Mycotoxin kinetics: Did you know how quickly mycotoxins disappear?

Impacts of mycotoxins on farm animal performance and health are generally well known. However, what is often less well known are mycotoxin kinetics and the metabolism of mycotoxins, when they pass through the digestive tract. Based on the current scientific literature, this is also an area of research that still requires greater understanding.

Considering that most dietary mycotoxin solutions will act on mycotoxins in the gut, it is important to understand the time window for action available in the gut. Increasing knowledge of mycotoxin kinetics and metabolism highlights that speed can be a critical characteristic for the mode of action in mycotoxin solutions, as well as the location for mode of action in the animal’s body.


The pharmacokinetic behaviour of an orally ingested compound determines how readily it is absorbed from the gastrointestinal tract, which concentrations are reached in the various organs, and how long the agent and its metabolites will stay in the body. These aspects are of prime importance for the biological effects and risk assessment.

Mycotoxins have varying bio-availability. Some will be more rapidly absorbed, whilst others will travel further along the digestive tract. This is very important for a number of reasons:

1) Whether absorbed into the systemic circulation or not, the cells of the gastro intestinal tract (GIT) will potentially be exposed to the full range of ingested mycotoxins and in the highest concentrations.
2) Mycotoxins that are rapidly adsorbed can cause damage in other organs and their metabolism can result in more toxic metabolites as well as waste of metabolic energy.
3) The pace at which mycotoxins will be adsorbed from the gut, will affect the time window for dietary mycotoxin solutions to act on mycotoxins in the gut.

Intestinal absorption of mycotoxins in the gut

Mycotoxin uptake and subsequent tissue distribution is governed by GIT absorption. This passage across the intestinal barrier may be maximal, as with aflatoxins or very limited, as with fumonisins (Table 1). The rapid appearance of most mycotoxins in the circulation suggests, that the majority of the ingested toxin is absorbed in the proximal part of the GIT.

Absorption of deoxynivalenol (DON) is on average 55% in pigs, but very limited in poultry (Table 1). The relative tolerance of poultry to DON has been partly attributed to its low bioavailability. However, the potential impact of the remaining DON in the intestinal lumen is still unknown, and the tolerance level within the GIT might be different.

Further details on DON kinetics and metabolism are discussed later in the text.

mycotoxin absoprtion - gut

Kinetics and metabolism of zearalenone (ZEA)

In pigs zearalenone and its metabolites were found in the plasma of a pig less than 30 min after the beginning of feeding.

The first reported mammalian phase I metabolites of ZEA are the stereoisomers of zearalenol (ZOL) – α-ZOL and β-ZOL. α-ZOL is 92 times more oestrogenic than ZEA. β-ZOL is 2.5 times less oestrogenic than ZEA. The metabolization of ZON occurs primarily in the liver, but a variety of organs show metabolization activity, such as intestine, kidney, ovary and testis.

Observations in pigs indicate that ZEA is rapidly and efficiently absorbed after oral intake and metabolised to ZOL and glucuronides of ZEA and ZOL. The glucuronides are efficiently eliminated into the bile, but hydrolysed in the intestine and the aglycones reabsorbed, accounting for the secondary peaks in plasma level. The extensive enterohepatic circulation of ZEA and its metabolites slows the excretion and extends the half-life of this mycoestrogen in the pig. The enterohepatic recirculation of ZEA and α-ZOL was confirmed in a later study on the fate of a single dose of ZEA administered intravenously to young female pigs (Dänicke et al 2005).

In broilers, a large proportion of ZEA was changed into. α -ZOL and β -ZOL in the plasma and various tissues of broiler chickens following oral administration of ZEA. This suggests that ZEA was absorbed and metabolized rapidly. The absolute oral bioavailability of ZEA was 29.66% and was higher in broilers than in rats (2.7%) ZEA is excreted largely in the form of α -ZOL in the excreta of broiler chickens. (Buranatragool et al 2015).

In another study, the rate of reduction of zearalenone into α- and β-zearalenol was compared in geese, ducks, guinea-fowl, chickens, laying hens, and quail. Zearalenone reduction was lowest in geese and highest in quail. Although α-zearalenol was the main metabolite formed in all the avian species, the α:β ratio ranged from 1:8 in quail to 5:3 in chicken (Guerre 2015).

In ruminants, the nearly complete recovery of ingested ZON at the duodenum as a-ZOL, b-ZOL and ZON suggests only a minor complete degradation in the rumen under steady-state conditions or some interference with an intensive entero-hepatic cycling of these substances (Dänicke et al 2005b).

Studies in lactating dairy cows revealed that with daily doses of 50, 165 or 544 mg ZEA for 21 days, concentrations of 2.5 ng ZEA and 3.0 ng α-ZOL per ml milk were only detected as conjugated products in cows fed the highest dose of ZEA. Thus, even though minute amounts of ZEA and its metabolites are transmitted into the milk of cows from contaminated feed, this carry-over is minimal. (Metzler et al 2010)

Kinetics and metabolism of aflatoxin

Following ingestion, aflatoxin B1 (AFB1) more than 80% is rapidly absorbed in the intestinal tract in both poultry and pigs. The duodenum was found to be the major site of absorption. From the site of absorption, AFB1 enters the blood stream and is transported to the liver, the major site of metabolism.

Metabolism of AFB1 can be divided into three phases, bioactivation (phase I), conjugation (phase II) and deconjugation (phase III), all of which can occur directly at the site of absorption, in the blood, after entering the liver as the main metabolizing organ, or in several extra-hepatic tissues. Aflatoxin B1 itself is not a potent toxin, and phase I bioactivation is needed to exert toxic effects.
Phase I reactions are mainly oxidation of AFB1 to hydroxylated metabolites such as aflatoxin M1, aflatoxin Q1 and aflatoxin P1 and to the highly reactive AFB1-8,9-epoxide. Cytochrome P450 enzymes (CYPs) are known to play the major role in oxidation of AFB1 to the reactive epoxide in many tissues.

Phase II metabolism includes conjugation of phase I metabolites with glutathione or glucuronic acid and is considered detoxification to enhance water solubility and excretion. Conjugates of epoxide and hydroxylated AFB1 metabolites are readily excreted via the bile into the intestinal tract, where they might be subject to bacterial deconjugation as phase III reaction.
The major route of excretion of AFB1 and its metabolites is the biliary pathway, followed by the urinary pathway. In lactating animals, AFM1 and other metabolites are excreted in the milk.
(adapted from Gratz 2007)

Kinetics and metabolism of deoxynivalenol (DON)

After oral intoxication of pigs, DON starts to appear in the plasma after 30 min. A study on bioavailability of DON in pigs revealed that DON was rapidly absorbed following oral exposure and reached maximal plasma and serum concentrations after 99.1 min. The mean bioavailability of DON was 54%. DON was highly distributed and poorly metabolized. (Goyarts and Dänicke 2006).

In avian, species the levels of DON in plasma following oral administration are relatively low, recent results suggest that DON is highly metabolized, leading to the formation of sulfates, which are a detoxified form of the toxin. This metabolism differs from that observed in some mammal species, in which de-epoxidation is recognized to be the most important step. Although the persistence of DON in tissue and its transmission to eggs are limited, the metabolites of the toxin, especially 3α-sulfate, should be measured (Guerre 2015).

In ruminants, the low recovery of DON at the duodenum as de-epoxy-DON and DON would indicate either a nearly complete degradation of the molecule in the rumen and/or absorption at this site of the digestive tract (Dänicke et al 2005b). However, detoxification capacity for DON by rumen bacteria can be compromised in high producing dairy cows, which are fed greater amounts of concentrates and where feed passage rate is high. Both conditions will affect rumen pH and the time available to degrade DON into non-toxic metabolites. Low rumen pH has a negative impact on the rumen microbes that would otherwise detoxify DON. Jeong et al (2010) report that high concentrate to forage rations reduce the amount of DON detoxified by rumen bacteria by 14%. Similarly, Hildebrand et al (2012) observed that DON can negatively influence rumen fermentation and microbial protein synthesis to a greater extent in high concentrate rations than in low concentrate rations.

The rank order of sensitivity of animals to ingested DON is pigs > poultry/ruminants. Intestinal explants (cultured tissue samples) from poultry and pigs possess a similar ability to intestinally absorb DON, suggesting that the difference in their sensitivity to ingested DON does not rely on their ability to intestinally absorb DON.

It is more likely that the sensitivity of animals to oral DON relies on the localization of the intestinal bacteria in their gut in relation to their ability to generate 9,12-diene DON or DOM-1, the non-toxic de-epoxide derivative of DON (Maresca 2013). The presence of high bacterial contents that can convert toxic DON into its non-toxic de-epoxide metabolite DOM-1 before the small intestine in ruminants (rumen-associated bacteria) and poultry (crop-associated bacteria) hugely decreases the amount of native DON reaching the small intestine.

In pigs, due to the high absorption of DON by the small intestine, bacterial transformation of DON in DOM-1 could only be possible if a part of the ingested DON reaches the colon and/or in the case of intestinal/hepatic excretion of absorbed DON.

Differences between animal species

Mycotoxin metabolism can occur in both the liver and the digestive tract. Intestinal metabolism, be in the gut epithelium or by gut microorganisms, may limit the toxic effects of mycotoxins within the GIT. This is especially true for ruminants which can convert many mycotoxins into non-toxic metabolites. Greater resistance to zearalenone, DON or ochratoxin in ruminants has been attributed to the detoxifying role of the microbial population in the rumen. These mycotoxins are effectively transformed into non-toxic metabolites by rumen microorganisms before absorption. However, in non-ruminants, intestinal biotransformation of mycotoxins takes place predominantly in the large intestine and thus provides little detoxification prior to absorption. (Grenier and Applegate 2013)

Scientific data suggest that the toxicokinetics of fusariotoxins in avian species differs from those in mammals. The use of radio labelled DON, T2-toxin, and zearalenone revealed high biliary excretion of these toxins whereas the amount of the parent compound in plasma was low. This observation and the low level of radioactivity found in tissues led to the conclusion that fusariotoxins are weakly absorbed and rapidly eliminated in birds.

Metabolism appears to play a key role in avian species. For instance, the metabolic pathways of DON in avian species strongly differ from what was reported in rat, pig, cattle and sheep, which could contribute to the reported difference in sensitivity to DON. De-epoxidation of DON, which is the main detoxification mechanism in mammals, appears to play a less important role in avian species. In avian species, it seems that sulfation is a key protective mechanism. (Guerre 2015)

Speed matters

The message from the scientific literature is that the potential time window for action on some mycotoxins in the gut is short – for zearalenone in pigs 30 minutes or less, before they get absorbed into the blood system.
The consequence is that speed is of great importance, when it comes to solutions that act on mycotoxins in the gut to counteract their harmful effects. The alternative is that they also should be able to act on the mycotoxins or reduce their impact outside of the animal’s digestive tract, i.e. in the blood system or other target organs for mycotoxins in the animal.

Adapt vs attack – strategies for counteracting mycotoxins

Traditionally, feed additives have been developed to attack mycotoxins in the animal’s digestive tract directly to counteract harmful effects from mycotoxins in the animal. However, both mycotoxin binders and mycotoxin deactivators have their limitations.

It is well known that adsorption is not an effective strategy for most mycotoxins. Only certain bentonites work well with aflatoxins and some yeast cell wall components have been proven to bind zearalenone, based on specific structural fits. For other types of mycotoxins, particularly DON, binding strategies do not work effectively.

Biotransformation of mycotoxins is another strategy that directly attacks mycotoxins to transform their structure into non-toxic metabolites. Again, this strategy is very specific to certain target mycotoxins. On top of that, it takes time to complete the biotransformation of mycotoxins and time to do so in the digestive tract is limited. Find out how long it takes to transform mycotoxins in vitro in this scientific paper.

The question is, how does the animal deal with the mycotoxins left untouched by the highly specific feed solutions mentioned above?

A third and more cost-effective strategy to counteract mycotoxins focuses on disarming mycotoxins by supporting the animal’s resistance to the harmful effects of mycotoxins. This strategy empowers animals to adapt to nutritional stress factors such as mycotoxins and reduces the extent of the stress reactions generally seen in response to these stressors . Find out more about stress reactions

This strategy is not a direct attack on mycotoxins, but it helps the animal to shield itself efficiently from the negative effects of a broader range of mycotoxins, when challenged. It is non-specific for mycotoxins, but highly specific on the side effects of the most important mycotoxins.


Buranatragool et al (2015). Dispositions and tissue residue of zearalenone and its metabolites α-zearalenol and β-zearalenol in broilers. Toxicology Reports 2 ,351–356

Dänicke et al (2005). Kinetics and metabolism of zearalenone in young female pigs. Journal of Animal Physiology and Animal Nutrition 89, 268–276

Dänicke et al (2005b). Effects of Fusarium toxin-contaminated wheat grain on nutrient turnover, microbial protein synthesis and metabolism of deoxynivalenol and zearalenone in the rumen of dairy cows. Journal of Animal Physiology and Animal Nutrition 89, 303–315

Devreese et al (2013). Overview of the most important mycotoxins for the pig and poultry husbandry. Vlaams Diergeneeskundig Tijdschrift, 82

Goyarts and Dänicke (2006). Bioavailability of the Fusarim toxin deoxynivalenol (DON) from naturally contaminated wheat for the pigs. Toxicology Letters, Volume 163, Issue 3, Pages 171–182

Gratz (2007). Aflatoxin Binding by Probiotics, Experimental Studies on Intestinal Aflatoxin Transport, Metabolism and Toxicity, Doctorial Thesis; University of Kuopio, Finland

Grenier and Applegate (2013). Modulation of Intestinal Functions Following Mycotoxin Ingestion: Meta-Analysis of Published Experiments in Animals, Toxins 5, 396-430

Guerre (2015). Review: Fusariotoxins in Avian Species: Toxicokinetics, Metabolism and Persistence in Tissues, Toxins, 7, 2289-2305

Hildebrand et al (2012). Effect of Fusarium toxin-contaminated triticale and
forage-to-concentrate ratio on fermentation and microbial protein synthesis in the rumen. Journal of Animal Physiology and Animal Nutrition 96, 307–318

Jeong et al (2010), Effects of the Fusarium mycotoxin deoxynivalenol on in vitro rumen
fermentation, Animal Feed Science and Technology, 162, 144–148

Maresca (2013). From the Gut to the Brain: Journey and Pathophysiological Effects of the Food-Associated Trichothecene Mycotoxin Deoxynivalenol. Toxins (Basel); 5(4): 784–820.

Metzler et al (2010). Zearalenone and its metabolites as endocrine disrupting chemicals.
World Mycotoxin Journal, 3 (4): 385-401

Vekiru et al (2010). Cleavage of Zearalenone by Trichosporon mycotoxinivorans to a Novel Nonestrogenic Metabolite, Applied and environmental microbiology, vol. 76 no. 7 2353-2359

Marcelo Blumer joins ANCO to develop business in Brazil

Marcelo Blumer joins the ANCO team as designated Executive Director Anco Brazil. He has 15 years of commercial experience in the animal health and nutrition industry with a focus on the Brazilian market. His previous roles included senior level positions in sales and marketing in animal health companies.

In his new role, Marcelo will be responsible for all implementation and management of the ANCO Brazil operation. He will serve as the primary contact for all direct sales customers in Brazil.

Marcelo graduated from the University Estadual Paulista Julio de Mesquita Filho (UNESP) with a veterinary science degree. He also gained a MBA in Agribusiness Management from FGV in Brazil.

The ANCO team will benefit strategically from his knowledge of the Brazilian market and customers with experience in the management of high performance teams and is excited to gain his contribution to the global growth of the business.

Marcelo Blumer comments on his new challenge: “ I am looking forward to be part of the Anco team. Agriculture in Brazil is highly competitive and I think the Anco FIT product line provides solutions, which can provide excellent support to competitive businesses as we have them in Brazil.”

For more information on Anco in Portuguese please go to the Portuguese section of the Anco Homepage.  Anco Portuguese

Anco FIT – Managing cost-effectiveness of pig diets

Consistency in the cost-effectiveness of pig diets can be difficult to control, but determines profitability. Anco FIT focuses on managing gut agility for more reliable returns.

With up to 70% of production costs coming from the cost of feed, consistency in the cost-effectiveness of diets is key to profitability. To maximize profit opportunity, producers must be diligent in developing feeding strategies that result in best returns over feed and/or margin over feed and facility costs. However, nutritional stressors in the diet, such as reduced nutrient digestibility, endotoxins, antinutrients and mycotoxins, often throw a spanner in the works of consistency in performance in response to diets. Depending on the increased presence or absence of those stressors the same diet can differ in cost-effectiveness. These stressors are often not easy to control for the nutritionist and are part of the reality that animals are facing in modern production systems.

Nutritional stressors reduce cost-efficiency

When challenged with nutritional stress factors, stress reactions such as oxidative stress, reduced gut integrity, inflammation, reduced appetite and shifts in gut microflora will be triggered in the pig. This not only reduces growth performance, but also feed efficiency and thus the cost-effectiveness of diets. Feed efficiency is reduced due to energy wasted on stress reactions instead of being used for productive purposes.

For instance, under oxidative stress and inflammation, 30% of the performance drop is explained by the catabolism and feed conversion needed to manage inflammation.

Oxidative stress is defined as the presence of reactive oxygen species (ROS) in excess of the available antioxidant capacity of animal cells. Oxidative stress is a major factor related to the development of inflammatory diseases.

Increases in intestinal permeability raise the possibility of translocation of bacteria and/or their toxins across the more permeable gut barrier. The resulting endotoxemia can trigger disease onset and progression. The increase in translocation of endotoxins across the intestinal barrier can also stimulate immune cells to secrete pro-inflammatory cytokines and prostaglandins like PGE2, resulting in low-grade inflammation, which again can waste metabolic energy.

Regardless of the triggering cause, the innate immune and inflammatory response is triggered in the pig to achieve a better ability to deal with infectious and noninfectious stressors. At the same time this response needs to be accurately controlled to avoid tissue damage and waste of metabolic energy.

Certain mycotoxins, such as DON (deoxynivalenol) are known to cause the type of stress reactions mentioned above in pigs. DON also has a significant impact on feed intake in pigs, resulting in reduced growth performance. It is globally the most prevalent mycotoxin in feed stuffs and difficult to control. Therefore, it can also play a significant role in the cost-effectiveness of diets.

What if pigs were more resistant

Ideally the response to nutritional stress factors should consume as little energy as possible or stress reactions should be minimal for better and more consistent feed efficiency. This would be the case if animals were inherently more resistant to nutritional stress factors or were able to adapt to nutritional stressors more energy efficiently.

There is scientific evidence suggesting that for genetic selection, improving the ability of pigs to cope  with stressors may be a better way of improving pig performance than selecting only for increased growth potential. That means the pig needs to be able to adapt faster and more adequately to dietary changes and stress factors for efficient growth performance. Genetic selection is certainly going to play an important role for advancement in this capability of the pig.

Nutritional strategies supporting the speed and efficacy with which the pig adapts to stressors will bring a more immediate competitive advantage in pig production. Most importantly, the ability of the animal to cope with the stressors will also impact the return on investment of diet formulations and profitability of the producer.

Managing gut agility for robust pigs

The gut is particularly responsive to stressors, hence why the emphasis is on the gut when improving the pig’s adaptive response. Gut agility is a new term coined to describe the pig’s ability to adapt to nutritional stressors in a faster and more energy-efficient response than it normally would.

Agile nutritional concepts are designed to boost gut agility and empower animals to adapt to a variety of nutritional stress factors, including mycotoxins, making them more robust and energy efficient. They rely on bioactive substances derived from plants that reduce negative stress reactions, such as oxidative stress, inflammation, reduced gut integrity and reduced feed intake generally seen in response to stressors.

The animal becomes more robust in the face of dietary challenges, resulting in more consistent high performance and well-being. This again will contribute to consistency in the cost-effectiveness of diets under commercial conditions.

Application of Anco FIT

Anco FIT is a gut agility activator, designed to manage gut agility by dietary means and is applied as a feed additive to complete feed. Application of Anco FIT to pig diets empowers animals to adapt to nutritional stress factors more efficiently and live up to their performance potential. For the nutritionist, it provides greater control over the cost-effectiveness of diets.

Nursery diets: Anco FIT is recommended in nursery diets to help piglets adapt to feed transitions quicker and support its defense against nutritional stress factors, including mycotoxins. Expected results are improved feed intakes and growth performance during this important developmental stage of the pig.

Grow-finish diets: In group housing situations feed intake is generally constrained by physical and behavioural factors and energy available from diets will determine commercial performance particularly in the finishing phase.  Anco FIT is applied to grow-finish diets to reduce the waste of metabolic energy on stress reactions such as oxidative stress and inflammation. The boost to gut agility also supports efficient nutrient adsorption from the gut. Expected results are greater feed efficiency particularly in the face of nutritional stress factors.

Sow lactation diets: Energy demands on modern highly prolific sows are incredibly high during lactation. Efficient dietary energy utilization by the sow during lactation will not only affect litter performance, but also subsequent reproductive performance of the sow. Anco FIT is applied to sow lactation diets to reduce the waste of metabolic energy on stress reactions such as oxidative stress and inflammation. The boost to gut agility also supports efficient nutrient adsorption from the gut. Expected results are high lactation performance and subsequent reproductive capability from improved/more consistent energy efficiency in sows.

For more information on Anco FIT please contact
Anco Animal Nutrition Competence GmbH
Phone: 0043 2742 90502