Document ID: FDA-2011-N-0003-0006
Agency: fda
Document Type: Rule
Title: Tolerances for Residues of New Animal Drugs in Food: 2-Acetylamino-5-Nitrothiazole; Buquinolate; Chlorobutanol; Estradiol and Related Esters, etc.; Correcting Amendments
Posted Date: 2011-03-25T04:00Z

[Federal Register: March 23, 2011 (Volume 76, Number 56)]
[Rules and Regulations]               
[Page 16290-16291]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23mr11-13]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 556

[Docket No. FDA-2011-N-0003]

 
Tolerances for Residues of New Animal Drugs in Food; 2-
Acetylamino-5-Nitrothiazole; Buquinolate; Chlorobutanol; Estradiol and 
Related Esters; Ethylenediamine; Florfenicol; Flunixin; Furazolidone; 
Hydrocortisone; Methylparaben; Methylprednisolone; Prednisolone; 
Prednisone; Progesterone; Propylparaben; and Salicylic Acid

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule; correcting amendments.

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SUMMARY: The Food and Drug Administration (FDA) is amending the animal 
drug regulations to reflect the revocation of tolerances for residues 
of various substances in food because approval has been withdrawn for 
the underlying food additive petitions (FAPs) or new animal drug 
applications (NADAs). This action is being taken to improve the 
accuracy of the regulations.

DATES: This rule is effective March 23, 2011.

FOR FURTHER INFORMATION CONTACT: George K. Haibel, Center for 
Veterinary Medicine (HFV-6), Food and Drug Administration, 7519 
Standish Pl., Rockville, MD 20855, 240-276-9019, e[dash]mail: 
george.haibel@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: Section 512(i) of the Federal Food, Drug, 
and Cosmetic Act (the FD&C Act) (21 U.S.C. 360b(i)) (21 CFR 514.105(a)) 
directs FDA to establish tolerances by regulation, as necessary, when a 
new animal drug is approved for use in food-producing animals. However, 
section 512(i) of the FD&C Act (21 CFR 514.115(e)) also obligates FDA 
to revoke such tolerance regulations upon the withdrawal of approval of 
the related NADA.
    FDA has noticed that the animal drug regulations contain tolerances 
for residues of substances in food that were established by approval of 
FAPs for animal drug products prior to the Animal Drug Amendments of 
1968 or by NADA for which an underlying application for use in a food-
producing species is not currently approved. Following codification of 
the tolerance, the underlying FAP may have been withdrawn, or an NADA 
for the same drug product was not filed or was withdrawn, either 
voluntarily or for cause. When regulations for these products were 
removed or omitted from various redesignation rules, the appropriate 
conforming amendments to remove the revoked tolerances from part 556 
(21 CFR part 556) were not made. The following chemical substances and 
new animal drugs have codified tolerances for which FDA finds no 
applications with corresponding approved conditions of use in food-
producing animals:
    1. 2-Acetylamino-5-nitrothiazole (Sec.  556.20). In 1979, FDA 
acknowledged the voluntary withdrawal of approval of NADA 9-424 for use 
of 2-acetylamino-5-nitrothiazole for use in turkey feed and revoked 21 
CFR 558.25 (44 FR 40888, July 13, 1979), but did not amend part 556 to 
remove the associated tolerances.
    2. Chlorobutanol (Sec.  556.140). In 1963, FDA established a 
tolerance for chlorobutanol in milk of dairy animals at Sec.  121.1131 
(21 CFR 121.1131) incidental to the approval of an FAP for a 
combination drug, antibiotic/steroid intramammary infusion (28 FR 4948, 
May 17, 1963). Section 121.1131 was redesignated as 21 CFR 135g.31 (35 
FR 15372 at 15376, October 2, 1970) and as Sec.  556.140 (40 FR 13802 
at 13947, March 27, 1975).
    3. Estradiol and progesterone in edible tissues of lambs 
(Sec. Sec.  556.240 and 556.540). In 1973, FDA acknowledged the 
voluntary withdrawal of approval of a subcutaneous implant for use in 
lambs containing estradiol benzoate and progesterone under NADA 9-442 
(38 FR 7481, March 22, 1973). Subsequently, FDA removed the approved 
conditions of use in 21 CFR 522.1940 (44 FR 6707 at 6708, February 2, 
1979), but did not amend part 556 to remove the associated tolerances 
in uncooked edible tissues of lambs.
    4. Ethylenediamine (Sec.  556.270). In 1965, FDA established a 
tolerance for ethylenediamine in milk of dairy animals at Sec.  
121.1184 (21 CFR 121.1184) incidental to the approval of an FAP for a 
combination drug, antibiotic intramammary infusion (30 FR 11952 at 
11954, September 18, 1965). Section 121.1184 was redesignated as 21 CFR 
135g.48 (35 FR 15372 at 15378) and as Sec.  556.270 (40 FR 13802 at 
13950).
    5. Furazolidone (Sec.  556.290). In 1963, FDA established a 
tolerance for furazolidone in uncooked edible tissues of swine at Sec.  
121.2582 (21 CFR 121.2582) incidental to the approval of an FAP for use 
in medicated swine feed (28 FR 12664 at 12665, November 28, 1963). 
Section 121.2582 was redesignated as 21 CFR 121.1145 (30 FR 15845 at 
15917, December 23, 1965), as 21 CFR 135g.36 (35 FR 15372 at 15376), 
and as Sec.  556.290 (40 FR 13802 at 13950). In 1971, FDA proposed to 
withdraw approval of NADAs for use of furazolidone in food-producing 
animals on grounds that the drug, when administered to laboratory 
animals, was shown to produce tumors (36 FR 5927, March 31, 1971) and 
in 1991 withdrew approval after a full evidentiary hearing (56 FR 
41902, August 23, 1991). Currently, there is no approved application 
for use of furazolidone in a food-producing species. A 1996 order 
codified a prohibition of extralabel use of furazolidone in food-
producing animals (61 FR 57732 at 57743, November 7, 1996 as amended 67 
FR 5470 at 5471, February 6, 2002). See 21 CFR 530.41(a)(7).
    6. Hydrocortisone (Sec.  556.320). In 1970, FDA established a 
tolerance for hydrocortisone in milk of dairy animals at Sec.  135g.3 
(21 CFR 135g.3) incidental to the approval of an FAP for a combination 
drug, antibiotic/steroid intramammary infusion (35 FR 12332 at 12333, 
August 1, 1970). Section 135g.3

[[Page 16291]]

was redesignated as Sec.  556.320 (40 FR 13802 at 13950).
    7. Methylparaben (Sec.  556.390). In 1964, FDA established a 
tolerance for methylparaben in milk of dairy animals at Sec.  121.1158 
(21 CFR 121.1158) incidental to the approval of an FAP for a 
combination drug, antibiotic intramammary infusion (29 FR 14624, 
October 27, 1964). Section 121.1158 was redesignated as 21 CFR 135g.41 
(35 FR 15372 at 15376) and as Sec.  556.390 (40 FR 13802 at 13956).
    8. Methylprednisolone (Sec.  556.400). In 1970, FDA established a 
tolerance for methylprednisolone in milk of dairy animals at Sec.  
135g.67 (21 CFR 135g.67) incidental to the approval of an FAP for a 
combination drug, antibiotic/steroid intramammary infusion (35 FR 12332 
at 12333). Section 135g.67 was redesignated as Sec.  556.400 (40 FR 
13802 at 13956).
    9. Prednisolone (Sec.  556.520). In 1964, FDA established a 
tolerance for prednisolone in milk of dairy animals at Sec.  121.1147 
(21 CFR 121.1147) incidental to the approval of an FAP for a 
combination drug, antibiotic intramammary infusion (29 FR 3393, March 
14, 1964). Section 121.1147 was redesignated as 21 CFR 135g.37 (35 FR 
15372 at 15376) and as Sec.  556.520 (40 FR 13802 at 13956).
    10. Prednisone (Sec.  556.530). In 1964, FDA established a 
tolerance for prednisone in milk of dairy animals at Sec.  121.1157 (21 
CFR 121.1157) incidental to the approval of an FAP for a combination 
drug, antibiotic intramammary infusion (29 FR 14624). Section 121.1157 
was redesignated as 21 CFR 135g.40 (35 FR 15372 at 15376) and as Sec.  
556.530 (40 FR 13802 at 13956).
    11. Propylparaben (Sec.  556.550). In 1964, FDA established a 
tolerance for propylparaben in milk of dairy animals at Sec.  121.1159 
incidental to the approval of an FAP for a combination drug, antibiotic 
intramammary infusion (29 FR 14624). Section 121.1159 was redesignated 
as 21 CFR 135g.42 (35 FR 15372 at 15376) and as Sec.  556.550 (40 FR 
13802 at 13956).
    12. Salicylic acid (Sec.  556.590). In 2005, FDA acknowledged the 
voluntary withdrawal of approval of salicylic acid for use in cattle 
under NADA 010-481 and revoked 21 CFR 529.2090 (70 FR 50181, August 26, 
2005), but did not remove the associated tolerance.
    At this time, FDA is revoking the tolerances for 2-acetylamino-5-
nitrothiazole, buquinolate, chlorobutanol, estradiol in lamb, 
ethylenediamine, furazolidone, hydrocortisone, methylparaben, 
methylprednisolone, prednisolone, prednisone, progesterone in lamb, 
propylparaben, and salicylic acid. Accordingly, Sec. Sec.  556.20, 
556.140, 556.270, 556.290, 556.320, 556.390, 556.400, 556.520, 556.530, 
556.550, and 556.590 are being removed, and Sec. Sec.  556.240 and 
556.540 are being amended to reflect the revoked tolerances.
    Also, FDA is amending the animal drug regulations in Sec. Sec.  
556.283 and 556.286 to cross reference an approved combination drug 
injectable solution containing florfenicol and flunixin (75 FR 1274, 
January 11, 2010). FDA is further amending Sec.  556.286 to reflect the 
marker residue in milk for residues of flunixin meglumine. This action 
is being taken to comply with section. 512(i) of the FD&C Act and to 
improve the accuracy of the regulations.
    This rule does not meet the definition of ``rule'' in 5 U.S.C. 
804(3)(A) because it is a rule of ``particular applicability.'' 
Therefore, it is not subject to the congressional review requirements 
in 5 U.S.C. 801-808.

List of Subjects in 21 CFR Part 556

    Animal drugs, Foods.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs and 
redelegated to the Center for Veterinary Medicine, 21 CFR part 556 is 
amended as follows:

PART 556--TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD

0
1. The authority citation for 21 CFR part 556 continues to read as 
follows:

    Authority: 21 U.S.C. 342, 360b, 371.

Sec.  556.20  [Removed]

0
2. Remove Sec.  556.20.

Sec.  556.140  [Removed]

0
3. Remove Sec.  556.140.

Sec.  556.240  [Amended]

0
4. In Sec.  556.240, remove and reserve paragraph (b).

Sec.  556.270  [Removed]

0
5. Remove Sec.  556.270.

0
6. Revise Sec.  556.283 to read as follows:

Sec.  556.283  Florfenicol.

    (a) Acceptable daily intake (ADI). The ADI for total residues of 
florfenicol is 10 micrograms per kilogram of body weight per day.
    (b) Tolerances--(1) Cattle--(i) Liver (the target tissue). The 
tolerance for florfenicol amine (the marker residue) is 3.7 parts per 
million (ppm).
    (ii) Muscle. The tolerance for florfenicol amine (the marker 
residue) is 0.3 ppm.
    (2) Swine--(i) Liver (the target tissue). The tolerance for parent 
florfenicol (the marker residue) is 2.5 ppm.
    (ii) Muscle. The tolerance for parent florfenicol (the marker 
residue) is 0.2 ppm.
    (3) Catfish. The tolerance for florfenicol amine (the marker 
residue) in muscle (the target tissue) is 1 ppm.
    (4) Salmonids. The tolerance for florfenicol amine (the marker 
residue) in muscle/skin (the target tissues) is 1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.955, 522.955, 
522.956, and 558.261 of this chapter.

0
7. In Sec.  556.286, revise paragraphs (b)(1)(iii) and (c) to read as 
follows:

Sec.  556.286  Flunixin.

* * * * *
    (b) * * *
    (1) * * *
    (iii) Milk: 2 ppb 5-hydroxy flunixin.
* * * * *
    (c) Related conditions of use. See Sec. Sec.  522.956 and 522.970 
of this chapter.

Sec.  556.290  [Removed]

0
8. Remove Sec.  556.290.

Sec.  556.320  [Removed]

0
9. Remove Sec.  556.320.

Sec.  556.390  [Removed]

0
10. Remove Sec.  556.390.

Sec.  556.400  [Removed]

0
11. Remove Sec.  556.400.

Sec.  556.520  [Removed]

0
12. Remove Sec.  556.520.

Sec.  556.530  [Removed]

0
13. Remove Sec.  556.530.

Sec.  556.540  [Amended]

0
14. In Sec.  556.540, remove and reserve paragraph (b).

Sec.  556.550  [Removed]

0
15. Remove Sec.  556.550.

Sec.  556.590  [Removed]

0
16. Remove Sec.  556.590.

    Dated: March 17, 2011.
Leslie Kux,
Acting Assistant Commissioner for Policy.
[FR Doc. 2011-6796 Filed 3-22-11; 8:45 am]
BILLING CODE 4160-01-P