Mycotoxins in Ruminants

1. Introduction

Mycotoxins are fungal secondary metabolites, that specific fungal strains produce during stress conditions. These conditions could be draught, heat, cold, growth of the plant or competition with other microorganisms. These compounds or their metabolites elicit toxic response in farm animals and humans as well. The most concerning genera for mycotoxin production are Aspergillus, Fusarium and Penicillium spp[1]. Dues to their specific diets, Alternaria produced toxins also represent a significant risk in ruminants.
Mycotoxicoses are the syndromes resulting from ingestion, skin contact or inhalation of myoctoxins[2]. Acute manifestation of mycotoxicosis is rare under farm conditions due to awareness campaigns and legal recommendations on the acceptable mycotoxin levels in feedstuff. The effect of mycotoxin ingestion are mainly chronic, resulting in hidden disorders, reduced ingestion, productivity or fertility[3]. Ruminants are considered less susceptible to mycotoxins than monogastrics, attributing a protective effect to the rumen microbiota by degrading, deactivating or binding mycotoxins[4]. However, mycotoxins are extensively metabolized and adsorbed by ruminants, which then may be secreted to milk representing a significant risk to the consumers[5].
Ruminant diets include many unique ingredients, which increase the risk of mycotoxin exposure compared to monogastric animals that have less varied diets. In our previous mycotoxin series, we have reviewed the prevalence and distribution of mayor mycotoxins; Aflatoxin, Ochratoxin A, T-2 toxin, Deoxynivalenol, Zearalenone and Fumonisins. In the upcoming two articles, we will focus on mycotoxin prevalence in forages, it being a specific nutritional source for ruminants and on the specific mycotoxin effects on ruminants.

2. Prevalence and risk

Ruminants have the unique ability to digest energy sources that monogastric animals cannot utilize. By digesting the fiber in the diet, ruminants can benefit from unique feed sources.
Nonetheless, there is an important drawback, namely that mycotoxins tend to be more concentrated on surface of the grains, such as the wheat barn, which increases the exposure to mycotoxins of ruminants. Filamentous fungi can also grow on forages and their presence is frequently observed in silage or hay[6]. Usually, the three most important toxigenic genera occurring pre-harvest are Aspergillus, Fusarium and Alternaria spp[7]. The occurrence of these fungi in the field is related to several factors, including agricultural practices and climatic factors. High humidity of the diet also make it more susceptible to mycotoxin production post-harvest.
Silage is made from green crops by fermentation, ensilage to the point of acidification. It is usually made from grass crops, including corn, sorghum, or other cereals, using the entire green plant. During the ensiling most fungi may be eliminated[8]. However some mycotoxin producing species may tolerate both high levels of organic acids and carbon dioxide in addition to low availability of oxygen7. Silage is highly susceptible to spoilage by mycotoxin production filamentous fungi if mismanaged due to its high water content. In the next sections we are going to look at the prevalence of the key mycotoxins present in forages and other feed materials for ruminants.

2.1 Aspergillus toxins

Aflatoxins are potent carcinogenic substances and have been classified group 1 carcinogens[9]. These toxins are produced by Aspergillus flavuis and Aspergillus parasiticus in high moisture conditions, typically post-harvest. Sporadically, aflatoxins are detected in forages, contributing to the AF intake of lactating dairy cows[10]. The main concern is that these toxins produced in growing crops may not be uniformly distributed across the field and when samples are collected, they may or may not be representative of the whole material[11]. Although sampling guidance exists for foodstuff[12], no such guidance exists for hay and silages.
In other feedstuff; Aflatoxin B1 (AFB1) is the most prevalent and toxic among more than 18 types of aflatoxins presently identified[13]. Various research 13,[14],[15] reported that the most prevalent regions of aflatoxins in the world are South Asia, Sub-Saharan Africa, and Southeast Asia. A global mycotoxin survey for 10 years (from 2008 to 2017) 14 indicated that the prevalence of AFB1 was 82.2%, 76%, and 57.4% in South Asian, Sub-Saharan African, and Southeast Asian samples, respectively. The latest eBook on Mycotoxins (2023) by Vetanco showed 45 % of the samples were positive to Aflatoxin in Latin-America. The mean concentration of the samples was 7 μg/kg, while the maximum value was 139 μg/kg, which are both above the recommendation levels of feed for lactating cows.

2.2 Fusarium toxins

2.2.1 Deoxynivalenol (DON)

DON is considered the most prevailing mycotoxin in silages and other forages7. Incidence of DON in forages higher than 80% were reported in North America and North Europe with average contamination levels highly variable, but often exceeding 2 mg/kg4. Masked forms of DON, such as 15-acetyl DON and 3-acetly DON were also found in maize silage in numerous occasions[16]. Nonetheless, their concentration remained below 10% of that of DON, suggesting that the free DON is the key compound for the toxic effects.
In other feedstuff, the latest eBook on Mycotoxins (2023) by Vetanco showed 40 % of the samples were positive to DON in Latin-America. The mean concentration of the samples was 789 μg/kg, while the maximum value was 6515 μg/kg, that later highly exceed the recommended levels for ruminants.

2.2.2  Zearalenone (ZEN)

Zearalenone (ZEN) is a mycotoxin produced mainly by fungi belonging to the genus Fusarium in cereal and complete feeds[17]. Zearalenone contamination levels vary distinctly by region, country, and climate and this mycotoxin is commonly found contaminating cereals in cool temperatures and high humidity[18]. Many surveys revealed a potential interaction between ZEN concentrations in grains and balanced feed and the rainfall that occurred in a given year[19]. For instance, due to its severe wet climate conditions, there was an extreme 100% positive rate of ZEN in Serbia's corn in 2014 [20]. Several reports found ZEN in maize silage, grass silage and hay4. On average 52 % of the samples contained ZEN, with average contamination levels around 500 μg/kg4. Nonetheless, these studies focused on Europe and the United States, and no data could be found for other geographic regions.
Overall, global surveys indicate that ZEN is one of the top three mycotoxins with the highest pollution rate in all regions of the world except South Asia 14. In other feedstuff, the latest eBook on Mycotoxins (2023) by Vetanco showed 58 % of the samples were positive to ZEN in Latin-America. The mean concentration of the samples was 161 μg/kg, while the maximum value was 1604 μg/kg, that later highly exceed the recommended levels for ruminants.

2.2.3 Fumonisins (FBs)

FBs are primery produced by F. proliferatum and F. Verticilliodes[21], nad their contamination is typical pre-harvest. In maize, FUM show a higher prevalence (80% positive samples) and a higher median value (1,300 μg/kg) than in any other animal feed or cereals. Surveys show, that FUM not only have high positive rates but also have higher concentrations than those of other common mycotoxins; this means that feed mills and farmers should be vigilant in monitoring the rate of FUM in animal feeds and feed ingredients. For Fb1 incidences higher than 30 % were reported in maize silage in North America, whereas in the Netherlands and France the occurrence was low. About 50 % hay and silage sampled in Wisconsin were contaminated by FB14.
In other feedstuff, the latest eBook on Mycotoxins (2023) by Vetanco showed 71 % of the samples were positive to ZEN in Latin-America. The mean concentration of the samples was 1732 μg/kg, while the maximum value was 27 200 μg/kg, that later highly exceed the recommended levels for ruminants.

2.3 Alternaria toxins

Alternaria species are major plant pathogens, which are common allergens in humans. At least 20 % of agricultural spoilage is caused by these fungi, losses reaching up to 80 % of the yield[22]. The fungi produce alternariol, alternariol monomethyl ether, tenuazonic acid, iso-tenuazonic acid, altertoxins, tentoxin, altenuene and AAL-toxins during host invasion. EFSA reviewed the “the risks for animal and public health related to the presence of Alternaria toxins in feed and food” in 2011[23]. A recent review found that AAL TA and TB toxins were the most prevalent of the Alternaria toxins4. However, there is very limited data on the occurrence of these toxins, given that they are not part of the usual monitoring programs, and only limited analytical techniques are available for their regular surveillance. Nevertheless, due to the lifestyle of the fungi, all leafy feed sources, such as forage, hay, grass or alfalfa[24] are susceptible to infection and toxin presence.

3. Effects of mycotoxins and regulations

3.1 Aspergillus toxins

In general, ruminants, except sheep, are more tolerant to aflatoxins due to rumen microorganisms’ biodegradation[25]. Calves are more susceptible than mature ruminants because the rumen environment of the former does not complete development. In dairy cows, chronic exposure to aflatoxins can reduce growth and lactating performance, impair liver function, compromise immune function, and increase disease susceptibility 3,[26]. A previous report[27] indicated that feeding 75 μg/kg AFB1 of diet dry matter (DM) to dairy cows for 4 weeks reduced milk yield by 2.5 kg and 3.5% fat-corrected milk yield by 1.7 kg. It was shown that consuming 2.5 mg/kg aflatoxins of diet DM for 5 weeks caused liver damage, reduced body weight gain, feed intake, and feed efficiency of growing lambs but had no effects on rumen fermentation[28]. Another study showed that the negative impacts of aflatoxins on ruminal growth and lactating performance are due to the systematic toxicity effects, including immunosuppression, rather than direct toxicity to rumen microorganisms26b. Besides, some recent studies also confirmed the negative impact of aflatoxins on bull spermatozoa, fertilization competence, and preimplantation embryo development in dairy cows[29]. Table 1 shows a summary of the AFB1 effects on ruminant production performance.

When ruminants are fed with a contaminated diet containing AFB1, the mycotoxin is metabolized to AFM1 in raw milk[31]. Aflatoxin B1 and aflatoxin M1 are stable in heat with carcinogenic, mutagenic, and teratogenic effects in humans and animals[32]. It should be noted that the carcinogenic potency of AFM1 is almost as high as that of AFB1, and the toxicological properties are generally comparable[33]. Therefore, many countries have set AFM1 maximal concentrations in raw milk and milk products to avoid human exposure. The AFM1 maximum residue level permitted in milk has been set by the European Union (EU) and the United States Food and Drug Administration (FDA) at 50 ng/kg and 500 ng/kg of raw milk, respectively[34].

Table 1. The guidance values of the European Union (EU) Commission, United States Food and Drug Administration (FDA), and China for aflatoxin B1 concentrations (μg/kg) in complete feed [35], and maximum residue levels for AFM1 in milk34.

3.2  Fusarium toxins

3.2.1 Deoxynivalenol (DON)

The susceptibility of ruminants to DON is significantly lower than that of swine 5. The fact that the intact ruminal epithelium is a barrier against DON, most of the ingested DON is de-acetylated and de-epoxied by ruminal protozoans and some bacteria before absorption[36]. Ruminants can tolerate extremely high levels of DON for several weeks without negative effects on their growth and lactation performance. Previous research indicated dietary DON concentrations ranging between 3.1 and 3.5 mg/kg did not cause any significant adverse health effects but transiently increased post-prandial ammonia concentrations17. Similarly, in longer studies with lactating dairy cows, concentrations of up to 12 mg/kg of DON in concentrate (equivalent to 104 mg/cow/day) or 14.6 mg/kg of DON in concentrate (equivalent to 190 mg/cow/day) did not affect FI[37]. No adverse effect of dietary DON on milk yield and composition was observed in most studies. Only one report indicated that first-lactation cows consuming DON-contaminated diets (6.5 mg/kg) tended to produce 13% less milk production than cows consuming clean concentrate38. Besides, some field reports likely substantiated the association of DON with poor-performing ruminants because the synergistic effect due to mycotoxin combinations widely co-exist in the ruminant diet in fields, especially of DON and FUM or DON and ZEN. Beef cattle fed a diet contaminated with 1.7 mg/kg of DON combined with 3.5 mg/kg of FUM presented a decreased rumen pH, lower body weight, and poor crude protein digestibility[38]. On the other hand, dairy cows fed diets contaminated with DON (up to 0.9 mg/kg) and FUM (up to 1.3 mg/kg) presented a decrease in their dry matter and neutral detergent fiber digestibility, which in turn negatively influences milk production[39]. In addition, the combination of 1.96 mg/kg of DON and 0.36 mg/kg of ZEN in the diet of lactating cows induced shortened milk yield and decreased fat content in milk[40].

Table 4. Deoxynivalenol (DON) toxicities on growth performance in ruminants

In response to the ample research on DON toxicity recommendations have been issued for the acceptable levels on DON worldwide.

3.2.2 Zearalenone (ZEN)

Rumen microbes extensively metabolize ZEN to β-ZEL[42]. Therefore, ruminants usually do not show symptoms of ZEN poisoning[43] unless highly superior levels of ZEN or other mycotoxins (e.g., DON) are both present in concentrates and forage[44]. Furthermore, α-zearalanol is used as a growth promoter the United States and Canada in beef cattle. Previous studies found that dairy herds receiving a diet contaminated with both DON and ZEN at levels of about 500 and 750 μg/kg, respectively, showed unsynchronized ovarian cycles, vaginitis, and early development of mammary glands in heifers[45]. However, heifers fed a diet containing only 1.25 mg/kg of ZEN did not show reproductive issues[46]. Zearalenone is toxic to ruminants at extremely high levels (at high doses rarely seen in nature) in naturally occurring concentrates and forages. Britain's research showed decreasing fertility in the dairy cows fed hay and grass silage containing ZEN at 14 mg/kg[47]. Another study indicated that dairy cows fed with ZEN-contaminated grain (25 mg/kg) show vaginitis, extended estrus, and decreased feed intake, and milk yield 48.

Currently, the only known field case is grazing sheep in New Zealand that were poisoned by ZEN, which caused infertility [48]. Most field or case reports in which a direct relationship between ZEN exposition levels and symptoms of estrogenic effects was not found were reported, suggesting this might reflect the variability in rumen degradation of ZEN. Previous research orally administered virgin heifers with an extremely high ZEN dose (250 mg) for 66 days, resulting in a slightly decreased conception rate (62%) compared to 87% found in the untreated control group)[49]. In general, ZEN and its metabolites can be detectable in the liver and bile, but most studies are not detected in milk because of their endogenous ruminal detoxification17. However, when dairy cows ingest exceptionally high levels of concentrates, that typically induces ZEN to carry over into milk. For instance, previous researchers found that 0.7% of ZEN could carry over into milk when 200 mg of ZEN/day is detected in the concentrate for 7 days44.
 

Table 3. Zearalenone (ZEN) toxicities on growth performances and reproductive abilities in ruminants

AMH: anti-müllerian hormone; TMR: total mixed ration.

In response to the ample research on ZEN toxicity recommendations have been issued for the acceptable levels on ZEN worldwide.

^#FDA had  no guidance values for ZEN^[53].

3.2.3 Fumonisins (FBs)

Generally speaking, Fumonisins (FBs) are cytotoxic, hepatoxic and nephrotoxic to animals4. The key enzyme of lipid metabolism, CerS is the primary target of fumonisins for animals, resulting in a perfect storm of perturbed sphingolipid metabolism, signaling and disease[54]. FBs are poorly degraded in the rumen, thus causing slower rumen motility and decreased feed consumption in cattle5. Because of greater production stress, dairy cattle may be more sensitive to FBs than are beef cattle. Major clinical signs of FBs poisoning in cattle are decreased appetite accompanied by serum biochemical and histologic evidence of hepatic damage5. Lactating dairy Jersey cows were fed a diet contaminated at a level of 75 mg/kg of FB1 for 14 days, increasing serum cholesterol concentration and decreasing feed intake and milk production[55]. Other research indicated that carryover of FBs from feed to milk in dairy cows was insignificant[56]. When Holstein calves were fed a diet with a contamination level of 94 mg/kg of FB1 for 253 days, increases in serum aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT), as well as hepatocellular injury, were reported[57]. Similar metabolic changes, such as serum increase of AST, GGT, lactate dehydrogenase (LDH), bilirubin or cholesterol, and histological changes, were reported when calves were fed diets containing 105 mg/kg of FBs for 31 days[58]. In summary, diets containing 75 mg/kg of FB1 are hepatotoxic to cattle. Furthermore, necropsies of beef cattle having a sudden onset of blindness after grazing on standing corn contaminated with FBs revealed optic nerve degeneration and acute myelin edema[59]. Feeder calves showed signs of immunotoxicity in the form of significantly reduced lymphoblastogenesis60.

Table 3. Fumonisins toxicities on growth performance and production ability in cattle

AST: aspartate aminotransferase; GGT: γ-glutamyltransferase; LDH : lactate dehydrogenase.

In response to the ample research on FB toxicity recommendations have been issued for the acceptable levels on FBs worldwide.

3.3  Alternaria toxins

The most relevant information about the risks and effects on the Alternaria derived toxins is summarized the EFSA report23. Due to the lack of evidence however, it was impossible to establish recommendations on the safe levels of Alternaria toxins23. These toxins remain in the status of so-called “emerging mycotoxins”, as information on susceptibility of farm animals to Alternaria derived compounds is needed, as these are largely detected in food and feed[60]. A novel line of research hint toward substantial interplay between Alternaria toxins and the gut microbiome[61], which crucially important for rumen stability.
Newly developed LC-MS/MS methods being able to simultaneously detect traces of multiple Alternaria toxins are expected to be widely applied in testing food and feed for currently insufficiently assessed metabolites with potential toxicological relevance. Additionally, the implementation of such methods in biomonitoring and exposome approaches seems promising for complementing food and feed occurrence data toward a more accurate estimation of human and farm animal exposure[62]. 

[1] Council for Agricultural Science and Technology (CAST). Mycotoxins: Risks in Plant, Animal, and Human Systems; CAST: Ames, IA, USA, 2003.
[2] Richard, J.L. Some major mycotoxins and their mycotoxicoses-An overview. Int. J. Food Microbiol. 2007, 119, 3–10.
[3] Fink-Gremmels, J. The role of mycotoxins in the health and performance of dairy cows. Vet. J. 2008, 176, 84–92.
[4] Gallo A., Giuberti G., Frisvad J. C., Bertuzzi T., Nielsen K.F. Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effect, Toxins 2015, 7, 3057-3111;
[5] Fink-Gremmels, J. Mycotoxins in cattle feeds and carry-over to dairy milk: A review. Food Addit. Contam. A Chem. Anal. Control Expo. Risk Assess. 2008, 25, 172–180.
[6] Skládanka, J.; Nedělník, J.; Adam, V.; Doležal, P.; Moravcová, H.; Dohnal, V. Forage as a primary source of mycotoxins in animal diets. Int. J. Environ. Res. Public Health 2011, 8, 37–50.
[7] Storm, I.M.L.D.; Sørensen, J.L.; Rasmussen, R.R.; Nielsen, K.F.; Thrane, U. Mycotoxins in silage. Stewart Postharvest Rev. 2008, 4, 1–12.
[8] Mansfield, M.A.; Kuldau, G.A. Microbiological and molecular determination of mycobiota in fresh and ensiled maize silage. Mycologia 2007, 99, 269–278.
[9] International Agency for Research on Cancer (IARC). Aflatoxins. IARC Summ. Evaluation 2002, 82, 1–171.
[10] Richard, E.; Heutte, N.; Bouchart, V.; Garon, D. Evaluation of fungal contamination and mycotoxin production in maize silage. Anim. Feed Sci. Technol. 2009, 148, 309–320.
[11] Cheli, F.; Campagnoli, A.; Dell’Orto, V. Fungal populations and mycotoxins in silages: From occurrence to analysis. Anim. Feed Sci. Technol. 2013, 183, 1–16.
[12] European Commission (EC). Commission Regulation (EC) No 401/2006 of 23 February 2006 laying down the methods of sampling and analysis for the official control of the levels of mycotoxins in foodstuffs. Off. J. Eur. Union 2006, L70, 12–34.
[13] Benkerroum, N. Aflatoxins: Producing-Molds, Structure, Health Issues and Incidence in Southeast Asian and Sub-Saharan African Countries. Int J Environ Res Public Health 2020, 17, doi:10.3390/ijerph17041215.
[14] Gruber-Dorninger, C.; Jenkins, T.; Schatzmayr, G. Global Mycotoxin Occurrence in Feed: A Ten-Year Survey. Toxins (Basel) 2019, 11, doi:10.3390/toxins11070375.
[15] Siri-Anusornsak, W.; Kolawole, O.; Mahakarnchanakul, W.; Greer, B.; Petchkongkaew, A.; Meneely, J.; Elliott, C.; Vangnai, K. The Occurrence and Co-Occurrence of Regulated, Emerging, and Masked Mycotoxins in Rice Bran and Maize from Southeast Asia. Toxins (Basel) 2022, 14, doi:10.3390/toxins14080567.
[16] Schollenberger, M.; Müller, H.M.; Rüfle, M.; Suchy, S.; Plank, S.; Drochner, W. Natural occurrence of 16 Fusarium toxins in grains and feedstuffs of plant origin from Germany. Mycopathologia 2006, 161, 43–52.
[17] Seeling, K.; Boguhn, J.; Strobel, E.; Danicke, S.; Valenta, H.; Ueberschar, K.H.; Rodehutscord, M. On the effects of Fusarium toxin contaminated wheat and wheat chaff on nutrient utilisation and turnover of deoxynivalenol and zearalenone in vitro (Rusitec). Toxicol In Vitro 2006, 20, 703-711, doi:10.1016/j.tiv.2005.10.006.
[18] Caballero, B.; Finglas, P.; Toldra, F. Encyclopedia of Food and Health; Elsevier Science: 2015
[19] Bryden, W.L. Mycotoxin contamination of the feed supply chain: Implications for animal productivity and feed security. Anim Feed Sci Tech 2012, 173, 134-158, doi:https://doi.org/10.1016/j.anifeedsci.2011.12.014.
[20] Kos, J.; Janic Hajnal, E.; Malachova, A.; Steiner, D.; Stranska, M.; Krska, R.; Poschmaier, B.; Sulyok, M. Mycotoxins in maize harvested in Republic of Serbia in the period 2012-2015. Part 1: Regulated mycotoxins and its derivatives. Food Chem 2020, 312, 126034, doi:10.1016/j.foodchem.2019.126034.
[21] Chelkowski, J. Fusarium: Mycotoxins, Taxonomy, Pathogenicity; Elsevier Science Publishers B.V.: Amsterdam, The Netherlands, 2014.
[22] Nowicki, M., Nowakowska M., Niezgoda A., Kozik E.U.: Alternaria black bpot of crucifers: Symptoms, importance of disease, and perspectives of resistance breeding. Vegetable Crops Research Bulletin. 2012, 76, 5–19.
[23] European Food Safety Authority (EFSA). Scientific Opinion on the risks for animal and public health related to the presence of Alternaria toxins in feed and food. EFSA J. 2011, 9, 1–97.
[24] Pervaiz A. A., Shawkat A., W. Renderos, H. A. Naeem, Y. Papadopoulos; First report of Alternaria alternata causing leaf spot and blight symptoms on alfalfa in Canada, Canadian Journal of Plant Pathology, 2018, 40:3, 451-455.
[25] Loh, Z.H.; Ouwerkerk, D.; Klieve, A.V.; Hungerford, N.L.; Fletcher, M.T. Toxin Degradation by Rumen Microorganisms: A Review. Toxins (Basel) 2020, 12, doi:10.3390/toxins12100664.
[26] Jiang, Y.; Ogunade, I.M.; Vyas, D.; Adesogan, A.T. Aflatoxin in Dairy Cows: Toxicity, Occurrence in Feedstuffs and Milk and Dietary Mitigation Strategies. Toxins (Basel) 2021, 13,.
[27] Ogunade, I.M.; Arriola, K.G.; Jiang, Y.; Driver, J.P.; Staples, C.R.; Adesogan, A.T. Effects of 3 sequestering agents on milk aflatoxin M1 concentration and the performance and immune status of dairy cows fed diets artificially contaminated with aflatoxin B1, Journal of Dairy Science Volume 99, Issue 8, August 2016, Pages 6263-6273
[28] a. Edrington, T.S.; Harvey, R.B.; Kubena, L.F. Effect of aflatoxin in growing lambs fed ruminally degradable or escape protein sources. J Anim Sci 1994, 72, 1274-1281, doi:10.2527/1994.7251274x, b. Fernandez, A.; Hernandez, M.; Verde, M.T.; Sanz, M. Effect of aflatoxin on performance, hematology, and clinical immunology in lambs. Can J Vet Res 2000, 64, 53-58
[29] a. Komsky-Elbaz, A.; Kalo, D.; Roth, Z. Effect of aflatoxin B1 on bovine spermatozoa's proteome and embryo's transcriptome. Reproduction 2020, 160, 709-723, doi:10.1530/REP-20-0286. b. Jiang, Y.; Hansen, P.J.; Xiao, Y.; Amaral, T.F.; Vyas, D.; Adesogan, A.T. Aflatoxin compromises development of the preimplantation bovine embryo through mechanisms independent of reactive oxygen production. J Dairy Sci 2019, 102, 10506-10513, doi:10.3168/jds.2019-16839.
[30] Upadhaya, S.D.; Park, M.A.; Ha, J.K. Mycotoxins and Their Biotransformation in the Rumen: A Review. Asian Austral J Anim 2010, 23, 1250-1260, doi:10.5713/ajas.2010.r.06.
[31] Rahimi, E.; Bonyadian, M.; Rafei, M.; Kazemeini, H.R. Occurrence of aflatoxin M1 in raw milk of five dairy species in Ahvaz, Iran. Food Chem Toxicol 2010, 48, 129-131, doi:10.1016/j.fct.2009.09.028
[32] Yu, J. Current understanding on aflatoxin biosynthesis and future perspective in reducing aflatoxin contamination. Toxins (Basel) 2012, 4, 1024-1057, doi:10.3390/toxins4111024.
[33] Marchese, S.; Polo, A.; Ariano, A.; Velotto, S.; Costantini, S.; Severino, L. Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development. Toxins (Basel) 2018, 10, doi:10.3390/toxins10060214.
[34] Giovati, L.; Magliani, W.; Ciociola, T.; Santinoli, C.; Conti, S.; Polonelli, L. AFM(1) in Milk: Physical, Biological, and Prophylactic Methods to Mitigate Contamination. Toxins (Basel) 2015, 7, 4330-4349, doi:10.3390/toxins7104330.
[35] a. Park, D.L.; Troxell, T.C. U.S. perspective on mycotoxin regulatory issues., b. Commission, E. Commission recommendation of of 17 august 2006 on the presence of deoxynivalenol, zearalenone, ochratoxin a, T-2 and HT-2 and fumonisins in products intended for animal feeding. Commission, E., Ed. Official Journal of the European Union: 2006. c. General Administration of Quality Supervision, I.a.Q.o.t.P.s.R.o.C.a.S.A.o.t.P.s.R.o.C. Hygienic Standard for Feeds GB13078-2017. General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China and Standardization Administration of the People's Republic of China: 2018.
[36] Dänicke, S.; Matthäus, K.; Lebzien, P.; Valenta, H.; Stemme, K.; Ueberschär, K.-H.; Razzazi-Fazeli, E.; Böhm, J.; Flachowsky, G. 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. J Anim Physiol an N 2005, 89, 303-315.
[37] Charmley, E.; Trenholm, H.L.; Thompson, B.K.; Vudathala, D.; Nicholson, J.W.; Prelusky, D.B.; Charmley, L.L. Influence of level of deoxynivalenol in the diet of dairy cows on feed intake, milk production, and its composition. J Dairy Sci 1993, 76, 3580-3587,
[38] Roberts, H.L.; Bionaz, M.A.-O.; Jiang, D.; Doupovec, B.A.-O.; Faas, J.A.-O.; Estill, C.T.; Schatzmayr, D.; Duringer, J.A.-O. Effects of Deoxynivalenol and Fumonisins Fed in Combination to Beef Cattle: Immunotoxicity and Gene Expression. LID - 10.3390/toxins13100714
[39] Duringer, J.M.; Roberts, H.L.; Doupovec, B.; Faas, J.; Estill, C.T.; Jiang, D.; Schatzmayr, D. Effects of deoxynivalenol and fumonisins fed in combination on beef cattle: health and performance indices. World Mycotoxin Journal 2020, 13, 533-543,
[40] Marczuk, J.; Obremski, K.; Lutnicki, K.; Gajecka, M.; Gajecki, M. Zearalenone and deoxynivalenol mycotoxicosis in dairy cattle herds. Pol J Vet Sci 2012, 15, 365-372,
[41] Gallo, A.; Minuti, A.; Bani, P.; Bertuzzi, T.; Cappelli, F.P.; Doupovec, B.; Faas, J.; Schatzmayr, D.; Trevisi, E. A mycotoxin-deactivating feed additive counteracts the adverse effects of regular levels of Fusarium mycotoxins in dairy cows. Journal of Dairy Science 2020, 103, 11314-11331,
[42] Hartinger, T.; Grabher, L.; Pacifico, C.; Angelmayr, B.; Faas, J.; Zebeli, Q. Short-term exposure to the mycotoxins zearalenone or fumonisins affects rumen fermentation and microbiota, and health variables in cattle. Food Chem Toxicol 2022, 162, 112900,.
[43] Liu, J.; Applegate, T. Zearalenone (ZEN) in Livestock and Poultry: Dose, Toxicokinetics, Toxicity and Estrogenicity. Toxins (Basel) 2020, 12,
[44] Thapa, A.; Horgan, K.A.; White, B.; Walls, D. Deoxynivalenol and Zearalenone-Synergistic or Antagonistic Agri-Food Chain Co-Contaminants Toxins (Basel) 2021, 13,.
[45] Coppock, R.W.; Mostrom, M.S.; Sparling, C.G.; Jacobsen, B.; Ross, S.C. Apparent zearalenone intoxication in a dairy herd from feeding spoiled acid-treated corn. Vet Hum Toxicol 1990, 32, 246-248.
[46] Gallo, A.; Giuberti, G.; Frisvad, J.C.; Bertuzzi, T.; Nielsen, K.F. Review on Mycotoxin Issues in Ruminants: Occurrence in Forages, Effects of Mycotoxin Ingestion on Health Status and Animal Performance and Practical Strategies to Counteract Their Negative Effects. Toxins (Basel) 2015, 7, 3057-3111,
[47] Schuh, M. Clinical and subclinical events related to the presence of mycotoxins in cattle feed. The Bovine Practitioner 1998, 1998, 34-38,
[48] JF, S.; CA, M. Review of zearalenone studies with sheep in New Zealand. In Proceedings of Proceedings of the New Zealand Society of Animal Production, Napier, Jan; pp. 306-310.
[49] Chain, E.P.o.C.i.t.F.; Knutsen, H.K.; Alexander, J.; Barregard, L.; Bignami, M.; Bruschweiler, B.; Ceccatelli, S.; Cottrill, B.; Dinovi, M.; Edler, L., et al. Risks for animal health related to the presence of zearalenone and its modified forms in feed. EFSA J 2017, 15, e04851,
[50] Silva, L.A.; de Mello, M.R.B.; Oliveira Pião, D.; Silenciato, L.N.; de Quadros, T.C.O.; de Souza, A.H.; Barbero, R.P. Effects of experimental exposure to zearalenone on reproductive system morphometry, plasma oestrogen levels, and oocyte quality of beef heifer. Reprod Domest Anim 2021, 56, 775-782,
[51] Fushimi, Y.; Takagi, M.; Monniaux, D.; Uno, S.; Kokushi, E.; Shinya, U.; Kawashima, C.; Otoi, T.; Deguchi, E.; Fink-Gremmels, J. Effects of Dietary Contamination by Zearalenone and Its Metabolites on Serum Anti-Mullerian Hormone: Impact on the Reproductive Performance of Breeding Cows. Reprod Domest Anim 2015, 50, 834-839,
[52] Smith, J.F.; di Menna, M.E.; McGowan, L.T. Reproductive performance of Coopworth ewes following oral doses of zearalenone before and after mating. J Reprod Fertil 1990, 89, 99-106,
[53] https://www.fda.gov/food/natural-toxins-food/mycotoxins accessed: 2024.03.01.
[54] Ronald T Riley 1, Alfred H Merrill Jr 2: Ceramide synthase inhibition by fumonisins: a perfect storm of perturbed sphingolipid metabolism, signaling, and disease, J Lipid Res . 2019 Jul;60(7):1183-1189.
[55] Richard, J.L.; Meerdink, G.; Maragos, C.M.; Tumbleson, M.; Bordson, G.; Rice, L.G.; Ross, P.F. Absence of detectable fumonisins in the milk of cows fed Fusarium proliferatum (Matsushima) Nirenberg culture material. Mycopathologia 1996, 133, 123-126,
[56] Knutsen, H.K.; Alexander, J.; Barregård, L.; Bignami, M.; Brüschweiler, B.; Ceccatelli, S.; Cottrill, B.; Dinovi, M.; Edler, L.; Grasl-Kraupp, B., et al. Risks for animal health related to the presence of fumonisins, their modified forms and hidden forms in feed. Efsa j 2018, 16, e05242,
[57] Baker, D.C.; Rottinghaus, G.E. Chronic experimental fumonisin intoxication of calves. J Vet Diagn Invest 1999, 11, 289-292,
[58] Osweiler, G.D.; Kehrli, M.E.; Stabel, J.R.; Thurston, J.R.; Ross, P.F.; Wilson, T.M. Effects of fumonisin-contaminated corn screenings on growth and health of feeder calves. J Anim Sci 1993, 71, 459-466,
[59] Sandmeyer, L.S.; Vujanovic, V.; Petrie, L.; Campbell, J.R.; Bauer, B.S.; Allen, A.L.; Grahn, B.H. Optic neuropathy in a herd of beef cattle in Alberta associated with consumption of moldy corn. Can Vet J 2015, 56, 249-256.
[60] Streit, E.; Schwab, C.; Sulyok, M.; Naehrer, K.; Krska, R.; Schatzmayr, G. Multi-mycotoxin screening reveals the occurrence of 139 different secondary metabolites in feed and feed ingredients. Toxins 2013, 5, 504–523.
[61] Crudo, F., Aichinger, G., Mihajlovic, J. et al. Gut microbiota and undigested food constituents modify toxin composition and suppress the genotoxicity of a naturally occurring mixture of Alternaria toxins in vitro. Arch Toxicol 94, 3541–3552 (2020).
[62] Georg Aichinger Giorgia Del Favero Benedikt Warth Doris Marko: Alternaria toxins—Still emerging? Compr Rev Food Sci Food Saf. 2021;20:4390–4406.