**2.2. Ochratoxins**

AFM<sup>1</sup> (ng/kg milk) = 10, 95 + 0,787 X (1)

The FDA limits aflatoxins to no more than 20 ppb in lactating dairy feeds and to 0.5 ppb in

The aflatoxicosis is an acute or chronicle mycotoxicosis of mammals, as well as birds, pro-

*Etiologic agent, toxicity.* Aflatoxicosis is induced by the aflatoxins produced by some species of fungi such as *Aspergillus flavus, A. parasiticus, A. niger, A. ochraceus, Penicillium puberulum, P. citrinum* and *Rhizopus spp.* From these, the main aflatoxin producers are *A. flavus* and *A. parasiticus*. Mycotoxins, as well as their metabolic products, work on the act on the chromatin, inhibiting the synthesis of the nucleic acids DNA and RNA from the hepatic cells and, at the same time, on the cellular membranes and membranes of the different intracytoplasmic structures.

*Clinical signs.* Aflatoxins produce disorders at the level of the central nervous system, diges-

*In acute form,* it can be observed clinically: inappetence, anorexia, nervous depression, ataxia, dyspnea, and melena, anemia, while in sub-acute form: hemorrhagic enteritis, subcutaneous

*In chronicle form,* it can be observed: reduction of growth, rough and pale hair coat, anemia, jaundice, slower growth, apathy, diminished appetite, teeth grinding, fixed stare, circular movement, ataxia, diarrhea, rectal prolapse at mammals [24]; reduced resistance to diseases

The toxic effects depend on: the dosage of mycotoxin ingested, the way of ingestion/administration, duration of exposure, nutritive quality of the ration, species and animal age. The calves, fresh cows or dairy cows in early lactation are most affected because their immune system is suppressed. Alongside *Aspergillius flavus, A. parasiticus*, producers of aflatoxin and *Aspergillius fumigatus* producer of tremorgens or viritoxin, fumagillin, encountered both in fibrous fodder, as well as silos, is considered as pathogen agent, being associated with the

Adult taurines and sheep are the least sensitive to the action of the mycotoxin. It is considered though that with the ingestion of at least 100 ppb aflatoxin/day, ruminants (both meat and dairy cattle) are exposed to the risk of the development of aflatoxicosis which debuts with: the reduction of food ingestion, diminished live weight, lowering of milk production, decline of

present in the blood can be deter-

are 20 ppb for dairy feeds and 0.05 ppb in milk.

where X = μg AFB1

*2.1.2. Aflatoxicosis*

duced by aflatoxins.

hematoma and jaundice.

ingested/day.

milk; in Europe, the regulatory levels of AFB1

90 Ruminants - The Husbandry, Economic and Health Aspects

Similar studies have shown approximately 90% of AFM1

tive system, cardiovascular system and hematopoietic organs.

Aflatoxicosis evolves under acute, sub-acute and chronic form.

and interferes with vaccine induced immunity in livestock [25].

Mycotic Hemorrhagic Bowel Syndrome (HBS) at dairy cows [26].

the efficiency of the reproductive capacity [27, 28].

mined in the plasma and is found afterwards in the milk and urine [23].

Ochratoxins are compounds developed by different species of *Penicillium* (*P. viridicatum, P. commune, P. purpurescens)* and *Aspergillus* (*A. ochraceus, A. alliaceus, A. melleus,* etc.) which contaminate cereal grain, vegetables and combined forage.

Ochratoxins A (OTA), B (OTB), C (OTC), D are a group of compounds in whose chemical structure L-fenilalanin is coupled through an amidic link with an isocumarinic derivative. The production of these mycotoxins is frequent in molded or overheated fodder and is favored by the presence of oligoelements, a temperature of 20–28°C and a humidity of 18–19% at wheat, in the case of *P. viridicatum* or 22% in corn. In laboratory conditions, most strains of *A, ochraceus* produce OTB and OTC, while in natural environment conditions, the most frequent is OTA. Its precursors can also be seen in culture media [23].

OTA is passively absorbed, in unionized form, at the digestive tube level, especially at the level of the short intestine level, at a pH of 7.04. After OTA's penetration of the organism, the mycotoxin links itself to the albumines in the plasma and starts rapidly metabolizing, depending on the animal species. Among the organs, OTA's highest affinity is for the liver and kidney. OTA has the strongest inhibitor effect on animal growth, determining the excessive accumulation of glycogen in the liver of afflicted animals [31].

The halving time of OTA in studies on monkeys was 840 hours, or several days in the case of pigs [32] and 3 hours in chicken [23]. The most important transformation takes place at hepatic level, where OTA is metabolized through hydroxylation in 4-hydroochratoxin A, metabolite eliminated by the kidney [31, 32].

At the level of the digestive tube, where afterwards it is also absorbed, another important metabolite is formed, OT-α, which is finally eliminated through the digestive system or the kidneys. Other metabolites formed in the organism follow an enterohepatic circuit after which they are also eliminated through feces and urine [32].

The quantity of mycotoxin degraded by the intestinal and ruminal symbionts is dependent on the quantity of concentrates from the food, the absorption of mycotoxins being higher at a higher content of starch in the food compared to fibers. The inhibitor effect of OTA on the bacterial growth was only observed in the case of gram-positive bacteria, in general under a neutral or lower than 7 pH [9]. Müller estimated through *in vitro* studies that adult cows are capable of degrading 33 to 72 mg OTA/day, while sheep are capable of 3 up to 7 mg OTA/day. The food composition influences the structure of the ruminal microsymbionts and, implicitly, the capacity of degrading OTA. When the mycotoxin is found in a large quantity in the food, the microbial detoxification capacity is reduced and the symptoms of the ochratoxicosis appear. Moreover, the OTA metabolism in the rumen is much reduced in the case of the digestion of an increased

Due to the detoxifying capacity of ruminal symbionts for OTA, ruminants appear to be more resistant to the action of ochratoxins compared to monogastric animals. This capacity is the more evident the healthier the population of microsymbionts, especially protozoa. An alimentation rich in concentrated fodder affects the level of ruminal pH, consequently affecting the protozoa population and, implicitly, the capacity of metabolizing mycotoxins, in this case OTA. Moreover, after the administration of a dose similar to the one naturally found in fodder, OTA and OTA-α were not detected in milk, which is explained by the degradation of the

From the clinical signs of ochratoxicosis at ruminants, we distinguish the development of the pulmonary edema and the damaging of the animal health up to its death at OTA concentrations of over 3 ppm/kg in the fodder. At the same time, studies have shown that OTA does not cross the placenta barrier in the case of the oral administration of mycotoxin in reduced quantities (0.38 mg OTA/kg), although this was detected in the cow milk, as well as in ilk from

Zearalenone (ZEA) is a mycotoxin produced by fungi species of the *Fusarium* (*F. graminearum,* 

An experimental study followed the administration of 385–1925 ppb ZEA during 7 weeks din not show a change in milk production, nor the presence of ZEA residues in milk, serum, urine or tissue. Both ZEA and its metabolites are absorbed at intestinal level, covering the

α and β-zearalenol are derivatives of ZEA that are eliminated from the organism through feces and urine and, to a lower degree, through milk. From these, α-zearalenol is considered the metabolite with the strongest estrogenic activity. Another metabolite of ZEA, which only develops in reduced quantities in animals, is zeranol, substance with a strong anabolic effect [41].

) is a lactone of the resorcilic acid, with

Dairy Cows Health Risk: Mycotoxins http://dx.doi.org/10.5772/intechopen.72709 93

quantity of concentrated fodder compared to an alimentation richer in fiber [39].

*2.2.1. Ochratoxicosis*

ochratoxin in the rumen by the microsymbionts.

*F. tricictum*) and is most commonly found in cereal grain.

From a chemical point of view, zearalenone (C18H22O5

a structure similar to steroid hormones [5].

other animals (pig, rabbit, rat).

**2.3. Zearalenone**

enterohepatic cycle [40].

Höhler et al. affirm that sheep fed with fodder containing various concentrations of OTA multiple values were recorded. Thus, at 2 ppm added OTA in food, there were significant concentration of OTA and OTA-α in the sanguine serum (10 and 3 ng/ml) and much higher concentrations for both mycotoxines at 5 ppm added OTA in food (80 and 15 ng/ml) [33].

The quantity of mycotoxin degraded by the intestinal and ruminal microsymbionts is dependent on the quantity of concentrates from food, the absorption of mycotoxins being higher at a larger content of starch in the food compared to fibers. From the total quantity of OTA ingested, approximately 70% of it is eliminated as OTA – α (9% in feces and 61% in urine) compared to the underrated OTA form (1% in feces and 3.8% in urine) [9]. Recent studies have shown the ability of OTA to disturb the cellular signal and to influence the viability and proliferation of cells [34].

OTA was determined in quantity of 2.2 μg/kg in the oat assay and in amount of 3.2 μg/kg in the bran assay. In the case of this mycotoxin, the results obtained revealed a quantity of 0.1 ng/ml in blood serum, 0.018 ng/ml in milk and 0.009 ng/ml in urine. Although it can be observed that from the 5.4 μg/kg ingested OTA, 1.8% were transferred in the blood serum, 0.3% in milk and 0.1% in urine, the conclusion regarding the conversion rate is uncertain, as different studies regarding the absorption and excretion of OTA and OTA-α at ruminants have shown the major influence of the type of food on the metabolites transfer to blood, milk and urine. The protozoa population at the rumen level is largely influenced by the type of alimentation of the ruminants. For example, the transformation of OTA in OTA- α is favored by feed rich in starch more than one rich in fibers [23, 35]. In a study on sheep, Blank et al. administered OTA through wheat contaminated with mycotoxins, at a base ration of 70% concentrated feed and 30% silo. The study showed that a large part of the OTA quantity remained undegraded and was detected in the sheep serum (from 1.5 to 18 μg OTA/kg BW/day), regardless of the OTA level in the food, while the quantity of mycotoxin excreted in the urine remained almost constant (6–8% of the ingested dose), regardless of the food dose. Alongside OTA, small OTA-α were detected in the serum (from 0.5 to 1.6 μg OTA-α/kg BW/day), directly proportional with the of the quantity of OTA in the food [36].

An important aspect of the metabolization of OTA in the organism is represented by the renal absorption at the level of the proximal tubes (2/3) and at the level of the distal tubes and collector channel (1/3). This phenomenon takes place due to the disturbance of pH homeostasis at cellular level of the nephron walls, which affects the acid–base transepithelial transport and determines the acidification of urine. The latter favors the reabsorption of OTA leading to the accumulation of the mycotoxin in the organism through the reduction of the elimination rate [37, 38].

Protozoa are considered organisms with a major role in degrading OTA to OTA-α. Other factors that can significantly influence the metabolic rate of OTA in the ruminant organism are: the animal age, genetic structure, health of the ruminal microsymbionts, alimentary ration structure.

The quantity of mycotoxin degraded by the intestinal and ruminal symbionts is dependent on the quantity of concentrates from the food, the absorption of mycotoxins being higher at a higher content of starch in the food compared to fibers. The inhibitor effect of OTA on the bacterial growth was only observed in the case of gram-positive bacteria, in general under a neutral or lower than 7 pH [9]. Müller estimated through *in vitro* studies that adult cows are capable of degrading 33 to 72 mg OTA/day, while sheep are capable of 3 up to 7 mg OTA/day. The food composition influences the structure of the ruminal microsymbionts and, implicitly, the capacity of degrading OTA. When the mycotoxin is found in a large quantity in the food, the microbial detoxification capacity is reduced and the symptoms of the ochratoxicosis appear. Moreover, the OTA metabolism in the rumen is much reduced in the case of the digestion of an increased quantity of concentrated fodder compared to an alimentation richer in fiber [39].
