Introduction
The toxicokinetics of mycotoxins includes the phases of absorption, distribution, metabolism and excretion (ADME), covering all the stages from the moment the toxin enters the body and is metabolized until it is eliminated through excretion. These processes vary depending on the type of mycotoxin and the exposed animal species. In the case of pigs, the effect also depends on the production phases. Additionally, there is the concept of carry-over, which refers to the transfer of mycotoxins from contaminated feed consumed by the animals to animal-derived food products intended for human consumption, posing a risk to public health.
Aflatoxins
These mycotoxins are mainly absorbed in the intestine, specifically in the duodenal region. They are a family of mycotoxins with a low molecular weight and lipophilic nature, characteristics that contribute to their efficient oral absorption, reaching rates of approximately 90% (Schrenk et al., 2020).
Aflatoxins are widely distributed, reaching the digestive system, liver and renal system. Specifically, the target organ of these substances is the liver. Therefore, prolonged exposure to these mycotoxins can lead to lesions such as hepatocellular carcinomas (Schrenk et al., 2020).
Aflatoxins are metabolized in the liver, obtaining different types of metabolites, among which AFB1-8,9-epoxide stands out. This is a metabolite of aflatoxin B1 obtained from cytochrome P450, which turns out to be more toxic than the initial mycotoxin. Other products of the biotransformation of these mycotoxins are AFM1, AFQ1 and aflatoxicol (Coppock et al., 2018).
Regarding their elimination, it is known that porcine metabolism is not effective in detoxifying and excreting aflatoxins, making these animals more susceptible to aflatoxicosis. Elimination occurs mainly through the biliary tract, as well as through the urinary tract, in a slow and scarce manner. It has been recorded that around 20% of these substances are eliminated through the urinary tract during the 9 days following exposure (Popescu et al., 2022).
These mycotoxins also present carry-over, in fact, they have been detected in both meat and milk. In this way, aflatoxins and their metabolites can reach the human consumption chain, as well as piglets during the lactation period (Popescu et al., 2022; Lee et al., 2017).
Deoxynivalenol
In pigs, deoxynivalenol (DON) is rapidly absorbed after ingestion of contaminated feed, over a period of approximately 1 to 3 hours (Sun et al., 2022). Depending on the productive stage of the animal, the absorption percentage varies, with a generally high bioavailability of between 50 and 100% being considered for the pig species (Schelstraete et al., 2020; Danicke et al., 2013).
This mycotoxin is rapidly and widely distributed, reaching the blood serum, muscle, abdominal fat, stomach, intestine, liver, kidneys, heart, brain, lung, skin, spleen, testicles, ovaries and adrenal glands (Gallo et al., 2022). However, this distribution is transitory, as DON reaches these tissues, but does not accumulate in them (Dersjant-Li et al., 2004).
DON is metabolized by two main pathways, conjugation and de-epoxidation. In the pig species, conjugation with glucuronic acid is the most frequent reaction, giving rise to metabolites such as DON-3-GlcA and DON-15-GlcA. On the other hand, the biotransformation of DON to DOM-1 is controversial, because of some pigs are unable to carry it out, lacking de-epoxidizing intestinal microbiota (Sun et al., 2022; Maul et al., 2012).
Urinary excretion accounts for 90-95% of total DON excretion in pigs (Danicke et al., 2013). Less than 5% of this mycotoxin and its metabolites are considered to be excreted through feces in this species (Schelstraete et al., 2020). On the other hand, the elimination half-life of this substance is from 1.5 to 5 hours, which is considered a long clearance time, making pigs susceptible to the mycotoxin (Sun et al., 2022).
Despite the fact that the porcine species has the highest systemic bioavailability of DON, its carry-over in tissues such as muscle or fat has barely been determined (Schelstraete et al., 2020; Danicke et al., 2013). However, as in the case of aflatoxins, both DON and its metabolites have been detected in colostrum and milk of sows (Benthem de Grave et al., 2021). In addition, the transmission of these substances to piglets through the placenta during gestation has been reported (Sayyari et al., 2018; Danicke et al., 2007).
Zearalenone
The absorption rate of zearalenone (ZEN) in pigs has been estimated to be 80–85% (Liu et al., 2020), although its bioavailability may be lower in younger animals (Gallo et al., 2022; Catteuw et al., 2019). Its absorption is rapid, such that ZEN and its metabolites can be detected in plasma within 30 min after consumption of contaminated feed (Gallo et al., 2022).
After absorption, ZEN and its metabolites are distributed and can be detected in the liver, bile, plasma, urine and feces (Liu et al., 2020). On the other hand, the system most affected by this type of mycotoxin is the reproductive tract, with females, within the pig species, being the most susceptible group (Rai et al., 2019).
In pigs, the main metabolites are the glucuronide conjugates of ZEN and α-zearalenol (α-ZEL), the latter being the predominant one (Liu et al., 2020). This metabolite has a higher affinity for estrogen receptors than others, which justifies the high sensitivity of the porcine species to the pathological effects of ZEN (Schelstraete et al., 2020).
The main route of excretion of this mycotoxin in pigs is the urinary route, through which twice the amount is eliminated in feaces (Liu et al., 2020). After oral exposure to ZEN, between 14 and 45% is detected in urine, both in its original and metabolized form (Schelstraete et al., 2020). The elimination half-life of this mycotoxin in pigs is considered to be very variable, with recorded times between 2.63 and 86.6 hours (Catteuw et al., 2019).
Furthermore, the carry-over of this mycotoxin has been detected in meat and milk. Both ZEN and its metabolites have been detected in the muscle and different organs of these animals, which constitutes a risk for public health. In addition, its transfer to piglets during the lactation period has been recorded (Benthem de Grave et al., 2021; Liu et al., 2020).
Ochratoxin A
Ochratoxin A (OTA) is rapidly absorbed and exhibits a high bioavailability in pigs, with levels of up to 66% observed (Tolosa et al., 2020). Just a few hours after ingestion, this mycotoxin can already be detected in the blood, from where it is distributed through the portal system (Shrenk et al., 2020; Ringot et al., 2006).
In pigs, it is widely distributed, reaching the liver, kidney, muscle and fat. This mycotoxin has a high affinity for plasma proteins, specifically for albumin; it has been determined that only 0.1% of OTA remains unbound after entering the body (Ringot et al., 2006). This characteristic, together with its slow metabolism, means that OTA has a long half-life (Hagelberg et al., 1989).
The main OTA metabolite in pigs is OTα, generated by the intestinal microbiota in non-ruminant animals. The most important metabolic pathway is the hydrolysis of OTα followed by its conjugation with glucuronic acid. This metabolite is partially absorbed in the intestine, and is rapidly excreted in urine, since it does not accumulate at the renal level (Shrenk et al., 2020).
However, OTA excretion is complex, as it is eliminated slowly through urinary tract, over periods of more than 5 days (Shrenk et al., 2020). This mycotoxin accumulates in renal tissue and pigs are among the species most sensitive to the nephrotoxicity it causes (EFSA, 2006).
This mycotoxin presents carry-over in various animal tissues and has been detected in analysis of different pork-derived meat products (Ganesan et al., 2021; Tolosa et al., 2020). Additionally, it can be transferred to the fetus during pregnancy via the placenta (Ringot et al., 2016).
Fumonisins
Fumonisins have a low absorption rate in pigs, between 3 and 5% (Knutsen et al., 2018; Prelusky et al., 1994). After 30-40 minutes of oral exposure, these substances can be detected in blood, reaching their maximum concentration after 60 to 90 minutes (Schertzh et al., 2018).
These mycotoxins are rapidly distributed to different tissues, reaching the intestine, liver, pancreas and kidney. Their half-life in blood is less than 4 hours (Knutsen, et al., 2018). On the other hand, the presence of this mycotoxin alters the sphinganine/sphingosine ratio (Sa/So) of animals, due to its structural similarity with endogenous compounds such as ceramide synthetase (Schertzh et al., 2018).
In mammals, fumonisin B1 metabolism is attributed to a single metabolic pathway. This involves the hydrolysis of its side chains, from which metabolites such as HFB and pHFB are obtained (Schelstraete et al., 2020; Knutsen et al., 2018). Therefore, it is a mycotoxin that is poorly metabolized (Schertzh et al., 2018).
A large part of fumonisins is eliminated via biliary excretion without undergoing biotransformation. Their excretion occurs primarily through feces (up to 90%), and, to a very limited extent, through the urinary route. This process is slowly (Knutsen et al., 2018).
Carry-over of this group of mycotoxins has been detected in various tissues in cases of prolonged exposure to contaminated diets (Dersjant-Li et al., 2004). In addition, there is evidence of transfer of fumonisin B1 to the milk of exposed sows, and thus to piglets (Zomborszky-Kovács et al., 2000).
T-2 toxin
T-2 mycotoxin can be rapidly absorbed by both oral and inhalation routes (Schuhmacher et al., 2010). However, this mycotoxin has a very low oral bioavailability (Sokolovic et al., 2008).
Both T-2 mycotoxin and its metabolites are rapidly and widely distributed in the body, reaching mainly the liver, kidney and small intestine. In addition, these substances reach other tissues, such as fatty tissues, where they have a longer elimination time (Yongxue et al., 2014).
T-2 mycotoxin is rapidly metabolized, obtaining a wide variety of metabolites, among which HT-2 stands out, obtained from hydrolysis processes (CONTAM, 2011).
This mycotoxin and its metabolites are rapidly eliminated via the urinary tract, while only a minor amount is excreted via faeces (Yongxue et al., 2014; Schuhmacher et al., 2010). In this case, the study of distribution and elimination is complex, due to its rapid excretion (Schuhmacher et al., 2010). An average elimination time of 90 minutes has been estimated (Corley et al., 1986).
In relation to carry-over, the mycotoxin has not been detected so far in products from the food chain. This is because neither the T-2 mycotoxin nor its metabolites present a significant accumulation in tissues (Kalantari et al., 2010; Schuhmacher et al., 2010).
Conclusion
In recent years, the number of studies on the toxicokinetics of mycotoxins has progressively increased, providing essential information for understanding their passage through the organism of animals, and, therefore, their harmful effects on animal production. However, there are still many aspects about which we must continue to research, in order to understand the action of these substances in pigs, and to be able to implement effective strategies for their mitigation.
