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U.S. Department of Health and Human Services

Animal & Veterinary

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NADA 140-445 Monteban® + Roxarsone - original approval

I. GENERAL INFORMATION:

NADA140-445
Sponsor:Elanco Products Company
A Division of Eli Lilly and Company
Lilly Corporate Center
Indianapolis, Indiana 46285
Generic Name:narasin + roxarsone (3-nitro-4-hydroxyphenylarsonic acid)
Trade Name:Monteban® + Roxarsone
Marketing Status: 

II. INDICATIONS FOR USE

"For the prevention of coccidiosis in broiler chickens caused by Eimeria tenella, E. necatrix, E. acervulina, E. maxima, E. brunetti, and E. mivati including some field strains of E. tenella that are more susceptible to roxarsone combined with narasin than to narasin alone."

III. DOSAGE

A.DOSAGE FORMType C medicated feed manufactured from: 1.) MONTEBAN® - supplied as a Type A medicated article in 50 lb bags containing 36, 45, 54, 72 or 90 g narasin per pound; 2.) 3-NITRO® supplied as a Type A medicated article containing 10, 20, or 50 g roxarsone.
B.ROUTE OF ADMINISTRATIONOral administration via the feed.
C.RECOMMENDED DOSAGES:Narasin (from MONTEBAN®) at concentrations ranging from 54 to 72 g/ton in finished feed and roxarsone at a concentration of 45.4 g/ton in finished feed.

IV. EFFECTIVENESS

Introduction

MONTEBAN® (narasin) Type A medicated article is approved (51FR 29097, August 14, 1986; 21 CFR §558.363) for the prevention of coccidiosis in broiler chickens caused by E. tenella, E. necatrix, E. acervulina, E. maxima, E. brunetti, and E. mivati. It is to be incorporated into broiler rations to provide from 54 to 72 g narasin/ton.

Roxarsone (3-nitro-4-hydroxyphenylarsonic acid) originally became effective March 23, 1951. It is currently approved (21 CFR 558.530) for use in feed of growing chickens for increased rate of weight gain, improved feed efficiency, and improved pigmentation at 22.7 and 45.4 g roxarsone/ton. Roxarsone is presently approved with other ionophorous anticoccidials.

In the present NADA it has been further established that the addition of roxarsone at a concentration of 45.4 g/ton to finished feeds containing narasin in the range of 54-72 g/ton is effective for use in broiler chickens for the prevention of coccidiosis caused by E. tenella, E. necatrix, E. acervulina, E. maxima, E. brunetti, and E. mivati including some field strains of E. tenella that are more susceptible to roxarsone combined with narasin than to narasin alone.

The effectiveness tests conducted are outlined as follows:

  1. Battery Studies

    Series 1: A factorial arrangement of two levels of roxarsone (0 and 45.4 g/ton) and three levels of narasin (0, 54, and 72 g/ton) for a total of six treatments.

    Series 2: A factorial arrangement of three levels of roxarsone (0, 22.7 and 45.4 g/ton) and three levels of narasin (0, 54, and 72 g/ton) for a total of nine treatments.

  2. Floor Pen Studies

    A series of four floor pen trials to substantiate the results of the battery trials under simulated field conditions.

  3. Anticoccidial Compatibility of Narasin and Roxarsone

    A series of six battery experiments to evaluate the anticoccidial effectiveness compatibility of narasin and roxarsone fed in combination.

Effectiveness Study Summaries

  1. Battery Studies

    Anticoccidial efficacy of the combination of narasin and roxarsone against E. tenella

    Two series of battery trials were conducted to evaluate the combination of narasin and roxarsone for anticoccidial efficacy against E. tenella. The first series was a factorial arrangement of two levels of roxarsone (0, 45 g/ton) and three levels of narasin (0, 54, 72 g/ton) for a total of six treatments. The second series was a factorial arrangement of three levels of roxarsone (0, 22, 45 g/ton) and three levels of narasin (0, 54, 72 g/ton) for a total of nine treatments. There were 15 trials in each series with each trial using a different field strain of E. tenella.

    Eight-day-old Hubbard X White Mountain broiler cockerels were used for these experiments. All chicks were received at one day of age and housed in an isolation room within an isolation facility dedicated to the early brooding of coccidia-free chicks. Chicks from one hatch were kept within the same isolation room unit and transferred to a second building for experimentation. The rooms for conducting the experiments were contained within an isolation wing of this second building. Temperature within the rooms was thermostatically controlled. The testing cages consisted of wire-floored suspended drawer-type units especially constructed to utilize disposable cardboard feeders. An individual feeder was used for one cage in one experiment only. Water was constant flowing with access at the rear of each cage.

    A typical broiler starter ration was used in the mash form for testing in battery units. Testing was also conducted with this ration in a crumble form following pelleting. The feeds were routinely assayed for narasin and roxarsone. The chicks were pen balanced by weight in groups of five birds/pen and medication was initiated 48 hours prior to oral inoculation with the oocyst suspensions. Five pen replicates were included in each treatment in the first series and six pen replicates were included in each treatment in the second series. The appropriate infected non-medicated and non-infected non-medicated controls were included in each experiment.

    The experiments were terminated on the 7th day post-inoculation, the time at which the maximum expression of clinical signs of infection would be expected to be present in the infected non-medicated birds. Mean weight gains were calculated as the mean weight gain per survivor. Fecal samples were collected to determine oocyst passage and the results are present as millions of oocysts per bird. The severity of lesions due to cecal coccidial infection was scored (0 -4) as follows:

    Cecal Lesion Scores
    (E. tenella)

    0 = negative, no macroscopic lesions
    1 = very few, discrete lesions
    2 = mucus, some hemorrhage, moderate cecal involvement
    3 = moderate hemorrhage, cecal walls thickened, cecal atrophy
    4 = massive hemorrhaging cores, cecal walls thin, cecal hypertrophy; or death due to coccidiosis

    Results

    When significant difference is stated in this summary, it refers to P< or = 0.05 unless otherwise stated.

    Results of Series 1

    The results of series 1 are presented in Tables 1, 2, 3 and 4 for average cecal lesion scores, average number of oocysts passed per bird, weight gain per bird, and mortality, respectively.

    Cecal Lesion Scores

    1. Each combination of narasin + roxarsone resulted in significant reduction in cecal lesion scores when compared to non-medicated control and either narasin or roxarsone alone.
    2. The high level of narasin in combination with roxarsone, 72 + 45 g/ton, resulted in a numerical improvement over the 54 + 45 g/ton combination.

    Oocyst Count

    1. Each combination of narasin + roxarsone resulted in significant reduction in numbers of oocyst passed when compared to non-medicated control and either narasin or roxarsone alone.
    2. The high level of narasin in combination with roxarsone, 72 + 45 g/ton, resulted in significant (P<.06) reduction in oocyst passed as compared to the 54 + 45 g/ton combination.

    Weight Gain

    1. Each combination of narasin + roxarsone and either narasin or roxarsone alone resulted in significant improvement in weight gain over the non-medicated control.
    2. There were no significant differences in weight gain among the treated groups.

    Mortality

    1. Each combination of narasin + roxarsone and either narasin or roxarsone alone resulted in reduced mortality when compared to the non-medicated control.
    2. The high level of narasin in combination with roxarsone resulted in reduced mortality when compared to roxarsone alone.
    3. The 72 + 45 g/ton combination of narasin + roxarsone resulted in reduced mortality when compared to the 54 + 45 g/ton combination.

    Results of Series 2

    The results of series 2 are presented in Tables 5, 6, 7 and 8 for average cecal lesion scores, average oocyst passed per bird, weight gain per bird and mortality.

    Cecal Lesion Scores

    1. Each combination of narasin + roxarsone resulted in significant reduction in cecal lesion scores when compared to non-medicated control and either narasin or roxarsone alone.
    2. The high level of roxarsone in combination with narasin at each level resulted in significant reduction in cecal lesion scores when compared to corresponding low level of roxarsone in combination with narasin (54 + 22 g/ton vs 54 + 45 g/ton and 72 + 22 g/ton vs 72 + 45 g/ton).
    3. The high level of narasin in combination with the low level of roxarsone significantly reduced lesion scores as compared to the low level of narasin plus the low level of roxarsone (54 + 22 g/ton vs 72 + 22 g/ton).
    4. The high level of narasin in combination with the high level of roxarsone resulted in a numerical decrease in lesion scores as compared to the low level of narasin plus the high level of roxarsone (54 + 45 g/ton vs 72 + 45 g/ton).

    Oocyst Count

    1. Each combination of narasin with 45 g/ton of roxarsone resulted in significant reduction in oocyst count when compared to non-medicated control and to either narasin or roxarsone alone.
    2. The high level of roxarsone in combination with narasin at each level resulted in significant reduction of oocyst count when compared to corresponding low level of roxarsone in combination narasin (54 + 22 g/ton vs 54 + 45 g/ton and 72 + 22 g/ton vs 72 + 45 g/ton).
    3. The high level of narasin in combination with the high level of roxarsone resulted in significant decrease in oocyst count as compared to the low level of narasin plus the high level of roxarsone (54 + 45 g/ton vs 72 + 45 g/ton).

    Weight Gain

    1. Each combination of narasin and roxarsone resulted in significant improvement in weight gain over the non-medicated control and over either narasin or roxarsone alone at their respective low levels.
    2. Among the four treatments which were combinations of narasin and roxarsone, there were no differences in weight gain.

    Mortality

    1. Each level of narasin in combination with roxarsone at 45 g/ton resulted in reduced mortality as compared to each of the other treatments.

    Conclusion from Battery Studies

    The data from the two battery studies show that some field strains of E. tenella are more susceptible to roxarsone at 22.5 or 45.4 g/ton combined with 54 or 72 g/ton of narasin than to either drug alone.

    The above battery studies were conducted by:

    T. K. Jeffers, Ph.D.
    Lilly Research Laboratories
    Greenfield, Indiana

    Ed. note: The following table has 7 columns.

    TABLE 1 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 1
    Cecal Lesion Scores

     Roxarsone, 0  g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin,  54 g/tonNarasin, 72 g/ton
    853.802.282.362.201.880.86
    863.721.080.440.440.00.0
    873.792.001.812.470.960.41
    883.921.801.362.200.680.64
    902.680.881.161.040.040.24
    913.722.922.562.320.840.72
    922.720.510.240.800.120.08
    933.000.520.601.770.440.12
    943.962.972.103.722.081.64
    953.762.201.062.861.150.80
    963.961.441.723.190.980.56
    972.600.520.00.040.00.0
    981.2O0.160.00.320.00.0
    A43.843.642.123.402.561.78
    A53.963.622.163.522.041.56
    L.S.Means3.411.681.271.731.040.90
    Selected treatment contrasts
    N+RN+RDifferenceP
    0+054+452.37<0.0001
    0+072+452.52<0.0001
    72+054+450.23<0.0500
    72+072+450.370.0134
    0+4554+450.69<0.0001
    0+4572+450.83<0.0001
    +4572+450.140.1944

    Ed. note: The following table has 7 columns.

    TABLE 2 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 1
    Average Oocyst Count millions per bird

     Roxarsone, 0 g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    858.323.892.157.403.460.28
    869.360.830.150.040.00.0
    8717.165.390.788.000.210.05
    8821.186.854.2110.060.260.19
    901.540.080.110.280.00.03
    9116.1920.7222.706.663.511.39
    926.480.050.010.180.00.0
    9318.610.040.112.630.140.01
    9413.7117.446.0921.817.472.64
    959.884.770.4616.920.890.83
    9615.000.924.7510.080.160.09
    9713.381.150.010.030.00.0
    980.480.010.00.020.00.0
    A47.5813.096.2512.055.613.07
    A59.1614.978.8314.225.813.50
    L.S.Means2.791.460.541.420.250.12
    Selected treatment contrasts
    N+RN+RDifferenceP
    0+054+452.54<0.0001
    0+072+452.67<0.0001
    54+054+451.21<0.0001
    72+072+450.410.0010
    0+4554+451.160.0002
    0+4572+451.29<0.0001
    54+4572+450.130.0595

    Ed. note: The following table has 7 columns.

    TABLE 3 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 1
    Average Weight Gain (g)

     Roxarsone, 0 g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    85154249229235234237
    86200250248256255248
    87200235242239263244
    88181257265263267261
    90279277284282277279
    91203257250254269265
    92262263271269267263
    93260268276271270262
    94113175217166222228
    95142224243220228238
    96160258251218261269
    97237244251257245255
    98220219231241225212
    A4152200235221226233
    A5147204217201239229
    L.S.Means206238245241245243
    Selected treatment contrasts
    N+RN+RDifferenceP
    0+054+4539<0.0001
    0+072+4537<0.0001
    54+054+4570.2571
    72+072+45-20.7657
    0+4554+4540.5329
    0+4572+4520.7115
    54+4572+45-20.7992

    Ed. note: The following table has 7 columns.

    TABLE 4 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 1
    Mortality Due to Cecal Coccidiosis number died/total birds

     Roxarsone, 0 g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    856/250/250/250/250/250/25
    862/250/250/250/250/250/25
    876/251/250/250/251/250/25
    886/250/250/250/250/250/25
    900/250/251/250/250/250/25
    913/252/250/251/251/250/25
    920/250/250/250/250/250/25
    930/250/250/250/250/250/25
    945/253/251/252/251/250/25
    957/251/250/251/250/250/25
    963/250/250/252/251/250/25
    970/250/250/250/250/250/25
    98v0/250/250/250/250/250/25
    A414/255/251/254/253/251/25
    A56/256/252/252/252/251/25
    Total58/37514/3755/37512/3759/3752/375

    Ed. note: The following table has 10 columns.

    TABLE 5 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 2
    Cecal Lesion Scores
    Trial

     Roxarsone, 0 g/tonRoxarsone, 22 g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    582.671.501.102.771.330.930.730.300.20
    593.150.670.472.260.200.100.480.030.03
    602.843.272.973.003.002.932.331.921.30
    613.033.212.802.902.432.031.670.671.33
    623.332.602.303.102.101.732.001.271.21
    633.033.202.773.142.642.302.031.601.27
    703.112.672.932.972.872.602.751.661.97
    712.632.001.372.731.931.601.711.130.77
    722.872.632.062.832.682.182.361.101.15
    732.632.902.552.972.632.361.831.070.83
    773.171.771.031.800.770.100.300.130.0
    783.153.223.173.073.052.501.521.881.33
    793.552.532.403.202.702.302.231.171.27
    803.503.003.103.422.502.071.871.660.71
    813.403.233.403.302.932.872.572.102.30
    L.S.Means3.142.542.262.942.191.891.741.191.07
    Selected treatment contrasts
    N+RN+RDifferenceP
    0+054+22-0.95<0.0001
    0+072+22-1.25<0.0001
    54+054+22-0.350.0111
    72+072+22-0.370.0075
    0+2254+22-0.75<0.0001
    0+2272+22-1.05<0.0001
    54+2272+22-0.300.0260
    54+2254+45-1.00<0.0001
    72+2272+45-0.82<0.0001
    0+054+45-1.95<0.0001
    0+072+45-2.07<0.0001
    54+054+45-1.35<0.0001
    72+072+45-1.19<0.0001
    0+4554+45-0.55<>0.0002
    0+4572+45-0.67<0.0001
    54+4572+45-0.120.2185

    Ed. note: The following table has 10 columns.

    TABLE 6 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 2
    Average Oocyst Count millions per bird

     Roxarsone, 0 g/tonRoxarsone, 22 g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    5811.328.696.508.684.011.235.651.030.21
    5914.633.141.448.010.250.042.940.040.02
    6011.4616.5915.6912.2911.155.5010.698.422.72
    6110.739.8513.4313.2410.788.8610.285.094.31
    629.094.234.658.483.841.719.501.830.72
    635.306.578.519.5811.416.3810.558.725.81
    706.6312.4512.1516.6212.3610.1511.458.106.91
    7116.7315.3611.2913.6111.728.9510.574.953.82
    729.5410.3010.1312.7611.8915.409.213.173.69
    736.6311.799.479.7010.4712.0610.925.651.93
    776.921.200.261.550.010.030.180.100.0
    7811.1511.2716.3214.4913.5310.814.333.752.27
    7911.1022.0017.6522.5319.269.1419.527.682.88
    809.9510.166.6514.947.289.938.927.281.13
    8112.4814.1613.4212.8912.6113.2012.027.718.56
    L.S.Means6.187.216.778.066.234.906.033.221.91
    Selected treatment contrasts
    N+RN+RDifferenceP
    0+054+220.050.5139
    0+072+22-1.280.1147
    54+054+22-0.980.2234
    72+072+22-1.870.0476
    0+2254+22-1.830.0912
    0+2272+22-3.160.0055
    54+2272+22-1.330.1082
    54+2254+45-3.01<0.0050
    72+2272+45-2.99<0.0050
    0+054+45-2.960.0005
    0+072+45-4.27<0.0001
    54+054+45-3.99<0.0001
    72+072+45-4.86<0.0001
    0+4554+45-2.810.0008
    0+4572+45-4.12<0.0001
    +4572+45-1.310.0039

    Ed. note: The following table has 10 columns.

    TABLE 7 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 2
    Average Weight Gain (g)

     Roxarsone, 0 g/tonRoxarsone, 22 g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    58257266272255276263259271268
    59227287284274283283264284273
    60208209206203209229217225224
    61222230252224276277280277278
    62202272272230267281270283278
    63212234259248265283283294285
    70199210222203232228203241220
    71231251260233254249236244245
    72237251257234237247250260260
    73239261269248269278278280271
    77253264264258277274263263272
    78258256260276266277289287285
    79208242241208251255250246250
    80190243233193279268272260272
    81205229237207259265250273278
    L.S.Means227249255237259261255263261
    Selected treatment contrasts
    N+RN+RDifferenceP
    0+054+2232<0.0001
    0+072+2234<0.0001
    54+054+22100.0368
    72+072+2260.1480
    0+2254+2221<0.0001
    0+2272+2224<0.0001
    54+2272+2220.5827
    0+054+4536<0.0001
    0+072+4534<0.0001
    54+054+45140.0017
    72+072+4560.1679
    0+4554+4580.0579
    0+4572+4560.1967
    54+4572+45-20.5382

    Ed. note: The following table has 10 columns.

    TABLE 8 COMBINATION OF NARASIN AND ROXARSONE IN BATTERY STUDIES

    E. tenella Challenge
    Series 2
    Mortality Due to Cecal Coccidiosis Number died/Total Birds

     Roxarsone, 0 g/tonRoxarsone, 22 g/tonRoxarsone, 45 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    580/300/300/300/301/300/300/300/300/30
    591/300/300/301/300/300/300/300/300/30
    601/304/302/302/302/301/300/300/300/30
    614/301/301/302/302/301/300/300/300/30
    625/301/300/305/302/300/300/300/300/30
    635/304/301/306/301/301/301/300/300/30
    702/301/301/300/303/303/301/300/301/30
    710/300/301/300/300/300/300/300/300/30
    722/301/300/301/300/300/300/300/300/30
    731/301/300/300/300/300/300/300/300/30
    773/300/300/300/300/300/300/300/300/30
    783/304/302/301/301/301/300/300/302/30
    799/300/300/303/300/302/300/300/300/30
    8012/305/306/309/300/300/301/302/301/30
    8111/302/306/308/303/303/304/301/300/30
    Total59/45024/45020/45038/45015/45012/4507/4503/4504/450
  2. Floor Pen Trials with High Challenge of E. tenella

    Four floor pen trials were conducted to substantiate the results of the battery trials under simulated field conditions. Two trials were conducted at Wheeler, Arkansas, and two were conducted at Greenfield, Indiana. Each trial had the experimental design of 3 x 3 factorial arrangements of 0, 54, 72 g/ton of narasin and 0, 22.7, 45.4 g/ton of roxarsone. The trial results and treatment contrasts are presented in Tables 1, 2, and 3 for cecal lesion scores, weight gain, and mortality, respectively.

    Cecal Lesion Scores

    1. All combinations of narasin + roxarsone resulted in significant reduction in lesion scores when compared to the non-medicated control.
    2. The combination of 45 g/ton of roxarsone with either 54 or 72 g/ton of narasin resulted in significant reduction in cecal lesion scores when compared to either product alone.

    Average Weight Gain

    1. All combinations of narasin + roxarsone resulted in significantly greater weight gains than the non-medicated control.
    2. None of the combinations resulted in decreased weight compared to either product alone.

    Mortality

    1. The non-medicated control treatment group resulted in having the least mortality of all the treatments.
    2. All the narasin + roxarsone combinations had similar mortality.

    Conclusion from Floor Pen Studies

    These floor pen studies conducted under simulated use conditions confirm the effect observed in the battery studies. Some field strains of E. tenella are more susceptible to roxarsone at 45.4 g/ton combined with 54 or 72 g/ton of narasin than to either drug alone.

    Investigators for these studies were:

    B. F. Schlegel, D.V.M.
    Lilly Research Laboratories
    Fayetteville, Arkansas K. W. Bafundo, Ph.D.
    Lilly Research Laboratories
    Greenfield, Indiana

    TABLE 1 Combination of Narasin and Roxarsone in Floor Pen Studies Cecal Lesion Score
    Means and Analysis Results

    Ed. note: The following portion of this table has 4 columns.

    Roxarsone, g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    02.792.121.78
    222.121.971.91
    452.121.380.81

    Standard Error is 0.29

    Ed. note: The following portion of this table has 5 columns.

    QuestionComparisonDecreasepAnswer*
    A. is the combination better than control?0+0 -54+220.820.0377Yes
    -72+220.880.0300Yes
    -54+451.410.0041Yes
    -72+451.980.0006Yes
    B. Does narasin contribute to the combination?0+22 -54+220.150.3529No
    -72+220.210.3028No
    0+45 -54+45 0.740.0533Maybe
    -72+451.310.0059Yes
    C. Does roxarsone contribute to the combination?54+0 -54+220.150.3529No
    -54+450.740.0517Maybe
    72+0 -72+22-0.130.6248No
    -72+450.970.0218Yes
    D. Does the larger narasin level increase efficacy?54+22 -72+220.060.4437No
    54+45 -72+450.570.0513Maybe
    E. Does the larger roxarsone level increase efficacy?54+22 -54+450.590.0931Maybe
    72+22 -72+45 1.101.10Yes

    * At the 0 .05 level of significance

    Table 2 Combination of Narasin and Roxarsone in Floor Pen Studies Weight Gain Means and Analysis Results

    Ed. note: The following portion of this table has 4 columns.

    Roxarsone, g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    04.3024.4704.570
    224.3784.5294.509
    454.4174.5444.478

    Standard Error is 0.051

    Ed. note: The following portion of this table has 5 columns.

    QuestionComparisonDecreasepAnswer*
    A. Is the combination worse than control?
    0+0 -54+22-0.2270.9933No
    -72+22-0.2070.9898No
    -54+45-0.2420.9951No
    -72+45-0.1760.9501No
    B. Does the contribution of narasin produce a disease?0+22 -54+22-0.1510.9658No
    -72+22-0.1310.9478No
    0+45 -54+45-0.1270.9433No
    -72+45-0.0610.7918No
    C. Does the contribution of roxarsone produce a decrease?54+0 -54+22-0.0590.7808No
    -54+45-0.0740.8340No
    72+0 -72+220.0610.2103No
    -72+45-0.0920.1185No
    D. Does the larger narasin level produce a decrease?54+22 -72+220.0200.3958No
    54+45 -72+450.0660.1923No
    E. Does the larger roxarsone level produce a decrease?54+22 -54+45-0.0150.5833No
    72+22 -72+450.0310.3395No

    *At the 0.10 level of significance

    TABLE 3 Combination of Narasin and Roxarsone in Floor Pen Studies Percent Mortality Means and Analysis Results(1)
     
    Ed. note: The following portion of this table has 4 columns. 

    Roxarsone, g/tonNarasin, 0 g/ton Narasin, 54 g/ton Narasin, 72 g/ton 
    02.394.642.56
    224.443.034.91
    45 3.103.504.16

    Standard Error is 0.60

    QuestionComparisonDecrease Answer* 
    A. Is the combination worse than control?
     
     
     
    54+22-0+0 0.64 0.2263 No 
    72+22-2.52 0.0020 Yes 
    54+45-1.11 0.0975 Yes 
    72+45-1.770.0203Yes
    B. Does the contribution of narasin produce an increase?
     
     
     
    54+22-0+0-1.41 0.9483 No 
    72+22-0.47 0.2912 No 
    54+45-0+450.400.3193No 
    72+45-1.06 0.1083 Maybe 
    C. Does the contribution of roxarsone produce an increase?
     
     
     
    54+22-54+0 -1.61 0.9685 No 
    54+45--1.14 0.9071 No 
    72+22-72+02.350.0036Yes
    72+45-1.60 0.0320 Yes 
    D. Does the larger narasin level produce an increase?
     
    72+22-54+221.800.0153Yes
    72+45-54+450.660.2208No
    E. Does the larger roxarsone level produce an increase?
     
    54+45-54+22 0.470.2920No
    72+45-72+22-0.750.8080No

    *At the 0.10 level of significance.

    (1) The mortality reflected in this table is not drug related or medically significant.
     

  3. Anticoccidial Compatibility of Narasin and Roxarsone

    Six battery experiments were conducted to evaluate the anticoccidial compatibility of 54 g/ton narasin in combination with 45 g/ton roxarsone. In three of these experiments the inoculum consisted of a mixture of E. acervulina, E. maxima and E. tenella oocysts, while in the remaining three experiments the inoculum consisted of a mixture of E. brunetti, E. mivati, and E. necatrix oocysts. The anticoccidial effectiveness of each of the respective treatments was assessed by weight gain relative to controls, the efficiency of feed utilization (feed/gain ratios), and reduction in mortality and the severity of coccidial lesions. The results of these studies are presented in Tables 1 - 6.

    The addition of 45 g/ton roxarsone to 54 g/ton narasin did not interfere with the anticoccidial effectiveness of narasin. Furthermore, the addition of 45 g/ton roxarsone to 54 g/ton narasin enhanced anticoccidial effectiveness as measured by reduction in the severity of cecal lesions in birds infected with E. tenella.

    The investigator for these studies was:

    Mr. M. E. Callender
    Lilly Research Laboratories
    Box 708
    Greenfield, Indiana 46140

    Ed. note: The following table has 11 columns.

    TABLE 1 Percent Mortality, Weight Gain, Feed/Gain, Intestinal and Cecal Lesion Scores of Broiler Cockerels Inoculated with E. acervulina, E. maxima, and E. tenella

    Lesion Scores

    Treatmentg/ton % Mort.(1) - # % Mort.(1) - MeanWt. Gain(2) - #Wt. Gain(2) - MeanFeed/Gain(3) - #Feed/Gain(3) - MeanIntestinal - #Intestinal - MeanCecal -#Cecal - Mean
    Non-inoculated Controls060.06273.251.643    
    Inoculated Controls0623.36167.367.8863.10  
    Narasin5460.06259.831.64560.9861.27
    Roxarsone4560.06192.062.12268.7062.27
    Narasin+Roxarsone54+4560.06263.151.71860.7360.45


     

    (1) Due to coccidiosis
    (2) Per survivor
    (3) Reps without mortality

    Ed. note: The following table has 9 columns.

    TABLE 2 Percent Mortality, Weight Gain, Feed/Gain, and Intestinal Lesion Scores of Broiler Cockerels Inoculated with E. mivati, E. necatrix, and E. brunetti

    Lesion Scores

    Treatmentg/ton % Mort.(1) - # % Mort.(1) - MeanWt. Gain(2) - #Wt. Gain(2) - MeanFeed/Gain(3) - #Feed/Gain(3) - MeanIntestinal - #Intestinal - Mean
    Non-inoculated Controls060.06309.961.563  
    Inoculated Controls060.06229.761.81166.57
    Narasin5460.06281.561.60261.63
    Roxarsone4560.06259.261.65066.33
    Narasin+Roxarsone54+4560.06290.651.55361.22
    -----------------------------------------------------------------
    (1) Due to coccidiosis
    (2) Per survivor
    (3) Reps without mortality
     
    Ed. note: The following table has 11 columns.

    TABLE 3 Percent Mortality, Weight Gain, Feed/Gain, Intestinal and Cecal Lesion Scores of Broiler Cockerels Inoculated with E. acervulina, E. maxima, and E. tenella

    Lesion Scores

    Treatmentg/ton % Mort.(1) - # % Mort.(1) - MeanWt. Gain(2) - #Wt. Gain(2) - MeanFeed/Gain(3) - #Feed/Gain(3) - MeanIntestinal - #Intestinal - MeanCecal -#Cecal - Mean
    Non-inoculated Controls060.06281.961.582    
    Inoculated Controls0620.06147.922.47667.7363.37
    Narasin5460.06271.641.61961.8461.65
    Roxarsone4566.76182.432.14168.3562.53
    Narasin+Roxarsone54+4560.06264.561.63661.0760.57
    ----------------------------------------------------------------------------
    (1) Due to coccidiosis
    (2) Per survivor
    (3) Reps without mortality

    Ed. note: The following table has 9 columns.

    TABLE 4 Percent Mortality, Weight Gain, Feed/Gain, and Intestinal Lesion Scores of Broiler Cockerels Inoculated with E. mivati, E. necatrix, and E. brunetti

    Lesion Scores

    Treatmentg/ton % Mort.(1) - # % Mort.(1) - MeanWt. Gain(2) - #Wt. Gain(2) - MeanFeed/Gain(3) - #Feed/Gain(3) - MeanIntestinal - #Intestinal - Mean
    Non-inoculated Controls060.06273.061.929  
    Inoculated Controls060.06192.162.16967.30
    Narasin5460.06232.052.00262.14
    Roxarsone4560.06216.441.95767.35
    Narasin+Roxarsone54+4560.06239.251.94362.25
    ------------------------------------------------------------------
    (1) Due to coccidiosis
    (2) Per survivor
    (3) Reps without mortality

    Ed. note: The following table has 11 columns.

    TABLE 5 Percent Mortality, Weight Gain, Feed/Gain, Intestinal and Cecal Lesion Scores of Broiler Cockerels Inoculated with E. acervulina, E. maxima, and E. tenella

    Lesion Scores

    Treatmentg/ton % Mort.(1) - # % Mort.(1) - MeanWt. Gain(2) - #Wt. Gain(2) - MeanFeed/Gain(3) - #Feed/Gain(3) - MeanIntestinal - #Intestinal - MeanCecal -#Cecal - Mean
    Non-inoculated Controls060.06260.351.583    
    Inoculated Controls0610.06170.932.08167.8763.03
    Narasin5460.06242.151.61161.5661.22
    Roxarsone4560.06183.552.01067.8162.63
    Narasin+Roxarsone54+4560.06257.161.57160.9360.57
    ----------------------------------------------------------------------------
    (1) Due to coccidiosis
    (2) Per survivor
    (3) Reps without mortality

    Ed. note: The following table has 9 columns.


    TABLE 6 Percent Mortality, Weight Gain, Feed/Gain, and Intestinal Lesion Scores of Broiler Cockerels Inoculated with E. mivati, E. necatrix, and E. brunetti

    Lesion Scores

    Treatmentg/ton % Mort.(1) - # % Mort.(1) - MeanWt. Gain(2) - #Wt. Gain(2) - MeanFeed/Gain(3) - #Feed/Gain(3) - MeanIntestinal - #Intestinal - Mean
    Non-inoculated Controls060.06248.161.838  
    Inoculated Controls060.06188.262.22468.33
    Narasin5460.06256.851.78764.62
    Roxarsone4560.06237.151.96167.42
    Narasin+Roxarsone54+4560.06256.751.89662.19
    -------------------------------------------------------------------
    (1) Due to coccidiosis
    (2) Per survivor
    (3) Reps without mortality

V. ANIMAL SAFETY

Narasin Type A medicated article is approved (21 CFR 558.363) for incorporation into the rations of broiler chickens to provide levels of 54 to 72 g narasin per ton of complete feed.

Roxarsone is approved (21 CFR 558.530) for incorporation into the rations of growing chickens at levels of 22.7 and 45.4 g/ton.

Three series of trials were conducted to confirm the safety of the feeding of a combination of narasin and roxarsone to broiler chickens.

  1. Field Studies
    A series of five trials conducted in commercial broiler production facilities over a wide geographical area.
  2. Floor Pen Trials (Series 1)
    A series of six trials conducted to evaluate the performance of broiler chickens fed various levels of narasin and roxarsone.
  3. Floor Pen Trials (Series 2)
    A series of five trials to evaluate the difference between feeding narasin alone at 72 g/ton and narasin at 72 g/ton combined with roxarsone at 45 g/ton.

Safety Study Summaries

  1. Field Studies
    The feeding of narasin alone and in combination with roxarsone to broilers was evaluated in a series of five trials conducted in commercial broiler production facilities. The trials were located in four geographical locations (Arkansas, Pennsylvania, Alabama, and North Carolina), and involved 259,883 birds from three broiler strains. At each of the trial sites the day-old straight run broiler chicks were placed in the test houses on a farm on the same day. Narasin at 72.5 g/ton was fed to the broilers in one house(s) and narasin at 72.5 g/ton plus roxarsone at 45.4 g/ton were fed until withdrawn five days prior to slaughter.

    The overall results are summarized as follows:

    Ed. note: The following table has 6 columns.

    TreatmentNumber Broilers StartedAverage Age (days)Average Weight/gainAverage FeedTotal mortality %
    Narasin 72.5 g/t129,932463.6811.9884.59
    Narasin 72.5 g/t plus
    roxarsone 45.4 g/t
    129,951463.6691.9963.17

    Obvious roxarsone toxicity was observed in broilers fed 72.5 g narasin and 45.4 g roxarsone/ton of feed in one house of broilers in the trial conducted at the Doyce Smith Farm, Almond, Arkansas.

    In that trial 14,970 chicks were placed in House 1 (narasin 72.5 g/t) and 15,020 chicks were placed in House 2 (narasin 72.5 g/t, roxarsone 45.4 g/t). During the first ten days the chicks were watered with individual water jugs. Automatic 8 ft. long trough waterers were used thereafter.

    A mild diarrhea was observed to cause wet litter in House 2. Signs of ataxia and birds chirping loudly when forced to move were also observed. Upon termination of the trial the birds were observed to have dirty feathers and mildly wet litter. None of these effects was observed in House 1.

    According to L. H. Jones, et al, in Veterinary Pharmacology and Therapeutics, 1977, page 1281, "Poultry may be poisoned by roxarsone. If birds have diarrhea and are debilitated or dehydrated or if water supply is restricted, even the recommended concentrations of roxarsone can cause toxicosis. Poultry manifest incoordination and ataxia after poisoning with roxarsone.

    The cause of the diarrhea in this instance was undetermined, but it is likely that the condition contributed to the dehydration of the birds and manifestation of signs of roxarsone toxicity.

    No signs of such toxicity were observed in the other field trials involving approximately 117,000 birds which received 72 g/ton narasin plus 45 g/ton roxarsone. No signs of toxicity were observed in the floor pen safety studies or in the battery or floor pen efficacy studies described under "IV. EFFICACY".

    Investigators for these studies were:

    Dr. L. J. Camp
    3109 Poplarwood Court, Suite 101
    Raleigh, North Carolina 27625-1011 Dr. J. T. Hays
    3035 Directors Row Ste 408
    Memphis, Tennessee 38131

    Dr. B. F. Schlegel
    314 Fairway Lane
    Fayetteville, Arkansas 72701

    Dr. D. L. Snyder
    800 Weadley Rd.
    Radnor, Pennsylvania 19087

  2. Floor Pen Trials Series

    Six trials were conducted to evaluate the performance of broiler chickens fed various levels of narasin plus roxarsone. Two trials were conducted at Fayetteville, Arkansas, one at Raleigh, North Carolina, one at Puyallup, Washington, and two at Greenfield, Indiana. Each trial had the same basic experimental design of a 3 x 4 factorial arrangement of narasin at 0, 54 and 72 g/ton with roxarsone at 0, 11, 22 and 45 g/ton. These trials were not challenged with coccidia. The results of this series are in Tables 1, 2 and 3 for weight gain, feed/gain ratio, and mortality, respectively.

    Weight Gain

    There were no differences among the treatments in weight gain.

    Feed/Gain Ratio

    Combinations of each level of narasin plus 45 g/ton of roxarsone resulted in improvement in feed/gain ratio when compared to the non-medicated control.

    Combinations of each level of narasin plus 45 g/ton of roxarsone resulted in improvement in feed/gain ratio as compared to the levels of narasin alone.

    Combinations of each level of narasin plus either 22 or 45 g/ton of roxarsone resulted in improvement in feed/gain ratios as compared to roxarsone alone.

    Mortality

    There were no differences in mortality between the non-medicated control and any of the combinations of narasin + roxarsone.

    There was a tendency for the combination of narasin + roxarsone to have less mortality than either narasin or roxarsone alone.

    Investigators in these studies were:

    P. W. Waldroup, Ph.D. University of Arkansas Fayetteville, Arkansas C. R. Parkhurst, Ph.D.
    North Carolina State University
    Raleigh, North Carolina

    L. E. Ousterhout, Ph.D.
    Western Washington Research and Extension Center
    Puyallup, Washington

    M. E. Callender
    Lilly Research Laboratories
    Greenfield, Indiana

    Ed. note: The following table has 13 columns.

    TABLE 1 SIX TRIALS WITHOUT COCCIDIAL CHALLENGE IN FLOOR PENS

    Average Weight Gain in Grams

     Roxarsone, 0 g/ton
     
    Roxarsone, 11.3 g/tonRoxarsone, 22.7 g/ton
     
    Roxarsone, 45.4 g/ton
     
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    1169017831755172617861762176617801808180517961825
    2174117701756175718181767178818521825183318421887
    3174017971852182918751824179818611870178318591853
    4181118451796179518341794181018051772177917941735
    5241724132404237223862381237123902394238923532339
    6227423212218231923252262232522962256222922252267
    L.S. Means184518841851185718901852186918801886185318591853

    Ed. note: The following table has 13 columns.

    TABLE 2 SIX TRIALS WITHOUT COCCIDIAL CHALLENGE IN FLOOR PENS

    Average Feed/Gain Ratio

     Roxarsone, 0 g/ton
     
    Roxarsone, 11.3 g/ton
     
    Roxarsone, 22.7 g/ton 
     
    Roxarsone, 45.4 g/ton
     
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/ton
    12.1562.0742.0872.2082.0822.0912.1212.0882.0732.0982.0342.049
    22.1132.0882.0882.1762.0822.1242.1382.0622.0532.0702.0132.019
    32.0172.0201.9581.9231.9842.0382.1061.9421.9402.0521.9681.918
    41.9031.8531.8461.8681.8471.8561.8871.8671.8211.8781.8451.859
    52.0182.1522.1432.2432.1702.1212.2162.1752.1242.1802.1202.106
    62.1082.0052.0202.1412.0352.0332.1122.0942.0762.0932.0292.015
    L.S. Means2.0552.0182.0172.0972.0212.0282.0682.0272.0002.0391.9 841.989

    Ed. note: The following table has 13 columns.

    TABLE 3 SIX TRIALS WITHOUT COCCIDIAL CHALLENGE IN FLOOR PENS

    Average Percent Mortality

     Roxarsone, 0 g/ton
     
    Roxarsone, 11.3 g/ton
     
    Roxarsone, 22.7 g/tonRoxarsone, 45.4 g/ton
    TrialNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin, 72 g/tonNarasin, 0 g/tonNarasin, 54 g/tonNarasin 72 g/ton
    10.753.817.573.751.833.182.912.364.792.213.342.21
    22.213.281.915.034.431.815.163.061.954.912.484.32
    35.905.717.555.144.695.015.283.712.747.144.164.57
    41.521.052.793.181.224.514.442.252.164.053.404.07
    53.336.023.556.679.434.906.567.206.023.754.902.20
    63.184.864.125.434.122.433.854.382.167.631.381.38
    L.S. Means2.623.874.414.523.863.434.403.372.904.753.033.00
  3. Floor Pen Studies Series 2

    Five trials were conducted to evaluate the difference between feeding narasin alone at 72 g/ton and narasin at 72 g/ton + roxarsone at 45 g/ton. Two trials were conducted at French Village, Wisconsin, one at Athens, Georgia, one at College Station, Texas, and one at Fayetteville, Arkansas. None of the chickens were challenged with coccidia. The results of these trials are presented in Tables 1 and 2 for weight gain and feed/gain ratio, respectively.

    Weight gain

    1. The combination of narasin + roxarsone at 72 + 45 g/ton resulted in an improvement in weight gain.

    Feed/gain ratio

    1. The combination of narasin + roxarsone at 72 + 45 g/ton resulted in an improvement in feed/gain ratio.

    Investigators in these studies were:

    O. W. Charles
    Extension Poultry Science
    University of Georgia
    Athens, Georgia 30601 W. F. Krueger
    Department of Poultry Science
    Texas Agricultural Experiment Station
    College Station, Texas 77843

    Randall A. Primo
    Ponderosa Research Company
    French Village, Missouri 63036

    P. W. Waldroup
    Department of Animal Science
    University of Arkansas
    Fayetteville, Arkansas 72701

    Ed. note: The following table has 3 columns.

    TABLE 1 COMBINATION OF NARASIN AND ROXARSONE IN FLOOR PEN STUDIES

    Five Trials without Challenge
    Weight Gain (g)

    TrialNarasin, 72 g/tonRoxarsone, 45 g/ton + Narasin, 72 g/ton
    AR8419821993
    GA8517931777
    MO8319451947
    M08518821893
    TX8517161749
    L.S.Means18611875

    Ed. note: The following table has 3 columns.

    TABLE 2 COMBINATION OF NARASIN AND ROXARSONE IN FLOOR PEN STUDIES

    Five Trials without Challenge
    Feed/Gain Ratio

    TrialNarasin, 72 g/tonRoxarsone, 45 g/ton + Narasin, 72 g/ton
    AR842.0652.033
    GAS52.0532.026
    M0832.2032.131
    M0852.0692.015
    TX851.9811.965
    L.S.Means2.0762.034
  4. VI. HUMAN SAFETY

    1. Data to Support Human Safety

      The toxicity, metabolism and total residue depletion studies that were used to establish human safety for narasin and roxarsone are described in the FOI Summaries for the individual products (51FR 29097, August 14, 1986; 21 CFR §558.363 and 52 FR 2686, January 26, 1987; 21 CFR §558.530).

    2. Residue Depletion/Non-Interference Studies

      The depletion of roxarsone in the presence of narasin was determined. The Agency accepted tissue residue depletion data using three-way combination studies in lieu of the two-way combination of narasin and roxarsone alone because it was not expected that inclusion of the other antibiotic would have an effect on the depletion of drug residues of either narasin or roxarsone.

      The tissue residue study in chickens fed narasin 90 g/ton, roxarsone 45 g/ton and another antibiotic was conducted at Cook College/Rutgers University (January 7, 1982 to March 6, 1982). The narasin assays were conducted by Lilly Research Laboratories, Greenfield, Indiana. The roxarsone assays were conducted by Salsbury Laboratories, Charles City, Iowa.

      Positive narasin responses were observed within each zero time tissue sample group: skin/fat, kidney, lean (muscle), and liver (Table 1). No narasin residues were detected in skin/fat or kidney tissue after one day's withdrawal from the treatment feed. Narasin residues were detected in liver through the two-day withdrawal period samples. No narasin residues were confirmed in muscle after the zero-day withdrawal. The presence of roxarsone does not affect the narasin tissue residue depletion profile in broiler tissues.

      The roxarsone assays show that the arsenic levels in muscle, liver, kidney, and skin/fat tissues were below the tolerance levels for roxarsone when these tissues were taken while the birds were on medicated feed.

      Ed. note: The following table has 7 columns.

      SUMMARY OF NARASIN TISSUE RESIDUES

      Sample BirdNarasin Found (ppm)
      DayNo.SexFat/SkinKidneyLeanLiver
      09F0.063<0.010<0.0100.023
      010M0.042<0.010NDR*10.016
      011F0.052<0.010NDR0.017
      012M0.057<0.010NDRNDR
      013F0.160.012<0.0100.028
      014M0.028<0.010NDR0.015
      19FNDRNDRNDR<0.010
      110MNDRNDRNDR<0.010
      111FNDRNDRNDR0.011
      112MNDRNDRNDR<0.010
      113FNDRNDRNDR<0.010
      114MNDRNDRNDR0.011
      29FNDRNDRNDR<0.010
      210MNDRNDR<0.010<0.010
      211FNDRNDR<0.010<0.010
      212MNDRNDRNDR<0.010
      213FNDRNDRNDR<0.010
      214MNDRNDRNDR<0.010

      NDR = no detectable narasin residue at the plate test sensitivity (usually 0.010 mcg narasin/g tissue).

      Ed. note: The following table has 5 columns.

      TOTAL ARSENIC ANALYSIS OF POULTRY TISSUE FROM BIRDS MEDICATED WITH BAMBERMYCINS, NARASIN AND ROXARSONE COMBINATION Tissue Residue Study - 0 Days Off Medication

      Arsenic Found

      As-N-No.Kidney
      ppm
      Liver
      ppm
      Muscle
      ppm
      Skin
      ppm
      381-3840.781.130.090.15
      385-3880.620.900.090.15
      389-3920.690.930.090.14
      394-3970.751.530.110.13
      398-4010.590.980.120.15
      402-4050.651.180.110.20

    VII. AGENCY CONCLUSIONS

    The data submitted in support of this NADA satisfy the requirements of Section 512 of the Act and demonstrate that narasin (from Monteban) at concentrations ranging from 54 to 72 g/ton and Roxarsone at a concentration of 45.4 g/ton in finished feed are safe and effective when fed to broiler chickens for the indications stated in the product labeling.

    The submitted data are adequate to satisfy the Agency's food safety requirements. The safe concentration for total narasin residues in noncooked edible chicken tissues are: 0.6 ppm in muscle; 1.8 ppm in liver; and 1.2 ppm in skin with adhering fat.

    Tolerances for total residues of combined arsenic in food are established as follows: 0.5 ppm in uncooked muscle, 2 ppm in uncooked edible by-products (21 CFR §556.60).

    Five day withdrawal time before slaughter is satisfactory.

    VIII. LABELING

    (Attached)

    Copies of applicable labels may be obtained by writing to the:

    Freedom of Information Office
    Center for Veterinary Medicine, FDA
    7500 Standish Place
    Rockville, MD 20855