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Zilpaterol hydrochloride (ZH) is an orally active β-adrenergic marketed under the name Zilmax, and is approved for use in fed cattle. It was approved by the US food and Drug Administration (FDA) in 2006. This substance can be fed to feedlot cattle at a rate of 8.3 mg/kg in the final 20 to 40 days of the finishing period that is then followed by a withdrawal period of a minimum of three days. The label claims approved by the FDA increased the rate of BW gain, improved the efficiency of feed, and increased the leanness of carcass in cattle fed in confinement for slaughter in the last 20 to 40 days on feed. Before Zilpaterol was approved in the US, it was first approved in South Africa in the year 1997 and in Mexico in the year 1999 for its use in feedlot cattle. It was approved for use in beef cattle in Canada in 1999. These many approvals in different countries mean that this product has been internationally accepted in improving the growth and efficiency of beef cattle. Although the FDA approved Zilpaterol in 2006, its manufacturers did not begin marketing it for commercial use in the US until May 2007. The approval for use of Zilpaterol in the US led to research into all the aspects of production and also the quality of meat of the cattle fed on Zilmax. This paper will look at the effects and advantages of this product (Rogers et al 2010).
Patent and Approval
This product was patented by Jean A. Grandadam on February 13th 1990. It is under the US patent number 4,900,735 and the patent owner is Intervet International B.V. the product was developed in the early years of the 1990s but was not approved until late into the 1990s. The patent is valid up to 2026 (Patent, 2008).
Food and Drug Administration
The Proprietary name of this drug is Zilpaterol hydrochloride and is pharmacologically categorized as Beta adrenergic agonist. Zilpaterol hydrochloride consists of 21.77 grams per pound in active ingredients. It is supplied in 22.05 or 10kg bags. The drug is fed at a concentration of 6.8 g of Zilpaterol hydrochloride per ton of complete feed to give 60 to 90 mg Zilpaterol per head per day for an increased rate of weight gain, increased carcass leanness, and improved feed efficiency in cattle fed in confinement for slaughter in the last 20 to 40 days on feed. The drug is administered orally in feed for heifers in confinement for slaughter. The application of Zilpaterol has been proved to be safe by FDA in cattle as it helps in getting increased weight gain, improved food efficiency and also increases carcass leanness. According to FFDCA rules which allow that if a drug or its active ingredients used in animal feed has already been approved for its particular use then the drug can not fail to be approved on grounds of human food safety, what this means is that because Zilpaterol has been approved then there is no harm on humans so long its administration is done correctly. It has been established that the active ingredients in Zilpaterol does not exceed the tolerance levels that are established. The safety of this drug has been established.
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Research carried out show that steers fed on Zilpaterol in the last 20 to 40 days of the feeding period with a withdrawal of three days show that there was a significant increase in ADG during the feeding period. The changes led to an average increase in weight of 9kg in the steers. Because it is a beta adrenergic compound, Zilpaterol is also a repartitioning agent, it moves energy consumed by the animal in feed towards muscle production and encouraging lipid degradation. This means that as the animal consumes energy via the diet, many of the nutrients are directed towards muscle development. As energy is being directed away from fat deposition, adipose tissue is broken down. This causes better feed conversion rates and high efficiencies in livestock production. A Change in the mass of muscles occurs through an increase in the length and diameter of the fibers of muscles but not increase in the number of fibers. These changes come about due to Zilpaterol supplementation but not DNA addition and as such, they are temporary meaning they can not be sustained for a long time.
Recommended use and warnings
The product is parked with labels that give information on the safety of humans handling, administering, or those who are exposed to it. The label warns that Zilpaterol hydrochloride which is a beta adrenergic agonist is not for use in humans. Because of this, an anti dust product has been applied to this drug to reduce risks of inhalation. It also states that extended handling tasks that have chances of dust generation need respiratory protection. Persons using it should wear skin protection that is appropriate, protective eye wear if there are chances of eye contact, and if there is contact, then one should rinse with water immediately or consult a physician. Treated animals are not to be slaughtered for use in food for at least a period of four days after the last treatment using the drug. It should not be used in calves that are to be processed for veal. Should not be used by humans and therefore should be kept away from children. The drug satisfies all the requirements of the Federal Food, Drug, and Cosmetic Act. This means that the drug, when used according to instruction, is safe and effective for increased rates of weight gain, increased feed efficiency, and increased carcass leanness. Results have also shown that residues in food products from cattle fed in confinement for slaughter treated with Zilpaterol will not represent a health concern to the public if the product is used as per instructions (Intervet n.d).
Effects from the use of Zilmax
The effects of feeding β-adrenergic agonists to animals have been under study for many years. Different researchers have come up with different findings. For instance, the physiological response to oral administration of Zilmax in beef animals is seen in the improvement of performance and a carcass with heavy muscles. In a study done to test the effect of ZH on performance, an increase in the average daily gain (ADG) was observed. The increased ADG brought about an improved gain to feed ratio (G: F). The research showed that Zilpaterol affected carcass characteristics, the effects included; increased rib eye area (REA), an increase in hot carcass weight (HCW), increased dressing percentage (DP), reduced grade of yield, and a reduction in the meet tenderness. In an experiment done on the feeding of Zilpaterol between 0 to 40 days to calf-fed Holstein steers, it was observed that there was an increase in the rib eye area in the cattle fed on ZH for 20 to 40 days. Cattles fed on ZH had increased live weights where by it was noted that more weight was gained during the ZH feeding period that also led to an increase in the dressing percentage. There was also an increase in the Warner Bratzler Shear force in the strip loin steaks in those cattle fed on ZH; this was reported to be because of hypertrophy but not hyperplasia. It is also recorded that animals fed on ZH for thirty days had loin eye muscle color, which was brighter cherry red in color than those which were not fed on ZH. The research also showed that ZH reduces the amount of metmyoglobin which brings about an improved beef color. It was also shown that when animals are fed on ZH for 20 to 30 days, then they will have brighter and redder sirloin steaks especially when packaged in high modified atmospheres packaging (Hosford 2010).
The results from this study showed that there was no effect of withdrawal period on any of the characteristics of carcass that were evaluated for tenderness in cattle fed on ZH for 20 days. It was also noted that ZH has no effect on fat and reported reductions may be as a result of the dilution effect due to an increase in the total amount of lean. In this study, feeding ZH did not bring about any increase in WBS values in the early aging periods and as the aging period increased, there was no much difference. It was also noted that if the calf-fed Holstein steers are held off Zilpaterol for 3 to 10 days the feeding effects do not change (Hosford 2010).
In another study, it was noted that β-AA have effects that are different on the composition and the quality of meet. Multiple studies done came to a conclusion that β-AA fed to pigs brought about a decrease in fat deposition in all locations apart from the back fat, while cattle experienced large reductions in adipose tissue in all depots. When they specifically looked at carcass traits they discovered minimal to slight benefits in the color of meat and some sensory attributes to pork or beef from those animals supplemented with ZH. Studies done on the calpain or calpastatin system and on the tenderness of steaks from steers fed on ZH for six weeks found out that calpain activity was normal in early postmortem; calpastatin activity was greater in the longitudinal muscle supplemented with β-AA. Steaks were found to be significantly tougher than the control ones. This was attributed to the high activity of calpastatin early postmortem in the supplemented cattle. Crossbred steers fed on ZH for 42 days had significantly increased weights, loin eye areas, and dressing percentages than the controls. It also brought about increased weight of bone-in rounds plus top rounds when compared to the control wholesale and sub primal counter parts. There was no major difference in hot carcass weight, subcutaneous fat or dressing percentage between the treatments. But there were higher carcass yields and larger longissimus muscle areas in those beef steers than in the control animals. A study exploring the effects of feeding duration on the composition of carcass of the beef steers found out that regardless of the duration of feeding, steers fed on ZH yielded heavier carcasses large dressing percentages and rib eye areas, but the yield grades were lower than in the control carcasses. The quality of grade of meat was also affected by ZH where control carcasses graded higher than those fed on ZH with increased duration of feeding. Therefore it was concluded that there was no added benefit in the carcass yield to merit ZH feeding for longer than 20 days before slaughter (Gunderson 2006).
The effect of ZH on tenderness was also looked at. It was found out that beef cattle supplemented with ZH for 30 days had tougher longitudinal steaks when compared to the control cattle. Lower tenderness scores were recorded in cattle fed on ZH for 45 days. There was no big difference in the values of shear force in steers fed on 0.15 mg/kg of ZH for 49 days. It was concluded that ZH supplementation for longer periods has detrimental effects on meat tenderness, variations in studies may be due level of dosage of ZH or duration and also due to the genetic variations in the cattle used. Effect on the color of meet was also examined in this study. It was noted that steaks from bulls fed on ZH in 30 days were lighter and more vivid than the control ones. When percentage metmyoglobin was measured it was found that it was lower in beef steaks from ZH fed bulls. It was therefore concluded that the display color was improved throughout storage with the level of ZH used. There is therefore a general minimal to slight positive effects regarding the display and instrumental color of the different cuts from cattle that are supplemented with ZH (Gunderson 2006
In the study done to evaluate the effects of ZH on feedlot performance, carcass characteristics, and the quality of meet from beef steers where the initial weight was the same from all treated groups, it was noted that the final weight was greater those supplemented with ZH than in the control steers. Those fed on ZH had 26% greater ADG values than the control steers. The effect on hot carcass weight was also noted where carcasses from steers fed on ZH were 7% heavier than the control carcasses. These therefore mean that carcass yields were improved on application of ZH. The LM area also increased in steers fed on ZH. This study also found out that there was an apparent LM area toughening and increased redness of the LM area than the control steers. There was an increase in the percentage of total wholesale carcass lean on supplementation with ZH. There was no observed effect of ZH treatment on the lean trim percentages. There was a significant reduction recorded in the bone percentage in the carcass side. Carcass fat did not change on supplementation of ZH. It was noted that although most primals were not affected by ZH treatment, many cuts were found to have increased in weight with the inclusion of ZH. ZH feeding brought about an increase in the weight of pectoral meat, rib blade meat, and in the pastrami meat. The inclusion of Zilpaterol also led to an increased weight of the whole brisket. It was also noted that most muscles and primals from the hind quarters showed greater response to the application of ZH when compared the ones from the forequarter. There was an increase in weight on supplementation with ZH in the more highly valued cuts like the strip loin, peeled tenderloin, and the sirloin butt. Many other cuts especially from the hindquarters were also heavier from the use of ZH such as the bottom sirloin tri-tip, the top inside round, bottom round flat, eye of round, and the flank steak. ZH also led to increases in weight in the heel, and the shank. It was generally noted that regardless of any other changes, carcass yields increased with the application of ZH. But when the carcasses were deboned, it was noted that there was no difference in the amount of lean when compared with the control steers (Shook et al. 2010).
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Effects of ZH withdrawal time on cold carcasses were also noted where it was observed that carcasses from animals withheld for three days had lighter weights in comparison to other carcasses. It was observed that when exposed for a longer time, ZH alters mRNA and the concentration of protein of β-adrenergic receptors of the cells of muscles, which in turn could affect the body's cellular response to ZH. The shear force of the strip loin steaks were seen to be significantly less in the control steers than in the ZH treated ones. There was no effect on moisture with the application of ZH on the ground beef trim and also on the moisture and fat content of the strip loin steaks. But increases were observed in the percentage protein of the ground beef trim having ZH supplementation. There was a different effect that withdrawal time had on the proximate analysis determination when compared with the ones having ZH supplements (Shook et al. 2010).
The amount of Zilpaterol residues in meat can be determined by many methods which are mostly traditional. These traditional methods need expensive procedures. Enzyme immunoassay (ELISA) is used instead as a screening system. It is simple, rapid, sensitive and also cost effective. Method of application is based on a competitive calorimetric ELISA assay. In the analysis, there is addition of the sample along with the primary antibody that is specific to the target organ. If present, the target will compete with the antibody preventing it from binding to the drug. The secondary antibody that is tagged with a peroxidase enzyme targets the primary antibody that is complexed to the drug coated on the wells of the plate. These see the resulting intensity of color, after adding the substrate, having an inverse relationship with intended concentration in the sample (ELISA test 2008).
The other test is the gas chromatography/ tandem mass spectrometry. The test identifies and simultaneously quantifies Clenbuterol-like substances that have anilinic moieties and drugs having phenolic and catecholic moieties in retinol tissue. This method was validated according to SANCO/1805/200. Samples were cleaned up after extraction in 0.1N HCL on a C18 non-endcapped solid phase extraction columns where it was analyzed as trimethylchlorosilane derivative (Bocca et al. 2003).
Zilpaterol is used as a food additive to promote leanness in beef animals for their meet. It brings about dramatic body growth a factor that makes it be confused with steroids or growth hormones which are prohibited for use. Many individuals usually attain and administer the drug illegally. Most illegal practices involve administering the drug outside registered feedlots, in show cattle, and in other types of animals that are not approved for its use. It is also implicated for making pigs more vulnerable to stress from handling, with physiological and behavioral changes and making them more aggressive. This has therefore seen many countries ban its use (Rampellini 2010).
Zilpaterol is a β-AA, an organic molecule that binds to β-AA receptors in the mammalian cells to increase their skeletal muscles and protein content via hypertrophy and reduce accretion of fats. The feeding of ZH to finishing cattle in the last 20 to 40 days has many effects on growth, lean meat deposition in carcasses, and efficiency. Changes in lean tissue bring about desirable fabrication yields of the carcasses. These also affect the quality characteristics of beef. These changes in turn affect consumer acceptance of these products and there Zilpaterol should be used appropriately so as to get good results that will satisfy both parties. There have been cases of abuse of the drug that has seen it banned from use in a number of countries where acute toxicity from the drug was recorded in some consumers. But it has been confirmed that appropriate use of this drug may optimize the performance of animals without compromising meat quality substantively.