Feed Additives AnSci 320 2-27-12 Lance Baumgard baumgard@iastate.edu

Feed Additives Antibiotics: disease prevention Coccidiostats: control parasites Xanthophyll: makes egg yolks yellow Hormones (hormone like): increases growth Yeast, Fungi, Direct fed microbials: Buffers: HCO3 etc.. Prevent rumen acidosis Antioxidants: prevents feed from getting rancid Pellet Binders: keeps feed in pellet form Flavoring Agents: makes feed taste better

FEED ADDITIVES Feed additives used in livestock supplements and rations to improve performance & animal health. Use of feed additives is strictly regulated in the developed countries, and many others, to ensure: Human food safety; Animal safety. Additive efficacy; Minimal environmental impact. Dramatic increase in globalization of marketing of animal products has led to more uniformity in regulations among countries. Animal products must comply with the laws of the countries to which they are being sold.

AFCO defines a feed additive as… FEED ADDITIVES AFCO (American Feed Control Officials) provides the U.S. mechanism for developing/implementing uniform & equitable laws, regulations, standards, and enforcement policies. Regulating manufacture, distribution, and sale of safe and effective animal feeds. AFCO defines a feed additive as… "an ingredient or combination of ingredients added to the basic feed mix …to fulfill a specific need." " …usually used in micro quantities and requires careful handling and mixing"

FEED ADDITIVES In practice, feed additives are defined as feed ingredients of a nonnutritive nature that… Stimulate growth or other types of performance. Improve the efficiency of feed utilization. Are beneficial in some manner to health or metabolism of the animal.

FEED ADDITIVES Of the groups of additives classed as drugs, the major groups include many different compounds: Antibiotics, nitrofurans and sulfa compounds. Coccidiostats, wormers (antihelminthics & others), and hormone-like compounds. Feed additives have been used extensively in the U.S. and many other countries since the discovery & commercial production of antibiotics and sulfa drugs in the late 1940s. The European Union recently banned feeding of antibiotics to animals meant for human consumption.

FEED ADDITIVES Animal products are routinely tested to ensure that feed additives are being used correctly. Use of feed additives has been beneficial to livestock producers under our modern methods of production. Development of intense systems of management and concentration of animals has been made possible only because additives could be used to help control various diseases and/or parasites. Broilers, laying hens, growing-finishing pigs, and fattening cattle and sheep.

USE OF FEED ADDITIVES CLASSED AS DRUGS In the U.S., use & regulation of additives classed as drugs is controlled by the Center for Veterinary Medicine, within the FDA. To determine that drugs & medicated feed are properly labeled for intended use and that animal feeds and food derived from animals are safe to eat. Federal law states no animal drug can be used in feed until adequate research submitted to the FDA proves the drug is both safe and effective. In developing a new drug for use with animals, manufacturers must go through extensive testing.

USE OF FEED ADDITIVES CLASSED AS DRUGS Requirements for Medicated Feed FDA requirements for medicated feed focus on mixers who use human-risk drug sources. Mixers who do not use human-risk drug sources are subject to less demanding regulation.

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics Antibiotics are compounds produced by microorganisms. With properties of inhibiting growth/metabolism of some (not all) other microorganisms. In some instances, they may be toxic to warm- blooded animals. Most antibiotic names end in -cin or -mycin. All antibiotics used commercially for growth promotion are produced by fermentation processes using fungi or bacteria.

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics Antibiotics have been effective, in general, as production improvers when fed at low levels to young, growing animals.

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics Use tends to result in an increased feed intake. Growth is nearly always increased, particularly with animals exposed to adverse environmental conditions. Feed intake usually decreases in ruminants Response in growth & feed efficiency varies by animal species, time of year and location. Antibiotic-fed animals are less apt to go off feed. Antibiotics may be useful for other purposes, such as the prevention and control of a wide variety of animal and poultry diseases. As a rule, reduce the incidence or severity of several types of diarrhea

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics Some are approved at low levels of continuous use for reducing the incidence of… Enterotoxemia (overeating disease) in lambs. Liver abscesses in fattening cattle Diarrhea in young mammals deprived of colostrum. In poultry, some claims include… Reduction in respiratory disease. Nonspecific enteritis (blue comb) & infectious sinusitis. Improved egg production and hatchability. Antibiotics are often used at therapeutic levels in treatment or control of many common diseases.

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics At higher levels for therapeutic treatments, antibiotics have been very useful for… Cattle for treating or preventing stresses associated with transportation and adjustment to new conditions. Treatment of diseases such as anaplasmosis in cattle and bacterial enteritis in swine. Respiratory diseases, diarrhea, fowl cholera, fowl typhoid, and breast blisters in poultry. In most instances, the higher levels are not approved for long-term usage.

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics Two antibiotics for use in cattle, monensin and lasalocid, are unusual in that they give a good response in both growing and mature animals. Approval was first received for use as coccidiostats with poultry. Both of these antibiotics are quite toxic to horses.

Dietary Polysaccharides Bacterial enzymes Monosacharides (glucose: 6 Carbons) CH4 Glycolysis H CO2 Pyruvate (3 C) Acetate (2 C) Propionate (3C) Butryate (4C)

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics Obtaining approval for new feed additive drugs has become more difficult in recent years. More investigative effort & expense are involved. As a result, not many new additives have been approved in recent years. Very few additives are approved for horses, rabbits, sheep, goats, ducks, pheasants & quail. No approvals are given for geese or pets such as cats and dogs. The primary reason is the cost of obtaining approval in relation to potential sales volumes.

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics Many antibiotics approved for cattle are tested with sheep, but few are ever approved for sheep. Even fewer for species other than cattle, swine, chickens, and turkeys, because of the costs.

USE OF FEED ADDITIVES CLASSED AS DRUGS Antibiotics In poultry, the trend is to use one or more antibiotics in nearly all broiler feeds. Most can be used for layers, except high levels of chlortetracycline and erythromycin. Manufacturer approval must be obtained for using different combinations of antibiotics. Or combinations of antibiotics & other controlled drugs. Far more drug combinations have been approved for chickens & turkeys than all other animals combined. It is illegal to feed antibiotics at different levels or in different combinations from those previously approved.

USE OF FEED ADDITIVES CLASSED AS DRUGS Arsenicals Arsenicals are all synthetic compounds (chemotherapeutic agent) & include a number of drugs used in turkey, chicken, and swine rations. Developed as a means of controlling parasites. Some compounds stimulate growth in the same manner as antibiotics. The effect can be additive to antibiotic stimulation. Several arsenicals have claims of improved growth production as well as improved feed efficiency for chickens, turkeys, or swine. And control of blackhead in poultry & diarrhea in swine.

USE OF FEED ADDITIVES CLASSED AS DRUGS Arsenicals Arsenicals have the disadvantage that they may accumulate in body tissues, particularly the liver. At the levels fed, they are not considered to be toxic. All have a minimum 5-day withdrawal period before animals are to be slaughtered for human food.

USE OF FEED ADDITIVES CLASSED AS DRUGS Coccidiostats Coccidia are microscopic parasites. Coccidiostats include a wide variety of compounds, ranging from a number of synthetic drugs to several of the antibiotics. These drugs are of considerable importance to the poultry producer because close confinement methods used in modern facilities accentuate the possibility of coccidiosis outbreaks. Evidence suggests coccidiosis is becoming a greater problem with sheep & cattle in close confinement.

USE OF FEED ADDITIVES CLASSED AS DRUGS Nitrofurans The nitrofurans are antibacterial compounds and are effective against a relatively large number of microbial diseases. Continued use of nitrofurans has not as yet developed bacterial resistance, as is the case for some antibiotics. Nitrofurans are often used in combination with other drugs, especially with swine and poultry.

USE OF FEED ADDITIVES CLASSED AS DRUGS Sulfas The first sulfa drug was synthesized in the 1930s, and early ones were used extensively against some human diseases very difficult to treat at the time. Most sulfas present problems with tissue residues, and some of the injectables result in tissue residues in edible cuts of meat. There has been a gradual withdrawal of sulfa drugs as feed additives. Most of problems alleviated by sulfas can be treated successfully with other drugs.

USE OF FEED ADDITIVES CLASSED AS DRUGS Hormone-like Production Improvers Melengestrol acetate is the only hormone-like production improver remaining on the approved list. Extensively used with beef heifers; it acts to suppress estrus, resulting in more efficient and more rapid gain.

USE OF FEED ADDITIVES CLASSED AS DRUGS Hormone-like Production Improvers Although not feed additives, several products are available for use as subcutaneous implants. Hexestrol, (outside the U.S.) Zeranol (Ralgro™), said to be an anabolic agent. Synovex™, a combination of estrogen & progesterone. Rapid Gain™, a combination of testosterone & estrogen Steer-oid™, a combination of progesterone and estradiol. A high percentage of growing- finishing cattle are treated with one or another of these implants.

Implants Implants for Growth Stimulation Designed for slow release Growth promotion, feed efficiency Products Ralgro Use in calves, growing cattle, feedlots animals 70-110d response Cattle should be reimplanted every 65-100d for maximum Magnum Double dose of Ralgro Best in initial 70-90d on feed

Implants Synovex or Implus Different forms for different cattle Stimulates muscle deposition Increases growth hormone secretion Revalor Claims to improve gain 15-20% Improves feed efficiency 15% Duration of response 100d May reduce marbling

Feed Additives and Implants Hormone Implants Most are pelleted Synthetic or natural Improves rate of gain and feed efficiency

Hormone Implantation

USE OF FEED ADDITIVES CLASSED AS DRUGS Hormone-like Production Improvers In ruminants, natural or synthetic hormones produce a response that results from increased nitrogen retention accompanied by an increased intake of feed. Increased growth rate; Improvement in feed efficiency. Reduced deposition of body fat, which may, at times, result in a lower carcass grade for animals fed to the same weight as nontreated animals.

Steroids (Estrogens and Androgens) Classification Estrogenic Androgenic Predominate illegal steroid in humans Progestin Non-steroidal

Steroids (Estrogens and Androgens) Animal agriculture Approved for beef Not as effective in pigs Effects Increased protein accretion Decreased fat accretion Increased average daily gain Increased feed efficiency

Negative side effects (humans) Both Genders Increased heart disease, liver cancer, acne, male pattern baldness Females: Decreased breast size, deepening of voice, increase in body hair Males: reduced sperm production, shrinking of the testicles, impotence, difficulty or pain in urinating, baldness, and irreversible breast enlargement, testicular shrinking

Improves animal performance Taken illegally by body builders Steroid summary Improves animal performance Approved for beef cattle Taken illegally by body builders Used legally for many health reasons

-agonists Reasons for interest: Human medicine Agriculture Branchodialators Agriculture Increase growth Enhanced muscle Decreased fat Approved for pigs and cattle Feed supplement Orally active

-agonists Molecules that structurally resemble epinephrine Caffeine, ephedrine, aspirin Easily made in the lab Muscle: Increase in muscle synthesis Decrease in muscle breakdown Fat Decrease in lipogenesis Increase in lipolysis

control 50 d/150.5 kg feed 100 kg of bw 46 d/132 kg feed -agonist Ham 14.3 kg 13.3 kg Loin 11.2 10.7 Shoulders 11.9 11.2 Belly 10.2 10.3 Carcass lean 43.9 39.4 Moody et al., 2000

 Agonist summary Structurally resembles epinephrine Increases muscle synthesis Need to increase the protein % of diet Decreases fat content Orally active Desensitization Recently approved for pigs and beef cattle

Buffers and Neutralizers Buffers & Neutralizers Compounds that minimize pH decreases Sodium bicarbonate Potassium bicarbonate Calcium carbonate Mag oxide Mag carbonate

DFMs and Yeast Lactobacillus, streptococcus, fungi, aspergillus, bacillus Probiotics Scientifically inconsistent Consist of microbial cultures Can stimulate cultural growth Reasons for use Increase/balance beneficial bacteria Reduce toxic byproducts of digestion Support rate of gain and feed efficiency Alleviate/minimize stress Various times for use When do you use them? Available forms Feed additives Water dispensing Bolus/gel form

Pet Food Pet food, including dry and canned food and pet treats, is considered to be animal feed. Like other animal feed, FDA regulates pet food and establishes standards for labeling. Pet food labeling is regulated at two levels: federal and state. The federal regulations, enforced by FDA’s Center for Veterinary Medicine, establish standards that apply to all animal feeds: proper identification of the product net quantity statement manufacturer’s address proper listing of ingredients FDA carries out its animal feed regulatory responsibilities in cooperation with state and local partners, and works together with AAFCO on uniform feed ingredient definitions and proper labeling.