Introduction
Mycotoxins are toxic compounds naturally produced by various types of fungi that enter the food chain following the infection of crops before or after harvest. In livestock production, these compounds represent a persistent and global threat, with an estimated 80% of agricultural raw materials showing some degree of contamination. This creates complex health challenges and severe economic losses resulting from the reduction in productive and reproductive parameters.
Unlike monogastric animals, ruminants have an adaptive advantage: a complex ruminal microbial ecosystem capable of acting as a biotransformation barrier. This barrier functions through enzymatic degradation and chemical modification of mycotoxins by the microbiota, transforming them into less toxic or inactive metabolites before systemic absorption (Bandyk C, 2024). According to Fink-Gremmels (2008), the microbial pre-digestion phase is the determining factor in the bioavailability of mycotoxins. This process is governed by toxicokinetic, which analyzes the interaction of the organism with the toxin through the stages of Absorption, Distribution, Metabolism, and Excretion (ADME).
Under equilibrium conditions, the ruminal microbiota tries to metabolize these compounds into less active forms. However, this detoxification capacity is finite and, at times, counterproductive. Certain biotransformation processes can increase the toxicity of the original compound, as occurs with the conversion of Zearalenone into α-Zearalenol, a metabolite with significantly higher estrogenic potency (Ogunade et al., 2018).
The vulnerability of the ruminant has been accentuated by the demands of intensive production. The use of diets rich in fermentable carbohydrates to maximize performance prejudice animals to Subacute Ruminal Acidosis (SARA) (Hasuda et al., 2022). This metabolic disorder drastically alters the ruminal environment, reducing the effectiveness of the degrading microbiota and increasing the passage rate of gastric content. Consequently, a larger fraction of mycotoxins reaches the small intestine intact, where absorption is higher, triggering systemic damage and clinical cases of mycotoxicosis that compromise the integrity and health of the herd (Bandyk C, 2024).
Carry-over is defined as the phenomenon of transferring mycotoxins from the ruminant diet into the human food chain through residues in meat and milk. This process depends on the bioavailability of the toxin, the animal’s hepatic metabolism, and the mammary excretion rate.
Aflatoxins
Aflatoxins, primarily produced by fungi of the genus Aspergillus, present a complex absorption dynamic in ruminants that determines their high toxicity. After ingesting contaminated feed, these toxins undergo ruminal degradation of approximately 40%. Nevertheless, the remainder reaches the small intestine where Aflatoxin B1 (AFB1) is rapidly absorbed, reaching bioavailability levels of up to 80% in animals suffering from acidosis (Kibugu et al., 2024).
Once in the bloodstream, AFB1 binds to albumin for systemic distribution, with the liver as its primary destination, although significant concentrations have also been reported in the digestive and renal systems (Robert W. et al., 2018). In the liver, acting as the primary target organ, the toxin triggers severe alterations such as hepatomegaly, jaundice, biliary stasis, and hepatic necrosis, in addition to critical reproductive effects including uterine prolapses and abortions documented between 100 and 260 days of gestation (Fink-Gremmels, 2007).
The metabolism of aflatoxins undergoes phases of activation and conjugation mediated by cytochrome P450 enzymes in the hepatocytes. This process yields the metabolite AFB1-8,9-epoxide (AFBO), responsible for genotoxicity, and the hydroxylation of AFB1 to become Aflatoxin M1 (AFM1). The latter form is highly soluble and has a high affinity for mammary glandular tissue, resulting in a carry-over phenomenon into milk detectable just 12 to 48 hours after ingestion (EFSA, 2020).
Excretion occurs prominently via biliary and urinary routes, but elimination through milk is the point of highest sensitivity for public health. It is estimated that around 75% of the excreted AFM1 is associated with the casein fraction, explaining its notable thermostability and persistence in byproducts such as butter and cheese (Robert W. et al., 2018).
Zearalenone
Zearalenone is absorbed primarily in the duodenum and proximal jejunum. Once it crosses the enterocytes, it enters the portal vein directly, heading to the liver. However, metabolites generated in the rumen have different absorption rates due to changes in their polarity, which increases their systemic bioavailability (Dohnal et al., 2021; Liu J., 2020).
Due to its lipophilic nature, it is widely distributed in fatty tissues and has a specific affinity for estrogen receptors in the uterus and mammary glands (Ogunade et al., 2018). Recent studies suggest that the passage rate and ruminal pH play a critical role; under SARA conditions, the degradation capacity decreases, allowing a greater proportion of intact toxin to reach the intestine (Hasuda et al., 2022).
The metabolic process is unique in ruminants; ruminal protozoa and bacteria transform ZEA into two key metabolites: α-zearalenol and β-zearalenol. α-zearalenol is significantly more estrogenic than the parent molecule, explaining why ruminants can show severe clinical signs even with low contamination levels (Hartinger et al., 2022; Salvat et al., 2015; Gruber-Dorninger, C et al., 2021).
Excretion occurs mostly through bile into the faeces, although enterohepatic recirculation exists, which prolongs its stay in the organism. This phenomenon allows the toxin to be reabsorbed in the intestine after being discharged by bile, exacerbating endocrine disruption, which clinically translates into vulvovaginitis, ovarian cysts, and a prolongation of open days in the herd (Fink-Gremmels, 2008; Gautier et al., 2020).
Ergot Alkaloids
Ergot alkaloids (such as ergotamine and ergometrine) are characterized by limited but highly impactful absorption, occurring mainly at the epithelium of the reticulo-rumen and, to a lesser extent, in the small intestine via facilitated transport. Unlike other mycotoxins, these compounds show reduced and highly variable ruminal degradation, allowing a significant fraction of the parent toxin to remain intact (Perusia & Arnesto, 2017).
Once in the bloodstream, their distribution is systemic, but with an affinity for adrenergic and serotonergic receptors in the walls of peripheral blood vessels.
Metabolism occurs mostly in the liver through hydrolysis and oxidation. However, the speed of this process is slow compared to the rate of receptor binding, causing a functional accumulation. This mechanism triggers severe and persistent vasoconstriction, responsible for dry gangrene in extremities and heat stress (hyperthermia) due to the failure of peripheral thermoregulation mechanisms (Manual MSD, 2023).
Excretion is predominantly biliary-fecal, within minimal urinary elimination, and it has been documented that its persistence in the body can inhibit prolactin secretion, resulting in persistent agalactia or hypogalactia even after removing the contaminated source (Cope, 2018; Fink-Gremmels, 2008).
T-2 Toxin
T-2 Toxin is considered one of the most potent and dangerous trichothecenes for ruminants, especially young animals. Its absorption begins from direct contact with mucous membranes but is consolidated in the small intestine. It is a highly lipophilic molecule that easily crosses cell membranes. In the rumen, degradation is less efficient than with other toxins, being partially hydrolyzed into the metabolite HT-2, which retains much of the original toxicity (Hartinger et al., 2022).
Distribution is wide and rapid, with a specific affinity for organs with high cell division rates, such as lymphoid organs and bone marrow, explaining its marked immunosuppressive effect (Cope, 2018).
Its metabolism occurs in the liver through hydrolysis reactions and subsequent conjugation, its presence manifests acutely through necrotizing stomatitis in the mouth and tongue, ulcerative abomasitis, and subcutaneous edema in the submandibular region (Meneely, J et al., 2023).
Excretion is carried out via urinary and fecal routes; however, due to its aggressiveness, even small residual amounts can cause a drastic drop in white blood cell production and general susceptibility to secondary diseases (Panisson et al., 2023).
Deoxynivalenol
Deoxynivalenol, commonly known as vomitoxin, presents a particular dynamic in ruminants due to the high detoxification capacity of the microbiota. Under stable ruminal pH conditions, between 70% and 90% of ingested DON is degraded into a significantly less toxic metabolite called DOM-1 (deepoxy-deoxynivalenol). Nonetheless, the absorption of the non-degraded fraction occurs mainly in the small intestine through passive diffusion. This absorption is drastically increased in animals suffering from SARA, as the rapid transit limits the contact time with the degrading microbes, allowing the intact toxin to reach the intestinal mucosa.
Its distribution occurs via the systemic route, although its greatest impact is observed locally in the gastrointestinal tract, where it alters « tight junctions » causing leaky gut syndrome (Radko L. et al., 2025).
Hepatic metabolism complements the ruminal action through conjugation with glucuronic acid, which facilitates its excretion, which is notably rapid and occurs mostly through the urine in the first 24 hours post-ingestion, minimizing the risk of residues in tissues, but seriously compromising the feed efficiency and immunological response of the animal (Cope, 2018; Hasuda et al., 2022).
Fumonisins
Fumonisins present low intestinal absorption in ruminants (less than 5%), as they are hydrophilic molecules that do not easily cross cell membranes by simple diffusion (Smith, 2018). In the rumen, unlike trichothecenes, fumonisins are notably resistant to microbial degradation, remaining practically intact during their transit through the forestomachs.
Despite their low systemic absorption, they have a selective distribution toward the liver and the kidneys. There, FB1 specifically interferes with the ceramide synthase enzyme, blocking the synthesis of sphingolipids and causing the accumulation of sphinganine, a cytotoxic compound (Fink-Gremmels, 2008).
The hepatic metabolism of fumonisins is low; they do not undergo significant biotransformation processes, which implies that the toxin maintains its original structure during its stay in the organism.
Excretion occurs almost entirely in unaltered form through the feces, due to its poor initial absorption and the biliary elimination of the systemic fraction. Clinically, although ruminants are more resistant than horses or pigs, chronic exposure results in hepatotoxicity, nephropathy, and a decrease in immunological efficiency. Due to their low absorption rate and rapid fecal elimination, fumonisins have a practically null risk of « carry-over » to milk, but they act as a persistent metabolic stress factor in high-production animals (Cope, 2018; Smith, 2018).
Ochratoxin A
The absorption of Ochratoxin A (OTA) in adult ruminants is significantly lower than in monogastrics due to the efficient rumen biotransformation barrier. Nonetheless, the fraction of the toxin that is not degraded or that enters animals with a compromised ruminal ecosystem (SARA) is absorbed through active transport mainly in the small intestine. The absorption rate is pH-dependent and is facilitated by the toxin’s high solubility in the intestinal chyme, allowing its rapid passage toward the portal circulation (Fink-Gremmels, 2008).
Once in the bloodstream, OTA presents a unique pharmacokinetic characteristic: a high affinity for plasma proteins, specifically albumin. This binding (greater than 90%) acts as a reservoir that prolongs the toxin’s half-life in the organism and hinders its rapid elimination. Its distribution is systemic, but it presents a marked tropism for renal tissue, which acts as its primary target organ. The accumulation in the cells of the proximal tubules of the kidney is responsible for its high nephrotoxicity (Smith, 2018; Battacone et al., 2010).
Regarding metabolism, in a balanced ruminal environment, bacteria and protozoa hydrolyze the amide bond of the OTA molecule, converting it into Ochratoxin alpha and phenylalanine. OTA-α is a metabolite that is practically harmless and lacks systemic toxicity. However, this metabolic capacity is finite; in the face of massive intakes of contaminated feed or in young animals with an immature rumen, OTA, evading this hydrolysis, reaches the liver intact, where it undergoes minimal oxidation processes by cytochrome P450 that fail to reduce its aggressiveness (Mobashar et al., 2010).
The primary excretion route is renal, although biliary-fecal excretion also exists. Due to its strong binding to albumin, glomerular filtration is slow, which prolongs the oxidative damage in the kidneys. Pathologically, this translates into nephropathy, with enlarged kidneys, that are pale or present « black kidneys » and are friable. In lactating females, excretion into the milk is considered minimal thanks to the microbial barrier of the rumen, but it can be significant in suckling calves if the mother consumes doses that saturate her biotransformation capacity (Fink-Gremmels, 2008; Smith, 2018).
Emerging mycotoxins
These toxins, mostly produced by Fusarium, are highly lipophilic. This facilitates a massive absorption through cell membranes and a persistent distribution in adipose tissue and milk fat.
Their metabolism in ruminants is still a subject of study, but they are known to act as ionophores, altering the mineral balance of cells.
Their excretion is slow due to their accumulation in fat deposits, which represents a risk of long-term residues in meat products (Gautier et al., 2020).
Conclusion
The toxicokinetics in ruminants presents a critical duality: while the ruminal ecosystem acts as protective barrier through the biotransformation of mycotoxins, this capacity is finite and highly vulnerable to intensive production management. Disorders such as Subacute Ruminal Acidosis (SARA) disrupt this balance, increasing the bioavailability of mycotoxins and allowing them to reach the intestine intact, which triggers severe systemic damage.
The carry-over phenomenon, particularly evident in aflatoxins and their transfer into milk as AFM1, underscores that mycotoxicosis is not only an animal health issue but a global public health challenge. Lately, managing mycotoxins requires a comprehensive approach that prioritizes the stability of the ruminal environment to preserve productive integrity and the safety of the human food chain.
