MYCOTOXINS AND DAIRY CATTLE
María Rodríguez-Blanco, Sonia Marín, Vicente Sanchis, Antonio J. Ramos Applied Mycology Unit, Department of Food Technology, ETSEA-University of Lleida, UTPV-XaRTA, Agrotecnio, Spain antonio.ramos@udl.cat
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Mycotoxins are low molecular weight secondary metabolites produced by certain genera of filamentous fungi under environmental conditions that are favourable for their synthesis (Bennett and Klich 2003).
Contamination of raw materials used for the formulation of feed with mycotoxins is a worldwide problem that causes significant economic losses. Furthermore, the intake of contaminated feed may lead to acute or chronic intoxication in the animals and may also contribute to its consumption
The main mycotoxins that can be
by humans, due to the possible
found contaminating feed and feed
transfer of these compounds to
materials are aflatoxins (AFs),
animal products such as milk,
deoxynivalenol (DON), fumonisins
meat or eggs (Fink-Gremmels
(FBs), ochratoxin A (OTA), T-2
2008a; Pinotti et al. 2016).
toxin and zearalenone (ZEN).
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Toxic effects of mycotoxins in dairy cows Ruminants are considered to be relatively resistant to mycotoxins, as ruminal microorganisms are able to degrade these compounds to less toxic, or even biologically inactive, compounds at normal exposure levels (Fink-Gremmels 2008b). However, it should be noted that the rumen’s degradation capacity can become saturated or affected by changes in the diet or as a result of metabolic diseases (Fink-Gremmels 2008b). Therefore, consumption of feed contaminated with these compounds can affect the health status of dairy cows. Some of the negative effects caused by mycotoxins in cattle are listed in Table 1.
Table 1. Main toxic effects in dairy cows derived from the consumption of feed contaminated with AFs, FBs, ZEN and DON.
MYCOTOXIN
TOXIC EFFECTS
AFLATOXINS
Impaired liver functions, reduced feed intake and milk production (Fink-Gremmels 2008b), decreased feed efficiency, immunosuppression, reduced reproductive performance (CAST 2003).
FUMONISINS
Reduced feed intake and milk production, mild hepatocellular lesions, immunocytotoxicity (Fink-Gremmels 2008b).
ZEARALENONE
Reproductive problems, infertility, reduced milk production and hyperestrogenism (Kallela and Ettala 1984).
DEOXYNIVALENOL
Reduced food intake and milk production (Jouany and Diaz 2005).
Liver alterations • AFs • FBs (mild hepatocellular lesions)
Immunological alterations • AFs (immunosuppression) • FBs (immunotoxicity)
Reproductive problems • AFs • ZEN (infertility and hyperestrogenism) Reduced feed intake • AFs • FBs • ZEN • DON
Reduced milk production • AFs • FBs • ZEN • DON
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Mycotoxins in feed for dairy cattle Dairy cows need fiber, proteins,
Among the materials included in
Silage is an important part of the
water, vitamins and minerals as
the formulation of dairy rations,
diet of dairy cows, as it usually
fundamental nutrients in daily
energy-rich components represent
represents a high percentage of the
diets. Furthermore, it is necessary
the main potential source of
final ration. These materials can be
to include a sufficient amount of
mycotoxins.
contaminated in the field, in post-
forage in their feed to maintain a functional ruminal microbiota. In addition, high amounts of energyrich components are needed, as they are essential to achieve high milk production and maintain the animal’s weight (Gonçalves et al.
2015). The great variety and variability of ingredients used in diets increases the risk of exposure to a wide range of different mycotoxins.
AFs, FBs, OTA, trichothecenes, and ergot alkaloids have been found contaminating some of these components such as cereals, soybeans, peanuts, or cottonseed. Fodder is the second source of mycotoxins, and preserved feeds such as silage, hay and straw are the third (Fink-Gremmels,
2008a).
harvest stages, as well as during storage.
Aspergillus, Fusarium, Alternaria and Penicillium are some of the filamentous fungi frequently found contaminating silage, so mycotoxins such as AFs, FBs, ZEN, trichothecenes, mycophenolic acid and roquefortine C can be detected in this raw material (Storm et al. 2008; Driehuis et al. 2008; Schmidt et al. 2015).
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Mycotoxin carry-over to milk In addition to the direct effects on animal health, one of the main problems associated with the presence of mycotoxins in animal feed is their possible carry-over to products derived from animals, such as milk.
AFM1 is detected in milk approximately 6 hours after consumption of the contaminated feed. Peaks of toxin can be detected 24 and 48 hours later if the intake of the feed continues and it disappears almost completely 72 hours after the withdrawal of the contaminated feed (Rodrigues 2014).
When dairy cows consume feed contaminated with aflatoxin B1 (AFB1), a part is broken down in the rumen to aflatoxicol, and another part reaches the liver where it is metabolized by liver enzymes through hydroxylation, hydration, demethylation and epoxidation.
Presence of AFM1 in milk after consumption of contaminated feed 6 hours
24 hours
48 hours
72 hours
The hydroxylation of AFB1 results in aflatoxin M1 (AFM1) and some of this compound is eventually excreted through the milk (Dhanasekaran et
First detection
Detection of peaks if intake continues
al. 2011).
Complete disappearence after removal of the contaminated feed
Liver metabolism
Hydroxylation
AFB1
Excretion of AFM1 in milk
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The transfer rate from AFB1 in feed to AFM1 in milk can vary from 1-2% in low yielding cows to 6% in high yielding cows (Britzi et al. 2013; RodrĂguezBlanco et al. 2019).
Carry-over rate from AFB1 in feed to AFM1 in milk
1-2 %
6%
Low yielding cows
High yielding cows
FACTORS THAT MAY AFFECT THE CARRY-OVER RATE
Lactation day (Veldman et al.
1992) Species Health status Ingestion and digestion rate Liver biotransformation capacity Integrity of the mammary alveolar cell membranes (FinkGremmels 2008a; Britzi et al. 2013)
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Monitoring AFM1 in milk has increased, especially since this toxin was classified as a human carcinogen (Group 1) by the International Agency for Research on Cancer (IARC) (IARC, 2012). To minimize the exposure of AFB1 in humans, different countries have established regulations for maximum allowed concentrations of AFM1 in milk.
The European Commission and the Codex Alimentarius Commission (EC 2006; Codex
Alimentarius 2001) established a limit of: 50 ng/kg AFM1 in raw milk, heat-treated milk and milk for dairy product fabrication. 25 ng/kg AFM1 in infant milk and follow-on milk.
AS FOR THE TRANSFER OF OTHER TOXINS TO MILK, FEWER STUDIES HAVE BEEN CARRIED OUT
The European Food Safety Authority (EFSA) reported that the carry-over of FBs to milk is limited and does not contribute
In other countries such as the
significantly to total human exposure (EFSA 2005).
United States, the maximum
Similarly, as regards to ZEN, EFSA reported
limit is:
that the carry-over rate of this toxin to
500 ng/kg toxin in raw milk. 25 ng/kg in baby milk products. The maximum limits of AFB1 established in feed for dairy animals (5 Âľg/kg) are aimed at reducing the presence of AFM1 in
milk is very low (EFSA 2004). On the other hand, several studies have shown that DON is transformed to de-epoxy-deoxynivalenol (DOM1) in the rumen (CotĂŠ et al. 1986; Seeling et al. 2006; Keese et al.
2008) and that the part that is not metabolized is excreted in the milk at a very low rate (Prelusky et al. 1984).
milk due to the transfer from feed to milk.
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Reduction of mycotoxin contamination Despite the limits for mycotoxins established in different countries to reduce the level of exposure to these compounds, their presence in food and feed is usually unavoidable. Mycotoxin contamination can occur
The implementation of good agricultural practices, good manufacturing practices, good hygiene practices and good storage practices is essential to reduce mycotoxin contamination.
at any point in the feed production chain, so strategies have been developed to prevent its occurrence as well as to eliminate them from contaminated products. However, they are very stable compounds and difficult to remove.
The problem of mycotoxins in feed
Physical treatments:
can be addressed from a preventive point of view, by avoiding post-
Some of the physical treatments that have been tested are
harvest mycotoxin production
thermal inactivation or the application of UV light (CAST 2003).
in crops, by controlling feed storage conditions, or once the
Chemical treatments:
contamination of the products
Among the chemical methods, treatments with acid/base
has occurred, by applying different
solutions or the use of additives have been successfully employed
technological strategies.
(CAST 2003). Although it should be noted that the use of chemical methods of mycotoxin detoxification is prohibited in the EU. Biological treatments: Moreover, biological methods based on the detoxifying action of microorganisms, such as yeasts, moulds, bacteria and algae, may represent in the future a more suitable alternative for the elimination of mycotoxins (EU 2018; EFSA 2013)
Another strategy, widely used in the field of animal nutrition, consists of adding adsorbent compounds to the feed, which bind to the toxins during its transit through the gastrointestinal tract, reducing its absorption, promoting its excretion or modifying its mechanism of action. Its use has already been authorized by the EU (EC, 2009).
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REFERENCES
Bennett JW, Klich M (2003) Mycotoxins. Clin Microbiol Rev 16:497–516. doi: 10.1128/CMR.16.3.497-516.2003 Britzi M, Friedman S, Miron J, Solomon R, Cuneah O, Shimshoni JA, Soback S, Ashkenazi R, Armer S, Shlosberg A (2013) Carry-over of aflatoxin B1 to aflatoxin M1 in high yielding Israeli cows in mid- and late-lactation. Toxins (Basel) 5:173–183. doi: 10.3390/toxins5010173 Codex Alimentarius Commissions (2001) Comments submitted on the draft maximum level for aflatoxin M1 in milk. Codex committee on food additives and contaminants 33 rd sessions, Hauge, The Netherlands: FAO, Rome Publishers Coté LM, Dahlem AM, Yoshizawa T, Swanson SP, Buck WB (1986) Excretion of deoxynivalenol and its metabolite in milk, urine, and faces of lactating dairy cows. J Dairy Sci 69:2416–2423. doi: 10.3168/jds.S0022-0302(86)80681-6 Council for Agricultural Science and Technology (CAST) (2003) Mycotoxins: risk in plant, animal and human systems. Council for Agricultural Science and Technology, Ames, Iowa, USA Dhanasekaran D, Shanmugapriya S, Thajuddin N, Annamalai P (2011) Aflatoxins and aflatoxicosis in human and animals In: Dr. Ramon G. Guevara-Gonzalez (Ed.), Aflatoxins-Biochemistry and Molecular Biology. Intech, Rijeka, Croatia, pp 221-254 Driehuis F, Spanjer MC, Scholten JM, Te Giffel MC (2008) Occurrence of mycotoxins in maize, grass and wheat silage for dairy cattle in the Netherlands. Food Addit Contam Part B 1:41–50. doi: 10.1080/19393210802236927 European Commission (EC) (2006) Commission Regulation No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs. Off J Eur Union L364:5–24 European Commission (EC) (2009) Commission Regulation No 386/2009 of 12 May 2009 amending Regulation (EC) No 1831/2003 of the European Parliament and of the Council as regards the establishment of a new functional group of feed additives. Off J Eur Union L118:66 European Commission (EC) (2018) Commission implementing regulation No 2018/1568 of 18 October 2018 concerning the authorisation of a preparation of fumonisin esterase produced by Komagataella phaffii (DSM 32159) as a feed additive for all pigs and all poultry species. Off J Eur Union L262:34–36 European Food Safety Authority (EFSA) (2004) Opinion of the Scientific Panel on contaminants in the food chain related to zearalenone as undesirable substance in animal feed. EFSA J 89:1–35. doi: 10.2903/j.efsa.2004.89 European Food Safety Authority (EFSA) (2005) Opinion of the Scientific Panel on contaminants in the food chain related to fumonisins as undesirable substances in animal feed. EFSA J 235:1–32. doi: 10.2903/j.efsa.2005.235 European Food Safety Authority (EFSA) (2013) Scientific Opinion on the safety and efficacy of micro-organism DSM 11798 when used as a technological feed additive for pigs. EFSA J 11(5):3203. doi: 10.2903/j.efsa.2013.3203 Fink-Gremmels J (2008a) Mycotoxins in cattle feeds and carry-over to dairy milk: a review. Food Addit Contam - Part A Chem Anal Control Expo Risk Assess 25:172–180. doi: 10.1080/02652030701823142 Fink-Gremmels J (2008b) The role of mycotoxins in the health and performance of dairy cows. Vet J 176:84–92. doi: 10.1016/j.tvjl.2007.12.034 Gonçalves BL, Corassin CH, Oliveira CAF (2015) Mycotoxicoses in dairy cattle: a review. Asian J Anim Vet Adv 10:752–760. doi: 10.3923/ajava.2015.752.760 International Agency for Research on Cancer (IARC) (2012) Monograph on the evaluation of carcinogenic risk to humans: Chemical agents and related occupations. A review of humans carcinogens, vol 100F. IARC, Lyon, France Jouany JP, Diaz DE (2005) Effects of mycotoxins in ruminants. In: Diaz, D.E. (Ed.), The Mycotoxin Blue Book. Nottingham University Press, Nottingham, United Kingdom, pp 295–321 Kallela K, Ettala E (1984) The oestrogenic Fusarium toxin (zearalenone) in hay as a cause of early abortions in the cow. Nord Vet Med 36:305–309 Keese C, Meyer U, Valenta H, Schollenberger M, Starke A, Weber IA, Rehage J, Breves G, Dänicke S (2008) No carry over of unmetabolised deoxynivalenol in milk of dairy cows fed high concentrate proportions. Mol Nutr Food Res 52:1514–1529. doi: 10.1002/mnfr.200800077 Pinotti L, Ottoboni M, Giromini C, Dell’Orto V, Cheli F (2016) Mycotoxin contamination in the EU feed supply chain: a focus on cereal byproducts. Toxins (Basel) 8:45. doi: 10.3390/toxins8020045 Prelusky DB, Veira DM, Trenholm HL, Foster BC (1987) Metabolic fate and elimination in milk, urine and bile of deoxynivalenol following administration of lactating sheep. J Environ Sci Health B 22:125–148. doi: 10.1080/10934528709375339 Rodrigues I (2014) A review on the effects of mycotoxins in dairy ruminants. Anim Prod Sci 54:1155–1165. doi: 10.1071/AN13492 Rodríguez-Blanco M, Ramos AJ, Prim M, Sanchis V, Marin S (2019) Usefulness of the analytical control of aflatoxins in feedstuffs for dairy cows for the prevention of aflatoxin M1 in milk. Mycotoxin Res. doi: 10.1007/s12550-019-00362-y Schmidt P, Novinski CO, Junges D, Almeida R, de Souza CM (2015) Concentration of mycotoxins and chemical composition of corn silage: a farm survey using infrared thermography. J Dairy Sci 98:6609–6619. doi: https://doi.org/10.3168/jds.2014-8617 Seeling K, Dänicke S, Valenta H, Van Egmond HP, Schothorst RC, Jekel AA, Lebzien P Schollenberger M, Razzazi-Fazeli E, Flachowsky G(2006) Effects of Fusarium toxin-contaminated wheat and feed intake level on the biotransformation and carry-over of deoxynivalenol in dairy cows. Food Addit Contam 23:1008–1020. doi: 10.1080/02652030600723245 Storm IMLD, Sørensen JL, Rasmussen RR, Nielsen KF, Thrane U (2008) Mycotoxins in silage. Stewart Postharvest Rev 4:1–12. doi: 10.2212/spr.2008.6.4 Veldman A, Meijs JAC, Borggreve GJ, Heeres-Van Der Tol JJ (1992) Carry-over of aflatoxin from cows’ food to milk. Anim Prod 55:163–168. doi: 10.1017/S0003356100037417
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