Oxytetracycline; Pesticide Tolerances, 62489-62494 [2018-26343]
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Federal Register / Vol. 83, No. 233 / Tuesday, December 4, 2018 / Rules and Regulations
§ 180.960 Polymers; exemptions from the
requirement of a tolerance.
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Polymer
CAS No.
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Propanesulfonic acid, 2-methyl-2-[(1-oxo-2-propen-1-y1)amino]-, homopolymer, sodium salt, minimum number average molecular weight (in amu) 14,000 .............................................................................................................................................................
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1-Propanesulfonic acid, 2-methyl-2-[(1-oxo-2-propen-1-y1)amino]-, sodium salt (1:1), homopolymer, minimum number average
molecular weight (in amu) 14,000 ...................................................................................................................................................
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BILLING CODE 6560–50–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2015–0820; FRL–9986–87]
Oxytetracycline; Pesticide Tolerances
This regulation establishes
tolerances for residues of
oxytetracycline in or on fruit, citrus,
crop group 10–10. Geo Logic
Corporation requested these tolerances
under the Federal Food, Drug, and
Cosmetic Act (FFDCA).
DATES: This regulation is effective
December 4, 2018. Objections and
requests for hearings must be received
on or before February 4, 2019 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–2015–0820, 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.
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Michael 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?
Environmental Protection
Agency (EPA).
ACTION: Final rule.
AGENCY:
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FOR FURTHER INFORMATION CONTACT:
[FR Doc. 2018–26347 Filed 12–3–18; 8:45 am]
SUMMARY:
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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:
• Crop production (NAICS code 111).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• 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 EPA’s tolerance
regulations at 40 CFR part 180 through
the Government Printing Office’s e-CFR
site at https://www.ecfr.gov/cgi-bin/textidx?&c=ecfr&tpl=/ecfrbrowse/Title40/
40tab_02.tpl.
C. How can I file an objection or hearing
request?
Under FFDCA section 408(g), 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
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proper receipt by EPA, you must
identify docket ID number EPA–HQ–
OPP–2015–0820 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
February 4, 2019. 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–
2015–0820, by one of the following
methods:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the online
instructions for submitting comments.
Do not submit electronically any
information you consider 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/contacts.html.
Additional instructions on
commenting or visiting the docket,
along with more information about
dockets generally, is available at https://
www.epa.gov/dockets.
II. Summary of Petitioned-For
Tolerance
In the Federal Register of March 16,
2016 (81 FR 14030) (FRL–9942–86),
EPA issued a document pursuant to
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FFDCA section 408(d)(3), 21 U.S.C.
346a(d)(3), announcing the filing of a
pesticide petition (PP 5F8415) by Geo
Logic Corporation, P.O. Box 3091,
Tequesta, FL 33469. The petition
requested that 40 CFR 180.337 be
amended by establishing tolerances for
residues of the bactericide
oxytetracycline,
(4S,4aR,5S,5aR,6S,12aS)-4(dimethylamino)-1,4,4a,5,5a,6,11,12aoctahydro-3,5,6,10,12,12a-hexahydroxy6-methyl-1,11-dioxo-2naphthacenecarboxamide, in or on fruit,
citrus, crop group 10–10 at 0.01 parts
per million (ppm).
That document referenced a summary
of the petition prepared by Geo Logic
Corporation, the registrant, which is
available in the docket, https://
www.regulations.gov. One comment was
received on the notice of filing. EPA’s
response to this comment is discussed
in Unit IV.C.
III. Aggregate Risk Assessment and
Determination of Safety
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. . . .’’
Consistent with FFDCA section
408(b)(2)(D), and 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 for oxytetracycline
including exposure resulting from the
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tolerances established by this action.
EPA’s assessment of exposures and risks
associated with oxytetracycline follows.
A. Toxicological Profile
EPA has evaluated the available
toxicity data and considered its validity,
completeness, and reliability as well as
the relationship of the results of the
studies to human risk. EPA has also
considered available information
concerning the variability of the
sensitivities of major identifiable
subgroups of consumers, including
infants and children.
At high doses, the target organ of
tetracycline toxicity is the liver. The
most common effect in intermediate- or
long-term oral exposures in rats and
mice was a decrease in body weight. In
the prenatal developmental study in
rats, clinical signs included increased
incidences of respiratory signs and
rough hair coat in the dams, in addition
to increased mortality and a decreased
percentage of dams found pregnant.
Also identified was a decrease in fetal
body weight. In the mouse prenatal
developmental study, there was no
toxicity identified in the dams or
fetuses. In all of the above animal
studies, adverse effects were seen at
doses that exceed the limit dose. There
is no adequate reproductive toxicity
study available in the database,
however, the data requirement was
waived based on the lack of
reproductive effects reported during the
history of use as a drug. No evidence of
neurotoxicity was observed in any
guideline study. A rat immunotoxicity
study demonstrated
immunosuppression at doses lower than
those for systemic toxicity.
Tetracyclines are known to inhibit bone
growth in developing tissue. When
oxytetracycline was administered orally
as a single dose to two female infant
rhesus monkeys, zygomatic arch bone
(lateral surface of temporal bone) growth
was inhibited for ∼12.5 days with no
recovery observed by 21 days. Effects on
bone growth are consistent with
oxytetracycline’s ability to chelate
calcium, and so are not unexpected.
Bone developmental effects were also
observed after administration of
chlortetracycline and
demethylchlortetracycline in adult
rhesus monkeys highlighting the
consistency of tetracycline treatment
across this class of chemicals.
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The Agency has classified
oxytetracycline as ‘‘Group D: Not
Classifiable as to Human
Carcinogenicity’’. Oxytetracycline has
low acute toxicity, being Toxicity
Category IV for oral toxicity, the only
acute lethality study available in the
database.
Specific information on the studies
received and the nature of the adverse
effects caused by oxytetracycline as well
as the no-observed-adverse-effect-level
(NOAEL) and the lowest-observedadverse-effect-level (LOAEL) from the
toxicity studies can be found at https://
www.regulations.gov in document
‘‘Oxytetracycline/Oxytetracycline
Hydrochloride/Oxytetracycline Calcium:
Draft Human Health Risk Assessment in
Support of Registration Review and
Tolerance Establishment in/on Citrus
Fruit Crop Group 10–10’’ in docket ID
number EPA–HQ–OPP–2015–0820.
B. 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 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://
www2.epa.gov/pesticide-science-andassessing-pesticide-risks/assessinghuman-health-risk-pesticides.
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TABLE 1—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR OXYTETRACYCLINE FOR USE IN HUMAN HEALTH
RISK ASSESSMENT
Exposure/scenario
Point of departure
and uncertainty/
safety factors
RfD, PAD, LOC for
risk assessment
Study and toxicological effects
Acute dietary (All populations) ..
None selected .........
N/A ...........................
No appropriate endpoint for females age 13–49 or for the general population attributable to a single exposure.
Chronic dietary (All populations)
NOAEL= 100 mg/kg/
day.
UFA = 10x
UFH = 10x
FQPA SF = 10x
Chronic RfD = 1 mg/
kg/day.
cPAD = 0.10 mg/kg/
day
WOE from 3 rats and 2 dogs chronic studies.
The NOAEL of 100 mg/kg/day was derived from these studies
and no specific LOAEL was established.
Cancer .......................................
Classified as a Group D carcinogen—not classifiable as to human carcinogenicity.
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level of concern. mg/kg/day =
milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-level. RfD = reference dose. UFA = extrapolation from
animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies).
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. In evaluating dietary
exposure to oxytetracycline, EPA
considered exposure under the
petitioned-for tolerances 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. Quantitative acute
dietary exposure and risk assessments
are performed for a food-use pesticide,
if a toxicological study has indicated the
possibility of an effect of concern
occurring as a result of a 1-day or single
exposure. No such effects were
identified in the toxicological studies
for oxytetracycline; therefore, a
quantitative acute dietary exposure
assessment is unnecessary.
ii. Chronic exposure. In conducting
the chronic dietary exposure assessment
EPA 2003–2008 food consumption data
from the USDA’s National Health and
Nutrition Examination Survey/What We
Eat in America. As to residue levels in
food, EPA used tolerance-level residues,
default processing factors (PFs), and
assumed 100 percent crop treated (PCT).
iii. Cancer. Based on the data
summarized in Unit III.A., EPA has
concluded that oxytetracycline does not
pose a cancer risk to humans. Therefore,
a dietary exposure assessment for the
purpose of assessing cancer risk is
unnecessary.
iv. Anticipated residue and PCT
information. EPA did not use
anticipated residue and/or PCT
information in the dietary assessment
for oxytetracycline. Tolerance-level
residues and/or 100 PCT were assumed
for all food commodities.
2. Dietary exposure from drinking
water. The Agency used screening-level
water exposure models in the dietary
exposure analysis and risk assessment
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for oxytetracycline in 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://www2.epa.gov/
pesticide-science-and-assessingpesticide-risks/about-water-exposuremodels-used-pesticide.
Based on the Pesticide Root Zone
Model version 5.02/Variable Volume
Water Body Model (VVWM V1.02) and
Pesticide Root Zone Model Ground
Water (PRZM GW), EDWCs of
oxytetracycline for chronic exposures
for non-cancer assessments are
estimated to be 2.85 ppb for surface
water and 0.323 ppb for ground water.
Modeled estimates of drinking water
concentrations were directly entered
into the dietary exposure model. For
chronic dietary risk assessment, the
water concentration of value 2.85 ppb
was used to assess the contribution to
drinking water.
3. From non-dietary exposure. The
term ‘‘residential exposure’’ is used in
this document to refer to nonoccupational, 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 for any
specific use patterns that would result
in residential exposure.
Tetracycline hydrochloride (97%
chemical similarity to oxytetracycline)
is approved by FDA for use as an oral
antibiotic to treat certain bacterial and
parasitic infections. EPA examined the
impact that additional pesticide
exposures to oxytetracycline would
have on a person who has been
prescribed the antibiotic. EPA
determined that the additional pesticide
exposure would not have more than a
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minimal impact on the total dose to the
pharmaceutical patient, and thus
concludes that there is a reasonable
certainty that the additional exposure
from pesticide uses of oxytetracycline
would result in no harm finding to a
user being treated therapeutically.
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
‘‘available information’’ concerning the
cumulative effects of a particular
pesticide’s residues and ‘‘other
substances that have a common
mechanism of toxicity.’’
EPA has assessed the potential for
oxytetracycline to share a common
mechanism of toxicity with any other
substances. Based on its assessment of
the available toxicological data, EPA has
determined that oxytetracycline does
not share a similar toxicological profile
with other pesticides, and no further
cumulative evaluation is necessary for
oxytetracycline.
D. 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 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 safety factor when reliable
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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), 2,100 mg/kg/day. In
addition, the effects seen in the rat
prenatal development study occurred
only at levels above the limit dose.
Although guideline toxicity studies do
not suggest an increased lifestage
sensitivity/susceptibility (effects above
the limit dose or no effects at the highest
doses tested), data from the literature
suggests that developing infants and
children may be more susceptible to
oxytetracycline side-effects than adults.
When oxytetracycline was administered
orally, as a single dose, to two female
infant rhesus monkeys, zygomatic arch
bone (lateral surface of temporal bone)
growth was inhibited for ∼12.5 days
with no recovery observed by 21 days.
The delayed bone growth occurs as a
result of chelation of calcium, the
mineral needed for bone growth. When
the monkeys are treated with a very
high dose of oxytetracycline (80 mg/kg),
the calcium can be bound up for several
days, leading to a delay in bone growth
during that short time frame. However,
once the oxytetracycline levels
diminish, bone growth continues
resulting in normal bones at maturity.
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, is adequate
for characterizing toxicity and
quantification of risk from the proposed
and existing uses of oxytetracycline.
EPA is retaining the 10X FQPA SF
because of the potential for pre-natal
toxicity. The Agency concludes that this
safety factor will be protective of
potential toxicity to infants and children
based on the following findings:
i. The toxicity database for
oxytetracycline is complete.
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. There is no evidence that
oxytetracycline results in increased
susceptibility in in utero rats in the
prenatal developmental studies. Within
the toxicity database, the mouse
prenatal developmental study did not
identify adverse effects up to the highest
does tested (HDT), 2,100 mg/kg/day.
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Based on the adverse effects seen in
infant rhesus monkeys after oral
administration of oxytetracycline, the
Food Quality Protection Act (FQPA)
Safety Factor (SF) is being retained at
10X.
iv. There are no residual uncertainties
identified in the exposure databases.
The dietary assessment overestimates
actual exposures to oxytetracycline as it
incorporated tolerance-level residues,
default PFs, assumed that 100% of the
proposed and existing crops are treated
with oxytetracycline, and included
high-end ground and surface drinking
water modeling estimates. EPA made
conservative (protective) assumptions in
the ground and surface water modeling
used to assess exposure to
oxytetracycline in drinking water. These
assessments will not underestimate the
exposure and risks posed by
oxytetracycline.
E. 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
and no acute dietary endpoint was
selected. Therefore, oxytetracycline is
not expected to pose an acute risk.
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 33% of
the cPAD for children 1–2 years old, the
population group receiving the greatest
exposure. There are no residential
pesticide uses for oxytetracycline.
3. Short-term risk and Intermediateterm risk. Short-term and intermediateterm aggregate exposures take into
account short-term residential exposure
plus chronic exposure to food and water
(considered to be a background
exposure level) and intermediate-term
residential exposure plus chronic
exposure to food and water (considered
to be a background exposure level),
respectively. Short and intermediate-
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term adverse effects were identified;
however, oxytetracycline is not
registered for any residential pesticide
uses that would result in short or
intermediate-term residential exposures.
Short-term risk is assessed based on
short-term residential exposure plus
chronic dietary exposure and
intermediate-term risk is assessed based
on intermediate-term residential
exposure plus chronic dietary exposure.
Because there are no short-term or
intermediate-term residential exposures
and chronic dietary exposure has
already been assessed under the
appropriately protective cPAD (which is
at least as protective as the POD used to
assess short-term risk), no further
assessment of short-term risk is
necessary, and EPA relies on the
chronic dietary risk assessment for
evaluating short-term risk for
oxytetracycline.
4. Aggregate cancer risk for U.S.
population. Based on the lack of
evidence of carcinogenicity in adequate
carcinogenicity studies in two animals,
oxytetracycline is not expected to pose
a cancer risk to humans and no cancer
risk assessment was necessary.
5. Pharmaceutical aggregate risk for
U.S. population. 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 and determine that ‘‘there
is a reasonable certainty of no harm’’
from those exposures. Because the Food
and Drug Administration (FDA) may
approve pharmaceutical drugs under
FFDCA section 505, notwithstanding
the possibility that some users may
experience adverse side effects. EPA
examines the impact that the additional
pesticide exposures would have to a
pharmaceutical user exposed to a
related (or, in some cases, the same)
compound in assessing the potential of
harm to the pharmaceutical user. Where
the additional pesticide exposure has no
more than a minimal impact on the
pharmaceutical user, EPA has
concluded that it can make a reasonable
certainty of no harm finding for the
pesticide tolerances of that compound
under section 408 of the FFDCA.
For oxytetracycline, EPA’s pesticide
exposure assessment has taken into
consideration the appropriate
population, exposure route, and
exposure duration for comparison with
pharmaceutical exposure to
oxytetracycline. EPA estimates that the
pharmaceutical exposure a person is
expected to receive from a typical
therapeutic dose (25 mg/kg/day for
children) is 750 to 2,800 times greater
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than the estimated dietary exposure
from the pesticidal sources of
oxytetracycline (0.0089334 mg/kg/day).
Therefore, because the pesticide
exposure has no more than a minimal
impact on the total dose to a
pharmaceutical user, EPA concludes
that there is a reasonable certainty that
the potential pesticide exposure will
result in no harm to a person being
treated therapeutically with
oxytetracycline.
6. 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 residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methods are
available for determining
oxytetracycline residues in/on plant
commodities. A high-performance
liquid chromatography method with
tandem mass spectrometry detection
(LC/MS/MS) has been proposed for
tolerance enforcement.
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 Alimentarius 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.
C. Response to Comments
One comment was received generally
opposing the use of any pesticides in or
on food. The Agency recognizes that
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16:14 Dec 03, 2018
Jkt 247001
some individuals oppose the use of
pesticides in or on food, but the FFDCA
authorizes the Agency to establish
tolerances for residues of pesticides in
or on food if the Agency determines that
the tolerance is safe. EPA has examined
all the available data and determined
that there is a reasonable certainty that
no harm will result from aggregate
exposure to the pesticide chemical
residue. The commenter has provided
no information to support a finding that
the tolerances would not be safe.
V. Conclusion
Therefore, tolerances are established
for residues of oxytetracycline, in or on
fruit, citrus, group 10–10 at 0.01 ppm.
VI. Statutory and Executive Order
Reviews
This action establishes tolerances
under FFDCA section 408(d) in
response to a petition submitted to the
Agency. 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); Executive
Order 13045, entitled ‘‘Protection of
Children from Environmental Health
Risks and Safety Risks’’ (62 FR 19885,
April 23, 1997); or Executive Order
13771, entitled ‘‘Reducing Regulations
and Controlling Regulatory Costs’’ (82
FR 9339, February 3, 2017). This action
does not contain any information
collections subject to OMB approval
under the Paperwork Reduction Act
(PRA) (44 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 on the basis of a petition
under FFDCA section 408(d), 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
PO 00000
Frm 00045
Fmt 4700
Sfmt 4700
62493
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).
VII. Congressional Review Act
Pursuant to the Congressional Review
Act (5 U.S.C. 801 et seq.), EPA will
submit 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: November 23, 2018.
Michael Goodis,
Director, Registration Division, Office of
Pesticide Program.
Therefore, 40 CFR chapter I is
amended as follows:
PART 180—[AMENDED]
1. The authority citation for part 180
continues to read as follows:
■
Authority: 21 U.S.C. 321(q), 346a and 371.
2. In § 180.337, add alphabetically the
entry for ‘‘Fruit, citrus, group 10–10’’ to
the table in paragraph (a) to read as
follows:
■
E:\FR\FM\04DER1.SGM
04DER1
62494
Federal Register / Vol. 83, No. 233 / Tuesday, December 4, 2018 / Rules and Regulations
§ 180.337 Oxytetracycline; tolerances for
residues.
on the suspension date or for further
information, contact Adrienne L.
Sheldon, PE, CFM, Federal Insurance
(a) * * *
and Mitigation Administration, Federal
Parts per
Emergency Management Agency, 400 C
Commodity
million
Street SW, Washington, DC 20472, (202)
212–3966.
SUPPLEMENTARY
INFORMATION: The NFIP
*
*
*
*
*
enables property owners to purchase
Fruit, citrus, group 10–10 .....
0.01 Federal flood insurance that is not
otherwise generally available from
*
*
*
*
*
private insurers. In return, communities
agree to adopt and administer local
floodplain management measures aimed
*
*
*
*
*
at protecting lives and new construction
[FR Doc. 2018–26343 Filed 12–3–18; 8:45 am]
from future flooding. Section 1315 of
BILLING CODE 6560–50–P
the National Flood Insurance Act of
1968, as amended, 42 U.S.C. 4022,
prohibits the sale of NFIP flood
DEPARTMENT OF HOMELAND
insurance unless an appropriate public
SECURITY
body adopts adequate floodplain
management measures with effective
Federal Emergency Management
enforcement measures. The
Agency
communities listed in this document no
longer meet that statutory requirement
44 CFR Part 64
for compliance with program
regulations, 44 CFR part 59.
[Docket ID FEMA–2018–0002; Internal
Accordingly, the communities will be
Agency Docket No. FEMA–8557]
suspended on the effective date in the
Suspension of Community Eligibility
third column. As of that date, flood
insurance will no longer be available in
AGENCY: Federal Emergency
the community. We recognize that some
Management Agency, DHS.
of these communities may adopt and
ACTION: Final rule.
submit the required documentation of
legally enforceable floodplain
SUMMARY: This rule identifies
management measures after this rule is
communities where the sale of flood
published but prior to the actual
insurance has been authorized under
suspension date. These communities
the National Flood Insurance Program
will not be suspended and will continue
(NFIP) that are scheduled for
to be eligible for the sale of NFIP flood
suspension on the effective dates listed
insurance. A notice withdrawing the
within this rule because of
suspension of such communities will be
noncompliance with the floodplain
published in the Federal Register.
management requirements of the
In addition, FEMA publishes a Flood
program. If the Federal Emergency
Insurance
Rate Map (FIRM) that
Management Agency (FEMA) receives
identifies the Special Flood Hazard
documentation that the community has
Areas (SFHAs) in these communities.
adopted the required floodplain
The date of the FIRM, if one has been
management measures prior to the
published, is indicated in the fourth
effective suspension date given in this
column of the table. No direct Federal
rule, the suspension will not occur and
financial assistance (except assistance
a notice of this will be provided by
publication in the Federal Register on a pursuant to the Robert T. Stafford
Disaster Relief and Emergency
subsequent date. Also, information
Assistance Act not in connection with a
identifying the current participation
flood) may be provided for construction
status of a community can be obtained
or acquisition of buildings in identified
from FEMA’s Community Status Book
SFHAs for communities not
(CSB). The CSB is available at https://
participating in the NFIP and identified
www.fema.gov/national-floodfor more than a year on FEMA’s initial
insurance-program-community-statusFIRM for the community as having
book.
flood-prone areas (section 202(a) of the
DATES: The effective date of each
Flood Disaster Protection Act of 1973,
community’s scheduled suspension is
42 U.S.C. 4106(a), as amended). This
the third date (‘‘Susp.’’) listed in the
prohibition against certain types of
third column of the following tables.
Federal assistance becomes effective for
FOR FURTHER INFORMATION CONTACT: If
the communities listed on the date
you want to determine whether a
shown in the last column. The
particular community was suspended
Administrator finds that notice and
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16:14 Dec 03, 2018
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PO 00000
Frm 00046
Fmt 4700
Sfmt 4700
public comment procedures under 5
U.S.C. 553(b), are impracticable and
unnecessary because communities listed
in this final rule have been adequately
notified.
Each community receives 6-month,
90-day, and 30-day notification letters
addressed to the Chief Executive Officer
stating that the community will be
suspended unless the required
floodplain management measures are
met prior to the effective suspension
date. Since these notifications were
made, this final rule may take effect
within less than 30 days.
National Environmental Policy Act.
FEMA has determined that the
community suspension(s) included in
this rule is a non-discretionary action
and therefore the National
Environmental Policy Act of 1969 (42
U.S.C. 4321 et seq.) does not apply.
Regulatory Flexibility Act. The
Administrator has determined that this
rule is exempt from the requirements of
the Regulatory Flexibility Act because
the National Flood Insurance Act of
1968, as amended, Section 1315, 42
U.S.C. 4022, prohibits flood insurance
coverage unless an appropriate public
body adopts adequate floodplain
management measures with effective
enforcement measures. The
communities listed no longer comply
with the statutory requirements, and
after the effective date, flood insurance
will no longer be available in the
communities unless remedial action
takes place.
Regulatory Classification. This final
rule is not a significant regulatory action
under the criteria of section 3(f) of
Executive Order 12866 of September 30,
1993, Regulatory Planning and Review,
58 FR 51735.
Executive Order 13132, Federalism.
This rule involves no policies that have
federalism implications under Executive
Order 13132.
Executive Order 12988, Civil Justice
Reform. This rule meets the applicable
standards of Executive Order 12988.
Paperwork Reduction Act. This rule
does not involve any collection of
information for purposes of the
Paperwork Reduction Act, 44 U.S.C.
3501 et seq.
List of Subjects in 44 CFR Part 64
Flood insurance, Floodplains.
Accordingly, 44 CFR part 64 is
amended as follows:
PART 64—[AMENDED]
1. The authority citation for part 64
continues to read as follows:
■
Authority: 42 U.S.C. 4001 et seq.;
Reorganization Plan No. 3 of 1978, 3 CFR,
E:\FR\FM\04DER1.SGM
04DER1
]]>Agencies
[Federal Register Volume 83, Number 233 (Tuesday, December 4, 2018)]
[Rules and Regulations]
[Pages 62489-62494]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-26343]
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2015-0820; FRL-9986-87]
Oxytetracycline; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: This regulation establishes tolerances for residues of
oxytetracycline in or on fruit, citrus, crop group 10-10. Geo Logic
Corporation requested these tolerances under the Federal Food, Drug,
and Cosmetic Act (FFDCA).
DATES: This regulation is effective December 4, 2018. Objections and
requests for hearings must be received on or before February 4, 2019
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-2015-0820, 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 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: [email protected].
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:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
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 EPA's
tolerance regulations at 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 FFDCA section 408(g), 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-2015-0820 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
February 4, 2019. 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-2015-0820, by one of
the following methods:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the online instructions for submitting comments. Do not submit
electronically any information you consider 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/contacts.html.
Additional instructions on commenting or visiting the docket, along
with more information about dockets generally, is available at https://www.epa.gov/dockets.
II. Summary of Petitioned-For Tolerance
In the Federal Register of March 16, 2016 (81 FR 14030) (FRL-9942-
86), EPA issued a document pursuant to
[[Page 62490]]
FFDCA section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of
a pesticide petition (PP 5F8415) by Geo Logic Corporation, P.O. Box
3091, Tequesta, FL 33469. The petition requested that 40 CFR 180.337 be
amended by establishing tolerances for residues of the bactericide
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, crop group
10-10 at 0.01 parts per million (ppm).
That document referenced a summary of the petition prepared by Geo
Logic Corporation, the registrant, which is available in the docket,
https://www.regulations.gov. One comment was received on the notice of
filing. EPA's response to this comment is discussed in Unit IV.C.
III. Aggregate Risk Assessment and Determination of Safety
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. . .
.''
Consistent with FFDCA section 408(b)(2)(D), and 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 for oxytetracycline including
exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with oxytetracycline
follows.
A. Toxicological Profile
EPA has evaluated the available toxicity data and considered its
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children.
At high doses, the target organ of tetracycline toxicity is the
liver. The most common effect in intermediate- or long-term oral
exposures in rats and mice was a decrease in body weight. In the
prenatal developmental study in rats, clinical signs included increased
incidences of respiratory signs and rough hair coat in the dams, in
addition to increased mortality and a decreased percentage of dams
found pregnant. Also identified was a decrease in fetal body weight. In
the mouse prenatal developmental study, there was no toxicity
identified in the dams or fetuses. In all of the above animal studies,
adverse effects were seen at doses that exceed the limit dose. There is
no adequate reproductive toxicity study available in the database,
however, the data requirement was waived based on the lack of
reproductive effects reported during the history of use as a drug. No
evidence of neurotoxicity was observed in any guideline study. A rat
immunotoxicity study demonstrated immunosuppression at doses lower than
those for systemic toxicity. Tetracyclines are known to inhibit bone
growth in developing tissue. When oxytetracycline was administered
orally as a single dose to two female infant rhesus monkeys, zygomatic
arch bone (lateral surface of temporal bone) growth was inhibited for
~12.5 days with no recovery observed by 21 days. Effects on bone growth
are consistent with oxytetracycline's ability to chelate calcium, and
so are not unexpected. Bone developmental effects were also observed
after administration of chlortetracycline and demethylchlortetracycline
in adult rhesus monkeys highlighting the consistency of tetracycline
treatment across this class of chemicals.
The Agency has classified oxytetracycline as ``Group D: Not
Classifiable as to Human Carcinogenicity''. Oxytetracycline has low
acute toxicity, being Toxicity Category IV for oral toxicity, the only
acute lethality study available in the database.
Specific information on the studies received and the nature of the
adverse effects caused by oxytetracycline as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at https://www.regulations.gov in document ``Oxytetracycline/Oxytetracycline
Hydrochloride/Oxytetracycline Calcium: Draft Human Health Risk
Assessment in Support of Registration Review and Tolerance
Establishment in/on Citrus Fruit Crop Group 10-10'' in docket ID number
EPA-HQ-OPP-2015-0820.
B. 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 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://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/assessing-human-health-risk-pesticides.
[[Page 62491]]
Table 1--Summary of Toxicological Doses and Endpoints for Oxytetracycline for Use in Human Health Risk
Assessment
----------------------------------------------------------------------------------------------------------------
Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
----------------------------------------------------------------------------------------------------------------
Acute dietary (All populations).. None selected....... N/A................ No appropriate endpoint for
females age 13-49 or for the
general population attributable
to a single exposure.
----------------------------------------------------------------------------------------------------------------
Chronic dietary (All populations) NOAEL= 100 mg/kg/day Chronic RfD = 1 mg/ WOE from 3 rats and 2 dogs chronic
UFA = 10x........... kg/day. studies.
UFH = 10x........... cPAD = 0.10 mg/kg/ The NOAEL of 100 mg/kg/day was
FQPA SF = 10x....... day. derived from these studies and no
specific LOAEL was established.
------------------------------------------------------------------------------
Cancer........................... Classified as a Group D carcinogen--not classifiable as to human
carcinogenicity.
----------------------------------------------------------------------------------------------------------------
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
of concern. mg/kg/day = milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
level. RfD = reference dose. UFA = extrapolation from animal to human (interspecies). UFH = potential
variation in sensitivity among members of the human population (intraspecies).
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to oxytetracycline, EPA considered exposure under the
petitioned-for tolerances 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. Quantitative acute dietary exposure and risk
assessments are performed for a food-use pesticide, if a toxicological
study has indicated the possibility of an effect of concern occurring
as a result of a 1-day or single exposure. No such effects were
identified in the toxicological studies for oxytetracycline; therefore,
a quantitative acute dietary exposure assessment is unnecessary.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA 2003-2008 food consumption data from the USDA's National
Health and Nutrition Examination Survey/What We Eat in America. As to
residue levels in food, EPA used tolerance-level residues, default
processing factors (PFs), and assumed 100 percent crop treated (PCT).
iii. Cancer. Based on the data summarized in Unit III.A., EPA has
concluded that oxytetracycline does not pose a cancer risk to humans.
Therefore, a dietary exposure assessment for the purpose of assessing
cancer risk is unnecessary.
iv. Anticipated residue and PCT information. EPA did not use
anticipated residue and/or PCT information in the dietary assessment
for oxytetracycline. Tolerance-level residues and/or 100 PCT were
assumed for all food commodities.
2. Dietary exposure from drinking water. The Agency used screening-
level water exposure models in the dietary exposure analysis and risk
assessment for oxytetracycline in 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://www2.epa.gov/pesticide-science-and-assessing-pesticide-risks/about-water-exposure-models-used-pesticide.
Based on the Pesticide Root Zone Model version 5.02/Variable Volume
Water Body Model (VVWM V1.02) and Pesticide Root Zone Model Ground
Water (PRZM GW), EDWCs of oxytetracycline for chronic exposures for
non-cancer assessments are estimated to be 2.85 ppb for surface water
and 0.323 ppb for ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For chronic dietary risk
assessment, the water concentration of value 2.85 ppb was used to
assess the contribution to drinking water.
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 for any specific use patterns that would result in
residential exposure.
Tetracycline hydrochloride (97% chemical similarity to
oxytetracycline) is approved by FDA for use as an oral antibiotic to
treat certain bacterial and parasitic infections. EPA examined the
impact that additional pesticide exposures to oxytetracycline would
have on a person who has been prescribed the antibiotic. EPA determined
that the additional pesticide exposure would not have more than a
minimal impact on the total dose to the pharmaceutical patient, and
thus concludes that there is a reasonable certainty that the additional
exposure from pesticide uses of oxytetracycline would result in no harm
finding to a user being treated therapeutically.
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 ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA has assessed the potential for oxytetracycline to share a
common mechanism of toxicity with any other substances. Based on its
assessment of the available toxicological data, EPA has determined that
oxytetracycline does not share a similar toxicological profile with
other pesticides, and no further cumulative evaluation is necessary for
oxytetracycline.
D. 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 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 safety factor when
reliable
[[Page 62492]]
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), 2,100
mg/kg/day. In addition, the effects seen in the rat prenatal
development study occurred only at levels above the limit dose.
Although guideline toxicity studies do not suggest an increased
lifestage sensitivity/susceptibility (effects above the limit dose or
no effects at the highest doses tested), data from the literature
suggests that developing infants and children may be more susceptible
to oxytetracycline side-effects than adults. When oxytetracycline was
administered orally, as a single dose, to two female infant rhesus
monkeys, zygomatic arch bone (lateral surface of temporal bone) growth
was inhibited for ~12.5 days with no recovery observed by 21 days. The
delayed bone growth occurs as a result of chelation of calcium, the
mineral needed for bone growth. When the monkeys are treated with a
very high dose of oxytetracycline (80 mg/kg), the calcium can be bound
up for several days, leading to a delay in bone growth during that
short time frame. However, once the oxytetracycline levels diminish,
bone growth continues resulting in normal bones at maturity.
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, is adequate for characterizing toxicity and quantification of
risk from the proposed and existing uses of oxytetracycline. EPA is
retaining the 10X FQPA SF because of the potential for pre-natal
toxicity. The Agency concludes that this safety factor will be
protective of potential toxicity to infants and children based on the
following findings:
i. The toxicity database for oxytetracycline is complete.
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. There is no evidence that oxytetracycline results in increased
susceptibility in in utero rats in the prenatal developmental studies.
Within the toxicity database, the mouse prenatal developmental study
did not identify adverse effects up to the highest does tested (HDT),
2,100 mg/kg/day. Based on the adverse effects seen in infant rhesus
monkeys after oral administration of oxytetracycline, the Food Quality
Protection Act (FQPA) Safety Factor (SF) is being retained at 10X.
iv. There are no residual uncertainties identified in the exposure
databases. The dietary assessment overestimates actual exposures to
oxytetracycline as it incorporated tolerance-level residues, default
PFs, assumed that 100% of the proposed and existing crops are treated
with oxytetracycline, and included high-end ground and surface drinking
water modeling estimates. EPA made conservative (protective)
assumptions in the ground and surface water modeling used to assess
exposure to oxytetracycline in drinking water. These assessments will
not underestimate the exposure and risks posed by oxytetracycline.
E. 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 and no acute dietary endpoint was selected. Therefore,
oxytetracycline is not expected to pose an acute risk.
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 33% of the cPAD for
children 1-2 years old, the population group receiving the greatest
exposure. There are no residential pesticide uses for oxytetracycline.
3. Short-term risk and Intermediate-term risk. Short-term and
intermediate-term aggregate exposures take into account short-term
residential exposure plus chronic exposure to food and water
(considered to be a background exposure level) and intermediate-term
residential exposure plus chronic exposure to food and water
(considered to be a background exposure level), respectively. Short and
intermediate-term adverse effects were identified; however,
oxytetracycline is not registered for any residential pesticide uses
that would result in short or intermediate-term residential exposures.
Short-term risk is assessed based on short-term residential exposure
plus chronic dietary exposure and intermediate-term risk is assessed
based on intermediate-term residential exposure plus chronic dietary
exposure. Because there are no short-term or intermediate-term
residential exposures and chronic dietary exposure has already been
assessed under the appropriately protective cPAD (which is at least as
protective as the POD used to assess short-term risk), no further
assessment of short-term risk is necessary, and EPA relies on the
chronic dietary risk assessment for evaluating short-term risk for
oxytetracycline.
4. Aggregate cancer risk for U.S. population. Based on the lack of
evidence of carcinogenicity in adequate carcinogenicity studies in two
animals, oxytetracycline is not expected to pose a cancer risk to
humans and no cancer risk assessment was necessary.
5. Pharmaceutical aggregate risk for U.S. population. 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 and
determine that ``there is a reasonable certainty of no harm'' from
those exposures. Because the Food and Drug Administration (FDA) may
approve pharmaceutical drugs under FFDCA section 505, notwithstanding
the possibility that some users may experience adverse side effects.
EPA examines the impact that the additional pesticide exposures would
have to a pharmaceutical user exposed to a related (or, in some cases,
the same) compound in assessing the potential of harm to the
pharmaceutical user. Where the additional pesticide exposure has no
more than a minimal impact on the pharmaceutical user, EPA has
concluded that it can make a reasonable certainty of no harm finding
for the pesticide tolerances of that compound under section 408 of the
FFDCA.
For oxytetracycline, EPA's pesticide exposure assessment has taken
into consideration the appropriate population, exposure route, and
exposure duration for comparison with pharmaceutical exposure to
oxytetracycline. EPA estimates that the pharmaceutical exposure a
person is expected to receive from a typical therapeutic dose (25 mg/
kg/day for children) is 750 to 2,800 times greater
[[Page 62493]]
than the estimated dietary exposure from the pesticidal sources of
oxytetracycline (0.0089334 mg/kg/day). Therefore, because the pesticide
exposure has no more than a minimal impact on the total dose to a
pharmaceutical user, EPA concludes that there is a reasonable certainty
that the potential pesticide exposure will result in no harm to a
person being treated therapeutically with oxytetracycline.
6. 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 residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methods are available for determining
oxytetracycline residues in/on plant commodities. A high-performance
liquid chromatography method with tandem mass spectrometry detection
(LC/MS/MS) has been proposed for tolerance enforcement.
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:
[email protected].
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 Alimentarius 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.
C. Response to Comments
One comment was received generally opposing the use of any
pesticides in or on food. The Agency recognizes that some individuals
oppose the use of pesticides in or on food, but the FFDCA authorizes
the Agency to establish tolerances for residues of pesticides in or on
food if the Agency determines that the tolerance is safe. EPA has
examined all the available data and determined that there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue. The commenter has provided no
information to support a finding that the tolerances would not be safe.
V. Conclusion
Therefore, tolerances are established for residues of
oxytetracycline, in or on fruit, citrus, group 10-10 at 0.01 ppm.
VI. Statutory and Executive Order Reviews
This action establishes tolerances under FFDCA section 408(d) in
response to a petition submitted to the Agency. 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); Executive Order 13045, entitled
``Protection of Children from Environmental Health Risks and Safety
Risks'' (62 FR 19885, April 23, 1997); or Executive Order 13771,
entitled ``Reducing Regulations and Controlling Regulatory Costs'' (82
FR 9339, February 3, 2017). This action does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA) (44 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 on the basis
of a petition under FFDCA section 408(d), 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).
VII. Congressional Review Act
Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.),
EPA will submit 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: November 23, 2018.
Michael Goodis,
Director, Registration Division, Office of Pesticide Program.
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, add alphabetically the entry for ``Fruit, citrus,
group 10-10'' to the table in paragraph (a) to read as follows:
[[Page 62494]]
Sec. 180.337 Oxytetracycline; tolerances for residues.
(a) * * *
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
* * * * *
Fruit, citrus, group 10-10.............................. 0.01
* * * * *
------------------------------------------------------------------------
* * * * *
[FR Doc. 2018-26343 Filed 12-3-18; 8:45 am]
BILLING CODE 6560-50-P
