**2.4. Trichothecene**

*2.3.1. Toxic effects at ruminants*

94 Ruminants - The Husbandry, Economic and Health Aspects

plasmic estrogen receptor.

The symptoms of ZEA toxicosis are: uterus hypertropia, swelling of the vulva and mammary glands, decline in the ovulation rate and disturbance of the heat cycle, conception rate is low at dairy cows, the estrogen effect of ZEA being owed to the link of the mycotoxin to the cyto-

It was discovered that the milk production decreased, infertility and hypoestrogenism appeared in the case of cows that consumed fodder contaminated with ZEA or with other fungi of the *Fusarium* type. Coppock et al. have shown that the effects of ZEA over the reproductive apparatus (vaginitis, vaginal secretions, mammary gland enlargement) at dairy cows can be strengthened through the synergic action of 600 ppb ZEA and 440 ppb DON in food; the consumption of food decreases which leads to the reduction of milk production, cases of diarrhea, increased infections of the reproductive tract and the entire reproductive activity is compromised. In general, it is considered that 400 ppb ZEA in the food is the maximum con-

A secretory activity of the mammary gland was observed at heifers that consumed fungi contaminated corn in the pre-puberty period. The administration during three estral cycles, at a heifer lot, of 250 mg purified ZEA, determined the reduction of the conception rate with 62%

Signs of hyperestrogenism were shown in cows that consumed fodder contaminated with 1 mg ZEA/kg fodder, over 5 days, while at sheep that received small doses of up to 24 mg ZEA/day/animal administered through fodder during the same period did not produce any

In general, it is considered that the transfer of ZEA and its metabolites in milk is very low [44]. Many researchers associate the reduced milk production, low fertility and hyperestrogenism at cows with the presence of ZEA in cereal or hay. Shreeve et al. ascertained that dairy cows fed with a ration containing 385–1982 μg ZEA/kg fodder, over 7 weeks, had a normal production of milk and there were no cases mycotoxin residues in milk, urine, serum or tissue [45]. In a 2004 study regarding the contamination with aflatoxin, ochratoxin and zearalenone, wheat and barley bran samples which were administered as a supplement to the food of dairy cows were analyzed. At the same time, determinations were done regarding the mycotoxin transfer in blood, milk and urine for the cows that consumed the contaminated feed. The results

, AB<sup>2</sup>

ZEA (values under 5 ppb in fodder and under 1 ppb in serum, milk and urine) in the fodder samples analyzed (values under the detection limit of 0.1 ppb). In a significant proportion, of approximately 90%, ZEA is transformed in α-zearalenone whose toxicity is very high and, in a smaller proportion, in β-zearalenol. As in the case of OTA, protozoa are 9 times more active than bacteria in the degrading of ZEA [23]. The transformation at ruminal level of ZEA in zearalenol, together with the reduction in polarity, affects the absorption and excretion rate of the toxin thus, [23] in accordance with many other studies, reducing the elimination rate of

, AG1

and AG2

, as well as the absence of

centration for which the reproductive activity of dairy cows is not affected [42].

while at the control lot, the rate of conception was reduced by 87% [43].

evident clinical effects over them, after the breeding period [42].

*2.3.2. Transmission of zearalenone to milk of dairy cows*

obtained showed the absence of aflatoxins AB1

ZEA and its metabolites in milk.

Trichothecenes are a group of 43 mycotoxins (DON or vomitoxin, NIV, DAS, T-2 toxin etc.) with a similar chemical structure, developed by species of fungi from the following types: *Fusarium* (*F. graminearum*, *F. sporotrichioides*, *F. culmorum, F. poae*), *Myrothecium sp., Phomopsis sp., Stachybotrys sp., Trichoderma sp.* and *Trichothecium sp.* [23].

From a chemical point of view, trichothecenes are derivative compounds of a tetracyclic sesquiterpene nucleus containing the epoxy- stable group in positions 12 and 13 and double C-C link in positions 9 and 10 [5].

Trichothecenes are metabolized *in vivo* in four ways: hydrolysis at the ester group level, hydroxylation, epoxy reduction and conjugation in the digestive tract, liver and other target organs of the animal organism [46]. The metabolization of trichothecenes is relatively simple, the halving time in the plasma varying between several minutes and several hours, depending on the mycotoxin. Within 24 hours of the oral administration, in the digestive tract of bovines were found both parental compounds and their metabolites, free and glucorono-conjugated [47].

In general, the DON, T-2 toxin and DAS mycotoxins do not accumulate in significant quantities in the organism, regardless of the administration method, since their metabolic compounds are eliminated from the organism within days. In certain situations though, there can be accumulations of the lipophilic trichothecenes, T-2 toxin and DAS, at the skin and fat tissue level. *In vitro* incubation in ruminal fluid of the DON mycotoxin, for 48 hours, determined its partial conversion into deepoxy-DON, metabolite non-toxic for ruminants.

Charmley et al. administered a ration of contaminated wheat and corn to 18 primiparous cows, formulated in order to induce a daily consumption of 0.59 mg, 42 mg and 104 mg DON. The authors saw that an increased concentration of DON in the ration did not affect fodder consumption or milk production. There were however modifications of the fat percentage in the milk and of the fat production, for the cows that received 42 mg of toxin daily. The authors did not observe the transfer of DON or deepoxy-DON in milk [48].

Ruminal microsymbionts can degrade DON resulting in the formation of 12,13-de-epoxideoxinivalenol (DOM-1). Côté et al. ascertained, following the administration of a ration with 66 mg DON/kg fodder, the presence of the DOM-1 metabolite in amount of 30 μg/l in milk and the absence of the parental mycotoxin [49]. In a study on lactating sheep, Prelusky et al. administered 880 mg DON/kg fodder, for 3 days and highlighted the presence in the milk of 220 μg/l mycotoxin, of which the majority was DOM-1 [44].

In a study done in North Carolina, Whitlow et al. found a significant decrease in the production of milk at cows that consumed concentrated fodder contaminated with 0.8 mg DON/kg DM. Such a result can be explained through the synergic effect of mycotoxins associated with DON even though these were not identified. The presence of DON residue in the animal tissue was not identified in this study [50].

As is the case for other mycotoxins, studies regarding the adding of DON to fodder din not reveal the same toxicity compared to the food naturally contaminated with DON [51]. This is explicable due to the multiple interactions between mycotoxins in fodder, under natural conditions.

## *2.4.1. Micotoxicosis produced by trichothecenes*

Trichothecenes produce a large variety of gastrointestinal disorders such as: vomiting, diarrhea, dermic inflammation or irritation, abortion, hemorrhages and immunosuppression.

heat cycle disruption, vaginal edema and prolapse, hypertrophy of mammary glands, etc. These clinical forms appear after consuming fodder contaminated with more than 24 ppm of ZEA [29]. Other species of *Fusarium* produce through the mycotoxins they develop various clinical manifestation in cattle. Thus, *F. nivale* develop the mycotoxins nivanelon, fuzarenon and BT butenolid, same as *F. tricinctum*, producing after being ingested by dairy cow's peripheral vasoconstriction and gangrene injuries of extremities due to ischemia; *F. tricinctum* develops the toxin T-2, F-2 and DAS. The toxin T-2 has inflammatory action over teguments and, in large quantities, can lead to skin necrosis. The consumption of fodder that contain the toxin T-2 leads to clinical manifestations such as loss of appetite, vomiting, severe dysentery, drop

Dairy Cows Health Risk: Mycotoxins http://dx.doi.org/10.5772/intechopen.72709 97

*Anatomopathological modifications in toxic form.* At the necropsy exam hemorrhagic injuries can be seen, as well as catarrhal and sometimes hemorrhagic inflammation of the rennet, intes-

*Presumptive diagnosis* is established on the basis of epidemiologic enquiry, clinical exam and anatomopathological exam, while the certainty diagnosis is established on the basis of para-

105 samples of fodder were analyzed, of which 75 samples of concentrated feed (cereal grains, wheat and maize bran, peas, sunflower and soybean meal) and 30 samples of fodder feeds from 5 family dairy farms in Southern Romania. The mycotoxicologic analysis was performed

In the 105 feed samples analyzed, in descending order, OTA was identified in a proportion of 63.80% (67 samples), T-2 in a proportion of 40.90% (43 samples), AF, ZEA and DON in a proportion of 39.0% (41 samples). By mycotoxin categories, in descending order, the maximum admissible limit in the 105 feed samples analyzed was exceeded in proportion of 40.95% for

According to categories of feed, in descending order of the 30 analyzed fodder feed samples, the following were determined: 66.60% (20 samples) OTA, 36.60% (11 samples) ZEA, 33.30% (10 samples) DON, 26.6% (8 samples) T-2; in the concentrated feed analyzed, OTA was identified in proportion of 62.66% (47 samples), AF in proportion of 54.60% (41 samples), T-2 in proportion of 46.60% (35 samples), DON in proportion of 41.30% (31 samples) and ZEA in

Of 105 analyzed feed samples, in decreasing order, 29.50% (31 samples) had two mycotoxins, 27.60% (29 samples) had three mycotoxins, 23.80% (25 samples) had one mycotoxin, 9.25% (10 samples) had four mycotoxins, 5.71% (6 samples) had no mycotoxins, and 2.85% (3 samples)

Of the 25 samples with a mycotoxin, in decreasing order, the incidence was 9.52% (10 samples) for OTA, 4.76% (5 samples) for T-2, 3.80% (4 samples) for AF and ZEA and 1.90% (2

tines and, as blood modification, leukocytosis with neutrophilia and eosinophilia.

in coagulability of the blood and other signs of gastroenteritis [55].

by the ELISA immunoassay test for AF, OTA, DON, ZEA and T-2.

T-2 (43 samples), 33.30% for ZEA (35 samples) and 9.52% (2 samples) for OTA.

clinical examination.

**3. Combined mycotoxins**

proportion of 40.00% (30 samples).

had five mycotoxins.

samples) for DON.

Immunosuppression generated by trichothecenes is realized through a complex mechanism that makes the animals more sensitive to pathogen agents.

Deoxynivalenol (DON) or vomitoxin has a reduced impact on dairy cattle, clinical signals being associated between DON contamination of fodder and reduced performances in dairy herds, especially the reduction of milk production. A Canadian study on 18 first-lactation cows during mid-lactation, showed that the production of milk reduced with 13% or 1.4 kg when the cows consumed food contaminated with DON 2.6–6.5 ppm [48]. Meat cattle and sheep tolerated a diet with 21 ppm DON without visible effects on the health state or production [52].

Among the general effects of DON on the organism, we mention: inhibitor of protein synthesis, affliction of the gastrointestinal tract, immune system depression.

T-2 toxin is found in a relatively lower proportion in fodder compared to other trichothecenes, under 10% and, in general, data related to its effect on ruminant health are reduced. T-2 toxin reduces ingestion, lowers production and affects reproduction; depending on dosage and duration of toxin ingestion, it results in gastroenteritis, ulcers and death [53].

The hemorrhagic syndrome can be either absent although gastrointestinal injuries are produced as presented by Weaver et al. or present, combined with reduced ingestion, milk production and absence of estrus cycles in cows [43, 54].

#### **2.5. Fusariotoxicosis**

Fusariotoxicosis is a mycotoxicosis that manifests itself through a complex of clinical symptoms and injuries to the digestive and genital apparatuses, central and hematopoietic nervous system and of the blood, provoked by different toxins from some *Fusarium* species.

*Etiologic agent.* Fuzariotoxicosis is produced by the mycotoxins ZEA and DON developed by *F. graminearum* as well as other *Fusarium* species such as *F. nivale* and *F. tricinctum*.

Contamination sources are represented by cereals contaminated with *Fusarium*, most affected being corn grains. Development of *Fusarium* fungi is favored by high temperatures of 24–27°C, while the development of ZEA is favored by lower temperatures, of 12–14°C.

This ecologic characteristic explains the higher incidence of the mycotoxicosis in autumn or fall, when humidity is high and low and high temperatures alternate [29].

*The toxic form* begins at 5–6 hours from the consumption of contaminated fodder, with 1–4 days of evolution. It is manifested through salivation, chills, accelerated pulse and breathing, rumen hypotonia, teeth screeching. Clinically, we can also observe: loss of appetite, deviation, photophobia, arrhythmia, cutaneous hyposensitivity, exophthalmia, diarrhea, paresis, paralysis of the hindquarters.

*The estrogenic form* is rarely seen at taurines and is manifested through parturition and puerperal complications, metritis consequence of retained placenta, uterine involution, abortions, heat cycle disruption, vaginal edema and prolapse, hypertrophy of mammary glands, etc. These clinical forms appear after consuming fodder contaminated with more than 24 ppm of ZEA [29].

Other species of *Fusarium* produce through the mycotoxins they develop various clinical manifestation in cattle. Thus, *F. nivale* develop the mycotoxins nivanelon, fuzarenon and BT butenolid, same as *F. tricinctum*, producing after being ingested by dairy cow's peripheral vasoconstriction and gangrene injuries of extremities due to ischemia; *F. tricinctum* develops the toxin T-2, F-2 and DAS. The toxin T-2 has inflammatory action over teguments and, in large quantities, can lead to skin necrosis. The consumption of fodder that contain the toxin T-2 leads to clinical manifestations such as loss of appetite, vomiting, severe dysentery, drop in coagulability of the blood and other signs of gastroenteritis [55].

*Anatomopathological modifications in toxic form.* At the necropsy exam hemorrhagic injuries can be seen, as well as catarrhal and sometimes hemorrhagic inflammation of the rennet, intestines and, as blood modification, leukocytosis with neutrophilia and eosinophilia.

*Presumptive diagnosis* is established on the basis of epidemiologic enquiry, clinical exam and anatomopathological exam, while the certainty diagnosis is established on the basis of paraclinical examination.
