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Synthetic Tectosilicates: A Next Generation Toxin Binder Technology for Complete Protection from Toxic Substances
Sunday, 24 September 2017

Synthetic Tectosilicates: A Next Generation Toxin Binder Technology for Complete Protection from Toxic Substances

Rajendra Moorthy1, Rahul Mittal2 and Prakash Saini2
1 – Research & Development, Kemin Industries South Asia Pvt. Ltd.,
2- Marketing, Kemin Industries South Asia Pvt. Ltd.,
Chennai. India

Mycotoxins in animal feed:

Mycotoxin contamination in animal feed is a major threat to health and wellbeing of production animals and a serious threat to profitable animal farming1. Mycotoxins are secondary metabolites, predominantly produced by molds of the genera Aspergillus, Fusarium, and Penicillium2. It has been found that the same mold produces different mycotoxins and different molds produce the same mycotoxin. Among the several mycotoxins identified so far, the most important and well known mycotoxins are Aflatoxin B1, Ochratoxin A, Fumonisin B1, T-2, Deoxynivalenol (DON), and Zearalenone. Several reports have been published on the effect of these toxins on health and performance of animal2. Apart from these well-known mycotoxins, other mycotoxins like Cyclopiazonic acid (CPA) and Mycophenolic acid (MPA) are gaining importance because of their pronounced toxic effects on co-occurrence with well-known mycotoxins3.

Cyclopiazonic acid is produced by the same fungus which produces Aflatoxin B1, suggesting a higher probability of Afla B1 and CPA occurring together. Apart from immunosuppressive effects, each mycotoxin has a specific effect on target organs. For example, Afla B1, OTA and Zea affect liver, kidney and reproductive organs respectively2. Similarly, CPA also has a specific action which is different and unique from other mycotoxins. Calcium absorption mediated by Adenosine 5'-TriPhosphatase (ATPase) is known to be inhibited by CPA. This in-turn causes a Ca2+ deficiency in animals leading to leg weakness, thinning of egg shell and egg shell breakages3. The mycophenolic acid produced by Penicillium species causes immunosuppressive effects primarily by inhibiting the de novo pathway of guanosine nucleotide synthesis in the cells4.

Recently, the changes in climatic conditions also have influenced and changed the pattern of contamination in the agricultural commodities5. Earlier, Afla B1 was the predominant mycotoxin occurring individually or with other mycotoxins. Recent reports suggest that contamination of feed with mycotoxins produced by Fusarium genera are becoming very frequent6. All of these challenges persist in the Industry and need of an efficient and complete mycotoxin management program in poultry has become mandatory.

Mycotoxins: What happens inside the gut?

In most of the cases, mycotoxins are strongly bound to feed matrix. Such contaminated feed, on ingestion by the animal, will be acted upon by intestinal fluid of various pH, intrinsic and exogenous enzymes, which in turn, release the mycotoxin/s in the free form. Depending on the concentration, small sized organic molecules like mycotoxins follow different patterns (first order or zero order kinetics) of absorption in the gastrointestinal (G.I.) tract. In most of the cases, it was observed that mycotoxins occur in animal feed at levels as low as parts per billion (ppb). Such low level of contamination typically follows first order kinetics, in which the absorption of mycotoxin is concentration dependent. This indicates that the rate of absorption of mycotoxins inside the gut would be high if the mycotoxin levels are high. This is in contrast to zero order kinetics, wherein the rate of absorption is constant at any point of time irrespective of concentration. An illustration of different forms of kinetics is shown in Figure 1.

Mycotoxins: Structural perspective

Mycotoxins are diverse in nature and differ in terms of their physico-chemical properties7. On the basis of functional groups, mycotoxins are classified into neutral, acidic and basic mycotoxins. Whereas, based on partition coefficient, mycotoxins are classified into hydrophobic and hydrophilic. Such properties of mycotoxins have a greater role in terms of adsorption to toxin binders. Most of the mycotoxins fall into the category of hydrophobic property (Figure 2). Although Fum B1 is a hydrophilic mycotoxin but in its structure, it has a hydrophobic tail.

Pesticides: A new threat to the industry

A major part of animal feed is constituted of agricultural commodities. These materials are grown in fields where the attack of pests on crops is very often. Crops attacked with pests often have less nutritive value than what it usually has. Pesticides are used to protect the crop from the attack of pests. Such pesticides, leave its residues and contaminate the entire feed and food chain. Another route by which pesticides are transferred is through drinking water. Seeds are often treated with a number of pesticides, so, during rainfalls, these pesticides leach into groundwater and from there, through drinking water it enters into animals. Pesticide usage, although regulated but not easy to control at field level and pose a new threat to the poultry industry. Pesticides gets accumulated in meat, organs and some of them gets transferred to egg also. Since these products are meant for human consumption, it is essential to control it. Several regulatory bodies (FAO, EU) has set maximum residue limits (MRL) for such product and it differs to various class of pesticides8. However, the pesticide effect can be minimized by taking prophylactic measures which includes addition of toxin binder to animal feed.

Overall the contamination of mycotoxins and pesticides in animal feeds are not avoidable and uncontrollable. So preventive measure is the best way to manage the birds from such toxic substances.

Need for the next generation "Ideal Toxin Binder"

Clay based materials are extensively used as toxin binders in animal feed9. Using clay materials to mitigate mycotoxicosis was identified few decades ago when Afla B1 was considered as the only issue. Nowadays the scenario has changed where other mycotoxins are also posing a huge threat to the livestock industry as a whole. Using only normal clays as mycotoxin binder is no more an efficient method to control toxicosis.

Unique in vitro method to evaluate the toxin binders

In vitro biphasic net binding- a method developed by Kemin was adopted for evaluating the toxin binders. The method mimics the change of the pH conditions along the GIT of animals as pH plays a major role in adsorption process (Figure 4). The net binding for each molecule was arrived based on the below formula.

Mycotoxin (%) net binding= (Adsorption (%) at pH 3.2)- (Desorption (%) at pH 6.8

Toxfin™ 360°: Complete protection from mycotoxins and selected pesticides

The risk associated with mycotoxins and pesticide contamination in the animal feed are practically unavoidable and therefore adequate measures need to be taken to mitigate the risk seen not only for the profitability of animal farming, but also to reduce the toxin risk in the food chain. Kemin has identified and developed a synthetic tectosilicate (STS), first of its kind to optimally mitigate mycotoxicosis and pesticide toxicity. STS was developed to bind toxic substances more selectively and effectively.

The unique features of STS are,
1. Small and uniform pore size (around 5Å) - Since, a majority of toxic substances are small sized molecules, smaller pore size enables entrapment of these molecules to STS
2. Functionalized Bronsted and Lewis acidic sites- Most of the toxic substances possess different functional groups.
3. An appropriate silica-alumina ratio (SAR) - Since, most of the toxic substances are hydrophobic, unique SAR offers optimal hydrophobicity.

Because of the afore mentioned features, the ability of Toxfin™ 360° to bind mycotoxins and pesticides was found to be exceptional.

The binding efficacy of Toxfin™ 360° was also compared with other actives using biphasic in vitro method explained before and the results were shown in Figure 3 and Figure 410. Toxfin™ 360° has better binding towards multiple mycotoxins and pesticides compared to other actives.

 

As STS being the new material to the Industry, its safety was thoroughly evaluated in broiler birds. A performance trial was carried out for 35 days in Cobb-400 birds fed with diet in which mycotoxins were well below detectable limit. The treatment groups had Toxfin™ 360° at 3 kg/ton of feed (3X dose) and the control group was without toxin binders. The performance parameters such as body weight, feed intake, and FCR were unaffected with Toxfin™ 360° treated group (Table 1)10,11.

Researchers have often found that a drawback associated with toxin binder products is its non-specific interaction with important ingredients such as vitamins and therapeutic agents. Such assessment is of much importance in disease condition where the non-availability of such key ingredients will worsen the health condition9. The studies were also carried out with key ingredients (Figure 5 and Figure 6) using biphasic assay10. The results show that Toxfin™ 360° had very less/negligible interaction with nutrients as compared to other actives. Some actives showed high interaction with key ingredients which supports the findings observed by other researchers.

The results show Toxfin™ 360° binds mycotoxins and pesticides effectively compared to other actives. The product is also safe to use at 3 times of its recommended dose (1kg/ton of feed).

Conclusion:
To summarize, the poultry industry is challenged with different forms of toxic substances. The usage of toxin binders possessing ideal qualities such as high and selective binding to toxic substances would be the best solution to save the costs associated with such risks.

References
1. Fink-Gremmels, J. in 672 (Woodhead Publishing Limited, 2012). doi:10.1533/9780857093615.1.66.

2. Grenier, B. & Oswald, I. P. Mycotoxin co-contamination of food and feed: meta-analysis of publications describing toxicological interactions. World Mycotoxin J. 4, 285–313 (2011).

3. Dwyer, M. R. et al. Effects of Inorganic Adsorbents and Cyclopiazonic Acidin Broiler Chickens. Poult. Sci. 1141–1149 (1997).

4. Streit, E. et al. Multi-mycotoxin screening reveals the occurrence of 139 different secondary metabolites in feed and feed ingredients. Toxins (Basel). 5, 504–523 (2013).

5. Sofie, M. et al. Occurrence of mycotoxins in feed as analyzed by a multi-mycotoxin LC-MS/MS method. J. Agric. Food Chem. 58, 66–71 (2010).

6.Toxins | Free Full-Text | Multi-Mycotoxin Screening Reveals the Occurrence of 139 Different Secondary Metabolites in Feed and Feed Ingredients | HTML. (2016).

7. Bräse, S., Encinas, A., Keck, J. & Nising, C. F. Chemistry and Biology of Mycotoxins and Related Fungal Metabolites. Chem. Rev. 109, 3903–3990 (2009).

8. Standards for Pesticide Residue Limits in Livestock and Poultry Products. Available at: http://extwprlegs1.fao.org/docs/pdf/chn137937E.pdf. (Accessed: 9th May 2017)

9. Statement on the establishment of guidelines for the assessment of additives from the functional group ‘ substances for reduction of the contamination of feed by mycotoxins ’ 1 EFSA Panel on Additives and Products or Substances used in Animal Feed ( FEEDA. EFSA J. 8, 1–8 (2010).

10. Kemin Internal document - 17-00089.

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