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7
Nonnutritive Feed Additives
Nonnutrient feed additives are commonly included in swine diets. Of these, the antimicrobial agents are the additives most commonly used. Antimicrobial agents, along with anthelmintics, are defined as "drugs" by the Food and Drug Administration (FDA). Thus, their usage levels, allowable combinations, and periods of withdrawal prior to slaughter are regulated by the FDA and are published annually in the Feed Additive Compendium (1998). In addition, certain other additives are sometimes included in swine diets. The association of American Feed Control Officials (1998) has established guidelines for the use of many of these products in animal feeds.
Additives
Antimicrobial Agents
These are compounds that suppress or inhibit the growth of microorganisms. This class of compounds includes the antibiotics (naturally occurring substances produced by yeasts, molds, and other microorganisms) and the chemotherapeutics (chemically synthesized substances). They are added to feed at low (subtherapeutic) levels for growth promotion, improvement of feed utilization, reduction of mortality and morbidity, and improvement of reproductive performance. Antimicrobial agents also are used at moderate-to-high (prophylaxis) levels for the prevention of disease in exposed animals, and at high (therapeutic) levels for the treatment of certain swine diseases. Currently, 17 antimicrobial agents are approved for use in swine feed (Feed Additive Compendium, 1998). Of these, eight require withdrawal from the feed (on schedules ranging from 5 to 70 days) before animals are slaughtered, and nine do not require a withdrawal period.
The efficacy of antimicrobials in improving the rate and efficiency of growth in pigs is well documented, as reviewed by Hays (1978), Zimmerman (1986), and Cromwell (1991). A summary of 1,194 experiments involving 32,555 pigs indicated that antimicrobials improved growth rate by 16.4 percent in weanling pigs (7 to 25 kg body weight), by 10.6 percent in growing pigs (17 to 49 kg), and by 4.2 percent in growing-finishing pigs (24 to 89 kg) (Hays, 1978; Zimmerman, 1986). Improvements in efficiency of feed utilization for these same groups were 6.9, 4.5, and 2.2 percent, respectively. Responses in pig growth to the feeding of antimicrobials are greater under field conditions than in controlled experiments at research stations (Cromwell, 1991). A summary of 67 field trials with young pigs indicated that the feeding of antimicrobials reduced mortality by one-half (4.3 versus 2.0 percent), with even greater reductions in mortality when disease levels were high (15.6 versus 3.1 percent) (Maddox, 1985).
Antibacterial agents also are effective in improving reproductive performance (Cromwell, 1991). A summary of nine experiments (1,931 sows) indicated that farrowing rate was improved from 75.4 percent in controls to 82.1 percent in treated sows, and the number of live pigs born was increased from 10.0 to 10.4, respectively, when antimicrobials were included in the diet at the time of breeding. In 11 experiments (2,105 sows), inclusion of antimicrobials in the lactation diet increased survival of pigs to weaning (84.9 versus 87.1 percent of pigs born alive) and pig weaning weights (4.65 versus 4.70 kg).
Although the mechanism of action of antimicrobials is not well understood, their effects are generally grouped into three categories: a metabolic effect, a nutritional effect, and a disease-control effect. The first effect implies that these compounds directly influence certain metabolic processes in the animal (e.g., increased rate of protein synthesis). The second effect implies that antimicrobials cause changes in the microbial population that result in increased utilization of nutrients by the host animal. This effect is supported by evidence that antimicrobials reduce
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intestinal wall thickness (thus improving absorption of nutrients), and that they reduce total gut mass (thus reducing heat loss from tissues with high metabolic activity). Most of the data support the disease control effect as the primary mode of action. This effect implies that antimicrobials suppress microorganisms that cause nonspecific, subclinical disease, thereby allowing the host animal to achieve a growth rate closer to its maximum potential. This suggested mechanism of action is supported by the greater response to antimicrobials that occurs in young versus older pigs, in a "dirty" versus "clean" environment, and in low-health versus high-health animals.
Anthelmintics
This class of drugs, also called "dewormers," is included in feed to control internal parasites (e.g., roundworms, lungworms, threadworms). One drug, ivermectin, also is effective as a systemic for the control of external parasites (lice and mange). Of the seven anthelmintics currently approved for swine, five have specified withdrawal periods before slaughter (24 hours to 30 days) and two have no withdrawal period (Feed Additive Compendium, 1998). One compound in this group, dichlorvos, has been shown to reduce the incidence of stillbirths and increase pig weaning weights (Siers et al., 1976; Young et al., 1979) and may play a role in the immune response (Murray, 1983).
Microbial Supplements
Microbials that are directly fed, once referred to as "probiotics," consist of live (viable), naturally occurring microorganisms such as Lactobacillus acidophilus, Streptococcus faecium, and Saccharomyces cerevisiae. The suggested action of these supplements is that they enhance the intestinal microbial balance in the host animal. In some instances, these products have been reported to benefit pig performance under field conditions, generally under high-stress conditions (Pollmann, 1986; Stavric and Kornegay, 1995); however, most controlled experiments at research stations have failed to show consistent, beneficial responses from their inclusion. A review of these products was written by van Belle et al. (1990).
Oligosaccharides
Inclusion of certain oligosaccharides (e.g., mannooligosaccharides, fructooligosaccharides) in the diet has been proposed to alter the ability of specific pathogens to colonize the intestinal tract (Monsand and Paul, 1995; Newman, 1995). The effect of oligosaccharides on performance of pigs is not well established. Some reports have shown a benefit in performance of young pigs from fructooligosaccharide inclusion (Hidaka et al., 1986; Fukuyasu and Oshida, 1988), whereas others have not (Farnworth et al., 1991, 1992, 1995; Kornegay et al., 1992).
Enzymes
Mixtures of cellulases, hemicellulases, and proteases are sometimes added to feeds in an attempt to improve the digestibility of complex carbohydrates and proteins. They are more commonly used in Europe, where diets are composed of a more diverse group of feedstuffs, than in North America, where diets tend to be based on corn or grain sorghum and soybean meal. Some research has shown these enzymes to be beneficial (Wenk, 1992). In areas where barley or rye is used, β-glucanase and pentosanases sometimes are included to degrade the β-glucans and pentosans (complex carbohydrates that interfere with digestibility of other nutrients) found in these cereal grains (Newman et al., 1980; Li et al., 1996), but improvements in pig performance do not necessarily occur (Thacker, 1993; Thacker and Baas, 1996). Varied responses have been shown to the addition of amylases and proteases to diets for very young pigs to aid in nutrient digestibility (Lewis et al., 1955; Cunningham and Brisson, 1957a,b; Combs et al., 1960). Recent reviews contain additional information on feed enzymes (Wenk and Boessinger, 1993; van Hartingsveldt et al., 1995).
An enzyme that has recently received considerable attention is phytase. This enzyme cleaves the ortho-phosphate groups from phytic acid (phytate), the predominant form of phosphorus in cereal grains and oilseed meals. Phytase supplementation markedly improves the utilization of phytate phosphorus by pigs (Simons et al., 1990; Jongbloed et al., 1992; Cromwell et al., 1995) and reduces the excretion of phosphorus into the environment. For additional information on phytase, see Chapters 4 and 8.
Acidifiers
Citric acid, fumaric acid, or formic acid additions to starter diets have been shown to enhance performance in early-weaned pigs (Kirchgessner and Roth, 1982, 1987; Falkowski and Aherne, 1984; Giesting and Easter, 1985; Burnell et al., 1988; Ravindran and Kornegay, 1993). Inorganic acids, such as phosphoric acid and, in some instances, hydrochloric acid, also have been found to be beneficial to young pig performance (Schoenherr, 1994; Bergstrom et al., 1996; Mahan et al., 1996). The mechanism of action is not clear, but it may be related to a reduction in pH in the upper intestinal tract, thereby reducing the potential for proliferation of undesirable microorganisms in the stomach and small intestine. Organic acids also have been used to preserve high-moisture grains and as mold inhibitors in feeds (Crenshaw et al., 1986).
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Flavors
Synthetic flavors are added to feed to improve palatability and/or to mask off-flavors or off-odors in feed. Most research indicates that pigs may select diets with added flavors or aromatic compounds when given a choice; but when pigs are not given a choice, benefits from most flavors or aromatics are negligible (Hines, 1973; Hines et al., 1975; Kornegay et al., 1979; Ogunbameru et al., 1979). A review of flavors was written by McLaughlin et al. (1983).
Odor Control Agents
Sarsaponin, an extract from the yucca plant (Yucca schidigera), inhibits urease activity and is claimed to reduce odor in swine manure. In some instances, sarsaponin has been found to increase performance in weanling and growing-finishing pigs (Foster, 1983; Cromwell et al., 1985) and to reduce ammonia emissions (Sutton et al., 1992). Other products consisting of dried, live, naturally occurring microorganisms are claimed to reduce manure odor when added to feed. In some instances, zeolites have been shown to reduce odors and nitrogen volatilization (Barrington and El Moueddeb, 1995). Some of the oligosaccharides have been shown to alter hind gut microorganisms and reduce odor in swine manure (Sutton et al., 1991; Farnworth et al., 1995).
Antioxidants
These products are added to feeds to inhibit oxidation of fat or vitamins. Examples are ethoxyquin and butylated hydroxytoluene (BHT).
Pellet Binders
Certain clays (e.g., bentonite) are added to feed prior to pelleting in order to promote cohesiveness and inhibit crumbling of pellets. Some of the clays and zeolites also protect against aflatoxicosis in pigs by binding aflatoxins and preventing their absorption (Schell et al., 1993); however, they are not approved by the FDA for this purpose.
Flow Agents
These products are the same as or similar to pellet binders. Their purpose is to prevent caking and improve the flow characteristics of certain ingredients. An example is hydrated sodium calcium aluminosilicate. Although not approved for aflatoxicosis prevention, this product is also effective in binding aflatoxins (Lindemann et al., 1993).
Mineral Supplements
High levels of dietary copper (100 to 250 ppm copper, as copper sulfate) have been shown to stimulate growth rate, feed intake, and efficiency of feed utilization in pigs, especially during the postweaning and the early growth phases (Braude, 1945, 1975; Cromwell, 1991). Also, high dietary copper for sows has been found to increase pig weaning weights (Cromwell et al., 1993). Recent studies have also shown that high levels of zinc (3,000 ppm zinc, from zinc oxide) stimulate feed intake and growth rate in young pigs (Hahn and Baker, 1993; LeMieux et al., 1994; Hill et al., 1996). For further information and documentation, the reader is referred to the sections on copper and zinc in Chapter 4.
Carcass Modifiers
Several β-adrenergic agonists, including clenbuterol, cimaterol, and ractopamine, increase carcass leanness when included in the diet (Jones et al., 1985; Moser et al., 1986; Cromwell et al., 1988; Watkins et al., 1990; Bark et al., 1992). However, these substances are not yet approved in the United States for use in swine. Under certain conditions, betaine and carnitine have been found to improve carcass leanness (Odle, 1995). Chromium also has been shown to improve carcass leanness when added to the diet as chromium picolinate in some instances (Page et al., 1993; Lindemann et al., 1995; Mooney and Cromwell, 1995), but not in others (Mooney and Cromwell, 1996; Crow and Newcomb, 1997). There is recent evidence that positional and geometric isomers of conjugated dienoic fatty acids (derivatives of linoleic acid [CLA]) reduce body fat and increase lean tissue when fed to mice, rats, and chicks (Pariza et al., 1996; Park et al., 1997), and though data are limited, CLA may produce a similar effect when fed to pigs (Pariza, 1997; Parrish et al., 1997). Certain carcass modifiers (e.g., β-agonists) can alter nutrient requirements (Anderson et al., 1987).
Safety Concerns
There is concern by some that the feeding of antimicrobials to animals contributes to a reservoir of drug-resistant enteric bacteria that are capable of transferring their resistance to pathogenic bacteria, thereby causing a potential public health hazard (Smith, 1962; Falkow, 1975; Linton, 1977). The greatest concern is in regard to penicillin and the tetracyclines, because they also are used in human medicine.
Although transfer of antibiotic resistant plasmids (R-plasmids) occurs in vitro, the extent to which it occurs in the animal, and between animal bacteria and human
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bacteria, is not well documented. Animal bacteria do not colonize very effectively in humans unless extremely large doses are consumed; and even then, they are transient (Smith, 1969).
In 1987, the Food and Drug Administration asked the Institute of Medicine of the National Academy of Sciences to conduct an independent review of the human health consequences and make a quantitative risk assessment associated with the use of penicillin and the tetracyclines at subtherapeutic levels in animal feeds. The committee was unable to find a substantive body of direct evidence that established the existence of a definite health hazard in humans associated with the use of these antimicrobials in animal feeds (Institute of Medicine, 1988). Similarly, other task forces concluded that there was no conclusive evidence of human health being compromised by subtherapeutic antimicrobial usage in animals (National Research Council, 1980; Council for Agricultural Science and Technology, 1981).
Monitoring and surveillance of bacterial resistance in animals and in humans has continued, with no animal-to-human infection path being clearly delineated. Although the incidence of antimicrobial resistance in the human population remains high, there is no evidence that the levels or patterns have changed (Lorian, 1986). Although antimicrobial agents have been fed to billions of animals for over 45 years, there is still no convincing evidence of any unfavorable health effects in humans that can be directly linked to the feeding of subtherapeutic levels of antibiotics to animals.
Regulations
Regulations and constraints on the use of feed additives vary among countries. In addition, the approved uses of additives are subject to change. For official information concerning U.S. Food and Drug Administration approval of feed additives and other animal drugs, the Code of Federal Regulations, Title 21, should be consulted. A revised edition of Title 21 is available in April of each year. Individual issues of the Federal Register update the Code of Federal Regulations . The Federal Register and the Code of Federal Regulations must be used together to determine the latest version of any rule. Title 21 is published in six parts. Part 500-599 covers animal drugs, feeds, and related products. It is available from the Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402. The Federal Register is available from the same address and includes monthly issues of the "List of Code of Federal Regulations Sections Affected" and "The Federal Register Index."
Additional information on feed additives, usage levels, and legal requirements is available in the Feed Additive Compendium, which is published yearly by the Miller Publishing Company, 12400 Whitewater Drive, Minneapolis, MN 55343, and in the compendium of Medicating Ingredient Brochures, Feed and Fertilizer Division, published by Agriculture Canada, Ottawa, Ontario, Canada. The Compendium of Medicating Ingredient Brochures is available from Supply and Services Canada, Canada Communications Group, Ottawa, Ontario, Canada, K1A 0S9.
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Representative terms from entire chapter:
feed additives
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