New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food, 72254-72268 [2012-29322]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 77, Number 234 (Wednesday, December 5, 2012)]
[Proposed Rules]
[Pages 72254-72268]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2012-29322]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 500, 520, 522, 524, 529, 556, and 558

[Docket No. FDA-2012-N-1067]
RIN 0910-AG17


New Animal Drugs; Updating Tolerances for Residues of New Animal 
Drugs in Food

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to revise 
the animal drug regulations regarding tolerances for residues of 
approved and conditionally approved new animal drugs in food by 
standardizing, simplifying, and clarifying the determination standards 
and codification style. In addition, we are proposing to add 
definitions for key terms. The purpose of the revision is to enhance 
understanding of tolerance determination and improve the readability of 
the regulations.

DATES: Submit either electronic or written comments by March 5, 2013. 
See section VI of this document for the proposed effective date of a 
final rule based on this proposed rule.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2012-
N-1067 and RIN number 0910-AG17, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov/. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Fax: 301-827-6870.
     Mail/Hand Delivery/Courier (for paper or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency 
name, Docket

[[Page 72255]]

No. FDA-2012-N-1067, and Regulatory Information Number (RIN) 0910-AG17 
for this rulemaking. All comments received may be posted without change 
to https://www.regulations.gov, including any personal information 
provided. For additional information on submitting comments, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Dong Yan, Center for Veterinary 
Medicine (HFV-151), Food and Drug Administration, 7500 Standish Pl., 
Rockville, MD 20855, 240-276-8117, email: dong.yan@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: 

I. Background

    Sections 512(b)(1)(H), 512(i), and 571(a)(2)(A) of the Federal 
Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360b(b)(1)(H), 
360b(i), and 360ccc(a)(2)(A)) provide the authority for the Secretary 
of Health and Human Services (the Secretary) to establish and publish 
regulations setting tolerances for residues of approved and 
conditionally approved new animal drugs. The Secretary delegated this 
authority to the Commissioner of Food and Drugs. FDA's regulations 
setting forth the tolerances for residues of new animal drugs in food 
are codified in part 556 of Title 21 of the Code of Federal Regulations 
(21 CFR part 556) (40 FR 13802 at 13942, March 27, 1975). The part 556 
regulations describe general considerations regarding tolerances for 
residues of new animal drugs in food in subpart A and specific 
tolerances for residues of new animal drugs in subpart B. Subpart B has 
been amended frequently as new animal drugs have been approved for use 
in food-producing animals. Food from treated animals with new animal 
drug residues that exceed established tolerances is adulterated under 
section 402(a)(2)(C)(ii) of the FD&C Act (21 U.S.C. 342(a)(2)(C)(ii)).
    FDA's human food safety evaluation of residues of new animal drugs 
has evolved over the past 50 years. Before the mid-1970s, FDA based 
tolerances primarily on a small number of toxicity studies, typically 
90-day feeding studies in laboratory animals. From the results of these 
studies, FDA determined the ``no-observed-effect-level'' (NOEL). The 
acceptable daily intake (ADI) for total residue of a drug was 
calculated by dividing the NOEL by the appropriate safety factor to 
adjust for the differences between test animals and humans. To 
calculate the safe concentrations, FDA considered food consumption 
values and human body weight. Consumption was estimated as a total 
dietary exposure of 1,500 grams of food per day. Historically, FDA used 
an average human weight of 50 or 60 kilograms. Because these toxicology 
studies did not assess lifetime effects (which could only be observed 
in long-term feeding studies), FDA applied a 2,000-fold safety factor 
to the NOELs. FDA generally set the tolerance for ``negligible'' 
residues of these drugs at 0.1 part per million (ppm) in muscle and 10 
parts per billion in milk, even if the computed tolerance exceeded the 
calculated values.
    In later years, FDA assigned what it called ``finite tolerances.'' 
Finite tolerances were calculated using procedures similar to those 
described previously, except, unlike tolerances set for ``negligible'' 
residues, finite tolerances were set at the calculated level. Finite 
tolerances had to be supported, at a minimum, by lifetime feeding 
studies in two rodent species, a 6-month or longer study in a non-
rodent mammalian species, and a three-generation reproduction study. 
Because finite tolerances were based on more extensive studies, FDA 
generally applied a lower (100-fold) safety factor in calculating the 
ADI.
    The earliest established tolerances generally referred to the 
parent drug. Consequently, residue chemistry studies, including residue 
depletion studies that served as the basis for assigning withdrawal 
periods for tissues and for milk (milk discard time), and the 
analytical methods used to measure residue levels focused on the parent 
drug.
    From the mid-1970s to the present, FDA's human food safety 
evaluation of animal drug residues has evolved with advancements in 
science. As a result, the procedures described in the existing Sec.  
556.1 for setting drug tolerances no longer accurately reflect current 
regulatory science. In addition, current part 556 employs a patchwork 
of various styles for listing tolerances that have evolved over the 
past 40 years. As a result, the listings in part 556 are not uniform in 
format, and, in some instances, do not provide all relevant information 
in a consistent manner. For example, the regulations provide the ADI 
and safe concentrations for some, but not all, drugs. In addition, the 
regulations list some tolerances as being for ``negligible'' residue, 
and others as ``no residue,'' ``zero,'' or ``not required,'' but they 
do not explain what these important terms mean. The proposed rule 
addresses these inconsistencies by simplifying and standardizing the 
determination standards and codification style and by adding 
definitions for key terms.

II. Description of Proposed Rule

    FDA proposes to revise part 556 by standardizing and simplifying 
the codification style and adding definitions for key terms. First, 
proposed Sec.  556.1 provides a revised scope for part 556. Second, 
proposed Sec.  556.3 provides definitions of key terms FDA uses in the 
regulations. Third, proposed Sec.  556.5 explains the general 
considerations for using the tolerance information for veterinary drug 
residues. Finally, FDA proposes a uniform format for listing tolerances 
in subpart B, by, among other things, removing obsolete or confusing 
terms and cross-referencing tolerances to the approved conditions of 
use for that new animal drug.

A. Subpart A--General Provisions

1. Scope (Proposed Sec.  556.1)
    FDA proposes to delete existing Sec.  556.1 (``General 
considerations; tolerances for residues of new animal drugs in food'') 
and replace it with a description of the scope. FDA proposes to discuss 
general considerations for setting tolerances in new Sec.  556.5.
    Proposed Sec.  556.1 reiterates the requirement in sections 
512(b)(1)(H) and 571(a)(2)(A) of the FD&C Act that applicants seeking 
approval or conditional approval of new animal drugs must submit a 
proposed tolerance as part of new animal drug applications when 
necessary to assure that the proposed use of the new animal drug will 
be safe. The proposed section states that FDA assigns tolerances for 
animal drugs used in food-producing animals as part of the application 
approval process and then codifies them in subpart B of part 556. 
Proposed Sec.  556.1 also clarifies that compounds that have been found 
to be carcinogenic are regulated under subpart E of part 500 (21 CFR 
part 500).
2. Definitions (Proposed Sec.  556.3)
    FDA proposes to define in Sec.  556.3 certain key terms used in 
animal drug residue chemistry and some terms frequently used in part 
556. In the proposed rule, the definitions appear in alphabetical 
order. In this preamble, the definitions are discussed in an order

[[Page 72256]]

that facilitates the explanation of the interrelated concepts the terms 
represent.
    a. Terms related to determining tolerances. FDA's human food safety 
evaluation focuses on residues of new animal drugs in the edible 
tissues of the treated animal. FDA proposes to define ``edible 
tissues'' as muscle, liver, kidney, fat, skin with fat in natural 
proportions, whole eggs, whole milk, and honey. FDA proposes to define 
``residue,'' as it is defined in 21 CFR 530.3, to mean any compound 
present in edible tissues that results from the use of a drug, and 
includes the drug, its metabolites, and any other substance formed in 
or on food because of the drug's use. Under the proposed rule, the 
``total residue'' includes every residue of a given drug. FDA proposes 
to define total residue as the aggregate of all compounds that result 
from the use of an animal drug, including the drug, its metabolites, 
and any other substances formed in or on food because of such drug use.
    Under the proposal, the definition of a NOEL means the highest dose 
level of a drug tested that produces no observable effects. ADI means 
the amount of total residue that can safely be consumed per day over a 
human's lifetime. The ADI is calculated by dividing the NOEL (from the 
most appropriate toxicological study) by a safety factor. The safety 
factor reflects, among other things, the extrapolation of long-term 
effects from shorter-term exposures, extrapolation of animal data to 
humans, and variability in sensitivity among human populations. 
Sometimes, the concept of an ``acceptable single-dose intake'' or 
``ASDI'' is used to calculate tolerances. FDA is proposing to define 
``ASDI'' as the amount of total residue that may safely be consumed in 
a single meal. The ASDI may be used to derive the tolerance for 
residues of a drug at an injection site where the drug is administered 
according to the label.
    Under the proposed rule, a ``tolerance'' means the maximum 
concentration of a marker residue or other residue indicated for 
monitoring that can legally remain in a specific edible tissue of a 
treated animal. A ``marker residue'' means the residue selected for 
assay by the regulatory method. In general, the marker residue is a 
subset of the total residue; for example, the marker residue could be 
the parent drug, a metabolite, or a combination of residues. The 
concentration of the marker residue in the target tissue is in a known 
relationship to the concentration of the total residue in the target 
tissue. The ``regulatory method'' means the aggregate of all 
experimental procedures for measuring and confirming the presence of 
the marker residue in the target tissue of the target animal. The 
``target tissue'' means the edible tissue selected to monitor for 
residues in the target animals. When the marker residue or other 
residue indicated for monitoring is at or below the tolerance in the 
target tissue, the total drug residues in all the edible tissues 
(excluding milk and eggs unless otherwise specified) should be at or 
below the safe concentration.
    b. Terms used to characterize tolerances. In the past, FDA has used 
several terms to characterize tolerances in part 556, including 
``zero,'' ``no residue,'' ``not required,'' and ``not needed'' but has 
not included clear definitions in part 556 for these important terms. 
Because the differences in these terms has not always been evident, FDA 
is proposing to amend part 556 by eliminating redundant terminology and 
adding definitions for the terms that the Agency intends to continue 
using to help ensure that going forward the terms will be uniformly 
applied by the Agency and understood by the public.
    First, over the years, many people have mistakenly believed the 
term ``zero'' with respect to tolerances to mean there could be no 
residue remaining in an edible tissue. However, FDA acknowledges that 
some residue will remain in the animal, even if below a detectable 
level, and that a complete lack of drug residue is not achievable. In 
approving certain animal drugs, FDA assigned a ``zero'' tolerance, with 
``zero'' meaning that no residues could be detected using the approved 
analytical method to detect residues of that drug. Often, the 
analytical method chosen to determine ``zero'' represented the limit of 
technology at the time. FDA no longer assigns ``zero'' tolerances for 
new approvals, but instead assigns a tolerance for a drug based on a 
toxicological and residue chemistry evaluation (see proposed Sec.  
556.5). However, FDA is not proposing to remove the previously assigned 
``zero'' tolerances from the regulations at this time.
    Second, FDA uses the term ``no residue'' to apply specifically to 
compounds of carcinogenic concern. Under section 512(d)(1)(I) of the 
FD&C Act, ``no residue'' of any drug that induces cancer when ingested 
by man or animal is allowed in any edible tissue of a food-producing 
animal, when tested using methods of examination prescribed or approved 
by FDA. FDA historically has interpreted the term ``no residue'' to 
mean that any residue in the target tissue must be non-detectable or 
below the limit of detection of the approved regulatory method (67 FR 
78172, December 23, 2002). Consistent with this interpretation, FDA is 
proposing to define ``no residue'' to mean that the marker residue is 
below the limit of detection using the approved regulatory method. FDA 
is proposing to add this definition to Sec.  500.82 under subpart E 
entitled ``Regulation of Carcinogenic Compounds Used in Food-Producing 
Animals.''
    Third, FDA previously approved some animal drugs with a waiver of 
the requirement for a tolerance (i.e., a tolerance was ``not required'' 
or ``not needed'') because they met two conditions in place at the time 
they were evaluated by FDA. The first condition was an assurance that 
residues would deplete to or below safe levels by zero-day withdrawal 
(i.e., no withdrawal period was needed), or that an adequate withdrawal 
period was inherent in the proposed conditions of drug use. The second 
condition was a rapid depletion of residues, so there was no concern 
about residues resulting from misuse or overdosing. Sometimes the 
codified tolerance listings described these situations as ones where a 
tolerance was ``not needed''; other times the phrase ``not required'' 
was used to convey the same meaning. To ensure consistency, FDA 
proposes to revise part 556 to delete descriptions of tolerances as 
``not needed'' and replace such designations with the term ``not 
required.''
    Fourth, in the past, when a drug was approved with a zero 
withdrawal period, FDA would not set a tolerance for the particular 
drug. Historically, FDA generally recommended that a sponsor of a drug 
seeking a zero withdrawal period conduct a total residue depletion 
study in which target animals were dosed with 1.5 to 2 times the 
recommended maximum dose of drug to simulate overdosing. If a zero 
withdrawal period was approved, FDA would not set a tolerance for the 
drug.
    Currently, FDA continues to recommend these total residue depletion 
studies when sponsors propose zero withdrawal periods, but, when 
possible, FDA sets a tolerance for these drugs. Infrequently, 
circumstances preclude FDA from setting a tolerance. For example, some 
drugs may be poorly absorbed and/or metabolized rapidly to such an 
extent as to make selection of an analyte impractical or impossible. In 
these uncommon cases, FDA proposes to use the term ``not required'' 
when describing the tolerance.

[[Page 72257]]

    FDA is proposing to define ``not required'' with respect to 
tolerances as indicating that at the time of approval, the drug met one 
of the following conditions: (1) No withdrawal period (i.e., zero 
withdrawal) was necessary for residues of the drug to deplete to or 
below the concentrations considered to be safe or an adequate 
withdrawal period was inherent in the proposed drug use, and there was 
no concern about residues resulting from misuse or overdosing; or (2) 
the drug qualified for a zero withdrawal period because it was poorly 
absorbed or metabolized rapidly to such an extent as to make selection 
of an analyte impractical or impossible.
3. General Considerations (Proposed Sec.  556.5)
    Proposed Sec.  556.5(a) states that tolerances published in subpart 
B of part 556 pertain only to the species and production classes of the 
animal for which the drug use has been approved or conditionally 
approved. The proposed rule provides the approved use and conditionally 
approved use conditions, including species and production classes, in 
each tolerance listing under ``(c) Related conditions of use.'' 
Tolerances are not provided for extralabel (e.g., use in species or 
production classes in which the drug is not approved for use.) 
Extralabel use resulting in any residue above an established safe level 
or tolerance is unlawful and renders the drug product adulterated under 
section 501(a)(5) of the FD&C Act (21 U.S.C. 351(a)(5)), in that it is 
unsafe within the meaning of section 512 of the FD&C Act.
    Proposed Sec.  556.5(b) states that all tolerances refer to the 
concentrations of a marker residue, or other residue indicated for 
monitoring, permitted in uncooked tissues.
    Proposed Sec.  556.5(c) states that a finding that the 
concentration of a marker residue is at or below the tolerance in the 
target tissue from a tested animal indicates that all edible tissues 
(excluding milk and eggs unless otherwise specified) from that animal 
are safe. In the proposed listing format, if a listed tolerance is 
linked to a target tissue, the phrase ``target tissue'' will appear in 
parentheses immediately after the identified tissue. If a listed 
tolerance is not expressly linked to a target tissue, then the 
tolerance is meant to apply only to the named edible tissue, and 
inferences cannot be made about the safety of the other edible tissues 
from the target animal.
    Proposed Sec.  556.5(d) states that FDA requires that a drug 
sponsor develop a regulatory method to measure drug residues in edible 
tissues of approved target species at concentrations around the 
tolerance as provided in Sec.  514.1(b)(7) of this chapter. The 
tolerance is directly tied to the approved regulatory method because 
FDA determines the tolerance using data collected with that method.

B. Subpart B--Specific Tolerances for Residues of Approved and 
Conditionally Approved New Animal Drugs

    FDA proposes a uniform format for the individual drug tolerance 
listings in subpart B. FDA would list the ADI and ASDI if they are 
available. If the ADI and ASDI are both unavailable, FDA would reserve 
paragraph (a) for future use. FDA would list tolerances in paragraph 
(b) for each edible tissue for each species, as appropriate. When a 
tolerance listing states ``edible tissues,'' it would mean all edible 
tissues of that species unless otherwise specified. FDA intends the 
revised paragraph (c) to help readers locate approved or conditionally 
approved uses of each drug and to identify the form of the drug (e.g., 
free acid or base, salt, hydrate).
    FDA proposes to revise subpart B by deleting tolerances for certain 
drugs (or species of animals) whose approvals have been withdrawn, but 
the corresponding tolerances were not removed from the part 556 
listing; and adding tolerances for approved drugs not previously listed 
in this subpart. Specifically, FDA proposes to delete the tolerances 
for clopidol for all species other than chickens and turkeys (Sec.  
556.160) and nystatin for swine (Sec.  556.470). FDA proposes to add 
tolerance listings for: Azaperone, bambermycins, coumaphos, 
efrotomycin, fenprostalene (swine), fenthion, flurogestone, and 
poloxalene.
    Note that some listings provide more than one tolerance. For 
example, tilmicosin in cattle (Sec.  556.735(b)(1)) includes the 
following information: A marker residue (tilmicosin), a target tissue 
(liver), a tolerance of 1.2 ppm for tilmicosin in liver of cattle, and 
a tolerance of 0.1 ppm for tilmicosin in muscle of cattle.
    This means that if the concentration of tilmicosin in the liver of 
a treated animal is at or below 1.2 ppm, all the edible tissues 
(excluding milk and eggs unless otherwise specified) from the animal 
are considered to be safe if ingested daily by humans over a lifetime. 
If the concentration of tilmicosin is assayed for only the muscle 
tissue and the concentration is at or below 0.1 ppm, the muscle tissue 
from the animal is considered to be safe if ingested daily by humans 
over a lifetime. Because muscle is not the target tissue, the 
tilmicosin concentration in muscle alone does not predict residue 
safety for the other edible tissues.

C. Other Proposed Changes to Part 556

    This proposal includes other changes to the current part 556 
regulations. First, FDA proposes to delete salt designations from the 
tolerance listings in subpart B. For example, maduramicin ammonium, 
morantel tartrate, and sulfabromomethazine sodium will be listed as 
maduramicin, morantel, and sulfabromomethazine, respectively. FDA 
proposes this change for several reasons. The residues derived from 
salt formulations and hydrated forms of a given drug are the same. In 
addition, the approved regulatory methods ordinarily measure the free 
drug, a metabolite, or some combination of residues, not the salts. FDA 
also believes such a simplification of tolerance listings will improve 
their readability. However, when FDA lists the ADI for a compound, the 
specific compound that was administered in the pivotal toxicological 
feeding study will be indicated, as toxicological outcome could be 
affected by salt formulation.
    Second, FDA proposes to cross-reference drug tolerances in part 556 
to the approved or conditionally approved conditions of use listed in 
21 CFR parts 516, 520, 522, 524, 526, 529, and 558. These listings 
specify the drug, salt, dosage form, and indications for use (amount, 
animal species/production class, and limitations) of approved or 
conditionally approved animal drug products. In conjunction with adding 
these cross-references, FDA proposes to remove references to production 
classes from tolerance listings in subpart B. In a few past instances, 
FDA codified tolerances specifying the production class (e.g., beef or 
dairy cattle) of food-producing species. This was done in an effort to 
be consistent with the listed approved conditions of use, but for only 
a few animal drugs listed in part 556.
    FDA also proposes to delete safe concentrations from the tolerance 
listings in part 556. Although tolerances have been codified using the 
total residue, target tissue, and marker residue concepts for about 25 
years, the particular types of information codified have varied. For 
some drugs, FDA listed only tolerances. For other drugs, FDA listed 
safe concentrations as well as tolerances, leading some readers to 
misinterpret the safe concentrations as tolerances. Because a tolerance 
can be a small fraction of the safe concentration, such a 
misunderstanding could lead to referencing an incorrect residue safety 
standard for a specific drug. FDA

[[Page 72258]]

tentatively concludes that removing safe concentrations from the 
codified listings will reduce the potential for this confusion. The 
Agency invites comment on this removal.
    Further, FDA proposes to remove the word ``negligible'' from 
tolerance citations, because the word is outdated. A tolerance is the 
maximum concentration of a new animal drug residue that can legally 
remain in an edible tissue of a treated animal and raise no concern for 
human food safety. In other words, by definition, a tolerance 
essentially represents the negligible level of residue. Therefore, FDA 
no longer uses the word ``negligible'' to characterize residues.
    Finally, FDA is proposing to delete the word ``uncooked'' from the 
individual listings in subpart B. Because the general considerations 
and the proposed definition of tolerance clarifies that all tolerances 
refer to the concentrations of the marker residue, or other residues 
indicated for monitoring, permitted in uncooked edible tissues, 
including the word ``uncooked'' in individual listings is no longer 
necessary.
    FDA seeks comment on the proposed changes to part 556. In 
particular, the Agency is interested to know if the reorganization and 
standardization of content enhances the clarity and utility of part 556 
and if the definitions of terms are clear and understandable. FDA does 
not, however, seek comment on the numerical drug residue tolerance 
values listed in subpart B as these values were determined by FDA in 
conjunction with the approval or conditional approval of each new 
animal drug application and, as such, are not the subject of public 
comment. An exception would be the notation of a technical error where 
the numerical value cited in the published document does not conform to 
an approved application or application for conditional approval.

III. Environmental Impact

    The Agency has determined under 21 CFR 25.30(i) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

IV. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct Agencies to assess all 
costs and benefits of available regulatory alternatives and, when 
regulation is necessary, to select regulatory approaches that maximize 
net benefits (including potential economic, environmental, public 
health and safety, and other advantages; distributive impacts; and 
equity). The Agency believes that this proposed rule is not a 
significant regulatory action as defined by the Executive Order 12866.
    The Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because this proposed rule would not impose 
compliance costs on the current or future sponsors of any approved and 
conditionally approved new animal drugs, the Agency proposes to certify 
that the final rule will not have a significant economic impact on a 
substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that Agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $139 million, using the most current (2011) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.

V. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed rule, if finalized, would not contain policies that would 
have substantial direct effects on the States, on the relationship 
between the National Government and the States, or on the distribution 
of power and responsibilities among the various levels of government. 
Accordingly, the Agency tentatively concludes that the proposed rule 
does not contain policies that have federalism implications as defined 
in the Executive order and, consequently, a federalism summary impact 
statement is not required.

VI. Paperwork Reduction Act of 1995

    FDA tentatively concludes that this proposed rule contains no new 
collections of information. Therefore, clearance by the Office of 
Management and Budget under the Paperwork Reduction Act of 1995 (44 
U.S.C. 3501-3520) is not required.

VII. Proposed Effective Date

    FDA is proposing that any final rule that may issue based on this 
proposal be effective 60 days after the date of its publication in the 
Federal Register.

VIII. Comments

    Interested persons may submit either written comments regarding 
this document to the Division of Dockets Management (see ADDRESSES) or 
electronic comments to https://www.regulations.gov. It is only necessary 
to send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at https://www.regulations.gov.

List of Subjects

21 CFR Part 500

    Animal drugs, Animal feeds, Cancer, Labeling, Packaging and 
containers, Polychlorinated biphenyls (PCBs).

21 CFR Parts 520, 522, 524, and 529

    Animal drugs.

21 CFR Part 556

    Animal drugs, Foods.

21 CFR Part 558

    Animal drugs, Animal feeds.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR chapter I, subchapter E, be amended as follows:

PART 500--GENERAL

    1. The authority citation for 21 CFR part 500 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 342, 343, 348, 351, 352, 353, 
360b, 371, 379e.

    2. Amend Sec.  500.82, in paragraph (b), by alphabetically adding a 
definition for ``no residue'' to read as follows:


Sec.  500.82  Definitions.

* * * * *
    (b) * * *
    No residue means the marker residue is below the limit of detection 
using the approved regulatory method. The ``no residue'' designation 
applies only to compounds of carcinogenic concern.
* * * * *

[[Page 72259]]

PART 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS

    3. The authority citation for 21 CFR part 520 continues to read as 
follows:

    Authority:  21 U.S.C. 360b.

    4. In Sec.  520.1840, revise paragraph (c) to read as follows:


Sec.  520.1840  Poloxalene.

* * * * *
    (c) Related tolerances. See Sec.  556.517 of this chapter.
* * * * *
    5. In Sec.  520.2640, revise paragraph (c) to read as follows:


Sec.  520.2640  Tylosin.

* * * * *
    (c) Related tolerances. See Sec.  556.746 of this chapter.
* * * * *

PART 522--IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS

    6. The authority citation for 21 CFR part 522 continues to read as 
follows:

    Authority:  21 U.S.C. 360b.


    7. In Sec.  522.770, revise paragraph (c) to read as follows:


Sec.  522.770  Doramectin.

* * * * *
    (c) Related tolerances. See Sec.  556.222 of this chapter.
* * * * *
    8. In Sec.  522.2640, revise paragraph (d) to read as follows:


Sec.  522.2640  Tylosin.

* * * * *
    (d) Related tolerances. See Sec.  556.746 of this chapter.
* * * * *

PART 524--OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS

    9. The authority citation for 21 CFR part 524 continues to read as 
follows:

    Authority:  21 U.S.C. 360b.

    10. In Sec.  524.920, revise paragraph (c)(4) to read as follows:


Sec.  524.920  Fenthion.

* * * * *
    (c) * * *
    (4) Related tolerances. See Sec.  556.280 of this chapter.
* * * * *

PART 529--CERTAIN OTHER DOSAGE FORM NEW ANIMAL DRUGS

    11. The authority citation for 21 CFR part 529 continues to read as 
follows:

    Authority:  21 U.S.C. 360b.

    12. In Sec.  529.1003, add paragraph (d) to read as follows:


Sec.  529.1003  Flurogestone acetate-impregnated vaginal sponge.

* * * * *
    (d) Related tolerances. See Sec.  556.290 of this chapter.

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

    13. The authority citation for 21 CFR part 556 is revised to read 
as follows:

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

    14. Revise part 556 to read as follows:
Subpart A--General Provisions
Sec.
556.1 Scope.
556.3 Definitions.
556.5 General considerations.
Subpart B--Specific Tolerances for Residues of Approved and 
Conditionally Approved New Animal Drugs
Sec.
556.34 Albendazole.
556.36 Altrenogest.
556.38 Amoxicillin.
556.40 Ampicillin.
556.50 Amprolium.
556.52 Apramycin.
556.60 Arsenic.
556.68 Azaperone.
556.70 Bacitracin.
556.75 Bambermycins.
556.100 Carbadox.
556.110 Carbomycin.
556.113 Ceftiofur.
556.115 Cephapirin.
556.120 Chlorhexidine.
556.150 Chlortetracycline.
556.160 Clopidol.
556.163 Clorsulon.
556.165 Cloxacillin.
556.167 Colistimethate.
556.168 Coumaphos.
556.169 Danofloxacin.
556.170 Decoquinate.
556.180 Dichlorvos.
556.185 Diclazuril.
556.200 Dihydrostreptomycin.
556.222 Doramectin.
556.224 Efrotomycin.
556.226 Enrofloxacin.
556.227 Eprinomectin.
556.230 Erythromycin.
556.240 Estradiol and related esters.
556.260 Ethopabate.
556.273 Famphur.
556.275 Fenbendazole.
556.277 Fenprostalene.
556.280 Fenthion.
556.283 Florfenicol.
556.286 Flunixin.
556.290 Flurogestone.
556.292 Gamithromycin.
556.300 Gentamicin.
556.304 Gonadotropin.
556.308 Halofuginone.
556.310 Haloxon.
556.330 Hygromycin B.
556.344 Ivermectin.
556.346 Laidlomycin.
556.347 Lasalocid.
556.350 Levamisole.
556.360 Lincomycin.
556.375 Maduramicin.
556.380 Melengestrol.
556.410 Metoserpate.
556.420 Monensin.
556.425 Morantel.
556.426 Moxidectin.
556.428 Narasin.
556.430 Neomycin.
556.440 Nequinate.
556.445 Nicarbazin.
556.460 Novobiocin.
556.470 Nystatin.
556.480 Oleandomycin.
556.490 Ormetoprim.
556.495 Oxfendazole.
556.500 Oxytetracycline.
556.510 Penicillin.
556.513 Piperazine.
556.515 Pirlimycin.
556.517 Poloxalene.
556.540 Progesterone.
556.560 Pyrantel.
556.570 Ractopamine.
556.580 Robenidine.
556.592 Salinomycin.
556.597 Semduramicin.
556.600 Spectinomycin.
556.610 Streptomycin.
556.620 Sulfabromomethazine.
556.625 Sulfachloropyrazine.
556.630 Sulfachlorpyridazine.
556.640 Sulfadimethoxine.
556.650 Sulfaethoxypyridazine.
556.660 Sulfamerazine.
556.670 Sulfamethazine.
556.685 Sulfaquinoxaline.
556.690 Sulfathiazole.
556.700 Sulfomyxin.
556.710 Testosterone.
556.720 Tetracycline.
556.730 Thiabendazole.
556.733 Tildipirosin.
556.735 Tilmicosin.
556.738 Tiamulin.
556.739 Trenbolone.
556.741 Tripelennamine.
556.745 Tulathromycin.
556.746 Tylosin.
556.748 Tylvalosin.
556.750 Virginiamycin.
556.760 Zeranol.
556.765 Zilpaterol.
556.770 Zoalene.

Subpart A--General Provisions


Sec.  556.1  Scope.

    (a) The Federal Food, Drug, and Cosmetic Act requires an applicant 
seeking approval or conditional approval of a new animal drug to submit 
a proposed tolerance as part of its new animal drug application when 
such a tolerance is needed to assure that the proposed use of the new 
animal drug will be safe (see sections 512(b)(1)(H) and 571(a)(2)(A) of 
the Federal Food, Drug, and Cosmetic Act). FDA assigns tolerances for 
animal drugs used in

[[Page 72260]]

food-producing animals as part of the application approval process. 
Tolerances for approved and conditionally approved new animal drugs are 
codified in subpart B of this part.
    (b) Compounds that have been found to be carcinogenic are regulated 
under subpart E of part 500 of this chapter.


Sec.  556.3  Definitions.

    As used in this part:
    Acceptable daily intake (ADI) means the amount of total residue 
that can safely be consumed per day over a human's lifetime without 
adverse health effect. The ADI is calculated by dividing the no-
observed-effect-level (NOEL) (from the most appropriate toxicological 
study) by a safety factor. The safety factor reflects, among other 
things, the extrapolation of long-term effects from shorter-term 
exposures, extrapolation of animal data to humans, and variability in 
sensitivity among human populations.
    Acceptable single-dose intake (ASDI) means the amount of total 
residue that may safely be consumed in a single meal. The ASDI may be 
used to derive the tolerance for residue of the drug at the injection 
site where the drug is administered according to the label.
    Edible tissues means muscle, liver, kidney, fat, skin with fat in 
natural proportions, whole eggs, whole milk, and honey.
    Marker residue means the residue selected for assay by the 
regulatory method whose concentration in the target tissue is in a 
known relationship to the concentration of the total residue in the 
target tissue. A finding that the concentration of marker residue is at 
or below the tolerance in the target tissue from a tested animal 
indicates that all edible tissues (excluding milk and eggs unless 
otherwise specified) from that animal are safe.
    mg/kg means milligrams per kilogram.
    No-Observed-Effect Level (NOEL) means the highest dose level of a 
drug tested that produces no observable effects.
    Not required, in reference to tolerances in this part, means that 
at the time of approval, the drug met one of the following conditions:
    (1) No withdrawal period (i.e. zero withdrawal) was necessary for 
residues of the drug to deplete to or below the concentrations 
considered to be safe or an adequate withdrawal period was inherent in 
the proposed drug use, and there was no concern about residues 
resulting from misuse or overdosing; or
    (2) The drug qualified for a zero withdrawal period because it was 
poorly absorbed or metabolized rapidly so as to make selection of an 
analyte impractical or impossible.
    ppb means parts per billion (equivalent to nanograms per gram (ng/
g) or [mu]g/kg).
    ppm means parts per million (equivalent to micrograms per gram 
([mu]g/g) or mg/kg).
    ppt means parts per trillion (equivalent to picograms per gram (pg/
g) or nanograms per kilogram (ng/kg)).
    Regulatory method means the aggregate of all experimental 
procedures for measuring and confirming the presence of the marker 
residue in the target tissue of the target animal.
    Residue means any compound present in edible tissues that results 
from the use of a drug, and includes the drug, its metabolites, and any 
other substance formed in or on food because of the drug's use.
    Target tissue means the edible tissue selected to monitor for 
residues in the target animals.
    Tolerance means the maximum concentration of a marker residue, or 
other residue indicated for monitoring, that can legally remain in a 
specific edible tissue of a treated animal. (A finding, using the 
approved regulatory method, that the concentration of the marker 
residue or other residue indicated for monitoring is present in the 
target tissue at a concentration at or below the tolerance, indicates 
that all edible tissues (excluding milk and eggs unless otherwise 
specified) from the tested animal are safe. All tolerances refer to the 
concentrations of a marker residue, or other residue indicated for 
monitoring, permitted in uncooked tissues.)
    Total residue means the aggregate of all compounds that results 
from the use of an animal drug, including the drug, its metabolites, 
and any other substances formed in or on food because of such drug use.
    [mu]g/kg means microgram per kilogram.
    Zero, in reference to tolerances in this part, means no detectable 
residues are allowed when using a method of detection prescribed or 
approved by FDA. Any residue detectable using the prescribed or 
approved method renders the tissue unsafe.


Sec.  556.5  General considerations.

    (a) The tolerances listed in subpart B of this part pertain only to 
the species and production classes of the animal for which the drug use 
has been approved or conditionally approved. Approved use and 
conditionally approved use conditions, including the species and 
production classes of the animals, are cited under paragraph (c) 
Related conditions of use for each tolerance listing of subpart B of 
this part.
    (b) All tolerances refer to the concentrations of a marker residue, 
or other residue indicated for monitoring, permitted in uncooked 
tissues.
    (c) After a tolerance is listed, the finding that the concentration 
of the marker residue in the target tissue from a tested animal is at 
or below the tolerance indicates that all edible tissues (excluding 
milk and eggs unless otherwise indicated) from that tested animal are 
safe for human consumption. If a listed tolerance is not expressly 
linked to a target tissue, then the tolerance is specific only for the 
named edible tissue and inferences cannot be made about the safety of 
the other edible tissues from the tested animal.
    (d) FDA requires that a drug sponsor develop a regulatory method to 
measure drug residues in edible tissues of approved target species at 
concentrations around the tolerance as provided in Sec.  514.1(b)(7) of 
this chapter. Because FDA determines the tolerance for the marker 
residue using data collected with the approved regulatory method, the 
tolerance is directly tied to that method. Approved regulatory methods 
are available from the Division of Dockets Management (HFA-305), Food 
and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 
20852.

Subpart B--Specific Tolerances for Residues of Approved and 
Conditionally Approved New Animal Drugs


Sec.  556.34  Albendazole.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
albendazole is 5 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for albendazole 2-aminosulfone 
(marker residue) are:
    (1) Cattle--(i) Liver (target tissue): 0.2 ppm.
    (ii) Muscle: 0.05 ppm.
    (2) Sheep--(i) Liver (target tissue): 0.25 ppm.
    (ii) Muscle: 0.05 ppm.
    (3) Goat--(i) Liver (target tissue): 0.25 ppm.
    (ii) [Reserved]
    (c) Related conditions of use. See Sec.  520.45 of this chapter.


Sec.  556.36  Altrenogest.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
altrenogest is 0.04 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerance for altrenogest (the marker residue) 
is:
    (1) Swine--(i) Liver (target tissue): 4 ppb.

[[Page 72261]]

    (ii) Muscle: 1 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  520.48 of this chapter.


Sec.  556.38  Amoxicillin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for amoxicillin are:
    (1) Cattle--Edible tissues: 0.01 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.88, 522.88, and 
526.88 of this chapter.


Sec.  556.40  Ampicillin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for ampicillin are:
    (1) Cattle--Edible tissues: 0.01 ppm.
    (2) Swine--Edible tissues: 0.01 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.90e, 520.90f, and 
522.90 of this chapter.


Sec.  556.50  Amprolium.

    (a) [Reserved]
    (b) Tolerances. The tolerances for amprolium are:
    (1) Cattle--(i) Liver, kidney, and muscle: 0.5 ppm.
    (ii) Fat: 2.0 ppm.
    (2) Chickens and turkeys--(i) Liver and kidney: 1 ppm.
    (ii) Muscle: 0.5 ppm.
    (iii) Eggs:
    (A) Egg yolks: 8 ppm.
    (B) Whole eggs: 4 ppm.
    (3) Pheasants--(i) Liver: 1 ppm.
    (ii) Muscle: 0.5 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.100, 558.55, and 
558.58 of this chapter.


Sec.  556.52  Apramycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
apramycin is 25 [mu]g/kg of body weight per day.
    (b) Tolerance. The tolerance for apramycin (marker residue) is:
    (1) Swine--Kidney (target tissue): 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.110 and 558.59 of 
this chapter.


Sec.  556.60  Arsenic.

    (a) [Reserved]
    (b) Tolerances. The tolerances for total residue of combined 
arsenic (calculated as As) are:
    (1) Chickens and turkeys--(i) Muscle and eggs: 0.5 ppm.
    (ii) Other edible tissues: 2 ppm.
    (2) Swine--(i) Liver and kidney: 2 ppm.
    (ii) Muscle and fat: 0.5 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2087, 520.2088, 
520.2089, 558.62, 558.120, 558.369, and 558.530 of this chapter.


Sec.  556.68  Azaperone.

    (a) Acceptable daily intake (ADI). The ADI for total residues of 
azaperone is 0.63 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for azaperone are:
    (1) Swine--(i) Edible tissues: Not required.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.150 of this chapter.


Sec.  556.70  Bacitracin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
bacitracin is 0.05 mg/kg of body weight per day.
    (b) Tolerances. The tolerances for bacitracin are:
    (1) Cattle--Edible tissues: 0.5 ppm.
    (2) Chickens, turkeys, pheasants, quail--Edible tissues: 0.5 ppm.
    (3) Swine--Edible tissues: 0.5 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.154, 558.76, and 
558.78 of this chapter.


Sec.  556.75  Bambermycins.

    (a) [Reserved]
    (b) Tolerances. The tolerances for bambermycins are:
    (1) Cattle--Edible tissues (excluding milk): Not required.
    (2) Chickens and turkeys--Edible tissues (excluding eggs): Not 
required.
    (3) Swine--Edible tissues: Not required.
    (c) Related conditions of use. See Sec.  558.95 of this chapter.


Sec.  556.100  Carbadox.

    (a) [Reserved]
    (b) Tolerance. The tolerance for quinoxaline-2-carboxylic acid 
(marker residue) is:
    (1) Swine--Liver (target tissue): 30 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.115 of this chapter.


Sec.  556.110  Carbomycin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for carbomycin are:
    (1) Chickens--Edible tissues (excluding eggs): Zero.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  520.1660a of this chapter.


Sec.  556.113  Ceftiofur.

    (a) Acceptable daily intake and acceptable single-dose intake--(1) 
Acceptable daily intake (ADI). The ADI for total residue of ceftiofur 
is 30 [mu]g/kg of body weight per day.
    (2) Acceptable single-dose intake (ASDI). The ASDI total residue 
for ceftiofur is 0.830 mg/kg of body weight. The ASDI is the amount of 
total residue of ceftiofur that may safely be consumed in a single 
meal.
    (b) Tolerances. The tolerances for desfuroylceftiofur (marker 
residue) are:
    (1) Cattle--(i) Kidney (target tissue): 0.4 ppm.
    (ii) Liver: 2 ppm.
    (iii) Muscle: 1 ppm.
    (iv) Milk: 0.1 ppm.
    (2) Chickens and turkeys--Edible tissues (excluding eggs): Not 
required.
    (3) Goats--(i) Kidney (target tissue): 8 ppm.
    (ii) Liver: 2 ppm.
    (iii) Muscle: 1 ppm.
    (iv) Milk: 0.1 ppm.
    (4) Sheep--Edible tissues (excluding milk): Not required.
    (5) Swine--(i) Kidney (target tissue): 0.25 ppm.
    (ii) Liver: 3 ppm.
    (iii) Muscle: 2 ppm.
    (c) Related conditions of use. See Sec. Sec.  522.313 and 526.313 
of this chapter.


Sec.  556.115  Cephapirin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for cephapirin are:
    (1) Cattle--(i) Edible tissues (excluding milk): 0.1 ppm.
    (ii) Milk: 0.02 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  526.363 and 526.365 
of this chapter.


Sec.  556.120  Chlorhexidine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for chlorhexidine are:
    (1) Cattle--Edible tissues (excluding milk): Zero.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  529.400 of this chapter.


Sec.  556.150  Chlortetracycline.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
tetracyclines including chlortetracycline, oxytetracycline, and 
tetracycline is 25 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for the sum of tetracycline residues 
are:
    (1) Cattle--(i) Liver: 6 ppm.
    (ii) Kidney and fat: 12 ppm.
    (iii) Muscle: 2 ppm.
    (2) Chickens, turkeys, and ducks--(i) Liver: 6 ppm.
    (ii) Kidney and fat: 12 ppm.
    (iii) Muscle: 2 ppm.
    (iv) Eggs: 0.4 ppm for chlortetracycline only.
    (3) Sheep--(i) Liver: 6 ppm.
    (ii) Kidney and fat: 12 ppm.
    (iii) Muscle: 2 ppm.
    (4) Swine--(i) Liver: 6 ppm.
    (ii) Kidney and fat: 12 ppm.
    (iii) Muscle: 2 ppm.

[[Page 72262]]

    (c) Related conditions of use. See Sec. Sec.  520.445, 558.128, 
558.145, and 558.155 of this chapter.


Sec.  556.160  Clopidol.

    (a) [Reserved]
    (b) Tolerances. The tolerances for clopidol are:
    (1) Chickens and turkeys--(i) Liver and kidney: 15 ppm.
    (ii) Muscle: 5 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.175 of this chapter.


Sec.  556.163  Clorsulon.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
clorsulon is 8 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for clorsulon (marker residue) are:
    (1) Cattle--(i) Kidney (target tissue): 1.0 ppm.
    (ii) Muscle: 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.462 and 522.1193 
of this chapter.


Sec.  556.165  Cloxacillin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for cloxacillin are:
    (1) Cattle--Edible tissues: 0.01 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  526.464 of this chapter.


Sec.  556.167  Colistimethate.

    (a) [Reserved]
    (b) Tolerances. The tolerances for colistimethate are:
    (1) Chickens--Edible tissues (excluding eggs): Not required.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.468 of this chapter.


Sec.  556.168  Coumaphos.

    (a) [Reserved]
    (b) Tolerances. The tolerances for coumaphos (measured as coumaphos 
and its oxygen analog, O,O-diethyl O-3-chloro-4-methyl-2-oxo-2 H-1-
benzopyran-7-yl phosphate) are:
    (1) Cattle--(i) Edible tissues (excluding milk): 1 ppm.
    (ii) Milk fat: 0.5 ppm.
    (2) Chickens--(i) Edible tissues (excluding eggs): 1 ppm.
    (ii) Eggs: 0.1 ppm.
    (c) Related conditions of use. See Sec.  558.185 of this chapter.


Sec.  556.169  Danofloxacin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
danofloxacin is 2.4 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for danofloxacin (marker residue) 
are:
    (1) Cattle--(i) Liver (target tissue): 0.2 ppm.
    (ii) Muscle: 0.2 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.522 of this chapter.


Sec.  556.170  Decoquinate.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
decoquinate is 75 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for decoquinate are:
    (1) Cattle--(i) Muscle: 1 ppm.
    (ii) Other edible tissues (excluding milk): 2 ppm.
    (2) Chickens--(i) Muscle: 1 ppm.
    (ii) Other edible tissues (excluding eggs): 2 ppm.
    (3) Goats--(i) Muscle: 1 ppm.
    (ii) Other edible tissues (excluding milk): 2 ppm.
    (c) Related conditions of use. See Sec.  558.195 of this chapter.


Sec.  556.180  Dichlorvos.

    (a) [Reserved]
    (b) Tolerances. The tolerances for dichlorvos are:
    (1) Swine--Edible tissues: 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.205 of this chapter.


Sec.  556.185  Diclazuril.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
diclazuril is 25 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for diclazuril are:
    (1) Chickens and turkeys--(i) Liver: 3 ppm.
    (ii) Muscle: 0.5 ppm.
    (iii) Skin/fat: 1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.198 of this chapter.


Sec.  556.200  Dihydrostreptomycin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for dihydrostreptomycin are:
    (1) Cattle--(i) Kidney: 2.0 ppm.
    (ii) Other edible tissues (excluding milk): 0.5 ppm.
    (iii) Milk: 0.125 ppm.
    (2) Swine--(i) Kidney: 2.0 ppm.
    (ii) Other edible tissues: 0.5 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2158b, 520.2158c, 
522.650, and 526.1696b of this chapter.


Sec.  556.222  Doramectin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
doramectin is 0.75 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for doramectin (marker residue) are:
    (1) Cattle--(i) Liver (target tissue): 100 ppb.
    (ii) Muscle: 30 ppb.
    (2) Swine--Liver (target tissue): 160 ppb.
    (c) Related conditions of use. See Sec. Sec.  522.770 and 524.770 
of this chapter.


Sec.  556.224  Efrotomycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
efrotomycin is 10 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for efrotomycin are:
    (1) Swine--Edible tissues: Not required.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.235 of this chapter.


Sec.  556.226  Enrofloxacin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
enrofloxacin is 3 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for enrofloxacin are:
    (1) Cattle--Liver (target tissue): 0.1 ppm desethylene 
ciprofloxacin (marker residue).
    (2) Swine--Liver (target tissue): 0.5 ppm enrofloxacin (marker 
residue).
    (c) Related conditions of use. See Sec.  522.812 of this chapter.


Sec.  556.227  Eprinomectin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
eprinomectin is 10 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for eprinomectin B1a 
(marker residue) are:
    (1) Cattle--(i) Liver (target tissue): 1.5 ppm.
    (ii) Muscle: 100 ppb.
    (iii) Milk: 12 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  522.814 and 524.814 
of this chapter.


Sec.  556.230  Erythromycin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for erythromycin are:
    (1) Cattle--(i) Edible tissues (excluding milk): 0.1 ppm.
    (ii) Milk: Zero.
    (2) Chickens and turkeys--(i) Edible tissues (excluding eggs): 
0.125 ppm.
    (ii) Eggs: 0.025 ppm.
    (3) Swine--Edible tissues: 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.823, 522.820, 
526.820, and 558.248 of this chapter.


Sec.  556.240  Estradiol and related esters.

    (a) [Reserved]
    (b) Tolerances. Residues of estradiol are not permitted in excess 
of the following increments above the concentrations of estradiol 
naturally present in untreated animals:
    (1) Cattle--(i) Muscle: 120 ppt.
    (ii) Fat: 480 ppt.
    (iii) Kidney: 360 ppt.
    (iv) Liver: 240 ppt.
    (2) [Reserved]

[[Page 72263]]

    (c) Related conditions of use. See Sec. Sec.  522.840, 522.842, 
522.850, 522.1940, 522.2477, and 522.2478 of this chapter.


Sec.  556.260  Ethopabate.

    (a) [Reserved]
    (b) Tolerances. The tolerances for ethopabate, measured as 
metaphenetidine, are:
    (1) Chickens--(i) Liver: 1.5 ppm.
    (ii) Kidney: 1.5 ppm.
    (iii) Muscle: 0.5 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.58 of this chapter.


Sec.  556.273  Famphur.

    (a) [Reserved]
    (b) Tolerances. The tolerances for famphur including its oxygen 
analog are:
    (1) Cattle--Edible tissues (excluding milk): 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.1242g, 524.900, 
and 558.254 of this chapter.


Sec.  556.275  Fenbendazole.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
fenbendazole is 40 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for fenbendazole are:
    (1) Cattle--(i) Liver (target tissue): 0.8 ppm fenbendazole (marker 
residue).
    (ii) Muscle: 0.4 ppm fenbendazole.
    (iii) Milk: 0.6 ppm fenbendazole sulfoxide.
    (2) Goats--(i) Liver (target tissue): 0.8 ppm fenbendazole (marker 
residue).
    (ii) Muscle: 0.4 ppm fenbendazole.
    (3) Swine--(i) Liver (target tissue): 6 ppm fenbendazole (marker 
residue).
    (ii) Muscle: 2 ppm fenbendazole.
    (4) Turkeys--(i) Liver (target tissue): 6 ppm fenbendazole sulfone 
(marker residue).
    (ii) Muscle: 2 ppm fenbendazole sulfone.
    (c) Related conditions of use. See Sec. Sec.  520.905 and 558.258 
of this chapter.


Sec.  556.277  Fenprostalene.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
fenprostalene is 0.08 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for fenprostalene are:
    (1) Cattle--Edible tissues (excluding milk): Not required.
    (2) Swine--Edible tissues: Not required.
    (c) Related conditions of use. See Sec.  522.914 of this chapter.


Sec.  556.280  Fenthion.

    (a) [Reserved]
    (b) Tolerance. The tolerances for fenthion are:
    (1) Cattle--Edible tissues (excluding milk): 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  524.920 of this chapter.


Sec.  556.283  Florfenicol.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
florfenicol is 10 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for florfenicol amine (marker 
residue) are:
    (1) Cattle--(i) Liver (target tissue): 3.7 ppm.
    (ii) Muscle: 0.3 ppm.
    (2) Swine--(i) Liver (target tissue): 2.5 ppm.
    (ii) Muscle: 0.2 ppm.
    (3) Catfish--Muscle (target tissue): 1 ppm.
    (4) Freshwater-reared warmwater finfish (other than catfish) and 
salmonids--Muscle/skin (target tissue): 1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.955, 522.955, 
522.956, and 558.261 of this chapter.


Sec.  556.286  Flunixin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
flunixin is 0.72 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for flunixin are:
    (1) Cattle--(i) Liver (target tissue): 125 ppb flunixin free acid 
(marker residue).
    (ii) Muscle: 25 ppb flunixin free acid.
    (iii) Milk: 2 ppb 5-hydroxy flunixin (marker residue).
    (2) Swine--(i) Liver (target tissue): 30 ppb flunixin free acid 
(marker residue).
    (ii) Muscle: 25 ppb flunixin free acid.
    (c) Related conditions of use. See Sec. Sec.  522.956 and 522.970 
of this chapter.


Sec.  556.290  Flurogestone.

    (a) [Reserved]
    (b) Tolerances. The tolerances for flurogestone are:
    (1) Sheep--Edible tissues (excluding milk): Not required.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  529.1003 of this chapter.


Sec.  556.292  Gamithromycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
gamithromycin is 10 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for gamithromycin (marker residue) 
are:
    (1) Cattle--(i) Liver (target tissue): 500 ppb.
    (ii) Muscle: 150 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.1014 of this chapter.


Sec.  556.300  Gentamicin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
gentamicin is 60 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for gentamicin are:
    (1) Chickens and turkeys--Edible tissues (excluding eggs): 0.1 ppm.
    (2) Swine--(i) Liver: 0.3 ppm.
    (ii) Kidney (target tissue): 0.4 ppm gentamicin (marker residue).
    (iii) Fat: 0.4 ppm.
    (iv) Muscle: 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  522.1044, 524.1044e, 
and 529.1044b of this chapter.


Sec.  556.304  Gonadotropin.

    (a) Acceptable daily intake (ADI). The ADI for residues of total 
gonadotropins (human chorionic gonadotropin and pregnant mare serum 
gonadotropin) is 42.25 International Units per kilogram of body weight 
per day.
    (b) Tolerances. The tolerances for gonadotropin are:
    (1) Cattle--Edible tissues (excluding milk): Not required.
    (2) Fish--Edible tissues: Not required.
    (3) Swine--Edible tissues: Not required.
    (c) Related conditions of use. See Sec. Sec.  522.1077, 522.1078, 
522.1079, and 522.1081 of this chapter.


Sec.  556.308  Halofuginone.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
halofuginone hydrobromide is 0.7 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for halofuginone (marker residue) 
are:
    (1) Chickens--Liver (target tissue): 0.16 ppm.
    (2) Turkeys--Liver (target tissue): 0.13 ppm.
    (c) Related conditions of use. See Sec.  558.265 of this chapter.


Sec.  556.310  Haloxon.

    (a) [Reserved]
    (b) Tolerances. The tolerances for haloxon are:
    (1) Cattle--Edible tissues (excluding milk): 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  520.1120 of this chapter.


Sec.  556.330  Hygromycin B.

    (a) [Reserved]
    (b) Tolerances. The tolerances for hygromycin B are:
    (1) Chickens--Edible tissues: Zero.
    (2) Swine--Edible tissues: Zero.
    (c) Related conditions of use. See Sec.  558.274 of this chapter.


Sec.  556.344  Ivermectin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
ivermectin is 1 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for 22,23-dihydroavermectin 
B1a (marker residue) are:

[[Page 72264]]

    (1) American bison--Liver (target tissue): 15 ppb.
    (2) Cattle--(i) Liver (target tissue): 100 ppb.
    (ii) Muscle: 10 ppb.
    (3) Reindeer--Liver (target tissue): 15 ppb.
    (4) Sheep-- Liver (target tissue): 30 ppb.
    (5) Swine--(i) Liver (target tissue): 20 ppb.
    (ii) Muscle: 20 ppb.
    (c) Related conditions of use. See Sec. Sec.  520.1192, 520.1195, 
520.1197, 522.1192, 522.1193, 524.1193, and 558.300 of this chapter.


Sec.  556.346  Laidlomycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
laidlomycin is 7.5 [mu]g/kg of body weight per day.
    (b) Tolerance. The tolerance for laidlomycin (marker residue) is:
    (1) Cattle--Liver (target tissue): 0.2 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.305 of this chapter.


Sec.  556.347  Lasalocid.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
lasalocid is 10 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for lasalocid (marker residue) are:
    (1) Cattle--Liver (target tissue): 0.7 ppm.
    (2) Chickens--(i) Skin with adhering fat (target tissue): 1.2 ppm.
    (ii) Liver: 0.4 ppm.
    (3) Rabbits--Liver (target tissue): 0.7 ppm.
    (4) Sheep--Liver (target tissue): 1.0 ppm.
    (5) Turkeys--(i) Liver (target tissue): 0.4 ppm.
    (ii) Skin with adhering fat: 0.4 ppm.
    (c) Related conditions of use. See Sec.  558.311 of this chapter.


Sec.  556.350  Levamisole.

    (a) [Reserved]
    (b) Tolerances. The tolerances for levamisole are:
    (1) Cattle--Edible tissues (excluding milk): 0.1 ppm.
    (2) Sheep--Edible tissues (excluding milk): 0.1 ppm.
    (3) Swine--Edible tissues: 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.1242, 522.1244, 
and 524.1240 of this chapter.


Sec.  556.360  Lincomycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
lincomycin is 25 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for lincomycin are:
    (1) Chickens--Edible tissues (excluding eggs): Not required.
    (2) Swine--(i) Liver: 0.6 ppm.
    (ii) Muscle: 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.1263b, 520.1263c, 
522.1260, and 558.325 of this chapter.


Sec.  556.375  Maduramicin.

    (a) [Reserved]
    (b) Tolerance. The tolerance for maduramicin (marker residue) is:
    (1) Chickens--Fat (target tissue): 0.38 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.340 of this chapter.


Sec.  556.380  Melengestrol.

    (a) [Reserved]
    (b) Tolerance. The tolerance for melengestrol is:
    (1) Cattle--Fat: 25 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.342 of this chapter.


Sec.  556.410  Metoserpate.

    (a) [Reserved]
    (b) Tolerances. The tolerances for metoserpate are:
    (1) Chickens--Edible tissues (excluding eggs): 0.02 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  520.1422 of this chapter.


Sec.  556.420  Monensin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
monensin is 12.5 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for monensin are:
    (1) Cattle--(i) Liver: 0.10 ppm.
    (ii) Muscle, kidney, and fat: 0.05 ppm.
    (iii) Milk: Not required.
    (2) Chickens and turkeys--Edible tissues (excluding eggs): Not 
required.
    (3) Goats--Edible tissues (excluding milk): 0.05 ppm.
    (4) Quail--Edible tissues (excluding eggs): Not required.
    (c) Related conditions of use. See Sec.  558.355 of this chapter.


Sec.  556.425  Morantel.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
morantel tartrate is 10 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for N-methyl-1,3-propanediamine 
(marker residue) are:
    (1) Cattle--(i) Liver (target tissue): 0.7 ppm.
    (ii) Milk: Not required.
    (2) Goats--(i) Liver (target tissue): 0.7 ppm.
    (ii) Milk: Not required.
    (c) Related conditions of use. See Sec. Sec.  520.1450 and 558.360 
of this chapter.


Sec.  556.426  Moxidectin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
moxidectin is 4 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for moxidectin (marker residue) are:
    (1) Cattle--(i) Fat (target tissue): 900 ppb.
    (ii) Liver: 200 ppb.
    (iii) Muscle: 50 ppb.
    (iv) Milk: 40 ppb.
    (2) Sheep--(i) Fat (target tissue): 900 ppb.
    (ii) Liver: 200 ppb.
    (iii) Muscle: 50 ppb.
    (c) Related conditions of use. See Sec. Sec.  520.1454, 522.1450, 
and 524.1450 of this chapter.


Sec.  556.428  Narasin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
narasin is 5 [mu]g/kg of body weight per day.
    (b) Tolerance. The tolerance for narasin (marker residue) is:
    (1) Chickens--Abdominal fat (target tissue): 480 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.363 of this chapter.


Sec.  556.430  Neomycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
neomycin is 6 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for neomycin are:
    (1) Cattle--(i) Kidney (target tissue): 7.2 ppm.
    (ii) Liver: 3.6 ppm.
    (iii) Muscle: 1.2 ppm.
    (iv) Fat: 7.2 ppm.
    (v) Milk: 0.15 ppm.
    (2) Sheep and Goats--(i) Kidney (target tissue): 7.2 ppm.
    (ii) Liver: 3.6 ppm.
    (iii) Muscle: 1.2 ppm.
    (iv) Fat: 7.2 ppm.
    (v) Milk: 0.15 ppm.
    (3) Swine--(i) Kidney (target tissue): 7.2 ppm.
    (ii) Liver: 3.6 ppm.
    (iii) Muscle: 1.2 ppm.
    (iv) Fat: 7.2 ppm.
    (4) Turkeys--(i) Skin with adhering fat: 7.2 ppm.
    (ii) Liver: 3.6 ppm.
    (iii) Muscle: 1.2 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.1484, 524.1600b, 
and 558.364 of this chapter.


Sec.  556.440  Nequinate.

    (a) [Reserved]
    (b) Tolerances. The tolerances for nequinate are:
    (1) Chickens--Edible tissues (excluding eggs): 0.1 ppm.
    (2) [Reserved]

[[Page 72265]]

    (c) Related conditions of use. See Sec.  558.365 of this chapter.


Sec.  556.445  Nicarbazin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for nicarbazin are:
    (1) Chickens--(i) Muscle: 4 ppm.
    (ii) Liver: 4 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.366 of this chapter.


Sec.  556.460  Novobiocin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for novobiocin are:
    (1) Cattle--(i) Edible tissues (excluding milk): 1 ppm.
    (ii) Milk: 0.1 ppm.
    (2) Chickens, turkeys, ducks--Edible tissues (excluding eggs): 1 
ppm.
    (c) Related conditions of use. See Sec. Sec.  526.1590, 526.1696d, 
and 558.415 of this chapter.


Sec.  556.470  Nystatin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for nystatin are:
    (1) Cattle--Edible tissues (excluding milk): Zero.
    (2) Chickens and turkeys--Edible tissues: Zero.
    (c) Related conditions of use. See Sec. Sec.  524.1600b and 558.430 
of this chapter.


Sec.  556.480  Oleandomycin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for oleandomycin are:
    (1) Chickens and turkeys--Edible tissues (excluding eggs): 0.15 
ppm.
    (2) Swine--Edible tissues: 0.15 ppm.
    (c) Related conditions of use. See Sec.  558.435 of this chapter.


Sec.  556.490  Ormetoprim.

    (a) [Reserved]
    (b) Tolerances. The tolerances for ormetoprim are:
    (1) Chickens, turkeys, ducks, and chukar partridges--Edible tissues 
(excluding eggs): 0.1 ppm.
    (2) Salmonids and catfish--Edible tissues: 0.1 ppm.
    (c) Related conditions of use. See Sec.  558.575 of this chapter.


Sec.  556.495  Oxfendazole.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
oxfendazole is 7 [mu]g/kg of body weight per day.
    (b) Tolerance. The tolerance for fenbendazole (marker residue) is:
    (1) Cattle--Liver (target tissue): 0.8 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.1629 and 520.1630 
of this chapter.


Sec.  556.500  Oxytetracycline.

    (a) Acceptable daily intake (ADI). The ADI for total tetracycline 
residues (chlortetracycline, oxytetracycline, and tetracycline) is 25 
[mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for the sum of tetracycline residues 
are:
    (1) Cattle--(i) Muscle: 2 ppm.
    (ii) Liver: 6 ppm.
    (iii) Fat and kidney: 12 ppm.
    (iv) Milk: 0.3 ppm.
    (2) Chickens and turkeys--(i) Muscle: 2 ppm.
    (ii) Liver: 6 ppm.
    (iii) Fat and kidney: 12 ppm.
    (3) Finfish--Muscle (with adhering skin when edible): 2 ppm.
    (4) Lobster--Muscle: 2 ppm.
    (5) Swine and Sheep--(i) Muscle: 2 ppm.
    (ii) Liver: 6 ppm.
    (iii) Fat and kidney: 12 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.1660, 522.1660, 
522.1662, 524.1662b, 529.1660, and 558.450 of this chapter.


Sec.  556.510  Penicillin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for penicillin are:
    (1) Cattle--(i) Edible tissues (excluding milk): 0.05 ppm.
    (ii) Milk: Zero.
    (2) Chickens--Edible tissues: Zero.
    (3) Pheasants and quail--Edible tissues: Zero.
    (4) Sheep and Swine--Edible tissues: Zero.
    (5) Turkeys--Edible tissues (excluding eggs): 0.01 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.1696, 522.1696, 
526.1696, and 558.460 of this chapter.


Sec.  556.513  Piperazine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for piperazine are:
    (1) Chickens and turkeys--Edible tissues (excluding eggs): 0.1 ppm.
    (2) Swine--Edible tissues: 0.1 ppm.
    (c) Related conditions of use. See Sec.  520.1807 of this chapter.


Sec.  556.515  Pirlimycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
pirlimycin is 0.01 mg/kg of body weight per day.
    (b) Tolerances. The tolerances for pirlimycin (marker residue) are:
    (1) Cattle--(i) Liver (target tissue): 0.5 ppm.
    (ii) Muscle: 0.3 ppm.
    (iii) Milk: 0.4 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  526.1810 of this chapter.


Sec.  556.517  Poloxalene.

    (a) [Reserved]
    (b) Tolerances. The tolerances for poloxalene are:
    (1) Cattle--Edible tissues (excluding milk): Not required.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.1840, 558.464, 
and 558.465 of this chapter.


Sec.  556.540  Progesterone.

    (a) [Reserved]
    (b) Tolerances. Residues of progesterone are not permitted in 
excess of the following increments above the concentrations of 
progesterone naturally present in untreated animals:
    (1) Cattle and sheep--(i) Muscle: 5 ppb.
    (ii) Liver: 15 ppb.
    (iii) Kidney: 30 ppb.
    (iv) Fat: 30 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  522.1940 and 529.1940 
of this chapter.


Sec.  556.560  Pyrantel.

    (a) [Reserved]
    (b) Tolerances. The tolerances for pyrantel are:
    (1) Swine--(i) Liver and kidney: 10 ppm.
    (ii) Muscle: 1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.2045 and 558.485 
of this chapter.


Sec.  556.570  Ractopamine.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
ractopamine hydrochloride is 1.25 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for ractopamine (marker residue) 
are:
    (1) Cattle--(i) Liver (target tissue): 0.09 ppm.
    (ii) Muscle: 0.03 ppm.
    (2) Swine--(i) Liver (target tissue): 0.15 ppm.
    (ii) Muscle: 0.05 ppm.
    (3) Turkeys--(i) Liver (target tissue): 0.45 ppm.
    (ii) Muscle: 0.1 ppm.
    (c) Related conditions of use. See Sec.  558.500 of this chapter.


Sec.  556.580  Robenidine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for robenidine are:
    (1) Chickens--(i) Skin and fat: 0.2 ppm.
    (ii) Other edible tissues (excluding eggs): 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.515 of this chapter.

[[Page 72266]]

Sec.  556.592  Salinomycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
salinomycin is 5 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for salinomycin are:
    (1) Chickens--Edible tissues (excluding eggs): Not required.
    (2) Quail--Edible tissues (excluding eggs): Not required.
    (c) Related conditions of use. See Sec.  558.550 of this chapter.


Sec.  556.597  Semduramicin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
semduramicin is 3 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for semduramicin are:
    (1) Chickens--(i) Liver: 400 ppb.
    (ii) Muscle: 130 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.555 of this chapter.


Sec.  556.600  Spectinomycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
spectinomycin is 25 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for spectinomycin are:
    (1) Cattle--(i) Kidney (target tissue): 4 ppm spectinomycin (marker 
residue).
    (ii) Muscle: 0.25 ppm.
    (2) Chickens and turkeys--Edible tissues (excluding eggs): 0.1 ppm.
    (3) Swine--Edible tissues: Not required.
    (c) Related conditions of use. See Sec. Sec.  520.1265, 520.2123b, 
520.2123c, 522.2120, and 522.2121 of this chapter.


Sec.  556.610  Streptomycin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for streptomycin are:
    (1) Cattle and Swine--(i) Kidney: 2.0 ppm.
    (ii) Other edible tissues (excluding milk): 0.5 ppm.
    (2) Chickens--(i) Kidney: 2.0 ppm.
    (ii) Other edible tissues (excluding eggs): 0.5 ppm.
    (c) Related conditions of use. See Sec.  520.2158 of this chapter.


Sec.  556.620  Sulfabromomethazine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfabromomethazine are:
    (1) Cattle--(i) Edible tissues (excluding milk): 0.1 ppm.
    (ii) Milk: 0.01 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  520.2170 of this chapter.


Sec.  556.625  Sulfachloropyrazine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfachloropyrazine are:
    (1) Chickens--Edible tissues (excluding eggs): Zero.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  520.2184 of this chapter.


Sec.  556.630  Sulfachlorpyridazine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfachlorpyridazine are:
    (1) Cattle and Swine--Edible tissues (excluding milk): 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.2200 and 522.2200 
of this chapter.


Sec.  556.640  Sulfadimethoxine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfadimethoxine are:
    (1) Catfish and salmonids--Edible tissues: 0.1 ppm.
    (2) Cattle--(i) Edible tissues (excluding milk): 0.1 ppm.
    (ii) Milk: 0.01 ppm.
    (3) Chickens, turkeys, ducks and chukar partridges--Edible tissues 
(excluding eggs): 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2220, 522.2220, 
and 558.575 of this chapter.


Sec.  556.650  Sulfaethoxypyridazine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfaethoxypyridazine are:
    (1) Cattle--(i) Edible tissues (excluding milk): 0.1 ppm.
    (ii) Milk: Zero.
    (2) Swine--Edible tissues: Zero.
    (c) Related conditions of use. See Sec. Sec.  520.2240 and 522.2240 
of this chapter.


Sec.  556.660  Sulfamerazine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfamerazine are:
    (1) Trout--Edible tissues: Zero.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.582 of this chapter.


Sec.  556.670  Sulfamethazine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfamethazine are:
    (1) Cattle--Edible tissues (excluding milk): 0.1 ppm.
    (2) Chickens and turkeys--Edible tissues (excluding eggs): 0.1 ppm.
    (3) Swine--Edible tissues: 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2260, 520.2261, 
522.2260, 558.145, and 558.630 of this chapter.


Sec.  556.685  Sulfaquinoxaline.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfaquinoxaline are:
    (1) Cattle--Edible tissues (excluding milk): 0.1 ppm.
    (2) Chickens and turkeys--Edible tissues (excluding eggs): 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2325 and 558.586 
of this chapter.


Sec.  556.690  Sulfathiazole.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfathiazole are:
    (1) Swine--Edible tissues: 0.1 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.155 of this chapter.


Sec.  556.700  Sulfomyxin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for sulfomyxin are:
    (1) Chickens and turkeys--Edible tissues (excluding eggs): Zero.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.2340 of this chapter.


Sec.  556.710  Testosterone.

    (a) [Reserved]
    (b) Tolerances. Residues of testosterone are not permitted in 
excess of the following increments above the concentrations of 
testosterone naturally present in untreated animals:
    (1) Cattle--(i) Fat: 2.6 ppb.
    (ii) Kidney: 1.9 ppb.
    (iii) Liver: 1.3 ppb.
    (iv) Muscle: 0.64 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.842 of this chapter.


Sec.  556.720  Tetracycline.

    (a) Acceptable daily intake (ADI). The ADI for total tetracycline 
residues (chlortetracycline, oxytetracycline, and tetracycline) is 25 
[mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for the sum of tetracycline residues 
are:
    (1) Cattle and Sheep--(i) Kidney and fat: 12 ppm.
    (ii) Liver: 6 ppm.
    (iii) Muscle: 2 ppm.
    (2) Chickens and turkeys--(i) Kidney and fat: 12 ppm.
    (ii) Liver: 6 ppm.
    (iii) Muscle: 2 ppm.
    (3) Swine--(i) Kidney and fat: 12 ppm.
    (ii) Liver: 6 ppm.
    (iii) Muscle: 2 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2345c and 
520.2345d of this chapter.


Sec.  556.730  Thiabendazole.

    (a) [Reserved]
    (b) Tolerances. The tolerances for thiabendazole are:
    (1) Cattle--(i) Edible tissues (excluding milk): 0.1 ppm.

[[Page 72267]]

    (ii) Milk: 0.05 ppm.
    (2) Swine--Edible tissues: 0.1 ppm.
    (3) Sheep and Goats--(i) Edible tissues (excluding milk): 0.1 ppm.
    (ii) Milk: 0.05 ppm.
    (4) Pheasants--Edible tissues (excluding eggs): 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2380a, 520.2380b, 
520.2380c, and 558.615 of this chapter.


Sec.  556.733  Tildipirosin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
tildipirosin is 10 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for tildipirosin (the marker 
residue) are:
    (1) Cattle--(i) Liver (the target tissue): 10 ppm.
    (ii) [Reserved]
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.2460 of this chapter.


Sec.  556.735  Tilmicosin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
tilmicosin is 25 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for tilmicosin (marker residue) are:
    (1) Cattle--(i) Liver (target tissue): 1.2 ppm.
    (ii) Muscle: 0.1 ppm.
    (2) Sheep--(i) Liver (target tissue): 1.2 ppm.
    (ii) Muscle: 0.1 ppm.
    (3) Swine--(i) Liver (target tissue): 7.5 ppm.
    (ii) Muscle: 0.1 ppm.
    (c) Related conditions of use. See Sec. Sec.  522.2471 and 558.618 
of this chapter.


Sec.  556.738  Tiamulin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
tiamulin is 25 [mu]g/kg of body weight per day.
    (b) Tolerance. The tolerance for 8-alpha-hydroxymutilin (marker 
residue) is:
    (1) Swine--Liver (target tissue): 0.6 ppm.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  520.2455 and 558.600 
of this chapter.


Sec.  556.739  Trenbolone.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
trenbolone is 0.4 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for trenbolone are:
    (1) Cattle--Edible tissues (excluding milk): Not required.
    (2) [Reserved]
    (c) Related conditions of use. See Sec. Sec.  522.2476, 522.2477, 
and 522.2478 of this chapter.


Sec.  556.741  Tripelennamine.

    (a) [Reserved]
    (b) Tolerances. The tolerances for tripelennamine are:
    (1) Cattle--(i) Edible tissues (excluding milk): 200 ppb.
    (ii) Milk: 20 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  522.2615 of this chapter.


Sec.  556.745  Tulathromycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
tulathromycin is 15 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for CP-60,300 (marker residue) are:
    (1) Cattle--Liver (target tissue): 5.5 ppm.
    (2) Swine--Kidney (target tissue): 15 ppm.
    (c) Related conditions of use. See Sec.  522.2630 of this chapter.


Sec.  556.746  Tylosin.

    (a) [Reserved]
    (b) Tolerances. The tolerances for tylosin are:
    (1) Cattle--(i) Liver, kidney, fat, and muscle: 0.2 ppm.
    (ii) Milk: 0.05 ppm.
    (2) Chickens and turkeys--(i) Liver, kidney, fat, and muscle: 0.2 
ppm.
    (ii) Eggs: 0.2 ppm.
    (3) Swine--Liver, kidney, fat, and muscle: 0.2 ppm.
    (c) Related conditions of use. See Sec. Sec.  520.2640, 522.2640, 
558.625, and 558.630 of this chapter.


Sec.  556.748  Tylvalosin.

    (a) Acceptable daily intake (ADI). The ADI for total residues of 
tylvalosin is 47.7 [mu]g/kg of body weight per day.
    (b) Tolerances. A tolerance for tylvalosin in edible tissues of 
swine is not required.
    (c) Related conditions of use. See Sec.  520.2645 of this chapter.


Sec.  556.750  Virginiamycin.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
virginiamycin is 250 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for virginiamycin are:
    (1) Cattle--Edible tissues (excluding milk): Not required.
    (2) Chickens--Edible tissues (excluding eggs): Not required.
    (3) Swine--(i) Kidney, skin, and fat: 0.4 ppm.
    (ii) Liver: 0.3 ppm.
    (iii) Muscle: 0.1 ppm.
    (4) Turkeys--Edible tissues (excluding eggs): Not required.
    (c) Related conditions of use. See Sec.  558.635 of this chapter.


Sec.  556.760  Zeranol.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
zeranol is 1.25 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for zeranol are:
    (1) Cattle--Edible tissues (excluding milk): Not required.
    (2) Sheep--Edible tissues (excluding milk): 20 ppb.
    (c) Related conditions of use. See Sec.  522.2680 of this chapter.


Sec.  556.765  Zilpaterol.

    (a) Acceptable daily intake (ADI). The ADI for total residue of 
zilpaterol is 0.083 [mu]g/kg of body weight per day.
    (b) Tolerances. The tolerances for zilpaterol freebase (marker 
residue) are:
    (1) Cattle--Liver (target tissue): 12 ppb.
    (2) [Reserved]
    (c) Related conditions of use. See Sec.  558.665 of this chapter.


Sec.  556.770  Zoalene.

    (a) [Reserved]
    (b) Tolerances. The tolerances for zoalene and its metabolite 3-
amino-5-nitro-o-toluamide are:
    (1) Chickens--(i) Liver and kidney: 6 ppm.
    (ii) Muscle: 3 ppm.
    (iii) Fat: 2 ppm.
    (2) Turkeys--Liver and muscle: 3 ppm.
    (c) Related conditions of use. See Sec.  558.680 of this chapter.

PART 558--NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS

    15. The authority citation for 21 CFR part 558 continues to read as 
follows:

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

    16. In Sec.  558.95, add paragraph (c) to read as follows:


Sec.  558.95  Bambermycins.

* * * * *
    (c) Related tolerances. See Sec.  556.75 of this chapter.
* * * * *
    17. In Sec.  558.185, revise paragraph (c) to read as follows:


Sec.  558.185  Coumaphos.

* * * * *
    (c) Related tolerances. See Sec.  556.168 of this chapter.
* * * * *
    18. In Sec.  558.235, add paragraph (c) to read as follows:


Sec.  558.235  Efrotomycin.

* * * * *
    (c) Related tolerances. See Sec.  556.224 of this chapter.
    19. In Sec.  558.464, add paragraph (c) to read as follows:


Sec.  558.464  Poloxalene.

* * * * *

[[Page 72268]]

    (c) Related tolerances. See Sec.  556.517 of this chapter.
    20. In Sec.  558.465, add paragraph (c) to read as follows:


Sec.  558.465  Poloxalene free-choice liquid Type C feed.

* * * * *
    (c) Related tolerances. See Sec.  556.517 of this chapter.
    21. In Sec.  558.625, revise paragraph (e) to read as follows:


Sec.  558.625  Tylosin.

* * * * *
    (e) Related tolerances. See Sec.  556.746 of this chapter.
* * * * *
    22. In Sec.  558.630, revise paragraph (d) to read as follows:


Sec.  558.630  Tylosin and sulfamethazine.

* * * * *
    (d) Related tolerances. See Sec. Sec.  556.670 and 556.746 of this 
chapter.
* * * * *

    Dated: November 26, 2012.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2012-29322 Filed 12-4-12; 8:45 am]
BILLING CODE 4160-01-P