good morning afternoon or evening everyone so as it has been said i'm going to talk about the impact of mycotoxin on immune system so i'm not going to introduce what mycotoxins are because it's not the first seminar but i'm just going to give you an example of the multiple effect that mycotoxin can have and i will take the example in pigs so we know that there is there are different mycotoxin and we know for example that aflatoxin b1 has its main effect on liver it induced liver toxicity but has also an impact on growth as far as ocratoxin is concerned it more targets the kidney dioxin ivalenol and t2 toxin are two tricutican and trichotic and are known to affect growth and feed intake inducing anorexia femonism b1 is known especially in peak to target the lung and the alenon is known to target the reproductive tract but as you see all this mycotoxin have an effect on the immune system especially aflatoxin feminism and trichoticking in fact when talking about the immune system it can be divided into two kind of response there is first innate immune response this response is rapid but not specific and this innate immune response involves immune and non-immune cell such as epithelial cell endothelial cell and immune cells such as macrophage neutrophils or dendritic cell conversely the acquired immune response is very specific and it is the type of immune response that you have during vaccination but it's slow and the aqua immune response only involves immune cell especially lymphocyte so it's not possible during 40 minutes to give you an overview of the effect of all the mycotoxin on all the type of immune response so i'm just going to give you some example here is the first example that the mycotoxin aflatoxin b1 has an effect on macrophages and as you see on this slide on this part of the slide you see that it reduces the effect on production of nitrogen oxide and about oxygen reactive species in a dose-dependent manner and this lead to an increased cell death of macrophage in the type of apoptosis so we have an effect here showing that aflatoxin b1 decrease the functionality and increase the mortality within some immune cell in our lab we did quite a lot of experiment trying to investigate the effect of mycotoxin on the immune response in peace the experimental protocol that we use was most of the time the same the animal were exposed to mycotoxin for four weeks and during these four weeks they also were vaccinated with a model vaccine which is of albumin and during the this four week we look at the immune response both the immoral immune response which is mainly antibody and the cell mediated immune response which is mainly lymphocyte proliferation and we look at this immune response both with for towards the antigen we use the vaccine that we're using but also the total immune response so total antibody or total lymphocyte proliferation and here are some results that we get here is an expert is this experiment where we use t2 toxin and the animal receive either control food or food contaminated with 0.5 1.3 or 2.1 microgram per kilogram t2 toxin during the four weeks and they were vaccinated with this model vaccine of albumin and we look at the antibody response when we look at the total antibody response you clearly see that there were absolutely no effect but when we look at the specific antibody response meaning the antibody response towards the vaccine you clearly see that the group of animals receiving the highest level of mycotoxin had reduced antibody production compared to the control animal or the animal receiving the lowest dose of mycotoxin we did exactly the same response with the same experiment with another mycotoxin here it's aflatoxin b1 and the animal receive either control feed or feed contaminated with 0.4.9 or 1.8 microgram per kilogram aflatoxin per kilogram feed and we look at lymphocyte proliferation and when we stimulate all the lymphocytes we didn't have any effect but when we look when we stimulate the lymphocyte with the antigen that we use in vaccine you clearly see especially after two weeks that the control animal the animal receiving the control feed responds really well by contrast the animal receiving the feed contaminated didn't respond that way so it indicates that low dose of mycotoxin decrease the antigen-specific immune response without altering the global immune response so really to see an effect of mycotoxin on the immune system we need to stimulate the immune system so on as i show you here we look at the immoral and cellular immune response for two mycotoxin t2 toxin or aflatoxin b1 and i show you that for t2 toxin we have a decreased immune where the decrease in immune response especially in term of antibody production and with our flat oxygen we have to decrease lymphocyte proliferation but when we look at the antibody production for aflatoxin b1 there was even a specific antibody production there was absolutely no effect and when we look at the specific cellular immune response for t to toxin we didn't have any effect so it really indicates that each mycotoxin act differently on the immune response t2 toxin affect the immoral immune response where whereas aflatoxin affects the cellular immune response and so if we need to characterize the immune effect of mycotoxin we need to investigate different parameters of the immune response so to conclude on this first part we've shown that each mycotoxin act differently on the immune response i show you that t2 toxin alter the antibody specific production but doesn't alter the cellular immune response lymphocyte proliferation and this is the opposite effect for aflatoxin b1 so we really need to investigate the effect of mycotoxin on several parameters to be able to see what are the effects of mycotoxin on the immune response another conclusion of this experiment it shows that loads of mycotoxin decrease the specific immune response without altering the global immune response so we really need to stimulate the immune response to investigate the immunosuppressive effect of mycotoxin what is even more important than knowing exactly what mycotoxin are doing on the immune response is to is to study as a consequence of the modification of the immunity on pig health and basically the fact that mycotoxin alters the immune response has two consequences the first is an increased susceptibility to infection and the second is a decreased vaccinification and i'm going to give you some example on these two parameters so here is an experiment that we did also in our lab with piglet that were exposed to feminism b1 and they were after that infected with an oral infection with a pathogenic e coli and what you can see that at the end of the experiment when we look at the number of bacteria in the intestine there was much more bacteria in animal that were exposed to the mycotoxin this is a locked scale so the increase was at least tenfold to 100 for more bacteria in the intestine of the animal that get the mycotoxin and here in these photos you can see here the small dots are the bacteria that we're staying and you can clearly see the bacteria that are attached to the intestine so this really shows you that the fact that mycotoxin can increase susceptibility to inf to infection this is another example still with feminism v1 but here is in chicken and still e coli infection here's um 21 day old chicks that were injected with e coli and after the bacterial injection they were killed and the number of bacteria were determined in different organ spleen liver or lung and you clearly see that there was um 4.9 10 um in log 10 there was 4.9 bacteria in the control uh animal receiving no uh feminism but when they receive feminism it was more than one load one log higher meaning that it was more than tenfold higher and we see that in the spin there was also an increase but it was smaller in the liver and there was no effect in the lung this is just for example but if we go through literature there's quite a lot of examples that has been observed and here is just a survey of a literature survey of experiments that have been done in chicken so with done an acetyl form of dawn they are enormous and humanism and with emmeria maxima there was a decrease of cd4 and cda t cell in the mucosal in the mucosa with uh also done acetylated form and then there was um an effect after also infection with emery there was uh in effect with e coli salmonella clostridia salmonella salmonella clostridia san manila gallinarum or also e coli so there is a lot of evidence that really the fact that mycotoxin alter the immune system will increase susceptibility to infection here's a review on poultry but i can have the same slide on peaks for example this is an experiment that i like to show because here it's not an experimental infection in this experiment what happened is that it was in a in a farm the um they were given okra toxin in the field at 1 ppm or 3 ppm and basically what happened is in this form in animal that received the loaders of aquatoxin two out of the sixth animal develop salmonella infection and in the in the group of animals that received the high dose of mycotoxin they all developed a salmonella infection so here it really indicated that the sanitary status of the farm was not very good because there was some manila around but basically the animal receiving the normal the control feed didn't develop an infection their immune system was strong enough that they can fight again the infection but when they receive a mycotoxin they could not fight and then they develop an infection and what is even very interesting in this experiment then they did the experiment again and they say okay we have a salmonellosis problem in our farm so we are going to vaccinate again salmonella and they repeat the experiment the same way here they use only the animal feed with a control feed or with high level of okra toxin they didn't have to wait certain day they have to wait much longer but after 47 days in fact out of the animal receiving the high level of mycotoxin in the field one developed brachiospheral infection and one compilobacter infection so basically it really indicates that if you have mycotoxin in your feed and you don't have a good sanitary status whatever the pathogen that is around the animal will catch the pathogen and will be infected by this pathogen so this is the first set of examples that i show you indicating that the fact that mycotoxin decrease the immune system will increase susceptibility to infection but there is also the immune system is also used during vaccination and it has also been demonstrated that the fact that mycotoxin decreases the immunity will have an effect and will decrease vaccine efficacy here is some example so here it's an experiment with aflatoxin on viral infection so basically there was more than 600 chicks two months of age that received a feed contaminated with aflatoxin and they were vaccinated and then challenged they were vaccinated to different infection and then challenged with uh this the the pathogen and basically you can see that in the first set they were challenged with newcastle disease there was an increased antibody title and leading to an increased mortality in the animal that received aflatoxin exactly the same result with infectious bronchitis there was a decreased antibody title and increased mortality after challenge by contrast with infectious birth burst disease there wasn't decreased antibody title but there was no effect on mortality this is another experiment that we did in our lab with the vaccination and it was a microplasma vaccination again macroplasma and we when we look at the total antibody response there was absolutely no effect but when we look at the specific antibody response you clearly see that at the end of the experiment the animal that received the feet contaminated with aflatox with feminism sorry get a lower antibody response than animal receiving the control feed in this case because we are scientists we try to look to look at the mechanism involved and we see that it was because of cytokine because there was an alteration of the th1 th2 balance that is really important for antibody production and in addition we had a decrease in fossil proliferation that lead to decreased antibody production and lead to a decreased vaccine efficacy i think that's quite important because breakdown in vaccinal immunity induced by mycotoxin may lead to occurrence in disease even in properly vaccinated pigs and the problem also is when you get the disease um you don't you know that you have vaccinated your animal but you most of the time you don't remember what type of feed you were giving to your animals once or two months earlier when you were vaccinated your animals so if we try to conclude on this part we can see that mycotoxin can alter several aspects of the immune response i show you that t2 toxin alter the production of antibody whereas aflatoxin b1 alter the lymphocyte proliferation and this really have some consequence in term of pig health or even in animal health in general it increased susceptibility to infection i didn't show you but there are there have been experiments also showing that it did it reactivate chronic infection i show you that it decreases vaccine efficacy and there are also experiments that show that ingestion of mycotoxin may also decrease drug efficacy however in most of the case the underlying mechanism still need to be elucidated i show you in for feminism b1 we did some experiment and now we know uh what is the mechanism it it is due to uh cytokine production and lymphocyte proliferation but for some other case it's really not known for example the case of okra toxin that i show you that decreases that ingestion of okra okra toxin increase susceptibility to several infections we don't know exactly the mechanism so i'm almost finished this part of my talk but before finishing i wanted also to tackle a new problem that is today on mycotoxin and this is the problem of mycotoxin co-contamination co-contamination is a reality it's a reality for several reasons the first reason is that fungi produce several mycotoxins simultaneously because also feed may be contaminated by several fungi at the same time and because the animal diet is composed of multiple raw material for all this reason we have a co-contamination and this is for example a survey that has been done in almost 10 years ago on more than 7000 samples and in this survey it indicates that about 20 percent get low level of mycotoxin below the limit of detection that 33 percent in this sample there was ma one mycotoxin but in 48 percent they detect more than one mycotoxin and so contamination by several mycotoxins is a rule not the exception and most studies have investigated the effect of mycotoxin when present separately and we really need now to investigate the effect of mycotoxin co-contamination what are the effects of disco contamination so the experimental design to study mycotoxin mixture you need to have a two-step approach first you need to do a dose effect of each mycotoxin when used individually and this is quite important this is just two example two dose response example in the one on the top you see that when you multiply the level of a contaminant by two from two to four the response is only increased by thirteen percent but in other example in the bottom when you go from two to four th you increase the response by 11 fold so you really need to first have those response analysis and then when you have this dose response analysis for each mycotoxin you can compare the predicted effect of the combination with the single effect of the combination and then you can determine if they have no interaction of if they have synergistically or antagonistically and the big problem is that many studies addressing mycotoxin interaction are very difficult to interpret because there is no dose response experiment we did some experiment with mycotoxin mixture especially on cell on human cell or on porcine cell and we see that in the vast majority of the case we observed some synergy here it was with different trichotic and dawn and three acidity done done and 50 lasting done 15 and 3 are sitting and you see that at low concentration in the vast majority of the case the main type of interaction is um observe is a synergy so that really indicate that this energy need to be taken into account so um now i go to my conclusion so mycotoxin have multiple effects on the animal and among them they are able to modulate the immune system and the main consequence of this is in terms of susceptibility to infectious disease and in reduced vaccine efficacy something that i didn't show you also is that mycotoxins are able to alter the intestinal barrier function then the intestine is not a barrier anymore and this have some consequence in term especially in terms of pathogen translocation across the intestine what i show you is that despite of the frequent co-occurrence of different mycotoxin little is known about the interaction between this toxin and also something that is new is that there is more new new fungal metabolites that are identified emergent mycotoxin mass mycotoxin and now we really need to address their toxicity and with that i finished my presentation and i thank you for your attention okay thank you so um please feel free to use the questionnaire the chat area to type questions we will have as i said dr olga verkieva and dr julia dvorska to answer the questions and uh if you have questions in spanish and portuguese please type them as well and we can translate them to uh the panel so i will start reading some questions here first one is somebody asked about the concentration of aflatoxin in one of her studies i think he's asking if it point four parts per million enough of the toxins are low those i don't know if there's a miscommunication there can you answer that olga yeah i i was not sure myself because uh it looks like that's quite high if it's in ppm indeed but in her speech she was mentioning ppb i was pointing attention to that fact but it would be best to double check with her because it's possible that it was indeed 0.4 ppm it's high dosage but of course in her trials which are challenged trials she always refers to low or high dosage but in field conditions they might be really not considered the same low and high they could be considered in any case very high dosages but we will record this question and we check it later see thank you second question here is um should we also look at long-term effect of low doses those are seen in the field of single and multiple mycotoxins i'll ask that to dr uh julian yes long-term effect is very important as and as isabel showed today uh if you remember that slide on the like recurring effect infection or when they uh found their in normal condition this toxin in feed they found in four weeks they found if i remember right salmonella but in 14 uh 14 days they found brachiosphera meaning that when we have long-term effect we will we would expect even uh more chances to have some infection like uh from the pathogens if they are present on the on the farm or if they are present again they are also present in the in the gut and we have this barriers function uh decreased in in god so we would expect that all we have in the god could could get to the um good cause some negative effects so low that those low uh dosage and long term effect is very important yes sure okay i will follow that question with another one that is very similar but also mentioned about um the the synergistic effect of those my toxins so do you think that a combination of those is below limit by being might be significant about uh when you have synergistic effects synergistic effect is very important right and um again uh is it today it's only started like for in research conditions we are not when we talk about the field conditions we never uh never think about the synergism and on the maximum what we do we can have additive effect right we can try to add some trichotitis for example don plus uh the striatity aldone and nimalino for example maximum we can do to have the levels to to to analyze but um again as isabel mentioned it's difficult to know and difficult to uh to explain this for real conditions and it should be studied well and should be studied more to understand but yes uh at least at least for trihation she meant that synergy is in most of the cases it should be synergy synergistic effect meaning that it's not like one plus one is two it should be four or five or whatever yeah so it's very important if i may also add from my uh observations that at least we have to consider additive effect as julia mentioned but of course synergism is the main effect between most of microtoxins and some of them like dioxin evalinol and sierra leone are one of the most known synergists okay thank you i will keep uh with you now olga i have a question here with my toxins seldom found uh singularly what is the best standard program to control them that gives the best uh risk management and what binder product of our combo of molecules works best of course it depends on mycotoxin because sometimes we deal with aflatoxin and this is uh the easiest to bind and the binding mode of action is the best against this mycotoxin because it's bound and then excreted from the body because this is toxic mycotoxin which is destroying liver mainly and by a liver and circulating through the blood it also can affect immune system but if for instance we bind dioxin valeno the target organ is gastrointestinal tract and by increasing the level of dioxin valeno in the target organ probably it will be not the best mode of action against this mycotoxin so i think uh we can't address just all my catoxins as one issue you have to have a multiple approach and think about the consequences of each mycotoxin so i would say binders are standard solutions cheap and available for aflotoxins and ergot alkaloids and for other mycotoxins i would think i would recommend to use other more complex products with different modes of actions thank you next question would be when we see the mac toxins can reduce when we see the microscopes can reduce antibodies response of vaccines if we increase vaccine concentration could we re improve the immune response if not could we admit that it's a real necessary to control my toxins to protect immune responses from vaccines julia you want to respond um yes you remember isabel showed us their own research using the overwatch scene um and it shows that the antibody theta decreased but total immune response is not is not changed meaning that in this case only we have a negative effect only when we have challenge and this is the same as we have the like infections recurring infections or infections due to sanitary status meaning that uh if we increase the i i think that if we increase increase the level of vaccination or uh vaccine concentration the effect would be the same because uh in this case uh the immune system will not work properly due to uh during the vaccination process and then it should increase the level of antibody it should be activated well it will not work good so it will not help i believe so we need to control mycotoxins especially during vaccination not all other times it's also very important but when we have the vaccination program and at least during the vaccination mycotoxin control would be necessary i believe okay i also have some field observations that of course increasing the volume was vaccine will not help some people they are trying to re-vaccinate animals and even we have some uh customers met uh that were vaccinating with three times so with two dead vaccines and one life vaccine for instance against uh i think newcastle disease or even flu i i don't remember i'm not a vet i'm sorry for that but it didn't work it did not work because just the immune system could not respond neither to the number of vaccinations and no two type of vaccine so this is just blocked it's like yeah if someone is dying if you give more pills to that person or to this animal you can't really to bring it back to life okay thank you and i will follow that question with another one that is asking um about the age is there any effect on age of the on the animal on the response to immune system and my toxins or specific phases like uh breeders or young animals and also another one at the same area here that asks about the difference between poultry and swine if there's a difference between them on the responsive immune system for my toxins oh if you want to answer that i will try to answer but again i uh give my excuses because i am not a vet and i know that younger animals are really more so susceptible to mycotoxins because they are less protected especially in the gastrointestinal tract the barrier works worse in small animals or younger animals than in the adult animals but regarding the response to vaccine i think it depends of course at which age is made of course and also what type of immunization animal already got that for instance you give it to young piglet uh who could not develop yet uh the immune immunity via colostrum of sour milk of course there will be probably more susceptible to mycotoxins and the piglet of a little bit older age but already developed certain immune response but again uh i can't really answer this question good maybe if julie can add anything to this i agree with you olga exactly in in young animals uh immune system is not developed well and also god as as we know that 80 percent of immunity is happened in the gut and god is not developed and immunity is not developing so that's why uh young animal are especially sensitive speaking about for example piglets yes they are especially sensitive and um regarding the difference between poetry and peace and immune response on mycotoxins um well i don't think so that there is some uh some difference some really pronounced different in in effect of mycotoxins on immune system in different species but as uh isabel showed today there is some difference in uh in response in different mycotoxins like the the one they were tested like t2 and dawn and humanism and they all also different they have acting or working on the different parts of the immune system but results you see the results are the same so uh there should should not be much difference in this um i think that's it uh age and species red clear yep thank you well there's another question here on uh concentration of my toxins i think we talked a little bit about it but would be good to uh cover it again uh julie if you can it's asking i wonder what would happen with more realistic contamination doses of mac toxins some are around 20 to 30 parts per billion of half of toxins half to one parts per million of don and two to three parts per meter enough for monoxine what would be the realistic effect on the field on that yes uh it's it's good question because on the real situation we don't have such a high concentration as usually used by researchers when they have research they need to have some pronounced effects so we always use these high levels but i remember one of the papers on dawn dawned in broilers and vaccination against newcastle disease and level of dawn was 500 ppb so it's like not high at all it's like 10 10 times below the regulation levels uh recommendation levels right and it was negative effect on the antibody jitters and there are some uh papers in literature with low levels so we can we can find it also and again it's it is a effect negative effect on the antibodies always in any papers visual on on this topic always shows the negative effect and this levels you you mentioned is not that low so we will expect negative effect and we have scientific obedience on that uh if my i may add also my experience that for sure that these levels mentioned to 20 to 30 ppb of aflatoxins they are already quite toxic and for vaccination definitely there will be effect probably not on performance but on the health dioxin valinol is also one of the less toxic mycotoxins in terms of performance but one of the most toxic mycotoxins in terms of the health and immunity so the levels mentioned like uh 0.5 to 1 ppm or if i convert to ppb is 500 to 1000 ppb definitely will affect the immune response however i would doubt uh about the four monitoring level mentioned two to three ppm so it's quite low level for monisense are known to be important microtoxins but the levels must be significantly high and two to three ppm i have doubts that you will see the response or negative response on vaccination okay it makes sense oh i will keep with you now um there's another question on control methods for my toxins uh the question is what's the best metric to compare different uh comparative products in terms of my toxin control uh a very relevant question and this is really a frequent question and there is no uh ideal answer to that because in vivo trial is the best setup or the best comparison between two products so you put your animals in your conditions uh but feeding with the same feed but with two different products and you can see the effect because your conditions can be quite specific just using as now is fashionable to use just in vitro data for comparison i think it will mislead you to the conclusions if you want aflatoxin control probably you can rely on in vitro data but if you want to compare products against zeralan or against uh especially the oxygen neovalenol and formulas the in vitro binding data can really misguide you and even leads into the wrong conclusion because sometimes binding these micro toxins like dioxin valine and for monitoring can increase the problem as i mentioned already before because you will bring some mycotoxins to the target organ and higher concentrations like dioxin varianol will affect the gastrointestinal wall and then with all bad consequences so best is in vitro in vivo data uh if you can develop yourself this is the best and if not then you have to request this data from the producers of the additive but please ask for right animal category which is interesting for you and also mycotoxin on my catoxin combination which is interesting for you okay thank you question for julia what's the mode of action of gom on immunity in which organ this take place well um it's not known actually what is the mechanism of action of dawn uh and which organ meaning that it's decreasing lymphocyte proliferation and um well the taj organ for the uh dawn is god anyway and god is like 80 of immune cells so it's all happening in the gut and it's decreasing the lymphocyte proliferation and maybe again like change in this balance of cytokines which are necessary for good antibody production and that could all will be like mechanism of action but i am also be i also believe in one of um mechanisms of action on immune system is a decrease of antioxidant status most of mycotoxins can induce oxidative stress and oxidative stress can decrease their ability of immune system to work properly like one of the theories that all the immune cells cells has the receptors and they are really susceptible to lipid oxidation and these receptors are necessary for communication of all the cells like lymphocytes and microphages and all all of the all cells that they need to communicate and to like give the signals to produce cytokines or produce antibodies and so on and when we have oxidative stress like free radicals they can damage this this surfaces of cells receptors so they cannot communicate effective anymore and meaning that uh that's in this case we are going to have decreased all immune response it's another of theories there are a lot of theories it's all the theories and um this scientific evidence actually yeah and if i may add also the apoptosis of gastrointestinal cells can uh be also a contributor and lower immune response because gastrointestinal cells there are a lot of immune immune cells and if they die then they cannot anymore produce yeah exactly and lipid oxidation will will cause apoptosis so again right okay i think we have no more questions oh there's one more here pretty quick do we know about factors that can increase my toxins effects such as gut injuries water ph previous liver kidney etc i will answer this question i think all stress factors can increase uh the influence or severity of another stress factor so if microtoxins are present or if there is a certain stress factor that animal is ill or water is not really of the good quality that the effect of mycotoxins will be more pronounced but how much what kind of synergies more additive effect would be it's not known it's really your specific situation and the best of course when you are choosing for the product uh you test it in your conditions okay right i can edit the yes mycotoxins are also stress uh like stress uh conditions for animals and if we have some other stresses like anything it could be um heat stress or maybe some negative some something in the feet or so there's fat or anything that can again increase the severity of mycotoxins yeah i think was it the work of isabella's walt or someone else recently that combination of mycotoxins with heavy metals but even not at high levels at permitted levels in feed can be a really very crucial so that the severity of mycotoxicosis but also poison with lead or arsenic i i don't remember exactly which habitats it was that can be enhanced and it can be synergized yeah so all the stress factors together increasing the level of negative effect of mycotoxins right that's right okay um last question here we have one more until we finish um it's rightfully mentioned by olga don is almost impossible to bind with typical clay or east-based products what is your suggestion for efficient products would you like to continue your talk and then i will add okay i will do this uh in fact it's also depending a lot on the species if we look at the nature that for instance pigs they have a natural natural defense against dioxin evalinol they have a very high bioavailability so about 80 percent of the oxygen valineau is absorbed through the gastrointestinal wall in stomach already and in the upper parts of the small intestine it goes directly to the liver and liver metabolized dioxide valino to non-toxic metabolite don 3-glucoronite and it's excreted from the peak body with the urine so in fact in wild peaks dawn is not an issue because pig is able to decontaminate it but in modern agriculture it's not possible because the pigs are processing a lot of feed and without help of the of the product they cannot really utilize their natural mechanisms to control dawn or to level down in in the body so the additives that can help liver to work better so the animals with damaged liver will not be protected by nature from dawn better or it will be protected worse also to help to improve the gastrointestinal integrity because if the oxygen evalual is going to the gastrointestinal tract or stays there that it will affect tight junctions and gastrointestinal integrity in general so if you can use uh some alternative additives to help gastrointestinal tract to repair from the possible dawn damages it's also good so some antioxidants with in vivo effects can help because uh the one of the mechanisms of dioxin on the cellular level is oxidation uh so it's a combination uh if we speak about poultry it's a little bit different because poultry has quite a low bio availability of dioxin valinol however liver also can destroy dawn and excrete the non-toxic metabolite but in poultry the higher level of don is passing through the gastrointestinal tract and the higher levels of donor found in distal parts of gastrointestinal tract and then can cause necrotic enterices for instance being precursor so in that case of course uh the focus is on the supporting the gastrointestinal health of ever means um also using maybe some enzymes so bacterias can be potentially but you make sure that they are working in the right part of the intestine or gastrointestinal tract because what is now commercially available is working at ph at six and at page six all damage is already done so we need to catch down earlier or try to repair the consequences also earlier at ph 3 4 or 5. so there is no simple question on dawn protection yeah yes thank you really yes i just wanted to to it also and it's if you remember from our first episode by vito he said that it's not possible to bind dawn at the moment there is no effective binders for dawn meaning that uh yes in most of the cases for example for as mentioned by welcome for for pigs we need to help uh animals to help animals to recover to help them to deactivate like in liver to support liver support to support god again and um since we don't have anything to bind and if again if we bind it and take it to the gut like in embroiders it's it's not good yeah we don't know if the bound uh mycotoxin is inactive so we suggest or it's like uh logic to suggest that bound microtoxins are inactive but imagine that they are quite large molecules and even if they are bound to the clay or whatever adsorbent still they can be active because we don't know which part of molecule is bound so it's it was taken to god to the low god for example in brothers and still active so in this case would be better to to let's leave it to inactivate it okay thank you ladies appreciate it um so yeah we are about a one hour from uh when we start we are about time to finish i would like one more time to thank you everybody for joining us for this michael info series uh i think it's been a very informative session next one will be will be in april 13th uh same time 10 a.m uh eastern daylight saying uh side daylight time um and we'll be with dr hudi von meyer with uh my toxin's effect on reproductive pulmonary digestive on respiratory systems and how we can we help so looking forward to that next session and to your participation and i will let uh mattel now just to say a couple words before before we finish thank you very much and see you next time thank you very much thank you see you next time bye you