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 <!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.0 20120330//EN" "http://jats.nlm.nih.gov/publishing/1.0/JATS-journalpublishing1.dtd"> <article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="review-article" dtd-version="1.0" xml:lang="en">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JVHC</journal-id>
      <journal-title-group>
        <journal-title>Journal of Veterinary Healthcare</journal-title>
      </journal-title-group>
      <issn pub-type="epub">2575-1212</issn>
      <publisher>
        <publisher-name>Open Access Pub</publisher-name>
        <publisher-loc>United States</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="doi">10.14302/issn.2575-1212.jvhc-22-4105</article-id>
      <article-id pub-id-type="publisher-id">JVHC-22-4105</article-id>
      <article-categories>
        <subj-group>
          <subject>review-article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Review on Public Health Effects of Aflatoxins in Milk and Milk-Based Foodstuffs of Dairy Cow</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Sadik</surname>
            <given-names>Zakir Abadura</given-names>
          </name>
          <xref ref-type="aff" rid="idm1841514900">1</xref>
          <xref ref-type="aff" rid="idm1841513964">*</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Sufian</surname>
            <given-names>Abdo Jilo</given-names>
          </name>
          <xref ref-type="aff" rid="idm1841514900">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mukarim</surname>
            <given-names>Abdurahman</given-names>
          </name>
          <xref ref-type="aff" rid="idm1841514900">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Suresh</surname>
            <given-names>Kumar PNair</given-names>
          </name>
          <xref ref-type="aff" rid="idm1841513100">2</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1841514900">
        <label>1</label>
        <addr-line>School of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Jimma University, Jimma, Ethiopia.</addr-line>
      </aff>
      <aff id="idm1841513100">
        <label>2</label>
        <addr-line>Department of Biomedical Sciences, Institute of Health Jimma University, Jimma, Ethiopia. </addr-line>
      </aff>
      <aff id="idm1841513964">
        <label>*</label>
        <addr-line>Corresponding author</addr-line>
      </aff>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Akbar</surname>
            <given-names>Nikkha</given-names>
          </name>
          <xref ref-type="aff" rid="idm1841355748">1</xref>
        </contrib>
      </contrib-group>
      <aff id="idm1841355748">
        <label>1</label>
        <addr-line>University of Zanjan, Iran </addr-line>
      </aff>
            <author-notes>
        <corresp>
          Sadik Zakir Abadura
          <addr-line>School of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Jimma University, P.O. 309, Jimma, Ethiopia</addr-line>
          <email>sadikzakir82@gmail.com</email>
        </corresp>
        <fn fn-type="conflict" id="idm1841756684">
          <p>The authors have declared that no competing interests exist.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub" iso-8601-date="2022-03-17">
        <day>17</day>
        <month>03</month>
        <year>2022</year>
      </pub-date>
      <volume>2</volume>
      <issue>4</issue>
      <fpage>42</fpage>
      <lpage>53</lpage>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>02</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <year>Mar 15, </year>
        </date>
        <date date-type="accepted">
          <year>2022</year>
        </date>
        <date date-type="online">
          <day>17</day>
          <month>03</month>
          <year>2022</year>
        </date>
      </history>
      <permissions>
        <copyright-statement>© </copyright-statement>
        <copyright-year>2022</copyright-year>
        <copyright-holder>Sadik Zakir Abadura, et al.</copyright-holder>
        <license xlink:href="http://creativecommons.org/licenses/by/4.0/" xlink:type="simple">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
        </license>
      </permissions>
      <self-uri xlink:href="http://openaccesspub.org/jvhc/article/1797">This article is available from http://openaccesspub.org/jvhc/article/1797</self-uri>
      <abstract>
        <p>Aflatoxins are toxigenic metabolites that are definitely occurring by lethal strains of Aspergillus parasiticus and Aspergillus flavus that commonly dwell and colonize in feed components and various nutritive foodstuffs particularly milk and milk based products. This Review has three main objectives; those are causes of aflatoxin, effects and methods of control in milk and milk products. Drinking of cow milk polluted with aflatoxin may overwhelm immunity and subsidize to stunting in young children, as the young children are not immune-competent during early stage. It has been internationally assessed that aflatoxin is                  possibly accountable for 30% of the annual cases of liver cancer. Generally, control approaches of                     aflatoxin can be applied during pre-harvest, cautious management in the time of harvest and postharvest decontamination. Moreover, choosing breed for               aflatoxin impervious crop diversities, prevention of aflatoxin production through biological decontamination by microorganisms and their metabolites, rejection of aflatoxin by physical means in addition to inactivation by chemicals are the typical approaches that have been described in different studies. For the reason that cow milk is the most important and               principal diet of children, but the risk of exposed to the cancer are more in infants. In addition, according to various investigations it also well thought that young animals are also found to be more vulnerable to aflatoxin than adults. Thus; the contamination of cow milk and milk products by AFM1 should                      understood as undesirable for young human and                   animals.</p>
      </abstract>
      <kwd-group>
        <kwd>Aflatoxin</kwd>
        <kwd>Dairy cattle products</kwd>
        <kwd>Human health</kwd>
        <kwd>Milk and Micotoxin</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="2"/>
        <page-count count="12"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec id="idm1841360356" sec-type="intro">
      <title>Introduction</title>
      <p>Dairy cattle provides valuable source of      nutritious food for human particularly as a means of milk and milk products and they play an important role in supplying      human nutrition throughout the world <xref ref-type="bibr" rid="ridm1841528124">1</xref> Moreover, they are providing important sources of nutritious diets such as protein, calcium, phosphorus, iodine, riboflavin and vitamins A and B<sub>12</sub> constituents <xref ref-type="bibr" rid="ridm1841595228">2</xref>. However, the quality of dairy products is critical to the dairy industry and the consumers because of the milk production chain                     particularly in the most developing regions still faces many challenges related to the dairy products quality and safety to meet legislations and the needs of consumers <xref ref-type="bibr" rid="ridm1841538500">3</xref>.</p>
      <p>Besides, food safety and quality control packages for all food substances enclosing animal products are        raising issue in several countries predominantly from public health perspective <xref ref-type="bibr" rid="ridm1841595948">4</xref>. This incorporates                            controlling adulterants, obliterating intensities of                       contaminants, naturally occurring toxins and other                  constituent that may be able to cause food illness in                human. In the direction of sustaining public health and providing safe food for the consumer, milk and milk                  products need proper and aseptic environments.                       Producing milk products that are free of contaminants are obligatory for public health safety and satisfactory shelf of the products <xref ref-type="bibr" rid="ridm1841538500">3</xref>. Currently, any foodstuff specially milk products that having proper hygiene and reliable quality standards are in the high level of preferences for the                  consumers. Commonly, health hazards to the consumer relating to dairy products are mostly clustered into                    chemical, physical and microbiological hazards <xref ref-type="bibr" rid="ridm1841383564">5</xref>. </p>
      <p>From chemical hazards, Aflatoxin is one of the main chronic naturally occurred toxins chemical                  compounds (Mycotoxins) which are grouped under the potential chemical hazards for both animals and                        human <xref ref-type="bibr" rid="ridm1841378452">6</xref>. According to WHO, <xref ref-type="bibr" rid="ridm1841363772">7</xref> stated typically toxic metabolites of fungi pollute food and feedstuff and cause of food-borne illnesses which categorized under chemical hazards. In dairy products among the chemical hazards, Aflatoxin is one of most important frequently exhibited in milk and milk products <xref ref-type="bibr" rid="ridm1841528124">1</xref><xref ref-type="bibr" rid="ridm1841367444">8</xref>. They are belongs to the class of mycotoxins and fungal metabolites that are normally formed by Aspergillus species, specifically A. bombycis, A. parasiticus, A. fumigitus A. flavus, A. ochraceoroseus, A. pseudotamari and A. nomius <xref ref-type="bibr" rid="ridm1841357580">9</xref>. Among all species A.                   parasiticus and A. flavus are the most significant moulds in economy of milk and milk products producers because of that it creates entirely aflatoxin G1, G2, B1 and B2 <xref ref-type="bibr" rid="ridm1841354412">10</xref>.</p>
      <p>Morever, Aflatoxins are also can be formed in food and feed resources at low level by Aspergillus <italic>nomius</italic>and <italic>A. tamari </italic>in addition to further developing fungal                      species <xref ref-type="bibr" rid="ridm1841341716">11</xref>. The common Aflatoxins producing fungal spp. <italic>A. </italic><italic>parasiticus</italic><italic> and A. flavus </italic>ispredominantly polluted cereals crop such as peanuts and maize including their                               by-products and animal feeds <xref ref-type="bibr" rid="ridm1841339196">12</xref>. In general, storage problem is the major route for the contamination any food and feed resources by <italic>Aspergillus, </italic>particularly in the               period of reductions of soil moisture content and drought stress session <xref ref-type="bibr" rid="ridm1841333508">13</xref></p>
      <p>Generally, the framework of ensuring food safety and security has been a most important emphasis of                  national and international action over the world in the previous centuries <xref ref-type="bibr" rid="ridm1841354412">10</xref><xref ref-type="bibr" rid="ridm1841347260">14</xref>. This being the case, the major objective of this review paper is to review the effectsof aflatoxin in milk and milk products of dairy cattle with the following specific objectives; to discuss the causes of                 aflatoxin in milk and milk products, to highlight effects of aflatoxin in milk and milk products on animal and human health and finally to disclose means of controlling the                effect of aflatoxin in milk and milk products. </p>
    </sec>
    <sec id="idm1841338156">
      <title>Literature Review </title>
      <sec id="idm1841337508">
        <title>The Main Aflatoxin in Milk and Milk-Based Foodstuffs of Dairy Cattle</title>
        <p>Aflatoxins are toxigenic metabolites that are           certainly happening by lethal strains of Aspergillus                   parasiticus and A. flavus that frequently dwell and                    colonize feed components and various nutritive foodstuffs in addition to principal crops such as corn, groundnuts, rice and maize <xref ref-type="bibr" rid="ridm1841308492">15</xref><xref ref-type="bibr" rid="ridm1841306548">16</xref>. The four major naturally produced aflatoxins in milk foodstuffs of dairy animals are known as G1, G2, B1 and B2 <xref ref-type="bibr" rid="ridm1841354412">10</xref>. Where letter “B” talk about the blue fluorescent color whereas “G” substituted for green fluorescent that are formed on thin layer chromatography plates in Ultraviolet light, though the subscript numbers 1 &amp; 2 specify main and small mixtures <xref ref-type="bibr" rid="ridm1841354412">10</xref><xref ref-type="bibr" rid="ridm1841306548">16</xref>. The                  occurrence of aflatoxin B1 (AFB1) in milk is usually after ingested, then secrete enzyme and hydroxylated in order to form aflatoxin M1 (AFM1) that is secreted and                      concealed in the milk and its product <xref ref-type="bibr" rid="ridm1841302012">17</xref><xref ref-type="bibr" rid="ridm1841312812">18</xref>. According to International Agency for Research on Cancer WHO, <xref ref-type="bibr" rid="ridm1841265028">19</xref> aflatoxin B1 and aflatoxin M1 are categorized in type I cancer-causing agent. However, among both Aflatoxins (AFM1 and AFB1), aflatoxin B1 is the most serious one, since it is extremely oncogenic and producing liver cancer in humans in addition to its establishing power in most foods and feeds <xref ref-type="bibr" rid="ridm1841263012">20</xref>. Probably this indicates that different dairy foodstuffs may enclose contaminants that pose                   hazard to public health, predominantly for youngsters who devour the dairy products <xref ref-type="bibr" rid="ridm1841306548">16</xref> Moreover,                             immunosuppression and growth impairment can be caused in both animals and humans through frequent              acquaintance of aflatoxin <xref ref-type="bibr" rid="ridm1841312812">18</xref><xref ref-type="bibr" rid="ridm1841258404">21</xref>.</p>
      </sec>
      <sec id="idm1841337220">
        <title>Causes of Aflatoxin in Milk and Milk-Based Foodstuffs</title>
        <p>Aflatoxins are mainly caused by mycotoxins that introduced in milk and milk-based foodstuffs. The             aflatoxin B1 is naturally occurring in feed by means of    various metabolites including AFM1 that are hydroxylated copies of AFB1, through bio-transformation in mammary glands excreted in milk, which is causative agent for liver cancer <xref ref-type="bibr" rid="ridm1841378452">6</xref>.  The principal sources of alfatoxin for cattle and human are frequent exposure and consumption of groundnuts and maize due to greater susceptibility and high degree of contamination of both feedstuffs for                    aflatoxin throughout the world <xref ref-type="bibr" rid="ridm1841255452">22</xref>. Also, Wu and Khlangwiset, <xref ref-type="bibr" rid="ridm1841354412">10</xref> suggested that peanuts and Maize are the chief sources of dairy animal and human acquaintance to aflatoxin. For the reason that, existences of aflatoxin contaminated animal feeds can biologically be produces aflatoxin in milk. So this phenomenon is the most                    worrying delinquent through time in all over the world, as the most important cow milk is principally precious while feeding are contaminated everywhere in the world <xref ref-type="bibr" rid="ridm1841266468">23</xref>. As Nyaga, <xref ref-type="bibr" rid="ridm1841250436">24</xref> reported, milk is highly contaminated with aflatoxins in and around Addis Ababa milk shed.                   Moreover, totally dairy cow feeds exceeded 5 mg/kg of AFB1 can be produce the over conventional standard               perimeter of 0.05 mg/L aflatoxins in the milk. The result as well indicates that the major sources of aflatoxin in and around peri-urban areas of Addis Ababa dairy value chain is pollution of noug cake that is extensively used as dairy cattle feed AFB1.</p>
      </sec>
      <sec id="idm1841337436">
        <title>Aflatoxins in Food Products From Contaminated Animal Feed</title>
        <p>According to Elzupir &amp; Elhussein, <xref ref-type="bibr" rid="ridm1841245468">25</xref> investigation of different feeds shown that brewer's waterless yeast, wheat bran and maize grain had comparatively low levels of aflatoxin contamination, however noug cakes maize and groundnuts are extremely contaminated with aflatoxin B1. Besides, dairy cows that have consumed               aflatoxin B<sub>1 </sub>contaminated feed are secreted aflatoxin M<sub>1 </sub>in the milk <xref ref-type="bibr" rid="ridm1841244460">26</xref>. There was adequate and necessary                    association among AFB1 and AFM1, as presence of                  enormous amount of AFB1 in feed results in high                        contamination of milk by AFM1. After ingesting of AFB1 contaminated feeds, AFM1 is excreted within twelve hours of consumption <xref ref-type="bibr" rid="ridm1841238844">27</xref>. Additionally as Dawit et al. <xref ref-type="bibr" rid="ridm1841223964">28</xref> founds, there was a reasonable link between level of               AFB1contamination in feed ingested by animal and                   aflatoxin M<sub>1</sub> in milk. As authors found transference of        aflatoxin from animal feeds to milk and milk products are within an average of approximately 1%.  </p>
      </sec>
      <sec id="idm1841337796">
        <title>Aflatoxins in Milk Based Foodstuffs from Contaminated Dairy Cow </title>
        <p>Mycotoxin M1 and M2 is derivative of milk                 aflatoxins, that are heat impervious and hydroxylated      metabolites created by lactating cow that were consuming feeds contaminated by aflatoxin <xref ref-type="bibr" rid="ridm1841244460">26</xref><xref ref-type="bibr" rid="ridm1841220220">29</xref>. As various               authors indicated, the consumed AFB1 is metabolized into AFM1 while AFB2 is metabolized into AFM2 in dairy                cattle, with assessed transformation percentage of 1-3 among AFB1 and AFM1 <xref ref-type="bibr" rid="ridm1841217196">30</xref>.</p>
        <p>Moreover, the most important metabolite that excreted by various animals in milk is aflatoxin M1 <xref ref-type="bibr" rid="ridm1841244460">26</xref>. AFM1 is formed through bioconversion in mammary glands of dairy cattle by oxidative reactions catalyzed in liver CYP enzyme mechanism, which is principal to                    hydroxylation in the terminal furan ring of the parental molecule AFM1 represents the 95% of AFs detected in milk. Other metabolites, such as Q1 (AFQ1), aflatoxicol (AFL), M2 (AFM2), and M4 (AFM4) are distinguished in small quantities and then deliberated of less importance for human wellbeing.  </p>
        <p>
          <italic>Occurrences and Effects of Aflatoxin in Milk and its                    By-Products </italic>
        </p>
        <p>Aflatoxin has critically various occurrences                  degree, effects, concentration and character depends on prevalent substrate, nature of mould and weather                        conditions <xref ref-type="bibr" rid="ridm1841354412">10</xref><xref ref-type="bibr" rid="ridm1841244460">26</xref>. Aspergillus parasiticus formulate whole aflatoxin type (AFG1, AFG2, AFB1 and AFB2) on corn whereas A. flavus produces primarily aflatoxin B1and B2 on corn. Among the feed used for milk production there are three main feedstuffs; peanuts, cottonseed and corn have great character to be attacked by Aspergillus species throughout growing, yield and loading or                        storing <xref ref-type="bibr" rid="ridm1841354412">10</xref>. Generally, colonization arises and assisted through storage especially in the case of small grains and soybean. The formation of Aflatoxin can be promoted by high moisture content, poor storage surroundings, kernel damage, temperature, nonexistence of ventilation <xref ref-type="bibr" rid="ridm1841214676">31</xref>. Moreover as the production of milk and milk based                  foodstuffs needs various processes, the impacts of                     handling and storage process has great potential on the dissemination and stability of Alfatoxin M1. Due to that relatively the occurrence of Alfatoxin in milk is higher when comparing with occurrence of Alfatoxin in the other milk products such as cheese, yogurt, butter, butter milk, cream, and skim milk because of some mechanical,                   chemical and biological processes are performed                       depending on the types of the products <xref ref-type="bibr" rid="ridm1841209924">32</xref>.</p>
        <p>As many authors suggested incidence of aflatoxin in cheese may due to several potential reasons. The                   primary reason for occurrence AFM1 in the raw milk is the import of leftover of AFB1 from polluted feeds of animal to milk. The second one is production of AFB1, AFB2, AFG1, and AFG2 by molds that propagate on cheese although the minute amount of CHO does not create suitable                    environment and substrate. The 3<sup>rd</sup> one is the                           consumptions cheese made from milk powder                           contaminated with aflatoxin M<sub>1</sub>. However, several authors reported that increases in AFM1 concentration in cheese as a function of cheese variety machineries to be recycled to process it, and the quantity of water removed in the course of manufacture <xref ref-type="bibr" rid="ridm1841302012">17</xref>. As Barbiroli et al. <xref ref-type="bibr" rid="ridm1841207260">33</xref> stated, particular influences can be occurred by high                          temperature, renneting, pH, and duration of pressing can exaggerated the volume of water removed and increase the amount of AFM1 in the cheese.</p>
      </sec>
      <sec id="idm1841335996">
        <title>Effects of Aflatoxin </title>
        <p>Aflatoxicosis is illness initiated by the feeding of the metabolites of mold (aflatoxins) that formed by certain species of Aspergillus parasitisus and Aspergillus flavus. Among all aflatoxin, AFB1 is a strong cancer mediator through raising the actual protein necessity of dairy cow.</p>
      </sec>
      <sec id="idm1841341468">
        <title>Aflatoxin Effects on Animal Health </title>
        <p>In dairy animals, the harmfulness aflatoxins have an acute and chronic syndrome; also it shows relatively disparate properties on different individual animals based on vulnerability to aflatoxins. Effects aflatoxins on animal health are depend on age, species, nutrition, and sex as well as immunity status. In animals, acute toxicities caused by feeding of excessive amount of aflatoxins, whereas the chronic toxicities are initiated by ingesting of less                   quantity, this type of aflatoxicosis are the reason for liver impairment by cancer, GIT injury, reduction in desire for food, rate of reproduction, growth, production and body weight <xref ref-type="bibr" rid="ridm1841312812">18</xref>.  As Denli &amp; Pérez, <xref ref-type="bibr" rid="ridm1841202652">34</xref> reported clinical signs of acute aflatoxicosis involves anorexia, depression,                  malady, loss of weight, bleeding from GIT, liver damage and pulmonary edema. As well decreased feed intake, milk production and growth rate are the principal symptom of chronic aflatoxin exterminating. Furthermore, lactating cow do not exposed to alfatoxin polluted feeds since it deteriorate the feature of milk and milk based products and even can cause death of lactating dairy cow may               follow within 60 minutes/days mainly in acute aflatoxin toxicity <xref ref-type="bibr" rid="ridm1841306548">16</xref><xref ref-type="bibr" rid="ridm1841312812">18</xref><xref ref-type="bibr" rid="ridm1841202652">34</xref>.</p>
      </sec>
      <sec id="idm1841342692">
        <title>Aflatoxin Effect on Human Health</title>
        <p>Presence Mycotoxins particularly AFM1in milk and dairy products can create severe health problems on human. As International Agency for Research on Cancer classification, AFB1 and AFM1 are classified as class 1 and 2B are possible carouses for human carcinogens,                    correspondingly <xref ref-type="bibr" rid="ridm1841265028">19</xref>. Consequently, as dairy products are extensively consumed by children and infants as well as adults, the occurrence of aflatoxins in in milk and milk products particularly their substantial entrances in milk based foodstuffs has a severe suffering on human                    wellbeing. </p>
        <p>Generally the major effects of aflatoxin on human health are includes affects the nervous system (abnormal behavior and depression), reduced sperm count and              increase infertility, low birth weight and reduces the rate of growth in infants and children. Consumption of con          taminated milk with AFM1 particularly by the youngsters devastate their disease resistance mechanism and                   subsidize to poor growth because of in most countries youngsters are not consumed cow's milk and so there    immunity is less competent at their infant stage <xref ref-type="bibr" rid="ridm1841255452">22</xref>. Moreover, according to WHO, <xref ref-type="bibr" rid="ridm1841363772">7</xref> reported, possibly                    aflatoxin is accountable and play role in up to 30% of the cases of liver cancer internationally in every year.                    Subsequently as human affected by aflatoxins, liver cancer is followed in addition to manifesting of jaundice eye               sclera. </p>
        <p><xref ref-type="fig" rid="idm1841078420">Figure 1</xref>, <xref ref-type="fig" rid="idm1841078636">Figure 2</xref></p>
        <fig id="idm1841078420">
          <label>Figure 1.</label>
          <caption>
            <title> Contaminated maize with aflatoxin</title>
          </caption>
          <graphic xlink:href="images/image1.jpg" mime-subtype="jpg"/>
        </fig>
        <fig id="idm1841078636">
          <label>Figure 2.</label>
          <caption>
            <title> Jaundiced eye sclera of human (source: Gong et al. 22</title>
          </caption>
          <graphic xlink:href="images/image2.jpg" mime-subtype="jpg"/>
        </fig>
      </sec>
      <sec id="idm1841340604">
        <title>Acceptable Levels of Aflatoxin in Milk and Milk Products </title>
        <p>Currently, the acceptablelevels of aflatoxins in milk and milk based products are different based on various factors. Reasons like economic status of the                  countries and meteorological situations are the most            influencing factors in permitting levels of aflatoxin <xref ref-type="bibr" rid="ridm1841209924">32</xref>. Several countries are certified and set the acceptable               levels of aflatoxins in milk and milk products to reduce and control harmful properties of the aflatoxin. For              instance in US, Food and Drug Administration (FDA) has allowed overall quantity of 0 .5 g/kg or 50 ng/l in milk and 20 ng/g in dairy cattle feed <xref ref-type="bibr" rid="ridm1841198620">35</xref>. In Europe, the acceptable amount is 0.005 mg/kg AFM1 in milk foodstuffs of dairy cattle provided for young children <xref ref-type="bibr" rid="ridm1841228068">36</xref>. Moreover, the   determined levels of AFM1 in milk and milk based    products in different regions of the world are                           demonstrated in (<xref ref-type="table" rid="idm1841045860">table 1</xref>, <xref ref-type="table" rid="idm1841021124">table 2</xref>) </p>
        <table-wrap id="idm1841045860">
          <label>Table 1.</label>
          <caption>
            <title> Association among high level AFM1 in milk and level of AFB in feed composed from the dairy farm of some towns of Ethiopia.</title>
          </caption>
          <table rules="all" frame="box">
            <tbody>
              <tr>
                <th>
                  <bold>Municipality</bold>
                </th>
                <td>
                  <bold>Feed samples used for milk production</bold>
                </td>
                <td>
                  <bold>AFB (mg/kg)</bold>
                </td>
                <td>
                  <bold>AFM (mg/L)</bold>
                </td>
              </tr>
              <tr>
                <td>Addis Ababa</td>
                <td>Mixture of noug seed cake, wheat bran and sweet pea hull</td>
                <td>72</td>
                <td>2.92</td>
              </tr>
              <tr>
                <td>Debre Zeit</td>
                <td>Mixture of noug seed cake and wheat bran</td>
                <td>405</td>
                <td>4.98</td>
              </tr>
              <tr>
                <td/>
                <td>Mixture of sweet pea grain and maize</td>
                <td>30</td>
                <td> </td>
              </tr>
              <tr>
                <td/>
                <td>Mixture of noug seed cake, wheat bran and maize grain</td>
                <td>274</td>
                <td>2.16</td>
              </tr>
              <tr>
                <td>Sendafa</td>
                <td>Mixture of sweet pea hull and wheat bran</td>
                <td>14</td>
                <td>2.93</td>
              </tr>
              <tr>
                <td>Sululta</td>
                <td>Mixture of noug seed cake, heat bran and maize grain</td>
                <td>300</td>
                <td>4.79</td>
              </tr>
              <tr>
                <td/>
                <td>Mixture of calcium, noug seed cake, wheat bran and maize grain</td>
                <td>17</td>
                <td>1.23</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="idm1841275404">
              <label/>
              <p>Sources: Dawit et al. <xref ref-type="bibr" rid="ridm1841223964">28</xref></p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p> </p>
        <table-wrap id="idm1841021124">
          <label>Table 2.</label>
          <caption>
            <title> Maximum standard levels of aflatoxin M1 in milk and milk based foodstuffs in different countries  </title>
          </caption>
          <table rules="all" frame="box">
            <tbody>
              <tr>
                <th>
                  <bold>Country</bold>
                </th>
                <td>
                  <bold>Acceptable Level (ng/l)</bold>
                </td>
                <td>
                  <bold>Variety of products</bold>
                </td>
              </tr>
              <tr>
                <td>Australia</td>
                <td>20</td>
                <td>Milk</td>
              </tr>
              <tr>
                <td>European Union</td>
                <td>50</td>
                <td>Milk</td>
              </tr>
              <tr>
                <td>Germany</td>
                <td>50</td>
                <td>Milk</td>
              </tr>
              <tr>
                <td>Sweden</td>
                <td>50</td>
                <td>Liquid milk products</td>
              </tr>
              <tr>
                <td>USA</td>
                <td>50</td>
                <td>Milk</td>
              </tr>
              <tr>
                <td>France  </td>
                <td>30</td>
                <td>Youngsters' milk&lt; 3 years</td>
              </tr>
              <tr>
                <td/>
                <td>50</td>
                <td>Adult's milk</td>
              </tr>
              <tr>
                <td>Turkey</td>
                <td>50</td>
                <td>Milk and milk products</td>
              </tr>
              <tr>
                <td/>
                <td>250</td>
                <td>Cheese</td>
              </tr>
              <tr>
                <td>Switzerland</td>
                <td>50</td>
                <td>Milk and milk products</td>
              </tr>
              <tr>
                <td/>
                <td>250</td>
                <td>Cheese</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="idm1841258692">
              <label/>
              <p>Source: <xref ref-type="bibr" rid="ridm1841306548">16</xref>. </p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p> </p>
      </sec>
      <sec id="idm1841258980">
        <title>Economic Impacts of Aflatoxin</title>
        <p>Food safety problems generate massive problem on the country’s budget such as expenditures to outbreak surveys and food recalls, national supervisions from                    enlarged therapeutic payments, absenteeism from work and school due to food born disease, loss of consumer          confidence in the foodstuffs, improved burdens on                   previously imposed and unwell subsidized healthcare structures <xref ref-type="bibr" rid="ridm1841165212">37</xref>. </p>
        <p>Moreover along with economic loss and financial expenditures to public health, farmer and livestock                   husbandry manufacturing, fatalities attributable to                 aflatoxin pollution of foods involves expenditures to                 treatment of food intoxication and medication cost. As per Boutrif <xref ref-type="bibr" rid="ridm1841165212">37</xref> reports, yearly, around 20% of the foods              manufactured in the world are infected by mycotoxins; of which aflatoxins have a superior portion compared to   others. Occurrence of dairy cattle infection and cancer, decrease in milk production and productivity as well as declining of immune system in dairy cows are particular illustrations of charges to milk based foodstuffs as well as dairy cattle production. Bearing in mind such like                  enormous economic damages and public health safety, inhibition and frustration of the aflatoxin in food products of animal origin and dairy cow feed is critical <xref ref-type="bibr" rid="ridm1841163052">38</xref>.</p>
      </sec>
      <sec id="idm1841258908">
        <title>Control and Prevention Methods of Aflatoxin Effects </title>
        <p>Aflatoxicosis or contamination of milk based products by aflatoxin can only be prevented by feeding aflatoxin free rations to dairy animal which can be                   enhanced through preventing fungal growth in feed and good agricultural practice in dairy production farm and processing scheme. So preventing contamination of                 aflatoxin needs continues plus systematic scrutiny and analysis platform <xref ref-type="bibr" rid="ridm1841158156">39</xref>.</p>
        <p>Generally, to reduce the threat of animal and                human exposure to aflatoxins requires multidisciplinary and universal methodology due to the complex nature of aflatoxin contamination ways of milk and milk products. For that reason, it requires increasing of public perception on aflatoxins and applying scrutiny provision beside the whole dairy products. Commonly, elimination of aflatoxin requires both direct and indirect reduction approaches of aflatoxin in milk and dairy cow feed <xref ref-type="bibr" rid="ridm1841228068">36</xref>.</p>
      </sec>
      <sec id="idm1841258188">
        <title>Indirect Methods of Aflatoxin Reduction in Livestock Feed </title>
        <p>Using of aflatoxins polluted feed for dairy cattle are typically leads to the production of contaminated milk with aflatoxins. Hence, indirect controlling of dairy cattle feed hygiene is potential in decreasing aflatoxin                         contamination <xref ref-type="bibr" rid="ridm1841158156">39</xref><xref ref-type="bibr" rid="ridm1841154484">40</xref>. Strictly decreasing means of                   aflatoxin contamination in the course of crop production, traditional and industrial storage of livestock feed as well as livestock feed factories are obligatory to attain the               objective, value and wellbeing concerns <xref ref-type="bibr" rid="ridm1841154484">40</xref>.                                Furthermore, effective ways of decreasing the                            contamination can be gained through proper storing of crops which embraces keeping crops on dry and clean sides, keeping crops from wetness, high temperature, pests and practice of fungicidal drugs <xref ref-type="bibr" rid="ridm1841354412">10</xref>. Additional    central way of regulatory and decreasing aflatoxin                 pollution is strict observation of hygienic conditions in conventional and modern levels factories and livestock feed storerooms <xref ref-type="bibr" rid="ridm1841154484">40</xref>. Monitoring growth of fungus and formation of aflatoxin in old-style farms and storages are extremely imperative <xref ref-type="bibr" rid="ridm1841163052">38</xref><xref ref-type="bibr" rid="ridm1841158156">39</xref>. Level aflatoxin in milk can also be influenced by seasonal situation, for instance               occurrences of aflatoxin is greater in winter and autumn compared to summer and spring due to inaccessibility of fresh feeds and farmers use warehoused forages in this unfavorable time of year <xref ref-type="bibr" rid="ridm1841214676">31</xref><xref ref-type="bibr" rid="ridm1841228068">36</xref>. So, it is indispensable to advance improper storeroom and moisture conditions of livestock feed storage.</p>
        <p>To achieve effective prevention and control of aflatoxins, persistent and vigilant observation of diverse techniques of production and storage condition,                     controlling moisture content and adjustment of heat through ventilation methods, use of uncontaminated               materials aided for preparing livestock feed are                       compulsory <xref ref-type="bibr" rid="ridm1841148508">41</xref>. In order to avoid mold development and inhibit growth of the molds in the early occurrences of contamination, microbes, chemicals, ionizing rays and     absorbent material can be used <xref ref-type="bibr" rid="ridm1841143612">42</xref>. According to                  Dakovic´ et al. <xref ref-type="bibr" rid="ridm1841142028">43</xref> indication, outstanding approach of decreasing aflatoxin contamination in infected animal feed is using of aflatoxin absorbents. In the course of using  absorbents, aflatoxins existing in animal feed prevents from toxic reactions in livestock body as well as from             absorption into digestive tract by binding to absorbents Huwig et al. <xref ref-type="bibr" rid="ridm1841137780">44</xref>.</p>
        <p>In addition, prevention of aflatoxins by chemical compounds involves series organic acids like sorbic,              propionic, acetic acids and benzoic, organic acid slats such as potassium sorbate, calcium propionate, liquid or solid copper sulfate as well as diverse microbes such as                     lactobacillus brevis and lactobacillus pentose’s is                      alternative approach of decreasing aflatoxin in animals feed <xref ref-type="bibr" rid="ridm1841120764">45</xref>. </p>
      </sec>
      <sec id="idm1841256532">
        <title>Direct Methods of Aflatoxin Reduction in Milk </title>
        <p>The use of biological methods, chemical and               contaminant absorbents are also helpful for direct                     reduction of aflatoxin in milk and its product <xref ref-type="bibr" rid="ridm1841118100">46</xref>. Using of toxin absorbents is one of the chief direct methods of               decreasing amount of aflatoxin in milk as absorbent top soil such as vermiculite; bentonite, active carbon and               hydrated sodium calcium aluminosilicate (HSCAS) have been recognized as absorbent complexes for captivating different contaminants in aqueous atmospheres <xref ref-type="bibr" rid="ridm1841302012">17</xref>.</p>
        <p>Besides, hydrogen peroxide is the most effective chemical compounds reduced aflatoxin and used for               storing of milk based foodstuffs <xref ref-type="bibr" rid="ridm1841113780">47</xref>. Application of                 combined chemicals such as lactoperoxidase, riboflavin and hydrogen peroxide in addition to heat treatment is better to attain sufficient outcomes in reducing aflatoxin in milk. Also, use of potassium sulfite for neutralizing AFM1 in milk is well known <xref ref-type="bibr" rid="ridm1841118100">46</xref><xref ref-type="bibr" rid="ridm1841113780">47</xref>. </p>
        <p>Biological means of reducing aflatoxin is easiest and cheap approach and so it is interesting than other method. Currently, various investigations are conducted on detecting active microbes <xref ref-type="bibr" rid="ridm1841118100">46</xref>. For instance, as Line et al., <xref ref-type="bibr" rid="ridm1841110612">48</xref> indicated in their research, gram negative                      bacterium which is known as Flavobacterium                      aurantiacum, has been used for decreasing production of aflatoxin in milk. This microbe has special ability, as it          converts toxic ingredients of aflatoxin that exist in milk to harmless ingredients. </p>
      </sec>
    </sec>
    <sec id="idm1841255956" sec-type="conclusions">
      <title>Conclusion and Recommendations</title>
      <p>Aflatoxin is one of the main chronic naturally              occurred toxin chemical compounds (Mycotoxins) which are grouped under the potential chemical hazards for both animals and human. Normally there are two ways of               contamination of milk and milk based foodstuffs by                  aflatoxin. Both direct pollution of milk and its product with mold, or indirectly toxins pass to milk with ingestion of feeds polluted with Aflatoxin. Aflatoxin M1 is testified to be a reason for positive sanitation concerns in milk and milk based foodstuffs of dairy cattle.  Aflatoxins are                extremely toxic to dairy cattle and general community by causing serious impairments on human wellbeing and reducing production efficiency of cattle. Currently the            incidence of AFM1in dairy cow milk and milk based               products are extensive due to lack of proper controlled scheme in dairy value chain and due to inadequate efforts are made in maintaining squat amount of AFB1in the feeds of lactating cows. Many authors reported that, there is greater amount of AFM1 are appear in winter seasons than spring, the reason being in winter’s typically lactating cows are feeding with multiple feeds and so absorption of AFB1 rises, which in turn amplifies the meditation of AFM1 in produced milk. This is due to temperature and moisture matters are undesirably affecting the occurrence of AFB1 in feeds. Food safety problems (particularly milk and milk products) produce a massive burden on the country’s economy such as costs to administrations due to amplified medical costs, food recalls and outbreak                     examinations. </p>
      <p>Depending on the above conclusion the next      opinions are forwarded as recommendations:</p>
      <p>Awareness creation for dairy farmers, dairy               animal feed producers as well as for consumer are very important to minimize and eliminate effects of                           Aflatoxicosis.</p>
      <p>It is essential to keep and adjust continuously presence of AFM1contamination in milk and milk                   products of dairy cattle industry by accurate and reliable systematic methods and checking regularly AFB1                      contamination of dairy animal feeds.</p>
      <p>Moisture content and storage conditions of dairy animals feed should be kept and regulated at its proper level.</p>
      <p>Efforts should be made in attempt to provide           further and wide scientific information on human health hazards related to low-level long term Aflatoxins exposure and to standardize the already existing regulatory limits for Aflatoxins. </p>
      <p>Policymakers and developmental organizations should be disseminating evidence around virtuous                 pastoral and storing system as well as other conventional risk decrease actions.</p>
      <sec id="idm1841255668">
        <title>Abbreviations</title>
        <p>AFB1: Aflatoxin B1; AFB2: Aflatoxin B2; AFG1: Aflatoxin G1; AFG2: Aflatoxin G2; AFM1: Aflatoxin M1; EC: European Commission; EFSA: European Food Safety            Authority; EFTA: European Free Trade Association; EU: European Union; FAO: Food And Agriculture Organization Of The United Nations; FAPAS: Food Analysis Performance Assessment Scheme; HSCAS: Hydrated Sodium Calcium Alumino Silicate; ILRI: International Livestock Research Institute; WHO: World Health Organization</p>
      </sec>
    </sec>
    <sec id="idm1841253508">
      <title>Funding </title>
      <p>No funding sources for this article</p>
    </sec>
    <sec id="idm1841254300">
      <title>Ethics Approval and Consent </title>
      <p>This review article doesn’t included Animal or human investigation.</p>
    </sec>
    <sec id="idm1841254228">
      <title>Authors’ Contributions</title>
      <p>Sadik Zakir was the principal Author, who                   directed and prepared the original review paper. Sufian Abdo and Mukarim Abdurahman were participated in preparation of the final version of the manuscript. Suresh Kumar participated as supervisor and assisted in                         preparing and proof reading of manuscript. All Authors have read and approved the final version of manuscript and agreeing for publication.</p>
    </sec>
  </body>
  <back>
    <ack>
      <p>We would like to express our sincere gratitude to the <bold>Journal of Veterinary Health Care</bold>, for the chance given to as to publish this article without charge/freely. We acknowledge all staff of <bold>Editorial Office of OPEN          ACCESS PUB</bold>, United States for their wholehearted help. We are also thankful to <bold>Katharine Isabelle</bold>, <bold>Editorial  Office</bold><bold> of OPEN ACCESS PUB</bold> his support in the occasion.</p>
    </ack>
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