Oxytetracycline; Pesticide Tolerances for Emergency Exemptions, 13245-13251 [2017-04795]

Agencies

• ENVIRONMENTAL PROTECTION AGENCY

[Federal Register Volume 82, Number 46 (Friday, March 10, 2017)]
[Rules and Regulations]
[Pages 13245-13251]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-04795]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2016-0539; FRL-9959-19]


Oxytetracycline; Pesticide Tolerances for Emergency Exemptions

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a time-limited tolerance for 
residues of oxytetracycline in or on fruit, citrus, group 10-10. This 
action is in response to EPA's granting of an emergency exemption under 
the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) 
authorizing use of the pesticide in citrus production. This regulation 
establishes a maximum permissible level for residues of oxytetracycline 
in or on the commodities in this crop group. The time-limited tolerance 
expires on December 31, 2019.

DATES: This regulation is effective March 10, 2017. Objections and 
requests for hearings must be received on or before May 9, 2017, and 
must be filed in accordance with the instructions provided in 40 CFR 
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2016-0539, is available at https://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), West William Jefferson Clinton Bldg., Rm. 3334, 
1301 Constitution Ave. NW., Washington, DC 20460-0001. The Public 
Reading Room is open from 8:30 a.m. to 4:30 p.m., Monday through 
Friday, excluding legal holidays. The telephone number for the Public 
Reading Room is (202) 566-1744, and the telephone number for the OPP 
Docket is (703) 305-5805. Please review the visitor instructions and 
additional information about the docket available at https://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Michael L. Goodis, Registration 
Division (7505P), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-
0001; main telephone number: (703) 305-7090; email address: 
RDFRNotices@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
    [emsp14]Crop production (NAICS code 111).
    [emsp14]Animal production (NAICS code 112).
    [emsp14]Food manufacturing (NAICS code 311).
    [emsp14]Pesticide manufacturing (NAICS code 32532).

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of 40 CFR 
part 180 through the Government Printing Office's e-CFR site at https://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under section 408(g) of the Federal Food, Drug, and Cosmetic Act 
(FFDCA), 21 U.S.C. 346a, any person may file an objection to any aspect 
of this regulation and may also request a hearing on those objections. 
You must file your objection or request a hearing on this regulation in 
accordance with the instructions provided in 40 CFR part 178. To ensure 
proper receipt by EPA, you must identify docket ID number EPA-HQ-OPP-
2016-0539 in the subject line on the first page of your submission. All 
objections and requests for a hearing must be in writing, and must be 
received by the Hearing Clerk on or before May 9, 2017. Addresses for 
mail and hand delivery of objections and hearing requests are provided 
in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing (excluding any Confidential Business Information (CBI)) for 
inclusion in the public docket. Information not marked confidential 
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without 
prior notice. Submit the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2016-0539, by one of 
the following methods:

[[Page 13246]]

     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you considered to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at https://www.epa.gov/dockets/where-send-comments-epa-dockets.
    Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at https://www.epa.gov/dockets.

II. Background and Statutory Findings

    EPA, on its own initiative, in accordance with FFDCA sections 
408(e) and 408(l)(6) of 21 U.S.C. 346a(e) and 346a(1)(6), is 
establishing a time-limited tolerance for combined residues of 
oxytetracycline, including its metabolites and degradates, expressed as 
only oxytetracycline, (4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-
1,4,4a,5,5a,6,11,12a-octahydro-3,5,6,10,12,12a-hexahydroxy-6-methyl-
1,11-dioxo-2-naphthacenecarboxamide, in or on fruit, citrus, group 10-
10, at 0.4 parts per million (ppm). The time-limited tolerance expires 
on December 31, 2019.
    Section 408(l)(6) of FFDCA requires EPA to establish a time-limited 
tolerance or exemption from the requirement for a tolerance for 
pesticide chemical residues in food that will result from the use of a 
pesticide under an emergency exemption granted by EPA under FIFRA 
section 18. Such tolerances can be established without providing notice 
or period for public comment. EPA does not intend for its actions on 
FIFRA section 18-related time-limited tolerances to set binding 
precedents for the application of FFDCA section 408 and the safety 
standard to other tolerances and exemptions. Section 408(e) of FFDCA 
allows EPA to establish a tolerance or an exemption from the 
requirement of a tolerance on its own initiative, i.e., without having 
received a petition from an outside party.
    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue. . . 
.''
    Section 18 of FIFRA authorizes EPA to exempt any Federal or State 
agency from any provision of FIFRA, if EPA determines that ``emergency 
conditions exist which require such exemption.'' EPA has established 
regulations governing such emergency exemptions in 40 CFR part 166.

III. Emergency Exemption for Oxytetracycline on Citrus and FFDCA 
Tolerances

    The Florida Department of Agriculture and Consumer Services (FDACS) 
asserted that an emergency situation existed in accordance with the 
criteria for approval of an emergency exemption and requested the use 
of two oxytetracycline products on citrus to suppress Candidatus 
Liberibacter asiaticus (CLas) bacterium that causes Huanglongbing (HLB) 
also known as citrus greening. One product contains oxytetracycline 
calcium, and the other contains oxytetracycline hydrochloride. HLB was 
recently introduced to the US, is vectored by the invasive insect, the 
Asian citrus psyllid, and is the most serious disease of citrus 
worldwide. This disease has rapidly spread throughout Florida's citrus 
production area, causing severe losses with an overall decrease in 
production of more than 60% primarily due to HLB. Significant losses 
have occurred, many producers have gone out of business, and FDACS 
asserts that the long-term economic viability of the citrus industry in 
Florida is threatened by this disease. The bacteria reside in the 
phloem (the circulatory system of the tree), disrupting circulation of 
water and nutrients, which ultimately leads to death of the infected 
tree. Currently there is no cure. FDACS has submitted data that 
indicates that some treatments, including nutritional supplementation 
and use of pesticides like oxytetracycline, may help improve the health 
of infected trees. After reviewing the submission, EPA determined that 
an emergency situation exists for Florida, and that the criteria for 
approval of an emergency exemption are met. EPA has authorized a 
specific exemption under FIFRA section 18 for the use of 
oxytetracycline on citrus in Florida for management of the CLas 
bacterium that causes HLB (citrus greening) disease.
    Oxytetracycline is part of the tetracycline class, and is a broad-
spectrum antibiotic produced from the actinomycete Streptomyces 
rimosus. Two salts of oxytetracycline, oxytetracycline hydrochloride 
and oxytetracycline calcium, are the forms of oxytetracycline 
registered as pesticides for use against bacteria, fungi and 
mycoplasma-like organisms (there are no active registrations for 
oxytetracycline per se). The toxicity of all three forms of 
oxytetracycline is similar and they are considered equivalent for the 
purposes of assessing toxicity and establishing tolerances. Hereafter 
this document will use `oxytetracycline' to refer to all three of these 
materials. As part of its evaluation of the emergency exemption 
application, EPA assessed the potential risks presented by dietary 
exposure through residues of oxytetracycline in or on citrus fruit. All 
commodities in the crop group 10-10, citrus fruit were included in the 
dietary exposure estimates used. In assessing potential risks, EPA 
considered the safety standard in FFDCA section 408(b)(2), and EPA 
decided that the necessary tolerance under FFDCA section 408(l)(6) 
would be consistent with the safety standard and with FIFRA section 18. 
Consistent with the need to move quickly on the emergency exemption in 
order to address an urgent non-routine situation and to ensure that the 
resulting food is safe and lawful, EPA is issuing this tolerance 
without notice and opportunity for public comment as provided in FFDCA 
section 408(l)(6). Although this time-limited tolerance expires on 
December 31, 2019, under FFDCA section 408(l)(5), residues of the 
pesticide not in excess of the amounts specified in the tolerance 
remaining in or on commodities of fruit, citrus, group 10-10 after that 
date will not be unlawful, provided the pesticide was applied in a 
manner that was lawful under FIFRA, and the residues do not exceed a 
level that was authorized by this time-limited tolerance at the time of 
that application. EPA will take action to revoke this time-limited 
tolerance earlier if any experience with, scientific data on, or other 
relevant information on this pesticide indicate that the residues are 
not safe.
    Because the time-limited tolerance is being approved under 
emergency

[[Page 13247]]

conditions, EPA has not made any decisions about whether 
oxytetracycline meets FIFRA's registration requirements for use on 
fruit, citrus, group 10-10, or whether permanent tolerances for this 
use would be appropriate. Under these circumstances, EPA does not 
believe that this time-limited tolerance decision serves as a basis for 
registrations of oxytetracycline by a State for special local needs 
under FIFRA section 24(c). Nor does the tolerance by itself serve as 
the authority for persons in any State other than Florida to use this 
pesticide on the applicable crops under FIFRA section 18 absent the 
issuance of an emergency exemption applicable within that State. For 
additional information regarding the emergency exemption for 
oxytetracycline, contact the Agency's Registration Division at the 
address provided under FOR FURTHER INFORMATION CONTACT.

IV. Aggregate Risk Assessment and Determination of Safety

    Consistent with the factors specified in FFDCA section 
408(b)(2)(D), EPA has reviewed the available scientific data and other 
relevant information in support of this action. EPA has sufficient data 
to assess the hazards of and to make a determination on aggregate 
exposure expected as a result of this emergency exemption use and the 
time-limited tolerance for residues of oxytetracycline in or on fruit, 
citrus, group 10-10, at 0.4 ppm. EPA's assessment of exposures and 
risks associated with establishing the time-limited tolerance follows.

A. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern (LOC) to use in evaluating the risk posed by human exposure to 
the pesticide. For hazards that have a threshold below which there is 
no appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful analysis of the doses in each toxicological study to 
determine the dose at which no adverse effects are observed (the NOAEL) 
and the lowest dose at which adverse effects of concern are identified 
(the LOAEL). Uncertainty/safety factors are used in conjunction with 
the POD to calculate a safe exposure level--generally referred to as a 
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe 
margin of exposure (MOE). For non-threshold risks, the Agency assumes 
that any amount of exposure will lead to some degree of risk. Thus, the 
Agency estimates risk in terms of the probability of an occurrence of 
the adverse effect expected in a lifetime. For more information on the 
general principles EPA uses in risk characterization and a complete 
description of the risk assessment process, see https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks.
    The information available on the effects of oxytetracycline in 
humans from pharmaceutical uses, supplemented with the data available 
on the toxicity of oxytetracycline in laboratory animals is sufficient 
to evaluate the toxicity of oxytetracycline. Based on the information 
from these sources, the toxicity and exposure databases for 
oxytetracycline are considered complete, and exposure estimates are 
conservative. The emergency exemption allows use of two oxytetracycline 
compounds: Oxytetracycline hydrochloride and oxytetracycline calcium.
    Previously the endpoint for chronic dietary exposures to 
oxytetracycline was based on the NOAEL of 0.05 milligram/kilogram/day 
(mg/kg/day) from a special dog study, which demonstrated a change in 
intestinal flora at the LOAEL of 0.25 mg/kg/day, with a shift from a 
predominantly drug-susceptible population of enteric lactose-fermenting 
organisms to a multiple-antibiotic-resistant population. However in 
2011, the EPA changed its endpoint selection as recommended by the 
National Academy of Sciences (NAS) report, Toxicity Testing in the 21st 
century: a vision and a strategy. NAS Press (2007). This report advised 
selecting toxicity endpoints for assessing human health risk estimates 
based upon biological perturbations of toxicity pathways that can lead 
to adverse health outcomes under conditions of human exposure. Based on 
this NAS report, in the absence of a demonstrable adverse human health 
outcome, EPA no longer considers the changes in intestinal flora to be 
an appropriate basis for regulating dietary exposure to antibiotics.
    Instead, using a weight-of-the-evidence approach, EPA adopted an 
NOAEL of 100 mg/kg/day based on minor (toxicologically insignificant) 
effects seen in two chronic feeding studies in the rat (NOAELs = 50 and 
150 mg/kg/day) and two chronic toxicity studies in the dog (NOAELs = 
250 mg/kg/day for both, the highest dose tested in these studies), and 
taking into account a National Cancer Institute rat chronic 
carcinogenicity study, with an LOAEL of 1250 mg/kg/day (lowest dose 
tested) based on hyperplasia of the adrenal medulla, and fatty 
metamorphosis and increases in accessory structures of the liver. To 
this 100 mg/kg/day NOAEL, EPA applied the customary 100x UF for both 
interspecies and intraspecies variability resulting in a chronic 
reference dose (cRfD) of 1.0 mg/kg/day for adults. EPA has applied an 
additional 10x ``Food Quality Protection Act (FQPA) safety factor'' to 
provide an additional margin of protection for assessing risks to 
infants and children, resulting in a chronic population-adjusted dose 
(cPAD) of 0.1 mg/kg/day. This is further discussed in unit IV.C. of 
this document.
    A summary of the oxytetracycline toxicology data used for human 
health risk assessment is given in the Table of this unit.

                 Table--Oxytetracycline Toxicological Endpoints for Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                 RfD, PAD, and LOC for   Study and toxicological
          Exposure/scenario             POD, UFs, and FQPA SF       risk assessment              effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (All populations)......  NA.....................  NA.....................  No endpoint was
                                                                                          attributable to a
                                                                                          single exposure.
Chronic dietary (All populations)....  NOAEL = 100 mg/kg/day..  cRfD = 1 mg/kg/day.....  The NOAEL of 100 mg/kg/
                                       UFA = 10x..............  cPAD = 0.1 mg/kg/day...   day was derived using
                                       UFH = 10x..............  Chronic dietary           a weight of evidence
                                       FQPA SF = 10x..........   exposure LOC >=100% of   (WOE) approach based
                                                                 cPAD.                    on 3 rat and 2 dog
                                                                                          chronic studies. No
                                                                                          specific LOAEL was
                                                                                          established.
----------------------------------------------------------------------------------------------------------------

[[Page 13248]]

 
Risk assessments for occupational scenarios are not required because no adverse effects were observed from
 dermal or inhalation exposures. Evaluation of residential scenarios was not required because there are no
 registered residential oxytetracycline uses.
----------------------------------------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)....  The Agency's Peer Review Committee has classified oxytetracycline as a
                                        ``Group D'' carcinogen (``Not Classifiable as to Human
                                        Carcinogenicity'').
----------------------------------------------------------------------------------------------------------------
NA = Not Applicable. RfD = reference dose. PAD = population adjusted dose (a = acute, c = chronic). LOC-level of
  concern; mg/kg/day = milligram of pesticide per kilogram of body weight per day. NOAEL = no observed adverse
  effect level. LOAEL = lowest observed adverse effect level. UF = uncertainty factor. UFA = extrapolation from
  animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population
  (intraspecies). FQPA SF = Food Quality Protection Act Safety Factor. WOE = weight of evidence. NCI = National
  Cancer Institute.

    The complete human health risk assessment for this action may be 
found at https://www.regulations.gov in the following three documents 
``Oxytetracycline. Section 18 Emergency Exemption for Citrus Grown in 
Florida,'' and ``Oxytetracycline. Update to Section 18 Emergency 
Exemption for Citrus Grown in Florida to Consider 10X FQPA,'' in the 
docket for ID number EPA-HQ-OPP-2016-0539.

B. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to oxytetracycline, EPA considered exposure under the time-
limited tolerances established by this action as well as all existing 
oxytetracycline tolerances in 40 CFR 180.337. EPA assessed dietary 
exposures from oxytetracycline in food as follows:
    i. Acute exposure. No acute dietary effects were identified in the 
toxicological studies or literature for oxytetracycline; therefore, a 
quantitative acute dietary exposure assessment is unnecessary and was 
not conducted.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment EPA used 2003-2008 food consumption data from the US 
Department of Agriculture's (USDA's) National Health and Nutrition 
Examination Survey (NHANES). For residue levels in food, EPA assumed 
one hundred percent crop treated (PCT) and tolerance-level residues for 
all registered uses plus the subject tolerance of 0.4 ppm in or on all 
commodities of fruit, citrus, group 10-10. In addition, default 
processing factors were used for all processed commodities except 
citrus juice, oil, and peel, since concentration of oxytetracycline was 
not observed in these commodities. EPA's exposure assessment also 
included tolerance level residues for livestock commodities owing to 
use of oxytetracycline as an animal drug. No anticipated residue or PCT 
refinements were used.
    iii. Cancer. Based on the information referenced in Unit IV.A., EPA 
has concluded that oxytetracycline does not pose a cancer risk to 
humans. No evidence of carcinogenicity was found in a literature search 
of toxicity in animals. There was no evidence of carcinogenicity for 
male or female mice fed oxytetracycline at 1,875 mg/kg/day for two 
years. In the rat carcinogenicity study, there was equivocal evidence 
for carcinogenicity based upon increased incidences of 
pheochromocytomas of the adrenal gland at the highest doses tested for 
males of 2,500 and increased incidences of adenomas of the pituitary 
gland in females at 1,875 mg/kg/day; both doses are extremely high as 
compared to expected human exposure and above the limit dose. The 
mutagenicity assays were all negative except for the mouse lymphoma 
forward mutation assay which was positive only with metabolic 
activation. Based upon this information and the weight of the evidence 
as a whole, the EPA has classified oxytetracycline as a ``Group D'' 
carcinogen (``Not Classifiable as to Human Carcinogenicity''). A review 
of the same data by the National Toxicology Program's (NTP) Peer Review 
Committee was in agreement with this classification. Therefore, a 
dietary exposure assessment for the purpose of assessing cancer risk is 
unnecessary and was not conducted.
    iv. Anticipated residue and PCT information. EPA did not use 
anticipated residue or PCT information in the dietary assessment for 
oxytetracycline. Tolerance level residues and 100 PCT were assumed for 
all food commodities.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models to derive estimated water concentrations 
for dietary exposure analysis of oxytetracycline exposures through 
drinking water. These simulation models take into account data on the 
physical, chemical, and fate/transport characteristics of 
oxytetracycline. Further information regarding EPA drinking water 
models used in pesticide exposure assessment can be found at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/models-pesticide-risk-assessment#aquatic.
    Based on the Surface Water Calculator, using Pesticide Root Zone 
Model 5+ and the Variable Volume Water Body Model, the estimated 
drinking water concentration (EDWC) of oxytetracycline for non-cancer 
risk assessment due to chronic exposure was 149 parts per billions 
(ppb) for surface water, based on the highest registered rate for 
application to peach and nectarine. The PRZM-Ground Water model 
estimated that no residues of oxytetracycline would result in 
groundwater in any of the six standard scenarios (use modelled for 100 
years), presumably due to the chemical's strong soil sorption. The 
highest EDWC for surface water of 149 ppb was therefore used to assess 
chronic dietary exposure contribution from drinking water and was 
directly entered into the dietary exposure model.
    3. From non-dietary exposure. The term ``residential exposure'' is 
used in this document to refer to non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets).
    Oxytetracycline is not registered or proposed for any specific use 
patterns that would result in residential exposure (non-dietary), and 
therefore this risk assessment was not performed. Further information 
regarding EPA standard assumptions and generic inputs for residential 
exposures may be found at: https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/standard-operating-procedures-residential-pesticide.
    4. Cumulative effects from substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider

[[Page 13249]]

``available information'' concerning the cumulative effects of a 
particular pesticide's residues and ``other substances that have a 
common mechanism of toxicity.'' EPA has not found oxytetracycline to 
share a common mechanism of toxicity with any other substances, and 
oxytetracycline does not appear to produce a toxic metabolite produced 
by other substances. For the purposes of this tolerance action, 
therefore, EPA has assumed that oxytetracycline does not have a common 
mechanism of toxicity with other substances. For information regarding 
EPA's efforts to determine which chemicals have a common mechanism of 
toxicity and to evaluate the cumulative effects of such chemicals, see 
EPA's Web site at https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/cumulative-assessment-risk-pesticides.

C. Safety Factor for Infants and Children

    1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA 
shall apply an additional tenfold (10x) margin of safety for infants 
and children in the case of threshold effects, to account for prenatal 
and postnatal toxicity and the completeness of the database on toxicity 
and exposure, unless EPA determines, based on reliable data, that a 
different margin of safety will be safe for infants and children. This 
additional margin of safety, required under the Food Quality Protection 
Act, is commonly referred to as the FQPA Safety Factor (SF). In 
applying this provision, EPA either retains the default value of 10x, 
or uses a different additional SF when reliable data available to EPA 
support the choice of a different factor.
    2. Prenatal and postnatal sensitivity. Considering the toxicity 
database for oxytetracycline, the mouse prenatal development study did 
not identify adverse effects up to the highest dose tested (HDT), 2100 
mg/kg/day. In addition, the effects seen in the rat prenatal 
development study occurred only at levels above the limit dose. 
However, clinical use of tetracyclines administered to pregnant women, 
infants and children have resulted in discoloration of the teeth, 
enamel hypoplasia, and bone developmental effects in fetuses and 
children. A decrease in fibula growth in premature infants has been 
observed after an oral dose of 25 mg/kg every six hours, equivalent to 
a total dose of 100 mg/kg/day (though these effects reversed quickly 
after discontinuation of dosing). For these reasons, the FDA recommends 
not administering oral doses of tetracycline to children under 8 years 
of age. In addition, tetracyclines cross the placenta and should not be 
taken during the last half of pregnancy. The effect in premature 
infants dosed with tetracycline was observed at 100 mg/kg/day, the same 
level as that used as the POD for chronic risk assessment (derived from 
laboratory animal toxicity data). Thus, EPA concluded that some 
uncertainty remains regarding the potential sensitivity to infants, 
children under 8 years of age, and pregnant women based upon the 
literature database for therapeutic uses of oxytetracycline, and 
decided to retain the 10x FQPA SF to assure adequate protection for 
these populations.
    3. Conclusion. The existing database, together with the extensive 
literature and study reports available on oxytetracycline, including 
studies submitted to and reviewed by the EPA, the National Toxicology 
Program, and World Health Organization, the FDA and open literature 
studies, are adequate for characterizing toxicity and quantification of 
risk from the proposed and existing uses of oxytetracycline. EPA has 
determined that reliable data indicate that retaining the 10x FQPA SF 
will adequately protect the safety of infants and children. That 
decision is based on the following findings:
    i. The toxicity database for oxytetracycline is complete and there 
are no data gaps.
    ii. There is no indication that oxytetracycline is a neurotoxic 
chemical and there is no need for a developmental neurotoxicity study 
or additional UFs to account for neurotoxicity.
    iii. Although the guideline toxicity studies did not suggest an 
increased lifestage sensitivity/susceptibility (no effects at the 
highest doses tested or effects only above the limit dose), data from 
the pharmaceutical literature suggests that infants and children may be 
more susceptible to oxytetracycline side-effects than adults, and FDA 
does not recommend administering oral doses of tetracycline to children 
under 8 years of age or pregnant women. Therefore, a 10x FQPA SF has 
been retained.
    iv. There are no residual uncertainties with regard to the exposure 
databases. The dietary assessment overestimates actual exposures to 
oxytetracycline because it assumed 100% crop treated, and incorporated 
tolerance-level residues and default processing factors (PFs). EPA also 
made conservative (protective, high-end) assumptions in the 
environmental water modeling used to estimate potential levels of 
oxytetracycline in drinking water. All of the assumptions used for the 
exposure and risk estimates are likely to overestimate exposures that 
may actually occur. Therefore, these assessments will not underestimate 
the exposure and risks posed by oxytetracycline.

D. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA 
calculates the lifetime probability of acquiring cancer given the 
estimated aggregate exposure. Short-, intermediate-, and chronic-term 
risks are evaluated by comparing the estimated aggregate food, water, 
and residential exposure to the appropriate PODs to ensure that an 
adequate MOE exists.
    1. Acute risk. An acute aggregate risk assessment takes into 
account acute exposure estimates from dietary consumption of food and 
drinking water. No adverse effect resulting from a single oral exposure 
was identified (no acute dietary endpoint was determined). Therefore, 
oxytetracycline is not expected to pose an acute risk and no acute risk 
assessment was necessary.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
oxytetracycline from food and water will utilize 40% of the cPAD for 
children 1-2 years old, the population group receiving the greatest 
exposure. There are no residential uses for oxytetracycline. Although 
exposure may occur through therapeutic use of oxytetracycline as a 
drug, such pharmaceutical use is not included in this aggregate 
exposure assessment for agricultural uses of oxytetracycline as a 
pesticide. However, potential exposure through clinical drug use of 
oxytetracycline was considered and compared to the exposure estimates 
from the agricultural use, which is further discussed in Unit IV.D.6. 
below.
    3. Short-term risk. Short-term aggregate exposure takes into 
account short-term residential (non-dietary, non-occupational) exposure 
plus chronic exposure to food and water (considered to be a background 
exposure level). Oxytetracycline is not registered for any use patterns 
that would result in short-term residential exposure. Further, because 
no short-term adverse effect was identified, oxytetracycline is not 
expected to pose a short-term risk and the chronic risk assessment will 
be protective for any short-term exposures.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term

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residential (non-dietary, non-occupational) exposure plus chronic 
exposure to food and water (considered to be a background exposure 
level). Oxytetracycline is not registered for any use patterns that 
would result in intermediate-term residential exposure. Further, 
because no intermediate-term adverse effect was identified, 
oxytetracycline is not expected to pose an intermediate-term risk and 
the chronic risk assessment will be protective for any intermediate-
term exposures.
    5. Aggregate cancer risk for U.S. population. Based on the lack of 
evidence of carcinogenicity in two adequate rodent carcinogenicity 
studies, oxytetracycline is not expected to pose a cancer risk to 
humans and no cancer risk assessment was necessary.
    6. Pharmaceutical Aggregate Risk. Section 408 of the FFDCA requires 
EPA to consider potential sources of exposure to a pesticide and 
related substances in addition to the dietary sources expected to 
result from a pesticide use subject to the tolerance. In order to 
determine whether to issue or maintain a pesticide tolerance, EPA must 
``determine that there is a reasonable certainty of no harm'' resulting 
from the pesticide use subject to the tolerance. Under FFDCA section 
505, the Food and Drug Administration reviews human drugs for safety 
and effectiveness and may approve a drug notwithstanding the 
possibility that some users may experience adverse side effects. EPA 
does not believe that, for purposes of the section 408 dietary risk 
assessment, it is compelled to assume that combined exposures to 
pesticide and pharmaceutical residues that lead to a physiological 
effect in the user necessarily constitutes ``harm'' under the meaning 
of section 408 of FFDCA.
    Rather, EPA believes the appropriate way to consider the 
pharmaceutical use of oxytetracycline in its risk assessment is to 
examine the impact that the additional nonoccupational pesticide 
exposures would have to a pharmaceutical user exposed to the same, or a 
related chemical substance. Where the additional pesticide exposure has 
no more than a minimal impact on the pharmaceutical user, EPA can make 
a reasonable certainty of no harm finding for the pesticide tolerances 
of that compound under section 408 of the FFDCA. If the potential 
impact on the pharmaceutical user as a result of co-exposure from 
pesticide use is more than minimal, then EPA would not be able to 
conclude that dietary residues were safe and would need to discuss with 
FDA appropriate measures to reduce exposure from one or both sources.
    EPA's pesticide exposure assessment has taken into consideration 
the appropriate population, exposure route, and exposure duration for 
comparison with exposure to the pharmaceutical use of oxytetracycline. 
The typical pharmaceutical oxytetracycline dose for children is 25 mg/
kg/day. This dose is approximately 1,262 times greater than the dietary 
exposure estimate of 0.019809 mg/kg/day, the food and water exposure 
estimate for children 6-12 years old. This group represents the 
potential highest exposed population group, in terms of considering 
therapeutic use of oxytetracycline (children under 8 yrs old are not 
given therapeutic oxytetracycline). Therefore, because the pesticide 
exposure has no more than a minimal impact on the total dose to a 
pharmaceutical user, EPA believes that there is a reasonable certainty 
that no harm will result from the potential dietary pesticide exposure 
of a user being treated therapeutically with oxytetracycline.
    7. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, or to infants and children, from aggregate 
exposure to oxytetracycline.

V. Other Considerations

A. Analytical Enforcement Methodology

    The analytical method used to derive the citrus residue data for 
determining the appropriate tolerance levels was based on Method 
STM2028.06, which was found to be scientifically acceptable for 
enforcement of tolerances of oxytetracycline on apple, pear and peach. 
This method employs liquid chromatography with tandem mass spectrometry 
(LC/MS/MS) using turbo ion spray in the positive ion mode, monitoring 
two ion transitions for confirmation of oxytetracycline, and was 
adequately validated for the quantitation and confirmation of ion 
transitions using samples of apple and nectarine. A successful 
independent laboratory validation was performed as well using samples 
of apple, pear, peach, and nectarine. Since the method used for citrus 
was similar to this and provided adequate recoveries for citrus fruits, 
it is considered adequate to support the emergency exemption use and 
enforce the tolerance expression of oxytetracycline in or on 
commodities of fruit, citrus, group 10-10. The method may be requested 
from: Chief, Analytical Chemistry Branch, Environmental Science Center, 
701 Mapes Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-
2905; email address: residuemethods@epa.gov.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex is a joint United Nations Food and 
Agriculture Organization/World Health Organization food standards 
program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level. The Codex has not 
established a MRL for oxytetracycline.

VI. Conclusion

    Therefore, a time-limited tolerance is established for residues of 
oxytetracycline and its metabolites and degradates, expressed as only 
oxytetracycline, (4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-
1,4,4a,5,5a,6,11,12a-octahydro-3,5,6,10,12,12a-hexahydroxy-6-methyl-
1,11-dioxo-2-naphthacenecarboxamide, in or on fruit, citrus, group 10-
10 at 0.4 ppm. This tolerance expires on December 31, 2019.

VII. Statutory and Executive Order Reviews

    This action establishes a tolerance under FFDCA sections 408(e) and 
408(l)(6). The Office of Management and Budget (OMB) has exempted these 
types of actions from review under Executive Order 12866, entitled 
``Regulatory Planning and Review'' (58 FR 51735, October 4, 1993). 
Because this action has been exempted from review under Executive Order 
12866, this action is not subject to Executive Order 13211, entitled 
``Actions Concerning Regulations That Significantly Affect Energy 
Supply, Distribution, or Use'' (66 FR 28355, May 22, 2001) or Executive 
Order 13045, entitled ``Protection of Children from Environmental 
Health Risks and Safety Risks'' (62 FR 19885, April 23, 1997). This 
action does not contain any information collections subject to OMB 
approval under the Paperwork Reduction Act (PRA), 44

[[Page 13251]]

U.S.C. 3501 et seq., nor does it require any special considerations 
under Executive Order 12898, entitled ``Federal Actions to Address 
Environmental Justice in Minority Populations and Low-Income 
Populations'' (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established in accordance 
with FFDCA sections 408(e) and 408(l)(6), such as the tolerance in this 
final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply.
    This action directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes, nor does this 
action alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of FFDCA section 408(n)(4). As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled ``Federalism'' (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
``Consultation and Coordination with Indian Tribal Governments'' (65 FR 
67249, November 9, 2000) do not apply to this action. In addition, this 
action does not impose any enforceable duty or contain any unfunded 
mandate as described under Title II of the Unfunded Mandates Reform Act 
(UMRA) (2 U.S.C. 1501 et seq.).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology Transfer and Advancement 
Act (NTTAA) (15 U.S.C. 272 note).

VIII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
EPA submitted a report containing this rule and other required 
information to the U.S. Senate, the U.S. House of Representatives, and 
the Comptroller General of the United States prior to publication of 
the rule in the Federal Register. This action is not a ``major rule'' 
as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: February 23, 2017,
Michael Goodis,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

    Authority:  21 U.S.C. 321(q), 346a and 371.


0
2. In Sec.  180.337 revise paragraph (b) to read as follows:


Sec.  180.337  Oxytetracycline; tolerances for residues.

* * * * *
    (b) Section 18 emergency exemptions. Time-limited tolerances 
specified in the following table are established for residues of the 
fungicide/bactericide oxytetracycline, including its metabolites and 
degradates, in or on the commodities in the table in this paragraph. 
Compliance with the tolerance levels specified in this paragraph is to 
be determined by measuring only oxytetracycline, 
(4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-
octahydro-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-2-
naphthacenecarboxamide, in or on the specified agricultural 
commodities, resulting from use of the pesticide pursuant to FIFRA 
section 18 emergency exemptions. The tolerances expire on the dates 
specified in the table.

------------------------------------------------------------------------
                                           Parts per       Expiration/
               Commodity                    million      revocation date
------------------------------------------------------------------------
Fruit, citrus, group 10-10............            0.40       12/31/2019
------------------------------------------------------------------------

* * * * *
[FR Doc. 2017-04795 Filed 3-9-17; 8:45 am]
 BILLING CODE 6560-50-P