoxicity, hepatotoxicity. Morgavi and Riley, 2007;
Voss et al., 2007.

Aflatoxin B1 (AFB1), Aflatoxin B2 (AFB2), Aflatoxin G1 (AFG1), Aflatoxin G2 (AFG2), Deoxynivalenol (DON), T-2 toxin (T-2), HT-2 toxin (HT-2), Zearalenone (ZEN), Ochratoxin A (OTA),
Fumonisin B1 (FB1), Fumonisin B2 (FB2), Feed Intake (FI), 15-acetyldeoxynivalenol (15-Ac-DON), 3-acetyldeoxynivalenol (3-Ac-DON), Nivalenol (NIV).

mycotoxicoses when exposed to feed contaminated with toxins below contaminated with mycotoxins is restricted due to the problems asso-
the guideline levels (Wielogórska et al., 2016). Additionally, farmers ciated with safety issues, possible losses in nutritional quality coupled
generally notice acute adverse effects on animal performance, such as with limited efficacy and cost implications (EC, 2009; Kolosova and
low weight gain (WG), reproductive and metabolic disorders, with Stroka, 2011).
consequent economic losses, because not all mycotoxins found in an- As mycotoxins cause serious diseases in farm animals, the EU ap-
imal feed have been regulated (see section 1.4). Therefore, producers proved the use of mycotoxin-detoxifying agents, by including a new
often have to set internal limits more stringent than those regulated, in group of feed additives defined as ‘substances that can suppress or re-
order to avoid losses. duce the absorption, promote the excretion of mycotoxins or modify
Different strategies, including preventive measures at pre- and their mode of action’ (EC, 2009). At the same time, the EFSA reported a
postharvest, have been developed to neutralize mycotoxins in animal review of mycotoxin-detoxifying agents used as feed additives
feed such as good agricultural practices (GAP) and good storage prac- (Boudergue et al., 2009) that covered aspects such as mode of action,
tices (GSP). These actions are considered the best way of controlling efficacy and feed/food safety. Since then, numerous studies have been
mycotoxin contamination; however, even exercising of good practices published on the efficacy of the adsorbing agents (Di Gregorio et al.,
might not completely avoid or eliminate mycotoxins in the feed chain 2014; Magnoli et al., 2011; Neeff et al., 2013; Nesic et al., 2008; Pfohl-
(Di Gregorio et al., 2014). Moreover, the use of physical and chemical Leszkowicz et al., 2015; Santos et al., 2011; Wang et al., 2012). How-
methods for the detoxification of agricultural commodities ever, most studies still focus on the efficacy of adsorption of a specific

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P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

Table 2 as well as to classify mycotoxin adsorbing agents (minerals, organic and


Maximum levels for AFB1 in feed and feedingstuffs (Directive, 2002/32/CE, amended by synthetic) for feed decontamination, focusing on adsorbents with the
Directive, 2003/100).
ability to bind to multiple mycotoxins, which are in great demand by
Feedstuffs Maximum content of animal feed producers, but are still little studied in scientific literature.
AFB1 in mg/kga
1.2. Occurrence and co-occurrence of mycotoxins in animal feed
All feed materials 0.02
Complete feedingstuffs for cattle, sheep and goats with 0.02
the exception of: Despite efforts to control fungal contamination, extensive myco-
- Complete feedingstuffs for dairly cattle 0.005 toxin contamination has been reported in both developing and devel-
- Complete feedingstuffs for calves and lambs 0.01 oped countries. Recent surveys have been carried out to evaluate the
Complete feedstuffs for pigs and poultry (except young 0.02 worldwide incidence of mycotoxin contamination in feedstuffs and feed
animals)
raw materials (Pinotti et al., 2016; Streit et al., 2013). On a global level,
Other complete feedingstuffs 0.01
Complementary feedingstuffs for cattle, sheep and goats 0.02 30%–100% of food and feed samples are contaminated (Pinotti et al.,
(except complementary feedstuffs for dairy animals, 2016). According to Streit et al. (2012) 72% of feed samples surveyed
calves and lambs) contained detectable levels of mycotoxins, while only 1–18% samples
Complementary feedingstuffs for pigs and poultry 0.02
(depending on the toxin) presented levels above the EU guidelines or
(except young animals)
Other complementary feedingstuffs 0.005 regulations. Also, Rodrigues and Naehrer (2012) studied the prevalence
of mycotoxins in feedstuffs and finished feed worldwide between 2009
a
Relative to a feedingstuff with a moisture content of 12%. and 2010. Their results (from HPLC) revealed that 81% of the 6000
samples tested positive for at least one mycotoxin, although in many
Table 3 cases the regulatory and guidance levels were not surpassed. The most
Guidance values for DON, ZEN, FBs and OTA in feedstuffs (2006/576/EU) and for T-2 and commonly occurring mycotoxins were deoxynivalenol (DON) (65%),
HT-2 (2013/165/EU). FBs (56%) and ZEN (44%), followed by AFs (31%) and OTA (27%). AF
Mycotoxins Feedstuffs Guidance value in
production occurred primarily in cereal samples from regions with
mg/kga tropical or subtropical climates such as Southern Europe, Africa, South
and Southeast Asia. The amount of AFB1 was often the highest in the
OTA Feed materials: cereals and cereal products 0.25 mixtures of AFs (Rodrigues and Naehrer, 2012). While DON con-
Complete and complementary feedstuffs
tamination was observed worldwide, more than 60% of positive sam-
- For pigs 0.05
- For poultry 0.1 ples were found in samples (wheat, maize and barley) from North
DON Feed materials: America, Northern and Central Europe, and North Asia (Rodrigues and
- cereals and cereal products, with the 8 Naehrer, 2012; Streit et al., 2012). The highest incidence of ZEN con-
exception of maize by-products
tamination (more than 30% of positive samples) was found in North
- maize by-products 12
Complementary and complete feedstuffs 5
and South America, Central Europe, Africa, and North and Southeast
with the exception of: Asia (Rodrigues and Naehrer, 2012). On the other hand, FB con-
- Complementary and complete feedstuffs 0.9 tamination was found mostly in maize and maize products from South
for pigs America, Southern Europe, Africa, and Southeast Asia, FB1 being the
- Complementary and complete feedstuffs 2
most abundant (Rodrigues and Naehrer, 2012). Different Fusarium
for calves (< 4 months), lambs and kids
FB1, FB2 Feed materials: maize and maize by-products 60 mycotoxins were often found jointly in contaminated cereals (Cano-
Complementary and complete feedstuffs for: Sancho et al., 2010; Stanciu et al., 2017). Lastly, OTA prevalence was
- pigs, horses (Equidae), rabbits and pet 5 highest in South Asia and Africa, but its distribution in contaminated
animals
feed lots tended to be very heterogeneous (Rodrigues and Naehrer,
- fish 10
- poultry, calves (< 4 months), lambs and 20
2012).
kids However, occurrence patterns of mycotoxins are changing as a
- adults ruminants (> 4 months) and mink 50 consequence of rising average temperatures due to climate change
ZEN Feed materials: (Medina et al., 2015; Miraglia et al., 2009; Wielogórska et al., 2016). In
- cereals and cereal products, with the 2
Southern Europe, AF contamination, previously uncommon in Europe,
exception of maize by-products
- maize by-products 3 will become increasingly significant. In fact, Italian researchers de-
Complementary and complete feedstuffs: tected AFB1 in cattle feed and AFM1 in cow's milk surpassing the
⁃ for piglets and gilts (young sows) 0.1 maximum allowable in the EU, in 8.1% and in 1.7%, respectively
⁃ for sows and fattening pigs 0.25
(Decastelli et al., 2007).
⁃ for dairy cattle, sheep (including lambs) 0.5
and goats (including kids)
Nevertheless, studying the occurrence of any given mycotoxin
T-2, HT-2 Cereal products for feed and compound feed: alone, provides incomplete information about the risk associated with
- oat milling products 0.25 the respective feedstuff considering the fact that mycotoxigenic fungi
- other cereal products 0.5 are usually capable of producing more than one mycotoxin, so animal
- compound feed (with the exception of feed 2
feed is particularly vulnerable to multiple contaminations (Streit et al.,
for cats)
2012). Results of feed surveys performed in Europe also highlight the
Deoxynivalenol (DON), T-2 toxin (T-2), HT-2 toxin (HT-2), Zearalenone (ZEN), problem of high levels of co-contamination with a number of different
Ochratoxin A (OTA), Fumonisin B1 (FB1), Fumonisin B2 (FB2). mycotoxins (Zachariasova et al., 2014). Of the 82% of feed samples that
a
Relative to a feedingstuff with a moisture content of 12%. were contaminated, type B-trichothecenes and FBs occurred most often,
75% were co-contaminated with more than one mycotoxin while only
mycotoxin, usually tested at high levels which, as mentioned pre- two samples exceeded the recommended EU levels (Monbaliu et al.,
viously, in real settings is rarely the case. 2010). Along the same lines, Griessler et al. (2010) conducted a survey
In the light of the high co-occurrence of mycotoxins in agricultural on feed and feed ingredients sourced in Southern Europe. The Fusarium
commodities, the task of developing a more versatile solution for multi- mycotoxins (type B-trichothecenes, ZEN and FBs) were the major con-
toxin feed decontamination is challenging. The present review intends taminants, while AFs and OTA were detected less frequently. It was
to address the problem of animal feed multi-mycotoxin contamination, further reported that 23% of all samples from Spain contained at least

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P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

two mycotoxins. significantly reduced the feed intake (FI) by 9–11% (Rawal et al.,
Other researchers evaluated the level of mycotoxins in raw mate- 2010). Also reductions of WG of 30% in chickens following the con-
rials and products for animal nutrition in Poland in 2011–2014. A total sumption of feed contaminated at levels of 0.03 mg AFB1/kg of feed,
of 1384 samples (maize samples, maize silage samples, small grain were observed (Boudergue et al., 2009). In ruminants, first effects were
cereal samples and complete feed samples) were analysed for the oc- observed at levels of 1–2 mg AFB1/kg of feed such as lower feed in-
currence of DON, Nivalenol (NIV), T-2 and HT-2 toxins, ZEN, FBs, OTA, gestion and milk yield in cattle, while in pigs some mortalities and liver
and AFs. Also in this case, DON as well as ZEN were the most frequently diseases were observed within one month after ingestion of con-
occurring mycotoxins, present in 89% and 92% of maize samples, and taminated feeds at 0.8–3 mg AFB1/kg (Meissonnier et al., 2005). In fish
in 86 and 88% of maize silage samples, respectively. Additionally, in 24 (Oreochromis niloticus, Nile tilapia) a reduction in growth rate was ob-
samples the content of mycotoxins exceeded EU recommendations. served along with hepatic damage at levels from 0.245 mg AFB1/kg of
Regarding the complete feed, trichothecenes and ZEN were found in feed (Matejova et al., 2017). Rainbow trout is considered the most
more than 90% of the samples (Kosicki et al., 2016). sensitive fish species to AFs (Anater et al., 2016).
Multi-mycotoxin contamination is a topic of great concern and
seems to be increasing. The frequent detection of mycotoxin co-occur-
rence even in studies screening for a limited number of analytes un- 1.3.2. Ochratoxin A
derlines the importance of mycotoxin reduction strategies like the ad- OTA is a nephrotoxic mycotoxin that causes renal toxicity and
dition of multi-composition adsorbents in order to sequester a wider possesses carcinogenic, teratogenic, immunotoxic and possibly neuro-
range of mycotoxins. toxic properties. This toxin has been classified by the IARC as a possible
human carcinogen (Group 2B) (IARC, 2002). In animals, it has been
1.3. Toxic effects of major mycotoxins on farm animals shown that after a prolonged OTA intake, a nephropathy linked to the
degeneration of the convoluted tubule of the nephron and renal inter-
Animal feeds are routinely subject to contamination from diverse stitial fibrosis occurs, followed by a decrease in the thickness of the
sources. AFB1, DON, ZEN, OTA and FB1 are considered the most eco- basal membrane and glomerular hyalinization (Pfohl-Leszkowicz et al.,
nomically significant mycotoxins in terms of their prevalence and their 2015). Ruminants seem to be resistant to OTA exposure. In pigs, acute
negative effects on animal performance (Table 1), (Di Gregorio et al., ochratoxicosis episodes mention kidney diseases (nephropathy), while
2014). The diseases caused by short or long exposure to mycotoxins are in chronic ochratoxicosis the first signs were reductions of feed con-
known as mycotoxicoses. Clinical symptoms usually subside upon re- sumption and WG at the level of 1–1.4 mg OTA/kg of feed (Boudergue
moval of contaminated feed. In general, smaller organisms are more et al., 2009). In poultry, nephropathy was reported to occur from level
susceptible to mycotoxin poisoning. Poultry, pigs, and also aquatic of 2 mg OTA/kg of feed, and the first signs of chronic ochratoxicosis
vertebrates are very sensitive to mycotoxins. Due to their high con- were noticed at a minimal level of 0.5 mg OTA/kg of feed in laying hens
sumption of cereals, they are exposed to these toxins and to chronic and chickens (Boudergue et al., 2009). Also, in catfish adverse effects
contamination. Ruminants have, however, generally been more re- were observed at concentration of 1.0 mg OTA/kg feed (Matejova et al.,
sistant to the adverse effects of mycotoxins, since the rumen microbiota 2017).
is capable of degrading mycotoxins.
On the other hand, when mycotoxins are present simultaneously,
interactive effects can be classified as additive, antagonistic or sy- 1.3.3. Deoxynivalenol
nergistic. Numerous reports of synergistic or additive effects mainly for DON belongs to the trichothecene B group and, although being one
AFs in combination with FBs, trichothecenes, OTA or mixtures of var- of its least acutely toxic members, is of particular interest owing to its
ious Fusarium toxins have been published (Ruiz et al., 2011). The stu- high prevalence in cereals worldwide. DON is also known as vomitoxin,
dies show that co-contaminated samples may exhibit adverse health and it is primarily known for causing feed refusal, weight loss, de-
effects even with concentrations of toxins being within regulatory limits creases nutritional efficiency and causes lesions in the GI tract, vo-
(Grenier and Oswald, 2011). miting, bloody diarrhoea and severe dermatitis accompanied by hae-
The economic impact of mycotoxins includes loss of human and morrhaging (Bryden, 2012). Other symptoms are immune disorders,
animal life, increased health care and veterinary care costs, and re- such as immunosuppression or immunostimulation. In pigs, the most
duced livestock production (Zain, 2011). sensitive of the susceptible species, DON has also a neurotoxic effect
that produces an anorexic syndrome, by altering the concentration of
1.3.1. Aflatoxins neurotransmitters in the hypothalamus, cerebellum, and frontal cortex
AFs are relatively hydrophilic molecules produced by fungi of the (Marin et al., 2013). DON may be produced together with two acety-
genus Aspergillus. AFB1 is the most potent naturally occurring carci- lated derivatives, 3-acetyldeoxynivalenol (3-AcDON) and 15-acet-
nogen classified by the IARC as group 1 (IARC, 1993, 2002). It is the yldeoxynivalenol (15-AcDON), which have differential toxicity on pig
only mycotoxin with an established MPL in feedstuffs (see section 1.4 intestine (Pinton et al., 2012). The first signs of reduction of feed
and Table 2). Lactating animals fed AFB1 contaminated feeds will consumption in pigs, were observed at levels of 1–3 mg of DON/kg feed
produce milk contaminated with its monohydroxylated derivative (Marin et al., 2013). Regarding ruminants, the animal species least
AFM1, classified by the IARC as group 2B, possibly carcinogenic to sensitive to DON, feed refusal syndrome was noticed in cows after
humans (IARC, 1993, 2002). Chronic toxicity is the most common form consumption during 10 weeks of a wheat concentrate level of 6.4 mg
of aflatoxicosis and it is caused by the consumption of relatively small DON/kg feed (Boudergue et al., 2009). In poultry, which seem to be
amounts of these toxic compounds over an extended period. The main relatively resistant to DON compared to other livestock, the effects vary
target organ of AFB1 toxicity is the liver, where it may be metabolized according to the species. Yunus et al. (2010) found that dietary levels of
into different metabolites (Di Gregorio et al., 2014). The effects of long DON below and above the recommended limits (1.8 and 18 mg/kg,
term exposure of levels AFs are associated with reduction in WG, de- respectively) affected chicken performance and organ status to various
creased milk or egg production, increased disease susceptibility, re- degrees, while according to Awad et al. (2006), concentrations above
duced feed efficiency, tumours and teratogenicity (Table 1) (Streit 5 mg DON/kg of diet are necessary to cause detrimental effects in
et al., 2012). Poultry, cattle, and swine are the domestic species of poultry. Trout are extremely sensitive to DON. A significant decrease in
greatest economic concern in terms of aflatoxicosis. Some species of fish FI, WG, growth rate, and feed efficiency in trout exposed to diets
and birds are extremely sensitive to the toxic and carcinogenic action of naturally contaminated from 0.3 to 2.6 mg DON/kg of feed for 8 week
AFB1 (Anater et al., 2016). In poultry, dietary 2.5 mg AFs/kg was observed (Anater et al., 2016).

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P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

1.3.4. Zearalenone (Table 2), (Directive, 2003/100/EC). Additionally, guidance values


ZEN is a non-steroidal estrogenic toxin produced by certain have been recommended for a further five mycotoxins in feedstuffs:
Fusarium species. ZEN, and some of its metabolites, can competitively DON, ZEN, OTA and FBs (2006/576/EU) (Table 3). Recently the EC has
bind to oestrogen receptors leading to reproductive disorders and es- established recommendations on the presence of T-2 and HT-2 toxin in
trogenic dysfunction in humans and animals (especially in breeding cereals and cereal products for feed and compound feed (2013/165/
animals), impairing fertility and increasing the frequency of stillbirths EU) (Table 3). Also, a maximum level of 500 mg/kg of rye ergot (Cla-
along with reducing sperm quality (Zinedine et al., 2007). During viceps purpurea) sclerotia has been set for unprocessed cereals in order
pregnancy, ZEN reduces embryo survival and foetal weight. Ad- to avoid the presence of ergot alkaloids in food and feed (2015/1040/
ditionally, ZEN produces vulvar dilatation and redness, retention or EU). However, food/feed may be contaminated with a much wider
absence of milk, and rectal prolapse (Zinedine et al., 2007). Swine are range of mycotoxins. In fact, the EFSA has recently issued scientific
also the animal species most severely affected by ZEN. In pigs, first opinions on the risk to human and animal health related to the reported
signs of estrogenic syndrome appeared from 3 to 7 days on a ZEN presence of Alternaria toxins (EFSA, 2011).
contaminated diet at levels of 1.5 mg/kg feed (Boudergue et al., 2009). On the other hand, European regulations for animal-derived pro-
Regarding ruminants, a reduction of fertility in dairy cattle was ob- ducts have been imposed, especially for AFM1 in milk (0.025–0.05 μg/
served for levels of ZEN above 0.5 mg/kg feed (Boudergue et al., 2009). kg) (EC No, 1881/2006), which in particular imply a strict control of
Among the livestock species of interest, poultry seems to be the most the AFB1 content in feed for dairy cattle. Otherwise, the EC has not
resistant to ZEN. Based on experimental studies, levels above 100 mg established MPLs of OTA in meat or other animal products. However,
ZEN/kg feed are needed to see the first signs of intoxication (Boudergue some countries have enforced MPLs of OTA concentrations, for example
et al., 2009). Otherwise, a slight tendency toward prolonged clotting Denmark (pig kidney 10 μg/kg), Estonia (pig liver 10 μg/kg), Romania
time and lowered iron concentrations in the liver and ovary after ex- (pig kidney, liver and meat 5 μg/kg), Slovakia (meat 5 μg/kg, milk 5 μg/
posing rainbow trout to 10 mg ZEN/kg for 24, 72, and 168 h was ob- kg). Others countries have developed national guidelines for re-
served by Wozny et al. (2013). commended maximum OTA levels, for example Italy (pig meat and
derived products 1 μg/kg) (FAO, 2004).
1.3.5. Fumonisins
Acute and chronic toxicity by FBs has been largely demonstrated in 2. Prevention and decontamination of mycotoxins in food and
several animal species, including carcinogenicity and cardiovascular feed
toxic effects (Voss et al., 2007). Based on toxicological evidence, the
IARC has classified FB1 as possibly carcinogenic to humans (group 2B) There are multiple possible origins of fungal infection, so prevention
(IARC, 2002). The liver and kidney are the major target organs for FB strategies for fungal and mycotoxin contamination must be carried out
toxicity (Voss et al., 2007), but also the intestine is a possible target at an integrative level all along the food production chain (plant
(Bouhet and Oswald, 2007). In horses, consumption of FB contaminated growth, harvest, storage and distribution). The intervention should
feeds has been recognized as a cause of an illness known as equine occur before any fungal infestation, or during the period of mould in-
leukoencephalomalacia (ELEM). The first symptoms are lethargy, vasion of plant material and mycotoxin production, and also when the
blindness, and decreased feed intake, followed by convulsions and agricultural products have been identified as heavily contaminated
death after several hours or days (Morgavi and Riley, 2007). Similarly, (Jouany, 2007). Several codes of practices have been developed by
FB1 contaminated feeds have shown to cause a syndrome known as Codex Alimentarius for the prevention and reduction of mycotoxins in
porcine pulmonary edema (PPE) in pigs (Table 1). Clinical signs usually cereals, and raw materials. These recommendations are divided into
include decreased feed consumption, dyspnoea, weakness, cyanosis, two parts: recommended practices based on GAP and Good Manu-
and death (Morgavi and Riley, 2007). Based on several studies, levels facturing Practices (GMP), and the use of Hazard Analysis and Critical
above 100 mg FB1/kg feed are needed to get first signs of zootechnical Control Points (HACCP) (Awad et al., 2010; FAO, 2001).
disturbance in pigs (Boudergue et al., 2009). Cows and poultry are Different pre- and postharvest control strategies have been ex-
considerably less sensitive to FBs than horses and pigs (Boudergue tensively reviewed elsewhere (Awad et al., 2010; Jouany, 2007; Kabak
et al., 2009). et al., 2006). Common practical measures include planting of more
On the other hand, in fish, FBs have a disruptive effect on neural and resistant varieties of cereals, selection of high quality seeds, avoiding
liver tissues. Sensitivity to FB1 in fish is dependent on both species and high plant densities, preventive management towards insect infesta-
individual body weight (BW) (Anater et al., 2016). tions as well as suitable management of crop residues that are often the
primary inoculum of mycotoxigenic fungi. Appropriate field manage-
1.4. European regulation of mycotoxins in feedingstuffs ment practices such as crop rotation, soil cultivation, irrigation, and
fertilisation are known to influence mycotoxin formation in the field
Approximately 100 countries have developed specific limits for (Awad et al., 2010; Kabak et al., 2006). Prediction models integrating
mycotoxins, while the number of regulated mycotoxins differs for food some of these field parameters and weather input are being developed
and feed, for example between the US and the EU. According to FAO, to assess the risk of mycotoxin contamination of pre-harvest cereals
Europe has the most extensive regulations for mycotoxins in feed. (Jouany, 2007). Careful selection of harvest date, equipment and har-
Canadian regulations are among the most detailed, as they additionally vesting procedures to minimise crop damage and removal of damaged
include mycotoxins not regulated in EU feedstuffs such as diacetox- crops and high moisture plant parts also reduces mould infections.
yscirpenol, DAS (a type A trichothecene), with China and Iran also During postharvest, storage and distribution, the control of moisture
having demanding limits in place (FAO, 2004). Nevertheless, regula- levels of stored grains (less than 15%), maintenance at low tempera-
tions in the rest of the world undoubtedly focus mainly on AFs, with tures as well as preservation of the integrity of grains are critical in
only 15 countries in Africa having specific, feed oriented mycotoxin preventing mycotoxin production (Kabak et al., 2006). The develop-
regulations in place (FAO, 2004). All countries with mycotoxin reg- ment of resistant hybrids appears to be a very promising technology,
ulations have at least regulatory limits for AFB1 or the sum of aflatoxins but commercial hybrids are not always available (Abbas et al., 2009).
B1, B2, G1, and G2 in foods and/or feeds (Wielogórska et al., 2016). On the other hand, cereals modified by genetic engineering could be
Currently in the EU, AFB1 is the only mycotoxin with MPLs set in used to limit the risk of fungal infection. Commercially, this technology
feeds under Directive 2002/32. For animal feed, MPLs set by the EC for is based on the use of plants with resistance to insect attack, which
AFB1 is 0.02 mg/kg for all feed materials (EC, 2003). The current limits indirectly cause a reduction in fungal infection and mycotoxin con-
for AFB1 in animal feedingstuffs range from 0.005 to 0.02 mg/kg tamination. Genetic research is also being carried out on the induction

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of mycotoxin detoxification pathways or inhibition of mycotoxin pro- be stable throughout the entire digestive track, so its stability in varying
duction in the grain (Duvick, 2001; Karlovsky, 2011). However, in pH, which is influenced by the AA physical properties (total charge and
Europe genetically modified food is still not well received by the po- charge distribution, the size of the pores, and the accessible surface
pulation. area) and targeted toxins’ physicochemical properties (polarity, solu-
When prevention is not achieved at field level or during harvest, bility, and shape), is one of the crucial parameters to be evaluated in
decontamination procedures such as physical treatments of con- order to prevent desorption of the toxin (Avantaggiato et al., 2005;
taminated grains can be used including washing, polishing, mechanical Huwig et al., 2001; Kabak et al., 2006). AA are also known as myco-
sorting and separation, density segregation, and flotation. However, the toxin binders, mycotoxin binding agents, sequestering agents, or ad-
efficiency of these techniques depends on the level of contamination sorbents. These agents can be divided in three sub-groups: inorganic
and the distribution of mycotoxins throughout the grain. Additionally, compounds, organic or synthetic (Di Gregorio et al., 2014; Jard et al.,
the results obtained are uncertain and often connected with high pro- 2011).
duct losses.
With regard to chemical decontamination methods, they require not ⁃ Biotransforming agents (BA)
only suitable reaction facilities but also additional treatments (drying,
cleaning) that can make them time consuming and expensive (Jouany, Another strategy is the degradation of mycotoxins into non-toxic
2007). Nevertheless, various chemicals including oxidising and redu- metabolites by using BA. Biotransformation can be achieved by myco-
cing agents, acids, bases, salts and chlorinating substances have been toxin-degrading enzymes or by microorganisms producing such en-
tested for their ability to degrade mycotoxins in agricultural commod- zymes. Several microbial species, including bacteria, yeast and fungi
ities. Only a limited number of these are effective without diminishing have been recognized for their ability to biotransform mycotoxins into
the feed nutritional value or palatability (Kolosova and Stroka, 2011). less toxic metabolites through routes such as (de)acetylation, oxyge-
Chemically, some mycotoxins can be destroyed with calcium hydro- nation, ring/side chain cleavage, deepoxidation, isomerisation or glu-
xide, monoethylamine, ozone or ammonia. Particularly, ammoniation cosylation (Wielogórska et al., 2016). Eubacterium BBSH 797 strain
is an approved procedure for the detoxication of AF contaminated feed isolated from bovine rumen fluids was one of the most studied species
in several countries (Boudergue et al., 2009). However, the use of being able to efficiently degrade DON, and other trichothecenes, which
chemical decontamination processes is not legal within the EU (Direc- after in vitro and in vivo tests was introduced onto the market as the
tive, 2002/32). With regard to mycotoxin decontamination, the EC is in commercial biotransforming product Mycofix® BBSH (Biomin, Get-
favour of the use of physical decontamination processes such as the use zersdorf, Austria). Also, some of the enzymes responsible for bio-
of adsorbents (see section 3.1) and sorting procedures (Directive, 2002/ transforming characteristics recognized in these microbial species, have
32). been isolated and applied directly as detoxifying agents (Boudergue
et al., 2009). However, the application in practice of BA is limited due
3. Detoxifying agents to lack of information about transformation mechanisms, the toxicity of
products derived from biotransformation, the effect of transformation
Although prevention of mycotoxin contamination in the field and reactions on the nutritional values of feeds, and safety towards animals
during storage is the main goal of agricultural and feed industries, the (Wielogórska et al., 2016).
absence of mycotoxins in the ration of farm animals cannot be fully
assured. Due to the increasing number of reports on the presence of 3.1. Adsorbing agents (AA)
mycotoxins in feeds, there is a rise in demand for practical deconta-
mination procedures. It should be pointed out that the mixing of bat- 3.1.1. Inorganic adsorbents
ches with the aim of decreasing the level of contamination below the 3.1.1.1. Aluminosilicates. Aluminosilicates constitute the most
maximum tolerable level is not permitted under Directive 2002/32. abundant group of rock-forming minerals. The basic structural unit of
In 2009, a new functional group was added in the category of silicate clay minerals consists of the combination of silica tetrahedral
technological feed additives. This group is defined by the Commission and aluminium octahedral sheets, both with oxygen and hydroxyl
Regulation (EC) No 386/2009 as ‘substances for reduction of the con- groups (Di Gregorio et al., 2014). Most studies on the alleviation of
tamination of feed by mycotoxins: substances that can suppress or reduce the mycotoxicosis by the use of AA have focused on aluminosilicates.
absorption, promote the excretion of mycotoxins or modify their mode of Within this group, there are two major subclasses: phyllosilicates and
action’ (EC, 2009). These substances are known as detoxifying agents. tectosilicates. Phyllosilicates include bentonites, montmorillonites,
The use of such products does not mean that animal feed exceeding the smectites, kaolinites, and illites. They can adsorb substances on their
established MPLs may be used. The additives are added to the diet of surface or within their interlaminar space. The tectosilicates include
animals (mainly of swine, poultry and cattle) in order to reduce the zeolites. They provide a large and specific binding surface but also size,
absorption of mycotoxins from the GI tract and their distribution to shape and charge selectivity due to which they have been compared to
blood and target organs. Depending on their mode of action, they act molecular sieves (Huwig et al., 2001). Inactivation of mycotoxins by
either by binding mycotoxins to their surface (adsorption), or by de- adsorbents has been reviewed by many authors (Avantaggiato et al.,
grading or transforming them into less toxic metabolites (bio- 2007, 2005, 2003; Diaz and Smith, 2005; Jouany, 2007; Huwig et al.,
transformation). Therefore, we can define at least two main categories: 2001; Kabak et al., 2006; Kong et al., 2014; Phillips et al., 2008; Ramos
adsorbing agents and biotransforming agents. et al., 1996a; Vekiru et al., 2007; Vila-Donat et al., 2017a; b). However,
most of the AA appear to bind to only a limited group of mycotoxins
⁃ Adsorbing agents (AA) while showing very little or no binding to others (Jouany, 2007; Kabak
et al., 2006; Kong et al., 2014; Ramos and Hernández, 1997; Ramos
Mycotoxin-AA are large MW compounds which bind the mycotoxins et al., 1996a; Vekiru et al., 2007; Vila-Donat et al., 2017a; b).
present in contaminated feed without dissociating in the GI tract of the Furthermore, it should be noted that clays could adsorb
animal, thus limiting their bioavailability after ingestion, decreasing micronutrients and have negative effects on the bioavailability of
exposure of animals to mycotoxins. Mycotoxins may bind to AA by minerals and trace elements (Kolosova and Stroka, 2011). Also, the
different types of interactions such as hydrophobic binding, hydrogen risk of natural clays to be contaminated with dioxins and metals has to
bonds, electrostatic attraction or repulsion and coordination bonds (Di be considered (Jouany, 2007).
Gregorio et al., 2014). In this way the mycotoxin-AA complex passes
through the animal and is eliminated via the faeces. This complex has to ⁃ Hydrated sodium calcium aluminosilicate (HSCAS)

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HSCAS (calcium montmorillonite clay) are commonly used in an- 3.1.1.2. Other clays. Other mineral adsorbents such as diatomite (a
imal feed as anti-caking agents. HSCAS has shown to act as an en- mineral formed by the accumulation and fossilisation of diatomaceous
terosorbent that tightly and selectively binds AFs in the GI tract of algae shells in lacustrine and marine environments) and sepiolite (a
animals decreasing their bioavailability and associated toxicity (Harper complex magnesium silicate belonging to the group of hormites) have
et al., 2010; Neeff et al., 2013; Phillips et al., 2008). Evidence suggests been studied as mycotoxin adsorbents over the last few years. The
that AFs may react at multiple sites on HSCAS particles, especially the negative charges associated with the high specific surface area make
interlayer region, but also at edges and basal surfaces (Kolosova and sepiolite an adequate sorbent for some polar molecules. Sepiolite
Stroka, 2011). Other mechanisms of AFB1 sorption by HSCAS surfaces showed good results in the adsorption of AFs, however the efficiency
may involve the chelation or interaction of AFB1 with interlayer cations of adsorption of other mycotoxins is limited. Usually sepiolite is
(especially Ca) or various edge-site metals (Di Gregorio et al., 2014). associated with bentonite and both have similar properties such as
HSCAS is quite effective with respect to AFs but fails to prevent toxic high surface area and significant sorption capacity. However, the cation
effects of Fusarium mycotoxins, such as FBs, or trichothecenes exchange capacity of sepiolite is much lower than that of smectite (Di
(Avantaggiato et al., 2005; Harper et al., 2010; Kabak et al., 2006; Neeff Gregorio et al., 2014). Regarding diatomaceous earth, it is fossilized by
et al., 2013; Phillips et al., 2008; Ramos and Hernández, 1997). the deposit of silica in its structure, which is arranged in thin or thick
layers, interspersed by clay lenses. This material is very thin with a
⁃ Bentonites (montmorillonites) porous structure, high surface area and microstructure mainly
composed of amorphous silica, or opal and frustules. Diatomaceous
Bentonites are phyllosilicate clays with a layered crystalline mi- earth is used as anti-caking agent during feed processing (Weaver et al.,
crostructure of variable composition. They are frequently referred as 2013).
smectites because it is the dominant mineral clay. Smectite includes
mainly montmorillonite. The adsorption effectiveness of bentonite de- 3.1.2. Organic adsorbents
pends on the montmorillonite content and the interchangeable cations Facing the relative inefficacy of the clay adsorbents towards my-
(Kolosova and Stroka, 2011). Montmorillonite is composed of layers of cotoxins other than AFs, natural organic binders have been proposed
octahedral aluminium and tetrahedral silicon coordinated with oxygen (Avantaggiato et al., 2014; Jouany, 2007; Mezes et al., 2010; Ringot
atoms. The large surface area and high cation exchange capacity of the et al., 2007). The mixture of inorganic and organic adsorbents could
smectite group make them capable of adsorbing organic substances by make them more adapted to the most frequent cases of multi-con-
the penetration of both cations and polar molecules. Bentonites have taminated feeds.
demonstrated a large efficacy on mycotoxins adsorption, specifically
AFs (Kong et al., 2014; Magnoli et al., 2011; Ramos and Hernández, ⁃ Yeast cell wall (YCW)
1996; Thieu et al., 2008; Vekiru et al., 2007; Vila-Donat et al., 2017a,b),
and other mycotoxins (ZEN, OTA and FBs) in numerous in vitro and in Saccharomyces cerevisiae occurs as part of natural microbial popu-
vivo studies (Avantaggiato et al., 2005; Miazzo et al., 2005; Ramos lations in foods and it is used as a starter culture in fermented food and
et al., 1996a,b; Wang et al., 2012). According to Deng et al. (2010), beverages. YCW mainly consists of proteins, lipids and polysaccharides,
under dry conditions AF molecules bind to smectite by direct ion-dipole with glucans and mannans being the two main constituents of the latter
interactions and by coordination between exchangeable cations and fraction. In fact, YCW exhibits a great variety of accessible mycotoxin
carbonyl groups, whereas under humid conditions, AF molecules bind adsorption loci as well as different binding mechanisms (hydrogen
to smectite by H-bonding between the carbonyl oxygens and hydration- bonds, ionic or hydrophobic interactions) (Ringot et al., 2007). Ad-
shell water (the authors provide a graphical interpretation of the in- sorption on the cell wall surface is an interaction between the toxins
teraction between AF and smectite). and functional groups of the cell surface. YCW has shown much larger
The safety and efficacy of bentonite as feed additive has also been sorption capabilities across a wider spectrum of mycotoxins such as
evaluated by the EFSA. It has been observed that bentonites are not ZEN, OTA, and FBs (Fruhauf et al., 2012; Pfohl-Leszkowicz et al., 2015;
genotoxic and are not absorbed following application as a feed additive, Shetty and Jespersen, 2006), including DON, being the β-D-glucan
hence providing no direct toxicological risk for the animal (EFSA, fraction of YCW directly correlated with the binding process (Faucet-
2011). A bentonite/dioctahedral montmorillonite (Mycofix®, Biomin, Marquis et al., 2014). Also mannans (from S. cerevisiae) have demon-
Austria) has been the first-ever product authorized by the EU as AA strated to be effective at binding DON at different pH values, with
with proven mycotoxin counteracting properties that fulfils the strict adsorption rate decreasing as DON concentration increases (Cavret
requirements on AF-binding capability according to EC 1060/2013. et al., 2010). Furthermore, esterified glucomannans (EGM) have been
proved to be effective in counteracting the toxic effects of different
⁃ Zeolites mycotoxins simultaneously exposed (Aravind et al., 2003; Avantaggiato
et al., 2005; Li et al., 2012; Mohaghegh et al., 2017).
The zeolite structure consists of an assemblage of SiO4 and AlO4
tetrahedra joined together in various regular arrangements through ⁃ Lactic acid bacteria (LAB)
shared oxygen atoms to form an infinite three-dimensional cage-like
structure. The partial substitution of Si4+ by Al3+ results in an excess of LAB are a group of gram-positive, acid-tolerant, generally non-
negative charge which is compensated by alkali and earth alkaline ca- sporulating bacteria that have common metabolic and physiological
tions such as sodium, calcium and potassium ions (Dakovic et al., 2003; characteristics. These bacteria, usually found in decomposing plants
Huwig et al., 2001). Zeolites have a large internal surface, associated and dairy products, produce lactic acid as the major metabolic end-
with its elevated cation exchange capacity and with the adsorption of product of carbohydrate fermentation. Some LAB strains (Lactobacillus
polar molecules (Di Gregorio et al., 2014). Some studies have shown rhamnosus) displayed the ability to bind certain compounds (e.g. AFB1
that natural zeolite-clinoptilolite have the ability to adsorb AFs and and ZEN) in the small intestine with cell wall peptidoglycans, poly-
other mycotoxins such as FBs (Dakovic et al., 2010). However, modified saccharides and teichoic acid proposed as crucial elements in that
zeolites are more effective than natural ones towards FBs (Baglieri process. Gram-positive bacteria seem more efficient towards non-polar
et al., 2013) (see section 3.1.3). The role of zeolites as feed additives on toxins (such as ZEN) due to higher hydrophobicity of the cell surface
the prevention of certain farm animal diseases has been also reviewed (Kabak et al., 2006). The strength of the mycotoxin-LAB interaction
by Papaioannou et al. (2005). seems to be influenced by the peptidoglycan structure and, more pre-
cisely, by its amino acid composition (Dalié et al., 2010). Moreover L.

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rhamnosus is considered a safe and effective chemopreventive because natural clays towards FBs (Baglieri et al., 2013; Dakovic et al., 2010;
of its use in various dairy products including yogurt. Doll et al., 2005). Specifically, Baglieri et al. (2013) showed that the
addition of modified clays (2%) to contaminated maize allowed a re-
⁃ Micronized fibres and bio-sorbents duction of more than 70% of the amount of FB1 released in solution.
Also, in vitro adsorption of ZEN by a modified montmorillonite nano-
Micronized fibres can be obtained from different plant materials composite was reported by Feng et al. (2008). This material demon-
such as cereals or legumes (wheat, barley, alfafa, oat, pea hulls). They strated the ability to bind ZEN in aqueous solutions with little non-
consist mainly of cellulose, hemicellulose and lignin, and they have specific adsorption of common nutrients, such as vitamins. Moreover it
been utilised as mycotoxin adsorbents due to favourable gut adsorption showed very low desorption rate and higher adsorption capacity of ZEN
and enhanced faecal excretion (Aoudia et al., 2009). Particularly, mi- compared to unmodified montmorillonite nanocomposite. Nano grade
cronized wheat fibres exhibited beneficial effects against OTA adsorp- particle size and hydrophobic properties of modified montmorillonite
tion (Aoudia et al., 2009). However, the binding ability for AFB1 of the nanocomposite seems responsible for the specific adsorption (Feng
cellulose products is less compared with the values of other inorganic et al., 2008).
adsorbents (Kong et al., 2014).
Regarding bio-sorbents, red wine waste such as dehydrated grape ⁃ Polymers
pomace (rich in phenolic compounds) has recently been demonstrated
in vitro to be an excellent adsorbent for simultaneously removing sev- Polymers, such as cholestyramine (an anion exchange resin), divi-
eral mycotoxins in a liquid medium (AFB1, ZEN, OTA and FBs) nylbenzene-styrene and polyvinylpyrrolidone (a highly polar ampho-
(Avantaggiato et al., 2014). In addition, apple pomace (rich in fibres teric polymer) have been demonstrated to bind mycotoxins in vitro and
and pectin) was tested previously in pigs as mycotoxin adsorbent by in vivo (Avantaggiato et al., 2005; Jard et al., 2011; Jouany, 2007;
incorporating it in DON-contaminated feed, and authors suggested that Mezes et al., 2010; Ramos et al., 1996b). Cholestyramine is an insoluble
the negative effect of DON may be attenuated (Gutzwiller et al., 2007). quaternary ammonium exchange resin which strongly binds various
Furthermore, interesting findings were obtained from in vitro studies anionic compounds and may weakly adsorb neutral or cationic com-
regarding humic acids, originating from natural decaying of organic pounds by non-specific binding. This compound proved in vitro to be an
plant materials. They also have shown the capacity to adsorb myco- effective adsorbent for OTA, FBs and ZEN (Avantaggiato et al., 2005,
toxins, especially AFB1, OTA and ZEN (Sabater-Vilar et al., 2007; 2003; Doll et al., 2004; Ramos et al., 1996b). Its efficacy (inclusion up
Santos et al., 2011). 2% in feed) was confirmed by GI models (ZEN) and by in vivo experi-
ments (FBs) (Avantaggiato et al., 2003, 2005; Kolosova and Stroka,
⁃ Activated carbon (AC) 2011). Also, cholestyramine reduced DON levels in buffer (pH 7) by
approximately 60% (Cavret et al., 2010), while only 5% of DON could
AC is a non-soluble powder, produced by pyrolysis of several or- be adsorbed by cholestyramine in a dynamic digestive tract
ganic compounds, followed by its chemical or physical activation aimed (Avantaggiato et al., 2005).
at developing a highly porous structure. Based on literature data, AC However, the high cost of these polymers would be a limiting factor
seems to be the most effective adsorbent with high affinity for different for practical applications.
mycotoxins (including DON) in vitro (Avantaggiato et al., 2005, 2004,
2003; Diaz and Smith, 2005; Mezes et al., 2010; Ramos et al., 1996a,b; 4. Adsorbing agents with multi-toxin efficacy
Sabater-Vilar et al., 2007). Nevertheless the in vitro efficacy of AC to-
ward some mycotoxins was not confirmed in vivo (Avantaggiato et al., 4.1. In vitro studies
2005). Generally, the adsorption properties of AC depend on the source
materials, surface area and pore size distribution (Kolosova and Stroka, In binding studies in vitro, the efficacy of the AA seems to be mainly
2011). However, AC is unspecific, hence essential nutrients are also dependant on the physicochemical properties of the adsorbent and
adsorbed particularly if their concentrations in feed are much higher mycotoxin, as well as the pH. Also, binding efficiency of the adsorbent
compared to those of a mycotoxin. Vekiru et al. (2007) also reported is highly affected by the presence of the matrix or even gastric juice
that AC strongly adsorbed vitamins and minerals essential for growth which can decrease its performance compared to the results obtained in
and development. Moreover, when they were analysed in vivo, com- buffer (Jaynes et al., 2007; Vekiru et al., 2007). Other factors such as
ponents of the food matrix can compete or inhibit the interaction with a feed structure, moisture content and oxygen availability during testing
mycotoxin (Wielogórska et al., 2016). could heavily affect the results of binding studies (Paulick et al., 2015).
It should be noted that organic adsorbents, especially cereal or le- Moreover, they appear to be highly influenced by the levels of myco-
guminous fibres as well as pulp and peels of fruits, may contain fungal toxins themselves, their co-occurrence or possible co-operative effects
contamination, so they would have to be analysed before use to rule out (Faucet-Marquis et al., 2014; Santos et al., 2011).
the presence of mycotoxins. To date, most of the in vitro binding studies in scientific literature
has focused on the efficacy of adsorption of a specific mycotoxin,
3.1.3. Synthetics usually tested at high levels. Moreover, most of them have been carried
out using buffer solutions, and in many cases without feed matrix.
⁃ Organoaluminosilicates or modified clays However in the “real-world”, animal feed is rarely contaminated by a
single mycotoxin, and metabolic digestions are not taken into account
In animals, aluminosilicates appear to be selective in their ‘chemi- on in vitro testing, unless GI models or biological juices have been used.
sorption’ of AFs with little or no beneficial effect against ZEN, OTA and As a result, there are many discrepancies between in vitro and in vivo
FBs. This limitation can be overcome by chemical modifications. These studies. Accordingly, only in vitro studies focused on the adsorption of
consist of alterations of surface properties by exchange of structural multiple mycotoxins, and carried out taking into account the afore-
charge-balance cations with high molecular weight quaternary amines, mentioned points, have been highlighted in this section.
which results in an increased hydrophobicity (Papaioannou et al., Following this line, Avantaggiato et al. (2004) investigated for the
2005). In vitro results have verified the binding efficacy of modified first time the intestinal absorption of two mycotoxins (DON and NIV)
montmorillonite and clinoptilolite against ZEN and OTA (Dakovic et al., simultaneously. Before this, an in vitro screening test of 14 adsorbents
2003; Jiang et al., 2012; Papaioannou et al., 2005). Moreover, other (Mycorsorb®, Mycofix Plus®, Myco AD®, cholestyramine, bentonite,
authors have shown organically modified clays are more effective than zeolite, AC, glucomannans (GM), etc.) was carried out. Successively, the

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efficacy of AC (the only one that showed reductions) in adsorbing DON 4.2.1. Broilers
and NIV by using a dynamic GI model was tested. The in vitro intestinal With regard to studies with poultry, Miazzo et al. (2005) in-
absorptions were 51% and 21% respectively, of the 170 μg and 230 μg vestigated the use of sodium bentonite (0.3%) to detoxify diets con-
ingested through contaminated spiked wheat. The use of a GI model taining a combination of two mycotoxins (2.5 mg AFB1/kg and 200 mg
simulating animal conditions confirmed that DON absorption mainly FB1/kg) in broiler chicks. In broilers fed with co-contaminated feed
occurred at the small intestinal level and specifically the jejunum. (AFB1 and FB1), the relative weights of organs (liver, kidney, gizzard
Also, Santos et al. (2011) evaluated two different adsorbents (or- and spleen) increased. Particularly, livers of birds were enlarged, yel-
ganic activated bentonite and humic acid) intended for use as feed lowish, friable, and had rounded borders. Liver histopathology showed
additives in the prevention or reduction of the adverse effects exerted multifocal and varied cytoplasmatic vacuolization. The addition of
by 0.1 mg OTA/kg and 0.5 mg ZEN/kg in a common in vitro model, with bentonite to the contaminated diet counteracted these effects by re-
a pH course comparing pH that can be expected in the digestive system ducing the incidence and severity of the pathological changes. The
of a monogastric animal (pH 7.4, pH 3.0, and pH 8.4). Both AA showed authors concluded that sodium bentonite was effective to counteract
an adsorbing capacity of > 96% towards both mycotoxins, regardless only some of the AFB1 promoted effects. It could be attributed to
pH, except for the humic acid product, that showed extensive deso- competition between AFB1 and FB1 for the active surfaces sites of the
rption at pH 8.4. adsorbent, rendering a greater bioavailability of AFB1 in the presence
Later, Avantaggiato et al. (2007) investigated combined mycotoxin of high dose of FB1.
binding properties of different compounds to enhance multi-binding Some authors pointed out that combined use of different adsorbents
capacity. They performed an in vitro study to assess the multi-toxin- with diverse structural properties would provide versatile tools for
binding efficacy of a carbon/aluminosilicate-based product (a mixture preventing multi-mycotoxicosis by binding a wider range of mycotoxins
of six components, “Standard Q/FIS”) in a 2% concentration, by using a (Avantaggiato et al., 2007; Huwig et al., 2001). On these lines, Liu et al.
dynamic GI model. On the basis of the results, a reduction of mycotoxin (2011) performed experiments in vivo on the effects of different my-
absorption was observed (up to 88% for AFB1, 44% for ZEN, 29% for cotoxin adsorbents including EGM (0.05%), HSCAS (0.2%) and a
FB1 and OTA), suggesting that this multi-composed adsorbent could be combination of both (EGM + HSCAS, 0.1%) on performance, nutrient
beneficial in reducing both individual and combined adverse effects of retention and meat quality in broilers fed on mould-contaminated
mycotoxins in animals. Most recently, the same research team ex- maize (0.45 mg AFB1/kg, 0.06 mg OTA/kg, and 0.32 mg T-2/kg). The
amined the ability of an organic adsorbent, grape pomace (rich in results indicated that mycotoxins in contaminated feed retard growth,
phenolic antioxidants), to simultaneously adsorb different mycotoxins nutrient retention and meat quality, whereas the addition of HSCAS
from solution. Results showed that AFB1 was the most (83%) adsorbed helped correct the decreased FI and the retention of phosphorus. The
mycotoxin followed by ZEN (67%), OTA (62%), and FB1 (29%), addition of EGM decreased yellowness in breast muscle, and the com-
whereas the adsorption of DON was negligible. This study proved for bination of both adsorbents (EGM + HSCAS, 0.1%) significantly im-
the first time that grape pomace can simultaneously adsorb several proved BW gain and FI. Moreover, the retention of crude lipid, crude
mycotoxins, and that mycotoxins did not compete for adsorption in a protein, ash and phosphorus increased with the mix, making it the most
multi-mycotoxin system. Hydrophobic interactions may be associated effective treatment. The authors stressed that the addition of a combi-
with AFB1 and ZEN adsorption, whereas polar non covalent interac- nation of adsorbents to contaminated feed would be a versatile way of
tions may be associated with OTA and FB1 adsorption. So grape pomace preventing mycotoxicosis.
may have a wide range of technological applications as bio-sorbent to More recently, a Greek research group examined in vivo the use of
decontaminate multi-mycotoxin contaminated feed (Avantaggiato two bentonites (1%) differing in composition, as potential binders of
et al., 2014). three mycotoxins present in broiler diets at levels not exceeding the EU
In vitro studies have to be confirmed in vivo. Thus, studies with maximum (0.013 mg AFB1/kg, 0.1 mg OTA/kg and 1 mg ZEN/kg). The
animals would be necessary to prove the effectiveness of these ad- study revealed that the examined bentonites may maintain optimum
sorbents in reducing the toxic effects of mycotoxins without affecting broiler performance when mycotoxins present in the feed do not exceed
the regular utilization of essential nutrients in animal feed, such as EU limits and guidance values, possibly by ameliorating the negative
vitamins and minerals. effects of other mycotoxins, not regulated by EU, present at the same
time in the feed since multi-contamination is more likely to occur in the
field than single contamination (Pappas et al., 2014).
4.2. In vivo studies With regard to organic sorbents, Aravind et al. (2003) assessed the
ability of EGM (0.05%) to alleviate the adverse effects of several
Co-contamination is more likely to occur in the field than mono- combinations of mycotoxins (0.168 mg AFB1/kg, 0.0084 mg OTA/kg,
contamination by mycotoxins (Grenier and Oswald, 2011; Streit et al., 0.053 mg ZEN/kg and 0.032 mg T-2/kg) naturally found in broiler feed
2012; Zachariasova et al., 2014). The toxicity and clinical signs ob- (Table 4). The naturally contaminated diet significantly decreased BW,
served in animals when feed is multi-contaminated by mycotoxins are feed consumption and feed efficiency, and increased the relative
complex and diverse. The effects of specific mycotoxins and adsorbents weights of liver and gizzard. Moreover, it was associated with sig-
differ for each animal species (Magnoli et al., 2011). Consequently, the nificant decreases in urea nitrogen and haematocrit values along with
evaluation of the efficacy of the AA against the different mycotoxins altered γ-glutamyl transferase activity. However, the addition of EGM
present in feeds is undertaken separately for poultry, swine, ruminants, to a contaminated diet increased performance and serum levels of urea
and other species. Nevertheless, variability exists in the literature even nitrogen and decreased the activity of γ-glutamyl transferase. These
within the same species. These variations may arise due to differences results suggested that EGM at 0.05% counteracted the toxic effects of
in adsorbents and doses, mycotoxin levels, animals’ age, nutritional, the naturally multi-contaminated diet alleviating growth depression
health status, BW, as well as the sensitivity of the animals exposed and reducing organ weights.
(Neeff et al., 2013). Other researchers studied the effects of EGM as an adsorbent in feed
In this section, different in vivo trials, mainly with poultry and multi-contaminated with DON and ZEN (Girish et al., 2008; Swamy
swine, testing the efficacy of the adsorbents in counteracting mycotoxin et al., 2002; Yegani et al., 2006). Swamy et al. (2002) studied the effects
effects produced as a consequence of multi-toxin contaminated FI, have of feeding blends of grains naturally contaminated with Fusarium my-
been summarized below and on Table 4. Data on multi-mycotoxin trials cotoxins (9.7 mg DON/kg, 21.6 mg FA/kg and 0.8 mg ZEN/kg) on
with other animal species are scarce in scientific literature. production parameters, clinical chemistry, and muscle coloration in
broilers, and the possibility of EGM (0.2%) in counteracting these

254
Table 4
Multi-binding efficiencies of various mycotoxin adsorbents in different animal species.
P. Vila-Donat et al.

Species Feed Mycotoxins and concentrations (mg/kg) Adsorbents (% added to contaminated feed) Duration of the study Effect of the addition of the AA to the co- contaminated References
diets

Broilers Corn-soybean meal AFB1 (0.01 mg/kg) + OTA (0.1 mg/ Bentonite (1%) 42 days Maintained optimum broiler performance. Pappas et al., 2014
kg) + ZEN (1 mg/kg)
Contaminated corn AFB1 (2.5 mg/kg) + FB1 (200 mg/kg) Sodium bentonite (0.3%) 50 days Protective effects on gross hepatic changes induced by Miazzo et al.,
AFB1. 2005
Naturally contaminated AFB1 (0.45 mg/kg) + OTA (0.06 mg/ A: EGM (0.05%), 42 days A: decreased yellowness in breast muscle but no effect on Liu et al., 2011
maize kg) + T-2 (0.23 mg/kg) B: HSCAS (0.2%), A + B: EGM + HSCAS BW and FI
(0.1%) B: partially recovered nutrient retention but no effect on
BW and FI.
A + B: recovered FI, BW and nutrient retention.
Naturally contaminated AFB1 (0.168 mg/kg) + OTA (0.0084 mg/ EGM (0.05%) 35 days Increased performance and serum levels of urea nitrogen Aravind et al.,
maize kg) + ZEN (0.053 mg/kg) + T-2 and decreased the activity of γ-glutamyl transferase. 2003
(0.032 mg/kg) Counteracted the toxic effects produced by mycotoxins
present in diet, by alleviating growth depression and
reducing organ weights.
Naturally contaminated DON (9.7 mg/kg) + ZEN (0.8 mg/ EGM (0.2%) 56 days No effect on feed consumption, WG, and feed efficiency but Swamy et al.,
grains kg) + FA (21.6 mg/kg) counteracted most of the blood parameter alteration and 2002
reduced breast muscle redness.
Naturally contaminated AFB1 (0.4273 mg/kg) + DON EGM “Mycosorb®” (0.05, 0.1%) 49 days At 0.05%, improved the decreased BW gain and FI. At Mohaghegh et al.,
corn (0.20631 mg/kg) + OTA (0.0022 mg/kg) 0.1%, additionally ameliorated the negative impact of 2017
mycotoxins on feed conversion ratio.
Naturally contaminated AFB1 (102.08 mg/kg) + ZEN (281.9 mg/ YCW (2%) 42 days Significantly improved the relative weight of the liver, Li et al., 2012

255
corn kg) + FB1 (5874.3 mg/kg) + DON spleen, bursa of Fabricius, and thymus; increased anti-
(2038.9 mg/kg) Newcastle disease titers; positive protection effect on the
splenic mRNA expression of IL-1β, IL-6, and IFN-γ tested.
Naturally contaminated DON (12.6 mg/kg) + ZEN + 15- Ac- DON GM polymer (0.2%) 12 weeks Prevented the decrease of eggshell, and antibody titers Yegani et al., 2006
corn (lesser amounts) against infectious bronchitis virus.
Pigs Naturally contaminated DON (5.5 mg/kg) + FA (26.8 mg/ GM polymer (0.2%) 21 days Prevented some toxin-induced metabolic changes. Swamy et al.,
grains (mostly corn) kg) + ZEN (0.4 mg/kg) + 15-Ac-DON 2003
(0.3 mg/kg)
Contaminated wheat DON (2.1–3.2 mg/kg) + ZEN Apple pomace (8%) 5 weeks Alleviated the negative effects of DON on growth. Gutzwiller et al.,
(0.06–0.25 mg/kg) 2007
Naturally contaminated DON (8.6 mg/kg) + ZEN (1.2 mg/kg) Modified aluminosilicate (0.4%) 36 days No protective effects were observed Doll et al., 2005
maize
Contaminated diets for DON (0.14–0.31 mg/kg) + ZEN Clinoptilolite-Zeolite (2%) Duration of a complete Beneficial effect on sow's reproductive performance and Kyriakys et al.,
sows (0.16–1.55 mg/kg) sow's reproductive cycle protection against the detrimental consequences of 2002
zearalenone toxicosis.
Naturally contaminated DON (4.8 mg/kg) + ZEN (0.3 mg/kg) A: YCW (2%); B: Yeast fermentation additive 42 days A: reduced oxidative stress and internal damage; B: Weaver et al.,
corn (2%) improved the growth performance of pigs by increasing FI 2014
and WG
Naturally contaminated AFB1 (0.15 mg/kg) + DON (1.1 mg/kg) A: Montmorillonite (2%); B: sodium 42 days A, B: reduced effects caused by mycotoxins on the immune Weaver et al.,
corn and barley bentonite, sepiolite, yeast (1.5%); C: system and the liver, and improved growth. 2013
diatomaceous earth, yeast culture (1.1%) C: reduced liver damage
Cattle Naturally contaminated DON (10.27 mg/kg) + 15-Ac-DON Modified YCW (1%) 84 days Mycotoxin levels assayed did not produce negative effects Martin et al., 2010
corn (1.27 mg/kg) + ZEN (1.84 mg/kg) on calves, so effects of the binder could not be proven

Aflatoxin B1 (AFB1), Deoxynivalenol (DON), T-2 toxin (T-2), Fusaric acid (FA), Zearalenone (ZEN), Ochratoxin A (OTA), Fumonisin B1 (FB1), 15-acetyldeoxynivalenol (15-Ac-DON), 3-acetyldeoxynivalenol (3-Ac-DON), Nivalenol (NIV), Esterified
Glucomannan (EGM), Hydrated Sodium Calcium Aluminosilicate (HSCAS), Glucomannan polymer (GM), Yeast Cell Wall (YCW), Body Weight (BW), Feed Intake (FI), Weight Gain (WG).
Food and Chemical Toxicology 114 (2018) 246–259
P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

adverse effects. The feeding of contaminated grains caused significant contaminated grains (5.5 mg DON/kg, 20.9 mg FA/kg, 0.4 mg ZEN/kg
linear increases in blood erythrocyte count and serum uric acid con- and 0.3 mg 15-Ac-DON/kg) was also tested (Table 4). Supplementation
centration and a significant linear decline in the serum lipase activity. of GM polymer (0.2%) prevented some toxin-induced changes in me-
EGM supplementation did not have any effect on feed consumption, WG tabolism. This may have been because this material is a high-MW
or feed efficiency but counteracted most of the blood parameter al- polymer and acted by adsorbing mycotoxin molecules in the intestinal
terations caused by the Fusarium mycotoxin-contaminated grains and lumen and prevented uptake into blood and target tissues; however, GM
reduced breast muscle redness (Swamy et al., 2002). Similar results polymer did not prevent the mycotoxin-induced growth depression
were reported by Girish et al. (2008) who described the efficacy of GM (Swamy et al., 2003). More recently, Weaver et al. (2014) determined
included in naturally Fusarium contaminated feeds by preventing some the effects of feeding naturally contaminated corn (4.8 mg/kg DON and
blood and immunological parameter alterations on turkeys, and also by 0.3 mg/kg ZEN) on pig performance and health status, and the ability of
Yegani et al. (2006) on broiler breeder hens (Table 4). two yeast based feed additives (YCW and yeast fermentation product)
Li et al. (2012) also investigated the toxicity of feed-borne Fusarium to help pigs to manage the problem of mycotoxins. Results of this study
mycotoxins (102.08 mg AF/kg, 281.92 mg ZEN/kg, 5874.38 mg FB/kg indicated that the consumption of the contaminated feed reduced FI
and 2038.96 mg DON/kg) on physiological, biochemical and im- and BW gains, and increased oxidative DNA damage. However, the
munological parameters of broiler chickens and evaluated the efficacy yeast fermentation additive improved the growth performance of pigs
of YCW (2%) adsorbent in preventing adverse mycotoxin-induced ef- by increasing FI and WG, while the YCW product did not significantly
fects. They demonstrated that naturally contaminated diets induced improve the growth performance, but tended to reduce oxidative stress
adverse changes in organ weight, serum biochemistry, and im- associated with the consumption of mycotoxins (Weaver et al., 2014).
munological parameters as compared with broiler chickens fed the Thus, the addition of both, the YCW product and yeast fermentation
control diet. However, the addition of YCW (2%) adsorbent to con- product, showed some benefits in reducing the effects of mycotoxins on
taminated feeds showed a positive protective effect on the relative pigs. However, the authors underlined these responses may vary under
weight of the liver, spleen, bursa of Fabricius and thymus, antibody different mycotoxin concentrations, types, and mixtures.
titers of Newcastle disease, and splenic mRNA expression of IL-1β, IL-6, On the other hand, Gutzwiller et al. (2007) studied the effects of
and IFN-γ. The addition of YCW thus neutralized the detrimental effects Fusarium toxins (2.1–3.2 mg DON/kg and 0.06–0.25 mg ZEN/kg) on
of the naturally contaminated feed. growth, humoral immune response and internal organs in weaner pigs,
Very recently, Mohaghegh et al. (2017) evaluated the effect of and the efficacy of apple pomace (8%) in alleviating the negative effects
Mycosorb® (EGM 0.05–0.1%) on performance, immunity, blood hae- induced by these mycotoxins. Results showed that pomace may alle-
matological and serum biochemical parameters in broilers exposed to viate the negative effect of DON on growth but does not counteract the
diets naturally contaminated with mycotoxins (0.4273 mg AFB1/kg, hormonal effects of ZEN (Table 4).
0.20631 mg DON/kg, and 0.0022 mg OTA/kg), (Table 4). Mycotoxin
contamination affected chicken performance, organ weights, some 4.2.3. Veal
haematological and most of the serum biochemical parameters. Dietary Regarding veal, only one study was found in literature. Specifically,
EGM supplementation (0.5, 0.1%) considerably improved the decreased Martin et al. (2010) studied the effects of feeding veal calves with corn
BW gain and FI. However, only EGM (0.1%) ameliorated the negative naturally contaminated with the Fusarium mycotoxin (10.27 mg DON/
impact of mycotoxins on the feed conversion ratio. Results indicated kg, 1.27 mg 15-Ac-DON/kg and 1.84 mg ZEN/kg) and evaluated the
that supplementing EGM, particularly at 0.1% level, efficiently reversed modified YCW (1%) on performance, immunity and carcass character-
the adverse effects of mycotoxins on broiler chickens. istics of calves. Veal calves were able to tolerate a moderate feeding
level of corn grains naturally contaminated with Fusarium mycotoxins.
4.2.2. Swine As there were generally no negative effects of the mycotoxin level in the
In pigs, the presence of trichothecenes (mainly DON) in feed is diet, the efficacy of YCW as a mycotoxin adsorbent could not be as-
usually concomitant with ZEN (Gutzwiller et al., 2007; Swamy et al., sessed, but YCW alone had negligible effects on performance. The au-
2003; Weaver et al., 2014). Doll et al. (2005) investigated the effects of thors underlined that the reaction of calves depends on the compounds,
dietary inclusion of a modified aluminosilicate (0.4%) in maize con- concentration, duration of exposure and combinations of different
taminated with Fusarium toxins (8.6 mg DON/kg and 1.2 mg ZEN/kg) mycotoxins in the diet.
for piglets. They could not demonstrate any detoxifying capacity in the
tested additive. However, when much lower dosages were tested 5. Conclusions
(0.14–0.31 mg DON/kg and 0.16–1.55 mg ZEN/kg) in sows, a beneficial
effect of zeolite (clinoptilolite) was observed on the reproductive per- A very high percentage of cereal-based animal feed is contaminated
formance of the animals, since it resulted in larger litter sizes and with more than one mycotoxin, the major contaminants being Fusarium
piglets' BW at both birth and weaning (Kyriakys et al., 2002). mycotoxins (DON, ZEN and FBs). Only a low percentage of feed samples
Recently, Weaver et al. (2013) determined the ability of three dif- is contaminated above permitted/guideline levels. However, animals
ferent feed additives (A: calcium montmorillonite clay, 2%; B: sodium (poultry, fish, and pigs, particularly) exhibit symptoms of mycotoxicosis
bentonite, sepiolite clay and a dried brewer's yeast component, 1.5%; C: even when exposed to feed contaminated with mycotoxins below the
a mixture of diatomaceous earth and yeast culture, 1.1%) to ameliorate guidance levels, probably as a consequence of negative synergistic ef-
the chronic negative effects of feeding diets containing 0.15 mg AFB1/ fects produced when different mycotoxins are simultaneously present in
kg and 1.1 mg DON/kg to pigs. The additives A and B in co-con- feed.
taminated diets, reduced mycotoxin effects on the immune system and The use of many of the available physical and chemical methods for
the liver, and showed some ability to improve growth. The additive C the decontamination of agricultural commodities contaminated with
played a role in reducing liver damage. In general, the authors conclude mycotoxins is restricted due to the problems associated with safety is-
that AFB1 and DON can be harmful to the growth and health of pigs sues, possible losses in the nutritional quality of treated commodities
consuming mycotoxins chronically. The selected feed additives im- coupled with limited efficacy and cost implications. The use of the
proved pig health. However, the ability of feed additives to reduce adsorbents as feed additives is the only practical solution to feed de-
mycotoxin was variable, and their function may depended on other contamination, although it should be adapted to the current demands of
factors, such as mycotoxin type, contamination level and pig health. farmers and AA have to be widely studied to guarantee their effec-
Regarding organic adsorbents, the efficacy of a polymeric GM in tiveness and safety.
preventing Fusarium mycotoxicosis in pigs fed with a blend of naturally Based on the available data, inorganic adsorbents such as

256
P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

aluminosilicates (bentonites, HSCAS and some zeolites) have ex- Lleida for her postdoctoral contract.
tensively demonstrated efficacy towards AFs. However, their efficacy
against other mycotoxins, such as trichothecenes, is limited. Only Transparency document
bentonite and zeolite seem capable of partially adsorbing ZEN. On the
other hand, modified clays are proving to be quite more effective than Transparency document related to this article can be found online at
other unmodified clays in adsorbing FBs, OTA and ZEN. In addition, it http://dx.doi.org/10.1016/j.fct.2018.02.044.
has been showed that organic adsorbents (YCW, EGMs, dietary fibres or
bio-sorbents) are more effective in binding to a wider spectrum of References
mycotoxins (ZEN, OTA, FBs).
Regarding DON, only some YCW (β-glucans and mannans), AC or Abbas, H.K., Wilkinson, J.R., Zablotowicz, R.M., Accinelli, C., Abel, C.A., Bruns, H.A.,
synthetic polymers (cholestyramine) have been identified as potential Weaver, M.A., 2009. Ecology of Aspergillus flavus, regulation of aflatoxin production,
and management strategies to reduce aflatoxin contamination of corn. Toxin Rev. 28,
adsorbents. However, a mix of different AA could give a cumulative 142–153.
efficacy or synergy due to their specific characteristics. On the other Anater, A., Manyes, L., Meca, G., Ferrer, E., Bittencourt, F., Turra, C., Font, G., 2016.
hand, combining mycotoxin binding properties of different adsorbents Mycotoxins and their consequences in aquaculture. A review. Aquaculture 451, 1–10.
Aoudia, N., Callu, P., Grosjean, F., Larondelle, Y., 2009. Effectiveness of mycotoxin se-
(mineral and organic), could be further adapted to the most frequent questration activity of micronized wheat fibres on distribution of ochratoxin A in
cases of multi-contaminated feed. plasma, liver and kidney of piglets fed a naturally contaminated diet. Food Chem.
Most of the in vitro studies published in scientific literature are fo- Toxicol. 47, 1485–1489.
Aravind, K.L., Patil, V.S., Devegowda, G., Umakantha, B., Ganpule, S.P., 2003. Efficacy of
cused on adsorbent efficacy toward a single mycotoxin (very often
esterified glucomannan to counteract mycotoxicosis in naturally contaminated feed
AFB1, since it is the only one with MPLs in animal feed). Moreover, on performance and serum biochemical and hematological parameters in broilers.
many assays have been performed with buffer solutions, and by testing Poultry Sci. 82, 571–576.
Avantaggiato, G., Greco, D., Damascelli, A., Solfrizzo, M., Visconti, A., 2014. Assessment
with toxins and adsorbents far above regulated levels. Few in vitro
of multi-mycotoxin adsorption efficacy of grape pomace. J. Agric. Food Chem. 62,
binding studies have been performed by using GI models (with phy- 497–507.
siological juices at different pH) and focused on multi-mycotoxin ad- Avantaggiato, G., Havenaar, R., Visconti, A., 2003. Assessing the zearalenone-binding
sorption. The latter, conducted recently, cover interactions thus closing activity of adsorbent materials during passage through a dynamic in vitro gastro-
intestinal model. Food Chem. Toxicol. 41, 1283–1290.
the gap between in vitro and in vivo testing, and could reduce the Avantaggiato, G., Havenaar, R., Visconti, A., 2004. Evaluation of the intestinal absorption
number of animal studies. However in vitro predictions about the ability of deoxynivalenol and nivalenol by an in vitro gastrointestinal model, and the binding
of adsorbents to protect animals from the adverse effects of mycotoxins efficacy of activated carbon and other adsorbent materials. Food Chem. Toxicol. 42,
817–824.
should be approached with caution and should be confirmed in vivo Avantaggiato, G., Havenaar, R., Visconti, A., 2007. Assessment of the multi-mycotoxin-
with animals. binding efficacy of a carbon/aluminosilicate-based product in an in vitro gastro-
Regarding multi-binding in vivo studies, there are many studies with intestinal model. J. Agric. Food Chem. 55, 4810–4819.
Avantaggiato, G., Solfrizzo, M., Visconti, A., 2005. Recent advances on the use of ad-
chickens and even with pigs, but other animal species such as cows and sorbent materials for detoxification of Fusarium mycotoxins. Food Addit. Contam. 22,
fish have been studied very little or not at all, probably because of the 379–388.
long duration and the high costs of experiments. In addition, the con- Awad, W.A., Böhm, J., Razzazi-Fazeli, E., Zentek, J., 2006. Effects of feeding deox-
ynivalenol contaminated wheat on growth performance, organ weights and histolo-
centrations of adsorbent and mycotoxin used in the reviewed works are gical parameters of the intestine of broiler chickens. J. Anim. Physiol. Anim. Nutr. 90,
highly variable. Available data indicate that observed effects depend on 32–37.
the level and type of mycotoxin, as well as duration of exposure, type Awad, W.A., Ghareeb, K., Böhm, J., Zentek, J., 2010. Decontamination and detoxification
strategies for the Fusarium mycotoxin deoxynivalenol in animal feed and the effec-
and dose of adsorbent, on the animal species and physiological condi-
tiveness of microbial biodegradation. Food Addit. Contam. 27, 510–520.
tion of the animal. However, the combination of different adsorbents Baglieri, A., Reyneri, A., Gennari, M., Negre, M., 2013. Organically modified clays as
(mineral and organic) seems to be more effective in better counter- binders of fumonisins in feedstocks. J. Environ. Sci. Health 48, 776–783.
acting the adverse effects produced by the simultaneous exposure of Bhat, R., Rai, R.V., Karim, A.A., 2010. Mycotoxins in food and feed: present status and
future concerns. Compr. Rev. Food Sci. Food Saf. 9, 57–81.
several mycotoxins in feed. In any case, future in vivo studies should be Boudergue, C., Burel, C., Dragacci, S., Favrot, M.C., Fremy, J.M., Massimi, C., Prigent, P.,
done by assaying naturally multi-contaminated feed, using “real-world” Debongnie, P., Pussemier, L., Boudra, H., Morgavi, D., Oswald, I., Perez, A.,
mycotoxins and adsorbent concentrations, tested at levels within the Avantaggiato, G., 2009. Review of Mycotoxin-detoxifying Agents used as Feed
Additives: Mode of Action, Efficacy and Feed/Food Safety. External Scientific Report
EU-regulations, and taking into account EFSA report endpoints; paying Submitted to EFSA Available on: https://www.efsa.europa.eu/en/supporting/pub/
attention to their efficacy and safety, and their potential for interactions en-22, Accessed date: December 2017.
with critical nutrients (vitamins and minerals). Bouhet, S., Oswald, I.P., 2007. The intestine as a possible target for fumonisin toxicity.
Mol. Nutr. Food Res. 51, 925–931.
Animal feed is increasingly made from plant materials such as cer- Bryden, W.L., 2012. Mycotoxin contamination of the feed supply chain: implications for
eals and cereal by-products, and multiple contamination is increasingly animal productivity and feed security. Anim. Feed Sci. Technol. 173, 134–158.
observed in these raw materials. So a potential adsorbent would have to Cano-Sancho, G., Marin, S., Ramos, A.J., Sanchis, V., 2010. Biomonitoring of Fusarium
spp. mycotoxins: perspectives for an individual exposure assessment tool. Food Sci.
be efficient in dealing with several mycotoxins. The development of Technol. 16, 266–276.
such products would be an interesting trend in trying to counteract the Cavret, S., Laurent, N., Videmann, B., Mazallon, M., Lecoeur, S., 2010. Assessment of
toxic effects of co-occurring mycotoxins in animal feed. Therefore, deoxynivalenol (DON) adsorbents and characterisation of their efficacy using com-
plementary in vitro tests. Food Addit. Contam. 27, 43–53.
further research should be conducted towards the achievement of this
Dakovic, A., Kragovic, M., Rottinghaus, G.E., Sekulic, Z., Milicevic, S., Milonjic, S.K.,
goal. Zaric, S., 2010. Influence of natural zeolitic tuff and organozeolites surface charge on
sorption of ionizable fumonisin B1. Colloids Surf., B 76, 272–278.
Declaration of interest statement Dakovic, A., Tomasevic-Canovic, M., Rottinghaus, G., Dondur, V., Masic, Z., 2003.
Adsorption of ochratoxin A on octadecyldimethyl benzyl ammonium exchanged-
clinoptilolite-heulandite tuff. Colloids Surf., B 30, 157–165.
The authors declare there are no conflicts of interest. Dalié, D.K.D., Deschamps, A.M., Richard-Forget, F., 2010. Lactic acid bacteria - potential
for control of mould growth and mycotoxins: a review. Food Contr. 21, 370–380.
Decastelli, L., Lai, J., Gramaglia, M., Monaco, A., Nachtmann, C., Oldano, F., Ruffier, M.,
Acknowledgements Sezian, A., Bandirola, C., 2007. Aflatoxins occurrence in milk and feed in Northern
Italy during 2004-2005. Food Contr. 18, 1263–1266.
The authors are grateful to the Spanish government (projects RTC- Deng, Y.J., Velázquez, A.L.B., Billes, F., Dixon, J.B., 2010. Bonding mechanisms between
aflatoxin B1 and smectite. Appl. Clay Sci. 50, 92–98.
20153508-2 and AGL2014-52648-REDT) and to XaRTA (The Di Gregorio, M.C., de Neeff, D.V., Jager, A.V., Corassin, C.H., de Pinho Carão, A.C., de
Catalonian Reference Network in Food Technology) for funding. They Albuquerque, R., de Azevedo, A.C., Fernandes Oliveira, C.A., 2014. Mineral ad-
also would like to thank Arthur Kendall for editing the English usage in sorbent for prevention mycotoxins in animal feed. Toxin Rev. 33, 125–135.
Diaz, D.E., Smith, T.K., 2005. Mycotoxin sequestering agents: practical tools for the
the manuscript. P. Vila-Donat thanks MINECO and the University of

257
P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

neutralisation of mycotoxins. In: The Mycotoxin Blue Book. Nottingham University of food and animal feed: a review. Crit. Rev. Food Sci. Nutr. 46, 593–619.
Press, Nottingham, United Kingdom, pp. 323–339. Karlovsky, P., 2011. Biological detoxification of the mycotoxin deoxynivalenol and its use
Doll, S., Danicke, S., Valenta, H., Flachowsky, G., 2004. In vitro studies on the evaluation in genetically engineered crops and feed additives. Appl. Microbiol. Biotechnol. 91,
of mycotoxin detoxifying agents for their efficacy on deoxynivalenol and zear- 491–504.
alenone. Arch. Anim. Nutr. 58, 311–324. Kolosova, A., Stroka, J., 2011. Substances for reduction of the contamination of feed by
Doll, S., Gericke, S., Danicke, S., Raila, J., Ueberschar, K.H., Valenta, H., Schnurrbusch, mycotoxins. A review. World Mycotoxin J. 4, 225–256.
U., Schweigert, F.J., Flachowsky, G., 2005. The efficacy of a modified aluminosilicate Kong, C., Shin, S.Y., Kim, B.G., 2014. Evaluation of mycotoxin sequestering agents for
as a detoxifying agent in Fusarium toxin contaminated maize containing diets for aflatoxin and deoxynivalenol: an in vitro approach. SpringerPlus 3, 346–351.
piglets. J. Anim. Physiol. Anim. Nutr. 89, 342–358. Kosicki, R., Błajet-Kosicka, A., Grajewski, J., Twarużek, M., 2016. Multiannual mycotoxin
Duvick, J., 2001. Prospects for reducing fumonisin contamination of maize through ge- survey in feed materials and feedingstuffs. Anim. Feed Sci. Technol. 215, 165–180.
netic modification. Environ. Health Perspect. 109, 337–342. Kyriakys, S.C., Papaioannou, D.S., Alexopoulos, C., Polizopoulou, Z., Tzika, E.D., Kyriakis,
EC, European Commission, 2015. Comission Regulation EU 2015/1940 of 29 October C.S., 2002. Experimental studies on safety and efficacy of the dietary use of a clin-
2015 concerning maximum levels of ergot sclerotia in certain unprocessed cereals optilolite-rich tuff in sows: a review of recent research in Greece. Micropor. Mesopor.
and the provisions on monitoring and reporting. Off. J. EU. L 283, 3–6. Mat. 51, 65–74.
EC, European Commission, 2003. Commission directive 2003/100/EC of 31 october 2003 Li, Z., Yang, Z.B., Yang, W.R., Wang, S.J., Jiang, S.Z., Wu, Y.B., 2012. Effects of feedborne
amending annex I to directive 2002/32/EC of the european parliament and of the Fusarium mycotoxins with or without yeast cell wall adsorbent on organ weight,
council on undesirable substances in animal feed. Off. J. EU. L 285, 33–37. serum biochemistry, and immunological parameters of broiler chickens. Poultry Sci.
EC, European Commission, 2006. Commission Recommendation of 17 August 2006 on 91, 2487–2495.
the presence of deoxynivalenol, zearalenone, ochratoxin A, T-2 and HT-2 and fu- Liu, Y.L., Meng, G.Q., Wang, H.R., Zhu, H.L., Hou, Y.Q., Wang, W.J., Ding, B.Y., 2011.
monisins in products intended for animal feeding. Off. J. EU. L 229, 7–9. Effect of three mycotoxin adsorbents on growth performance, nutrient retention and
EC, European Commission, 2009. Commission regulation (EC) No. 386/2009 of 12 May meat quality in broilers fed on mould-contaminated feed. Br. Poultry Sci. 52,
2009 amending Regulation (EC) No. 1831/2003 of the European Parliament and of 255–263.
the Council as regards the establishment of a new functional group of feed additives. Magnoli, A.P., Monge, M.P., Miazzo, R.D., Cavaglieri, L.R., Magnoli, C.E., Merkis, C.I.,
Off. J. EU. L 118, 66. Cristofolini, A.L., Dalcero, A.M., Chiacchiera, S.M., 2011. Effect of low levels of
EC, European Commission, 2013a. Commission Recommendation of 27 March 2013 on aflatoxin B-1 on performance, biochemical parameters, and aflatoxin B1 in broiler
the presence of T-2 and HT-2 toxin in cereals and cereal products. Off. J. EU. L 91, liver tissues in the presence of monensin and sodium bentonite. Poultry Sci. 90,
12–15. 48–58.
EC, European Commission, 2013b. Commission Regulation (EU) No 1060/2013 of 29 Marin, S., Ramos, A.J., Cano-Sancho, C., Sanchis, V., 2013. Mycotoxins: occurrence,
October 2013 concerning the authorisation of bentonite as feed additive for all an- toxicology, and exposure assessment. Food Chem. Toxicol. 60, 218–237.
imal species. Off. J. EU. L 289, 33–37. Martin, L.M., Wood, K.M., McEwen, P.L., Smith, T.K., Mandell, I.B., Yannikouris, A.,
EFSA, 2011. European Food Safety Authority. Scientific Opinion on the risks for animal Swanson, K.C., 2010. Effects of feeding corn naturally contaminated with Fusarium
and public health related to the presence of Alternaria toxins in feed and food. EFSA J mycotoxins and/or a modified yeast cell wall extract on the performance, immunity
9, 2407. and carcass characteristics of grain-fed veal calves. Anim. Feed Sci. Technol. 159,
Faucet-Marquis, V., Joannis-Cassan, C., Hadjeba-Medjdoub, K., Ballet, N., Pfohl- 27–34.
Leszkowicz, A., 2014. Development of an in vitro method for the prediction of my- Matejova, I., Svobodoba, Z., Vakula, J., Mares, J., Modra, H., 2017. Impact of mycotoxins
cotoxin binding on yeast-based products: case of aflatoxin B1, zearalenone and on aquaculture fish species: a review. J. World Aquacult. Soc. 48, 186–200.
ochratoxin A. Appl. Microbiol. Biotechnol. 98, 7583–7596. Medina, A., Rodríguez, A., Sultan, Y., Magan, N., 2015. Climate change factors and
Feng, J.L., Shan, M., Du, H.H., Han, X.Y., Xu, Z.R., 2008. In vitro adsorption of zear- Aspergillus flavus: effects on gene expression, growth and aflatoxin production. World
alenone by cetyltrimethyl ammonium bromide-modified montmorillonite nano- Mycotoxin J. 8, 171–179.
composites. Micropor. Mesopor. Mat. 113, 99–105. Meissonnier, G.M., Oswald, I.P., Galtier, P., 2005. Aflatoxicosis in swine - a bibliographic
FAO, 2001. Food and Agriculture Organization of the United Nations. Manual on the review of clinical cases and experimental data. Rev. Méd. Vét. 156, 591–605.
Application of the HACCP System in Mycotoxin Prevention and Control. FAO Food Mezes, M., Balogh, K., Toth, K., 2010. Preventive and therapeutic methods against the
and Nutrition Paper 73. FAO, Rome, Italy Available at: http://www.fao.org/3/a- toxic effects of mycotoxins – a review. Acta Vet. Hung. 58, 1–17.
y1390e.pdf, Accessed date: December 2017. Miazzo, R., Peralta, M.F., Magnoli, C., Salvano, M., Ferrero, S., Chiacchiera, S.M.,
FAO, 2004. Food and Agriculture Organization of the United Nations. Worldwide Carvalho, E.C., Rosa, C.A., Dalcero, A., 2005. Efficacy of sodium bentonite as a de-
Regulations for Mycotoxins in Food and Feed. Available at: http://www.fao.org/ toxifier of broiler feed contaminated with aflatoxin and fumonisin. Poultry Sci.
tempref/docrep/fao/007/y5499e/y5499e00.pdf, Accessed date: December 2017. 84, 1–8.
Fruhauf, S., Schwartz, H., Ottner, F., Krska, R., Vekiru, E., 2012. Yeast cell based feed Miraglia, M., Marvin, H.J., Kleter, G.A., Battilani, P., Brera, C., Coni, E., Cubadda, F.,
additives: studies on aflatoxin B1 and zearalenone. Food Addit. Contam. 29, Croci, L., De Santis, B., Dekkers, S., Filippi, L., Hutjes, R.W., Noordam, M.Y., Pisante,
217–231. M., Piva, G., Prandini, A., Toti, L., van den Born, G.J., Vespermann, A., 2009. Climate
Girish, C.K., Smith, T.K., Boermans, H.J., Karrow, N.A., 2008. Effects of feeding blends of change and food safety: an emerging issue with special focus on Europe. Food Chem.
grains naturally contaminated with Fusarium mycotoxins on performance, hema- Toxicol. 47, 1009–1021.
tology, metabolism, and immunocompetence of turkeys. Poultry Sci. 87, 421–432. Mohaghegh, A., Chamania, M., Shivazada, M., Sadeghia, A.A., Afzalib, N., 2017. Effect of
Grenier, B., Oswald, I.P., 2011. Mycotoxin co-contamination of food and feed: meta- esterified glucomannan on broilers exposed to natural mycotoxin-contaminated diets.
analysis of publications describing toxicological interactions. World Mycotoxin J. 4, J. Appl. Anim. Res. 45, 285–291.
285–313. Monbaliu, S., Van Poucke, C., Detavernier, C., Dumoulin, F., Van De Velde, M., Schoeters,
Griessler, K., Rodrigues, I., Handl, J., Hofstetter, U., 2010. Occurrence of mycotoxins in E., Van Dyck, S., Averkieva, O., Van Peteghem, C., De Saeger, S., 2010. Occurrence of
southern Europe. World Mycotoxin J. 3, 301–309. mycotoxins in feed as analyzed by a multi-mycotoxin LC-MS/MS method. J. Agric.
Gutzwiller, A., Czegledi, L., Stoll, P., Bruckner, L., 2007. Effects of Fusarium toxins on Food Chem. 58, 66–71.
growth, humoral immune response and internal organs in weaner pigs, and the ef- Morgavi, D.P., Riley, R.T., 2007. An historical overview of field disease outbreaks known
ficacy of apple pomace as an antidote. J. Anim. Physiol. Anim. Nutr. 91, 432–438. or suspected to be caused by consumption of feeds contaminated with Fusarium
Harper, A.F., Estienne, M.J., Meldrum, J.B., Harrell, R.J., Diaz, D.E., 2010. Assessment of toxins. Anim. Feed Sci. Technol. 137, 201–212.
a hydrated sodium calcium aluminosilicate agent and antioxidant blend for mitiga- Neeff, D.V., Ledoux, D.R., Rottinghaus, G.E., Bermudez, A.J., Dakovic, A., Murarolli, R.A.,
tion of aflatoxin-induced physiological alterations in pigs. J. Swine Health Prod. 18, Oliveira, C.A.F., 2013. In vitro and in vivo efficacy of a hydrated sodium calcium
282–289. aluminosilicate to bind and reduce aflatoxin residues in tissues of broiler chicks fed
Huwig, A., Freimund, S., Kappeli, O., Dutler, H., 2001. Mycotoxin detoxication of animal aflatoxin B1. Poultry Sci. 92, 131–137.
feed by different adsorbents. Toxicol. Lett. 122, 179–188. Nesic, K., Resanovic, R., Nesic, V., Sinovec, Z., 2008. Efficacy of mineral and organic
IARC, 1993. International Agency for Research on Cancer. Monographs on the Evaluation adsorbent in alleviating harmful effects of zearalenone on pigs performance and
of Carcinogenic Risks to Humans, Some Naturally Occurring Substances, Food Items health. Acta Vet. Beograd. 58, 211–219.
and Constituents, Heterocyclic Aromatic Amines and Mycotoxins, vol. 56 Papaioannou, D., Katsoulos, P.D., Panousis, N., Karatzias, H., 2005. The role of natural
International Agency for Research on Cancer, Lyon. and synthetic zeolites as feed additives on the prevention and/or the treatment of
IARC, International Agency for Research on Cancer, 2002. IARC Monographs on the certain farm animal diseases: a review. Micropor. Mesopor. Mat. 84, 161–170.
Evaluation of Carcinogenic Risks to Humans, vol. 82 International Agency for Pappas, A.C., Tsiplakou, E., Georgiadou, M., Anagnostopoulos, C., Markoglou, A.N.,
Research on Cancer, Lyon. Liapis, K., Zervas, G., 2014. Bentonite binders in the presence of mycotoxins: results
Jard, G., Liboz, T., Mathieu, F., Guyonvarc’h, A., Lebrihi, A., 2011. Review of mycotoxin of in vitro preliminary tests and an in vivo broiler trial. Appl. Clay Sci. 99, 48–53.
reduction in food and feed: from prevention in the field to detoxification by ad- Paulick, M., Rempe, I., Kersten, S., Schatzmayr, D., Schwartz-Zimmermann, H.E.,
sorption or transformation. Food Addit. Contam. 28, 1590–1609. Danicke, S., 2015. Effects of increasing concentrations of sodium sulfite on deox-
Jaynes, W.F., Zartman, R.E., Hudnall, W.H., 2007. Aflatoxin B1 adsorption by clays from ynivalenol and deoxynivalenol sulfonate concentrations of maize kernels and maize
water and corn meal. Appl. Clay Sci. 36, 197–205. meal preserved at various moisture content. Toxins 7, 791–811.
Jiang, S.Z., Yang, Z.B., Yang, W.R., Wang, S.J., Liu, F.X., Johnston, L.A., Chi, F., Wang, Y., Pfohl-Leszkowicz, A., Hadjeba-Medjdoub, K., Ballet, N., Schrickx, J., Fink-Gremmels, J.,
2012. Effect of purified zearalenone with or without modified montmorillonite on 2015. Assessment and characterisation of yeast-based products intended to mitigate
nutrient availability, genital organs and serum hormones in post-weaning piglets. ochratoxin exposure using in vitro and in vivo models. Food Addit. Contam. 32,
Livest. Sci. 144, 110–118. 604–616.
Jouany, J.P., 2007. Methods for preventing, decontaminating and minimizing the toxicity Phillips, T.D., Afriyie-Gyawu, E., Williams, J., Huebner, H., Ankrah, N.A., Ofori-Adjei, D.,
of mycotoxins in feeds. Anim. Feed Sci. Technol. 137, 342–362. Jolly, P., Johnson, N., Taylor, J., Marroquin-Cardona, A., Xu, L., Tang, L., Wang, J.S.,
Kabak, B., Dobson, A.D.W., Var, I., 2006. Strategies to prevent mycotoxin contamination 2008. Reducing human exposure to aflatoxin through the use of clay: a review. Food

258
P. Vila-Donat et al. Food and Chemical Toxicology 114 (2018) 246–259

Addit. Contam. 25, 134–145. feeding blends of grains naturally contaminated with Fusarium mycotoxins on pro-
Pinotti, L., Ottoboni, M., Giromini, C., Dell'Orto, V., Cheli, F., 2016. Mycotoxin con- duction and metabolism in broilers. Poultry Sci. 81, 966–975.
tamination in the EU feed supply chain: a focus on cereal byproducts. Toxins 8, 45. Thieu, N.Q., Ogle, B., Pettersson, H., 2008. Efficacy of bentonite clay in ameliorating
Pinton, P., Tsybulskyy, D., Lucioli, J., Laffitte, J., Callu, P., Lyazhri, F., Grosjean, F., aflatoxicosis in piglets fed aflatoxin contaminated diets. Trop. Anim. Health Prod. 40,
Bracarense, A.P., Kolf-Clauw, M., Oswald, I.P., 2012. Toxicity of deoxynivalenol and 649–656.
its acetylated derivatives on the intestine: differential effects on morphology, barrier Vekiru, E., Fruhauf, S., Sahin, M., Ottner, F., Schatzmayr, G., Krska, R., 2007.
function, tight junctions proteins and MAPKinases. Toxicol. Sci. 130, 180–190. Investigation of various adsorbents for their ability to bind aflatoxin B1. Mycotox.
Ramos, A.J., Fink-Gremmels, J., Hernández, E., 1996a. Prevention of toxic effects of Res. 23, 27–33.
mycotoxins by means of nonnutritive adsorbent compounds. J. Food Prot. 59, Vidal, A., Marín, S., Ramos, A.J., Cano-Sancho, G., Sanchis, V., 2013. Determination of
631–641. aflatoxins, deoxynivalenol, ochratoxin A and zearalenone in wheat and oat based
Ramos, A.J., Hernández, E., 1996. In vitro aflatoxin adsorption by means of a montmor- bran supplements sold in the Spanish market. Food Chem. Toxicol. 53, 133–138.
illonite silicate. A study of absorption isotherms. Anim. Feed Sci. Technol. 62, Vila-Donat, P., Marín, S., Sanchis, V., Ramos, A.J., June 2017a. Personal Communication
263–269. a. Evaluación de nuevos adsorbentes multimicotoxínicos basados en bentonitas para
Ramos, A.J., Hernández, E., 1997. Prevention of aflatoxicosis in farm animals by means of alimentación animal. XXII Congreso Español de Toxicología y VI Iberoamericano
hydrated sodium calcium aluminosilicate addition to feedstuffs: a review. Anim. Feed (AETOX), Valencia (Spain). Rev. Toxicol. 34, 21.
Sci. Technol. 65, 197–206. Vila-Donat P., Marín, S., Sanchis, V., Ramos, A.J. Personal Communication a. Evaluación
Ramos, A.J., Hernández, E., Pla-Delfina, J.M., Merino, M., 1996b. Intestinal absorption of de nuevos adsorbentes multimicotoxínicos basados en bentonitas para alimentación
zearalenone and in vitro study of non-nutritive sorbent materials. Int. J. Pharm. 128, animal. XXII Congreso Español de Toxicología y VI Iberoamericano (AETOX), June
129–137. 2017, Valencia (Spain). Rev. Toxicol. 34, 21.
Rawal, S., Kim, J.E., Coulombe Jr., R., 2010. Aflatoxin B1 in poultry: toxicology, meta- Vila-Donat, P., Marín, S., Sanchis, V., Ramos, A.J. Personal Communication b. In vitro
bolism and prevention. Res. Vet. Sci. 89, 325–331. assessment of new efficient mycotoxin adsorbents based on bentonites. 31st EFFOST
Ringot, D., Lerzy, B., Chaplain, K., Bonhoure, J.P., Auclair, E., Larondelle, Y., 2007. In International Conference, November 2017, Sitges (Spain). Book of abstracts, P2-196.
vitro biosorption of ochratoxin A on the yeast industry by-products: comparison of Wang, J.P., Chi, F., Kim, I.H., 2012. Effects of montmorillonite clay on growth perfor-
isotherm models. Bioresour. Technol. 98, 1812–1821. mance, nutrient digestibility, vulva size, faecal microflora, and oxidative stress in
Rodrigues, I., Naehrer, K., 2012. Prevalence of mycotoxins in feedstuffs and feed surveyed weaning gilts challenged with zearalenone. Anim. Feed Sci. Technol. 178, 158–166.
worldwide in 2009 and 2010. Phytopatol. Mediterr. 51, 175–192. Weaver, A.C., See, M.T., Kim, S.W., 2014. Protective effect of two yeast based feed ad-
Rodríguez-Carrasco, Y., Ruiz, M.J., Font, G., Berrada, H., 2013. Exposure estimates to ditives on pigs chronically exposed to deoxynivalenol and zearalenone. Toxins 6,
Fusarium mycotoxins through cereals intake. Chemosphere 93, 2297–2303. 3336–3353.
Ruiz, M.J., Macáková, P., García, A.J., Font, G., 2011. Cytotoxic effects of mycotoxin Weaver, A.C., See, M.T., Hansen, J.A., Kim, Y.B., De Souza, A.L.P., Middleton, T.F., Kim,
combinations in mammalian kidney cells. Food Chem. Toxicol. 49, 2718–2724. S.W., 2013. The use of feed additives to reduce the effects of aflatoxin and deox-
Sabater-Vilar, M., Malekinejad, H., Selman, M.H.J., van der Doelen, M.A.M., Fink- ynivalenol on pig growth, organ health and immune status during chronic exposure.
Gremmels, J., 2007. In vitro assessment of adsorbents aiming to prevent deox- Toxins 5, 1261–1281.
ynivalenol and zearalenone mycotoxicoses. Mycopathologia 163, 81–90. Wielogórska, E., MacDonald, S., Elliot, C.T., 2016. A review of the efficacy of mycotoxin
Santos, R.R., Vermeulen, S., Haritova, A., Fink-Gremmels, J., 2011. Isotherm modeling of detoxifying agents used in feed in light of changing global environment and legis-
organic activated bentonite and humic acid polymer used as mycotoxin adsorbents. lation. World Mycotoxin J. 9, 419–433.
Food Addit. Contam. 28, 1578–1589. Wozny, M., Obremski, K., Jakimiuk, E., Gusiatin, M., Brzuzan, P., 2013. Zearalenone
Shetty, P.H., Jespersen, L., 2006. Saccharomyces cerevisiae and lactic acid bacteria as contamination in rainbow trout farms in north-eastern Poland. Aquaculture 416,
potential mycotoxin decontaminating agents. Trends Food Sci. Technol. 17, 48–55. 209–211.
Stanciu, O., Juan, C., Miere, D., Loghin, F., Mañes, J., 2017. Occurrence and co-occur- Yegani, M., Smith, T.K., Leeson, S., Boermans, H.J., 2006. Effects of feeding grains
rence of Fusarium mycotoxins in wheat grains and wheat flour from Romania. Food naturally contaminated with Fusarium mycotoxins on performance and metabolism of
Contr. 73, 147–155. broiler breeders. Poultry Sci. 85, 1541–1549.
Streit, E., Naehrer, K., Rodrigues, I., Schatzmayr, G., 2013. Mycotoxin occurrence in feed Yunus, A.W., Valenta, H., Abdel-Raheem, S.M., Döll, S., Dänicke, S., Böhm, J., 2010.
and feed raw materials worldwide: long-term analysis with special focus on Europe Blood plasma levels of deoxynivalenol and its de-epoxy metabolite in broilers after a
and Asia. J. Sci. Food Agric. 93, 2892–2899. single oral dose of the toxin. Mycotoxin Res. 26, 217–220.
Streit, E., Schatzmayr, G., Tassis, P., Tzika, E., Marin, D., Taranu, I., Tabuc, C., Nicolau, Zachariasova, M., Dzuman, Z., Veprikova, Z., Hajkova, K., Jiru, M., Vaclavikova, M.,
A., Aprodu, I., Puel, O., Oswald, I.P., 2012. Current situation of mycotoxin con- Zachariasova, A., Pospichalova, M., Florian, M., Hajslova, J., 2014. Occurrence of
tamination and Co-occurrence in animal feed-focus on Europe. Toxins 4, 788–809. multiple mycotoxins in European feedingstuffs, assessment of dietary intake by farm
Swamy, H.V.L.N., Smith, T.K., MacDonald, E.J., Karrow, N.A., Woodward, B., Boermans, animals. Anim. Feed Sci. Technol. 193, 124–140.
H.J., 2003. Effects of feeding a blend of grains naturally contaminated with Fusarium Zain, M.E., 2011. Impact of mycotoxins on humans and animals. J. Saudi Chem. Soc. 15,
mycotoxins on growth and immunological measurements of starter pigs, and the 129–144.
efficacy of a polymeric glucomannan mycotoxin adsorbent. J. Anim. Sci. 81, Zinedine, A., Soriano, J.M., Moltó, J.C., Mañes, J., 2007. Review on the toxicity, occur-
2792–2803. rence, metabolism, detoxification, regulations and intake of zearalenone, an oestro-
Swamy, H.V.L.N., Smith, T.K., Cotter, P.F., Boermans, H.J., Sefton, A.E., 2002. Effects of genic mycotoxin. Food Chem. Toxicol. 45, 1–18.

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