EFFECT OF DIETARY COPPER AND TYLOSIN AND SUBSEQUENT WITHDRAWAL ON GROWTH, HEMATOLOGY AND TISSUE RESIDUES OF GROWING-FINISHING PIGS
Nutrition Institute, Beltsville, MD 20705 and Food and Drug Administration, Bureau of Veterinary Medicine, Beltsville, MD 20705
SUMMARY Early-weaned pigs were fed O, 125, 250 and 500 ppm copper with or without 55 ppm tylosin supplement through 50 kg body weight and thereafter a standard finisher diet through 100 kg body weight. Blood samples were collected at 10, 30, 50, 60, 75, 80 and 100 kg body weights for copper analyses;liver, kidney and loin samples were obtained for copper analyses from randomly selected pigs sacrificied at 50, 75 and 100 kg body weights. Average daily gain and feed/gain were significantly depressed by 250 and 500 ppm copper, while tylosin effects were significant for average daily gain from initial to 10 kg body weight. Hemoglobin and hematocrit values were significantly decreased by 250 and 500 ppm supplemental copper beginning with 30 and 10 kg body weight, respectively. Recovery was rapid after copper withdrawal. Tissue copper residues were greatest in liver, intermediate in kidneys and lowest in longissimus and plasma at 50 kg body weight. The differences were significant for liver and kidneys when compared with those of controls. Although not significant, the tissue copper concentration was higher in presence than in absence of tylosin, especially for liver and kidneys at 50 kg body weight. Residue copper in the longissimus and blood plasma remained unchanged. After supplemental copper withdrawal, a drastic reduction in residue copper was noted for liver and kidneys; however, the differences were significant for liver
only. Tylosin effects were nonsignificant for residue copper despite the increased copper concentration in liver and kidneys at 50 and 75 kg body weights and in liver at 100 kg body weight. The results suggest that, if copper is to be included in grower swine diets, the supplemental copper level for maximum average daily gain, feed/gain, hematology and residue copper in tissues should not exceed 125 ppm and should be restricted to pigs under 50 kg body weight. (Key Words: Copper, Tylosin, Growth, Tissue Residues, Swine.)
INTRODUCTION
The role of supplemental copper in swine diets has been the subject of numerous investigations. An extensive literature review by Braude (1965) indicated beneficial effects of 250 ppm copper for pigs with respect to growth, feed/gain, hematopoiesis and other parameters. However, Wallace (1967) in his extensive review of copper research in the U.S.A. concluded that the optimum level of copper was not obvious from the compiled data, that copper was generally somewhat more effective than antibiotics and other additives and that the combination of copper with certain antibiotics produced an additive effect. By testing 26 comparisons of different chemotherapeutics or combinations of chemotherapeutics (antibiotics, copper, arsanilic acid, furazol), Clawson and Alsmeyer (1973) found significant differences among medicants in only five comparisons. Because of the discrepancies t U.S. Department of Agriculture, Nonruminant found in the literature, studies were initiated to Animal Nutrition Laboratory. determine (1) the effect of supplemental cop2Department of Health, Education and Welfare. per and subtherapeutic levels of tylosin on 3The authors express gratitude for the valuable growth performance and (2) the effect of statistical services rendered by Dr. Bernie Weirdand of the Biometrical Services Staff, A.R.S., U.S.D.A., Belts- copper and tylosin withdrawal on depletion of ville, MD 20705. body stores of pigs reared in total confinement. 100 JOURNAL OF ANIMALSCIENCE,Vol. 45, No. 1, 1977
Downloaded from https://academic.oup.com/jas/article-abstract/45/1/100/4697473 by Iowa State University user on 16 January 2019
R. J. Lillie I , L. T. Frobish I , N. C. Steele I and G. Graber 2,3
COPPER AND TYLOSIN FOR PIGS EXPERIMENTAL PROCEDURE
The 96 pigs were confined in a multiple-unit house equipped with automatic waterers, partially slotted floors and controlled gravity ventilation. Feed and water were available ad libiturn. Weekly records were taken for body weights and feed consumption. Dead pigs were autopsied at the Veterinary Laboratory. All replicates were ended when the average body weight of all surviving pigs was approximately 100 kilograms. A 4 • 2 factorial arrangement of dietary treatments consisting of four levels of copper as the sulfate salt (0, 125, 250 and 500 ppm Cu) and two levels of antibiotic supplement (0 and 55 ppm tylosin) was used. All supplements were added at the expense of ground yellow corn in the basal diet (table 1). At 50 kg body
weight, all dietary treatments were replaced by a standard finisher diet containing no antibiotic and 50 ppm copper for the rest of the experiment. For determination of the degree of retention and depletion of copper in the experimental animals, blood samples were obtained via anterior vena cava puncture at 10, 30, 50, 60, 75, 80 and 100 kg body weights. In addition, liver, kidney and longissimus samples were obtained from one pig per treatment per replicate sacrificed at 50, 75 and at 100 kg b o d y weights. Whenever mortality occurred, blood and tissue specimens were omitted at 75 kg b o d y weight for that particular treatment. Heparin was used at the rate of .2 mg per milliliter of blood to prevent coagulation. Hemoglobin (Hb) was determined by the cyanmethoglobin method of Crosby et al. (1954), and hematocrit (Hct) was determined by the microcapillary method of McGovern et al. (1955). After the Hb and Hct determinations were completed, the blood was centrifuged, and the resultant plasma reserved for residue copper analysis. The liver, kidney and longissimus samples were frozen at - 1 0 C, lypholized, ground and refrigerated at 0 C until the samples were analyzed for residue copper. Copper from plasma, liver, kidney and Ion-
TABLE 1. BASAL DIET COMPOSITION
Item Ingredient Corn, dent yellow, grain, gr US 2 ran, 54 wt (4) Soybean, see~ wo hulls, solv-extd grnd, mx 3% fiber (5) Vitamin-additive premixb Calcium carbonate Dicalcium phosphate Salt, iodized Trace mineral mix c Total Calculated analysis Protein, crude, % Energy, Met. Cal/kg Copper, ppm
Internat'l Ref. No. a
4.02-931 5-04-612 6-01-070 6-01-080
%
78.65 18.65 .10 .80 1.20 .50 .10 100.00 16.0 2753 15.9
alnternational Reference Number (Atlas of Nutritional Data on United States and Canadian Feeds.) 1971. National Academy of Sciences, Washington, DC. bsupplied the following (per kilogram of diet): vitamin A, 4,400 IU; vitamin D2,880 IU; riboflavin, 8.8 mg; pantothenic acid, 17.6 mg; niacin, 30.8 mg; choline, 220 mg; vitamin B~ 2,44 mcg; and vitamin E, 11 IU. CSupplied the following (ppm): manganese sulfate, 100; ferrous sulfate, 50; ferrous carbonate, 50; copper oxide, 10; cobalt carbonate, 1 ; potassium iodide, 3 ; and zinc sulfate, 100.
Downloaded from https://academic.oup.com/jas/article-abstract/45/1/100/4697473 by Iowa State University user on 16 January 2019
Four replicates with a total of 96 crossbred weaned pigs from 4 to 6 weeks o f age were started according to a randomized block design. In each replicate 24 pigs were randomly allotted eight dietary treatments of three pigs each on the basis of initial weights. Randomization was restricted in that littermates were distributed across treatments. The littermates were obtained from lactating sows fed a standard 16% protein diet containing 50 ppm copper.
101
102
LILLIE ET AL.
g i s s i m u s was determined by atomic absorption
RESULTS AND DISCUSSION
The average daily gain (ADG) and feed/gain (F/G) data through 50 kg are summarized in table 2. ADG decreased significantly as supplemental copper level increased in the 10 to 30, 30 to 50 and initial to 50 kg weight periods. F/G was also significantly increased by copper level in the 10 to 30 and 30 to 50 kg weight periods (P
Nutrition Institute, Beltsville, MD 20705 and Food and Drug Administration, Bureau of Veterinary Medicine, Beltsville, MD 20705
SUMMARY Early-weaned pigs were fed O, 125, 250 and 500 ppm copper with or without 55 ppm tylosin supplement through 50 kg body weight and thereafter a standard finisher diet through 100 kg body weight. Blood samples were collected at 10, 30, 50, 60, 75, 80 and 100 kg body weights for copper analyses;liver, kidney and loin samples were obtained for copper analyses from randomly selected pigs sacrificied at 50, 75 and 100 kg body weights. Average daily gain and feed/gain were significantly depressed by 250 and 500 ppm copper, while tylosin effects were significant for average daily gain from initial to 10 kg body weight. Hemoglobin and hematocrit values were significantly decreased by 250 and 500 ppm supplemental copper beginning with 30 and 10 kg body weight, respectively. Recovery was rapid after copper withdrawal. Tissue copper residues were greatest in liver, intermediate in kidneys and lowest in longissimus and plasma at 50 kg body weight. The differences were significant for liver and kidneys when compared with those of controls. Although not significant, the tissue copper concentration was higher in presence than in absence of tylosin, especially for liver and kidneys at 50 kg body weight. Residue copper in the longissimus and blood plasma remained unchanged. After supplemental copper withdrawal, a drastic reduction in residue copper was noted for liver and kidneys; however, the differences were significant for liver
only. Tylosin effects were nonsignificant for residue copper despite the increased copper concentration in liver and kidneys at 50 and 75 kg body weights and in liver at 100 kg body weight. The results suggest that, if copper is to be included in grower swine diets, the supplemental copper level for maximum average daily gain, feed/gain, hematology and residue copper in tissues should not exceed 125 ppm and should be restricted to pigs under 50 kg body weight. (Key Words: Copper, Tylosin, Growth, Tissue Residues, Swine.)
INTRODUCTION
The role of supplemental copper in swine diets has been the subject of numerous investigations. An extensive literature review by Braude (1965) indicated beneficial effects of 250 ppm copper for pigs with respect to growth, feed/gain, hematopoiesis and other parameters. However, Wallace (1967) in his extensive review of copper research in the U.S.A. concluded that the optimum level of copper was not obvious from the compiled data, that copper was generally somewhat more effective than antibiotics and other additives and that the combination of copper with certain antibiotics produced an additive effect. By testing 26 comparisons of different chemotherapeutics or combinations of chemotherapeutics (antibiotics, copper, arsanilic acid, furazol), Clawson and Alsmeyer (1973) found significant differences among medicants in only five comparisons. Because of the discrepancies t U.S. Department of Agriculture, Nonruminant found in the literature, studies were initiated to Animal Nutrition Laboratory. determine (1) the effect of supplemental cop2Department of Health, Education and Welfare. per and subtherapeutic levels of tylosin on 3The authors express gratitude for the valuable growth performance and (2) the effect of statistical services rendered by Dr. Bernie Weirdand of the Biometrical Services Staff, A.R.S., U.S.D.A., Belts- copper and tylosin withdrawal on depletion of ville, MD 20705. body stores of pigs reared in total confinement. 100 JOURNAL OF ANIMALSCIENCE,Vol. 45, No. 1, 1977
Downloaded from https://academic.oup.com/jas/article-abstract/45/1/100/4697473 by Iowa State University user on 16 January 2019
R. J. Lillie I , L. T. Frobish I , N. C. Steele I and G. Graber 2,3
COPPER AND TYLOSIN FOR PIGS EXPERIMENTAL PROCEDURE
The 96 pigs were confined in a multiple-unit house equipped with automatic waterers, partially slotted floors and controlled gravity ventilation. Feed and water were available ad libiturn. Weekly records were taken for body weights and feed consumption. Dead pigs were autopsied at the Veterinary Laboratory. All replicates were ended when the average body weight of all surviving pigs was approximately 100 kilograms. A 4 • 2 factorial arrangement of dietary treatments consisting of four levels of copper as the sulfate salt (0, 125, 250 and 500 ppm Cu) and two levels of antibiotic supplement (0 and 55 ppm tylosin) was used. All supplements were added at the expense of ground yellow corn in the basal diet (table 1). At 50 kg body
weight, all dietary treatments were replaced by a standard finisher diet containing no antibiotic and 50 ppm copper for the rest of the experiment. For determination of the degree of retention and depletion of copper in the experimental animals, blood samples were obtained via anterior vena cava puncture at 10, 30, 50, 60, 75, 80 and 100 kg body weights. In addition, liver, kidney and longissimus samples were obtained from one pig per treatment per replicate sacrificed at 50, 75 and at 100 kg b o d y weights. Whenever mortality occurred, blood and tissue specimens were omitted at 75 kg b o d y weight for that particular treatment. Heparin was used at the rate of .2 mg per milliliter of blood to prevent coagulation. Hemoglobin (Hb) was determined by the cyanmethoglobin method of Crosby et al. (1954), and hematocrit (Hct) was determined by the microcapillary method of McGovern et al. (1955). After the Hb and Hct determinations were completed, the blood was centrifuged, and the resultant plasma reserved for residue copper analysis. The liver, kidney and longissimus samples were frozen at - 1 0 C, lypholized, ground and refrigerated at 0 C until the samples were analyzed for residue copper. Copper from plasma, liver, kidney and Ion-
TABLE 1. BASAL DIET COMPOSITION
Item Ingredient Corn, dent yellow, grain, gr US 2 ran, 54 wt (4) Soybean, see~ wo hulls, solv-extd grnd, mx 3% fiber (5) Vitamin-additive premixb Calcium carbonate Dicalcium phosphate Salt, iodized Trace mineral mix c Total Calculated analysis Protein, crude, % Energy, Met. Cal/kg Copper, ppm
Internat'l Ref. No. a
4.02-931 5-04-612 6-01-070 6-01-080
%
78.65 18.65 .10 .80 1.20 .50 .10 100.00 16.0 2753 15.9
alnternational Reference Number (Atlas of Nutritional Data on United States and Canadian Feeds.) 1971. National Academy of Sciences, Washington, DC. bsupplied the following (per kilogram of diet): vitamin A, 4,400 IU; vitamin D2,880 IU; riboflavin, 8.8 mg; pantothenic acid, 17.6 mg; niacin, 30.8 mg; choline, 220 mg; vitamin B~ 2,44 mcg; and vitamin E, 11 IU. CSupplied the following (ppm): manganese sulfate, 100; ferrous sulfate, 50; ferrous carbonate, 50; copper oxide, 10; cobalt carbonate, 1 ; potassium iodide, 3 ; and zinc sulfate, 100.
Downloaded from https://academic.oup.com/jas/article-abstract/45/1/100/4697473 by Iowa State University user on 16 January 2019
Four replicates with a total of 96 crossbred weaned pigs from 4 to 6 weeks o f age were started according to a randomized block design. In each replicate 24 pigs were randomly allotted eight dietary treatments of three pigs each on the basis of initial weights. Randomization was restricted in that littermates were distributed across treatments. The littermates were obtained from lactating sows fed a standard 16% protein diet containing 50 ppm copper.
101
102
LILLIE ET AL.
g i s s i m u s was determined by atomic absorption
RESULTS AND DISCUSSION
The average daily gain (ADG) and feed/gain (F/G) data through 50 kg are summarized in table 2. ADG decreased significantly as supplemental copper level increased in the 10 to 30, 30 to 50 and initial to 50 kg weight periods. F/G was also significantly increased by copper level in the 10 to 30 and 30 to 50 kg weight periods (P
