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Studies on Drug Toxicity in Chicks
Studies on Drug Toxicity in Chicks 2. T H E I N F L U E N C E OF VARIOUS LEVELS O F SULFAQUINOXALINE ON G R O W T H AND D E V E L O P M E N T OF CHICKS PAUL M.
N E W B E R N E AND W I L L I A M B.
BUCK
Department of Veterinary Bacteriology and Parasitology, School of Veterinary Medicine, University of Missouri, Columbia (Received for publication May 26, 1956)
S
This experiment was conducted to further investigate the effect of sulfaquinoxaline on the growing chick.
ad libitum. Composition of the ration is shown in Table 1. The birds in group A were used as controls and received the basal ration. Birds in other groups received the basal ration with the addition of sulfaquinoxaline as follows: group B, 0.0125%; group C, 0.0250%; group D, 0.050%; and group E, 0.100%. The chicks were weighed weekly. One bird from each group was sacrificed at the time of each weighing for blood and tissue studies. The experiment extended through the sixth week. RESULTS AND DISCUSSION
Average weights (in grams) are shown in Table 2. There was no significant difference in average weight gains in groups A and TABLE
MATERIALS AND METHODS
Day old Lancaster chicks were used in this experiment. The chicks were housed in five-deck electrically heated batteries in lots of 25 with approximately equal sex distribution. Food and water were supplied
Journal Series No. 1629. Approved by the Director of the Missouri Agricultural Experiment Station, Columbia. Mr. Buck is a senior student in the University of Missouri, School of Veterinary Medicine. Mr. Buck's participation was supported in part by a Lederle Veterinary Medical Research Scholarship granted by Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York.
1259
^--Composthon of basal rakon
Ground Yellow Corn 59.0 Soybean Oil Meal (44% Protein, Solvent) 32.5 Fish Meal (60% Protein) 3.0 Dehyd. Alfalfa Meal 1.5 Special Steamed Bone Meal 1-5 Ground Limestone 1.5 Salt .5 A and D Oil 1500 A/gm. .25 600 D/gm. Manganese Sulfate .02 (70% technical grade) 2-49-C" b .1 Aurofac .25 0
b
Contains per pound: 2 gm. Riboflavin. 4 gm. Calcium Pantothenate. 9 gm. Niacin. 10 gm. Choline Chloride. Contains per pound: 1.8 gm. Aureomycin. 1.8 mg. Vitamin Bi».
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
ULFAQUINOXALINE is an anticoccidial agent. It has been used extensively in the poultry industry for the prevention and treatment of coccidiosis. Thorp et al. (1947); Delaplane and Milliff (1948); Peterson and Hymas (1950); Sadek et al. (1955); and others have reported on its use as a chemotherapeutic agent and on some toxic side effects. Delaplane and Milliff (1948); Peterson and Hymas (1950); and Sadek et al. (1955), attributed many symptoms and lesions to excessive dosage or prolonged administration. More recently sulfaquinoxaline has been associated with the hemorrhagic syndrome by Cover and co-workers (1955).
1260
P. M. NEWBERNE AND W. B. BUCK TABLE 2.—Average weights in grains
Group
Day old
1 week
2 week
3 week
4 week
5 week
6 week
A B C D E
37.0 37.2 37.6 36.2 36.4
87.0 90.5 86.5 81.4 79.0
172.0 176.0 168.0 164.4 156.3
301.4 306.7 291.2 295.0 276.8
414.5 402.5 413.1 420.4 383.1
569.5 590.5 560.7 563.2 488.1
755.6 773.9 746.4 775.4 677.0
cellular elements, as well as the hemoglobin, remained within the range considered normal throughout the six week period. There was an increase in eosinophils and a decrease in non-granular leucocytes in all treated groups during the sixth week. Thrombocyte counts fluctuated from week to week but there was no notable decrease on high levels of sulfaquinoxaline. Histological studies were made on the kidney, liver, spleen, bursa of Fabricius, femur, thymus and thyroid. Tissues were fixed in Bouin's fixative, embedded and sectioned in the usual manner. The formic acid-sodium formate method for decalcification was used for bones. Ffaematoxylin and eosin and Herxheimer fat stains were employed. There was a hyperplasia of the bile duct
FIG. la. Control. Bible duct epithelium (X400). H. and E. stain.
FIG. lb. Treated. Proliferation and folding of bile duct epithelium (X400). H. and E. stain.
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
B. Weight gains in group C paralleled those of group D. The most notable change was in group E which received the highest (0.100%) level. Few symptoms were observed. The birds in group E appeared anemic at four weeks; however, the anemic appearance was not substantiated by differential blood counts and hemoglobin determinations. There was a decrease in feed consumption in groups D and E, with some decrease in weight gains. At the end of the first week many young red cells were present in differential counts of groups D and E. In subsequent counts, however, only an occasional young cell was observed in any of the groups. Results of differential blood counts and hemoglobin determinations are shown in Table 3. Except for the sixth week, all of the
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Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
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1262
P. M.
NEWBEENE AND W. B. BUCK
FIG. 3b. Treated. Thyroid gland (X23S). Decreased colloid in acini. H. and E. stain.
epithelium (Fig. lb) that resulted in a piling up of the epithelial layer in the lumen of the ducts. Degeneration of the liver cells and a notable decrease in lymphoid areas was observed in groups C, D, and E (Fig. 2). There was a consistent depression of thyroid activity with varying degrees of interstitial proliferation and decreased colloid in the acini (Fig. 3b).
Lymphoid islands which are normal in the bone marrow of control birds were usually absent in the bone marrow of treated groups (Fig. 4b). There was some increase in the fat content of the bone marrow in groups C, D, and E. An occasional tubular cast was observed in the kidney in all treated groups (Fig. 5). Degeneration of the tubular epithelium occurred in groups D and E. Some degree
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
FIG. 2. Treated. Focal degeneration of liver (X90). H. and E. stain.
HBHHH9HHH FIG. 3a. Control. Thyroid gland (X23S). H. and E. stain.
FIG. 4a. Control. Bone marrow (X60). H. and E. stain.
•
E F F E C T OF SULFAQUINOXALINE ON GROWTH
•
1263
m m !
of glomerular swelling was observed in all treated groups (Fig. 6b). Under the conditions of this investigation sulfaquinoxaline did not produce the wide variety of symptoms and lesions attributed to it in some reports. Complicating factors encountered under field conditions might
FIG. 6a. Control. Kidney glomerulus (X28S). H. and E. stain. have some bearing on the varied observations reported by other investigators. The symptoms were negligible except for the decrease in feed consumption and weight gains on the two highest levels (groups D andE). , ,j c::..^*:.
i
FIG. 5. Treated. Kidney tubules (X28S). H. and E. stain. Tubular cast and epithelial degeneration.
•
FIG. 6b. Treated. Kidney glomerulus (X285). H. and E. stain. Glomerular swelling and tubular degeneration.
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
zSsNS© FIG. 4b. Treated. Bone marrow (X60). H. and E. stain. No lymphoid islands present. Decreased cellular density.
1264
P. M. NEWBERNE AND W. B. BUCK
SUMMARY
Sulfaquinoxaline at levels above 0.0125%
caused minor symptoms and a slight decrease in feed consumption and weight gains in young chickens. Lesions were observed in the liver cord cells, lymphoid areas of the liver, bile ducts, kidney, bone marrow and thyroid gland. There were moderate changes in the blood picture which became more pronounced during the sixth week. No muscular or subcutaneous hemorrhages were observed. REFERENCES Cover, M. S., W. J. Meller and E. Gill, 1955. Studies of hemorrhagic syndromes in chickens. Cornell Vet. 45: 366-386. Delaplane, J. P., and J. H. Milliff, 1948. The gross and micropathology of sulfaquinoxaline poisoning in chicks. Am. J. Vet. Res. 9: 92-96. Liechtenstein, L., and L. J. Fox,. 1946. Necrotizing arterial lesions resembling those of periarteritis nodosa and focal visceral necrosis following administration of sulfathiazole. Am. J. Path. 22: 66S-667. Peterson, E. H., and T. A. Hymas, 1950. Sulfaquinoxaline, NFZ, and Nitrophenide. Am. J. Vet. Res. 11: 278. Sadek, S. E., L. E. Hanson and J. O. Alberts, 1955. Suspected drug-induced anemias in the chicken. J. Am. Vet. Med. Assoc. 127: 201-203. Thorp, W. T. S., S. Gordeuk, P. J. Glanz and M. Learned, 1947. The chemotherapy of cecal coccidiosis. Am. J. Vet. Res. 8: 196-203.
Growth Rate and Plumage Color in Chickens R.
GEORGE JAAP
Ohio Agricultural Experiment Station, Columbus, Ohio AND J O H N F.
GRIMES
Nichols Incorporated, Kingston, New Hampshire (Received for publication May 28, 1956)
T
HE /-gene, an inhibitor of black (melanin) color, is currently being used in the development of the popular "dominant white" crossbreds for broiler production. Since none of the competitive
meat strains posessed this gene, poultry breeders have introduced it into sire lines by crossbreeding. In a program of transferring / into the Barred Plymouth Rock by a series of back-
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
Blood studies revealed little change in the hemopoietic system. This was further confirmed by the absence of hemorrhage in any of the birds at post-mortem. This observation lends support to the view that the role of sulfaquinoxaline in the hemorrhagic syndrome is minor. No attempt is made to explain the proliferation of the bile duct epithelium. Degeneration of the liver cells is a logical result of reaction to the toxic effects of the drug. Since the sulfa drugs belong tc-a group of compounds which exhibit antithyroid activity, the changes in this gland could be expected. Lesions found in the kidney were those that might be found in any condition of a mild, chronic toxicity. The decrease or absence of lymphoid areas in the bone marrow and liver in treated groups might contribute to a lower resistance in exposure to disease. The decrease in non-granular leucocytic cells in treated groups in the sixth week may have been caused by the loss of the lymphoid areas.
N E W B E R N E AND W I L L I A M B.
BUCK
Department of Veterinary Bacteriology and Parasitology, School of Veterinary Medicine, University of Missouri, Columbia (Received for publication May 26, 1956)
S
This experiment was conducted to further investigate the effect of sulfaquinoxaline on the growing chick.
ad libitum. Composition of the ration is shown in Table 1. The birds in group A were used as controls and received the basal ration. Birds in other groups received the basal ration with the addition of sulfaquinoxaline as follows: group B, 0.0125%; group C, 0.0250%; group D, 0.050%; and group E, 0.100%. The chicks were weighed weekly. One bird from each group was sacrificed at the time of each weighing for blood and tissue studies. The experiment extended through the sixth week. RESULTS AND DISCUSSION
Average weights (in grams) are shown in Table 2. There was no significant difference in average weight gains in groups A and TABLE
MATERIALS AND METHODS
Day old Lancaster chicks were used in this experiment. The chicks were housed in five-deck electrically heated batteries in lots of 25 with approximately equal sex distribution. Food and water were supplied
Journal Series No. 1629. Approved by the Director of the Missouri Agricultural Experiment Station, Columbia. Mr. Buck is a senior student in the University of Missouri, School of Veterinary Medicine. Mr. Buck's participation was supported in part by a Lederle Veterinary Medical Research Scholarship granted by Lederle Laboratories Division, American Cyanamid Company, Pearl River, New York.
1259
^--Composthon of basal rakon
Ground Yellow Corn 59.0 Soybean Oil Meal (44% Protein, Solvent) 32.5 Fish Meal (60% Protein) 3.0 Dehyd. Alfalfa Meal 1.5 Special Steamed Bone Meal 1-5 Ground Limestone 1.5 Salt .5 A and D Oil 1500 A/gm. .25 600 D/gm. Manganese Sulfate .02 (70% technical grade) 2-49-C" b .1 Aurofac .25 0
b
Contains per pound: 2 gm. Riboflavin. 4 gm. Calcium Pantothenate. 9 gm. Niacin. 10 gm. Choline Chloride. Contains per pound: 1.8 gm. Aureomycin. 1.8 mg. Vitamin Bi».
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
ULFAQUINOXALINE is an anticoccidial agent. It has been used extensively in the poultry industry for the prevention and treatment of coccidiosis. Thorp et al. (1947); Delaplane and Milliff (1948); Peterson and Hymas (1950); Sadek et al. (1955); and others have reported on its use as a chemotherapeutic agent and on some toxic side effects. Delaplane and Milliff (1948); Peterson and Hymas (1950); and Sadek et al. (1955), attributed many symptoms and lesions to excessive dosage or prolonged administration. More recently sulfaquinoxaline has been associated with the hemorrhagic syndrome by Cover and co-workers (1955).
1260
P. M. NEWBERNE AND W. B. BUCK TABLE 2.—Average weights in grains
Group
Day old
1 week
2 week
3 week
4 week
5 week
6 week
A B C D E
37.0 37.2 37.6 36.2 36.4
87.0 90.5 86.5 81.4 79.0
172.0 176.0 168.0 164.4 156.3
301.4 306.7 291.2 295.0 276.8
414.5 402.5 413.1 420.4 383.1
569.5 590.5 560.7 563.2 488.1
755.6 773.9 746.4 775.4 677.0
cellular elements, as well as the hemoglobin, remained within the range considered normal throughout the six week period. There was an increase in eosinophils and a decrease in non-granular leucocytes in all treated groups during the sixth week. Thrombocyte counts fluctuated from week to week but there was no notable decrease on high levels of sulfaquinoxaline. Histological studies were made on the kidney, liver, spleen, bursa of Fabricius, femur, thymus and thyroid. Tissues were fixed in Bouin's fixative, embedded and sectioned in the usual manner. The formic acid-sodium formate method for decalcification was used for bones. Ffaematoxylin and eosin and Herxheimer fat stains were employed. There was a hyperplasia of the bile duct
FIG. la. Control. Bible duct epithelium (X400). H. and E. stain.
FIG. lb. Treated. Proliferation and folding of bile duct epithelium (X400). H. and E. stain.
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
B. Weight gains in group C paralleled those of group D. The most notable change was in group E which received the highest (0.100%) level. Few symptoms were observed. The birds in group E appeared anemic at four weeks; however, the anemic appearance was not substantiated by differential blood counts and hemoglobin determinations. There was a decrease in feed consumption in groups D and E, with some decrease in weight gains. At the end of the first week many young red cells were present in differential counts of groups D and E. In subsequent counts, however, only an occasional young cell was observed in any of the groups. Results of differential blood counts and hemoglobin determinations are shown in Table 3. Except for the sixth week, all of the
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Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
c •a
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c
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1262
P. M.
NEWBEENE AND W. B. BUCK
FIG. 3b. Treated. Thyroid gland (X23S). Decreased colloid in acini. H. and E. stain.
epithelium (Fig. lb) that resulted in a piling up of the epithelial layer in the lumen of the ducts. Degeneration of the liver cells and a notable decrease in lymphoid areas was observed in groups C, D, and E (Fig. 2). There was a consistent depression of thyroid activity with varying degrees of interstitial proliferation and decreased colloid in the acini (Fig. 3b).
Lymphoid islands which are normal in the bone marrow of control birds were usually absent in the bone marrow of treated groups (Fig. 4b). There was some increase in the fat content of the bone marrow in groups C, D, and E. An occasional tubular cast was observed in the kidney in all treated groups (Fig. 5). Degeneration of the tubular epithelium occurred in groups D and E. Some degree
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
FIG. 2. Treated. Focal degeneration of liver (X90). H. and E. stain.
HBHHH9HHH FIG. 3a. Control. Thyroid gland (X23S). H. and E. stain.
FIG. 4a. Control. Bone marrow (X60). H. and E. stain.
•
E F F E C T OF SULFAQUINOXALINE ON GROWTH
•
1263
m m !
of glomerular swelling was observed in all treated groups (Fig. 6b). Under the conditions of this investigation sulfaquinoxaline did not produce the wide variety of symptoms and lesions attributed to it in some reports. Complicating factors encountered under field conditions might
FIG. 6a. Control. Kidney glomerulus (X28S). H. and E. stain. have some bearing on the varied observations reported by other investigators. The symptoms were negligible except for the decrease in feed consumption and weight gains on the two highest levels (groups D andE). , ,j c::..^*:.
i
FIG. 5. Treated. Kidney tubules (X28S). H. and E. stain. Tubular cast and epithelial degeneration.
•
FIG. 6b. Treated. Kidney glomerulus (X285). H. and E. stain. Glomerular swelling and tubular degeneration.
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
zSsNS© FIG. 4b. Treated. Bone marrow (X60). H. and E. stain. No lymphoid islands present. Decreased cellular density.
1264
P. M. NEWBERNE AND W. B. BUCK
SUMMARY
Sulfaquinoxaline at levels above 0.0125%
caused minor symptoms and a slight decrease in feed consumption and weight gains in young chickens. Lesions were observed in the liver cord cells, lymphoid areas of the liver, bile ducts, kidney, bone marrow and thyroid gland. There were moderate changes in the blood picture which became more pronounced during the sixth week. No muscular or subcutaneous hemorrhages were observed. REFERENCES Cover, M. S., W. J. Meller and E. Gill, 1955. Studies of hemorrhagic syndromes in chickens. Cornell Vet. 45: 366-386. Delaplane, J. P., and J. H. Milliff, 1948. The gross and micropathology of sulfaquinoxaline poisoning in chicks. Am. J. Vet. Res. 9: 92-96. Liechtenstein, L., and L. J. Fox,. 1946. Necrotizing arterial lesions resembling those of periarteritis nodosa and focal visceral necrosis following administration of sulfathiazole. Am. J. Path. 22: 66S-667. Peterson, E. H., and T. A. Hymas, 1950. Sulfaquinoxaline, NFZ, and Nitrophenide. Am. J. Vet. Res. 11: 278. Sadek, S. E., L. E. Hanson and J. O. Alberts, 1955. Suspected drug-induced anemias in the chicken. J. Am. Vet. Med. Assoc. 127: 201-203. Thorp, W. T. S., S. Gordeuk, P. J. Glanz and M. Learned, 1947. The chemotherapy of cecal coccidiosis. Am. J. Vet. Res. 8: 196-203.
Growth Rate and Plumage Color in Chickens R.
GEORGE JAAP
Ohio Agricultural Experiment Station, Columbus, Ohio AND J O H N F.
GRIMES
Nichols Incorporated, Kingston, New Hampshire (Received for publication May 28, 1956)
T
HE /-gene, an inhibitor of black (melanin) color, is currently being used in the development of the popular "dominant white" crossbreds for broiler production. Since none of the competitive
meat strains posessed this gene, poultry breeders have introduced it into sire lines by crossbreeding. In a program of transferring / into the Barred Plymouth Rock by a series of back-
Downloaded from http://ps.oxfordjournals.org/ at University of Sydney on June 6, 2016
Blood studies revealed little change in the hemopoietic system. This was further confirmed by the absence of hemorrhage in any of the birds at post-mortem. This observation lends support to the view that the role of sulfaquinoxaline in the hemorrhagic syndrome is minor. No attempt is made to explain the proliferation of the bile duct epithelium. Degeneration of the liver cells is a logical result of reaction to the toxic effects of the drug. Since the sulfa drugs belong tc-a group of compounds which exhibit antithyroid activity, the changes in this gland could be expected. Lesions found in the kidney were those that might be found in any condition of a mild, chronic toxicity. The decrease or absence of lymphoid areas in the bone marrow and liver in treated groups might contribute to a lower resistance in exposure to disease. The decrease in non-granular leucocytic cells in treated groups in the sixth week may have been caused by the loss of the lymphoid areas.