Mefenpyr-diethyl and Metabolites; Pesticide Tolerance, 74972-74977 [E8-29112]
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Federal Register / Vol. 73, No. 238 / Wednesday, December 10, 2008 / Rules and Regulations
possess, carry, and transport concealed,
loaded, and operable firearms within a
national wildlife refuge in accordance
with the laws of the state in which the
wildlife refuge, or that portion thereof,
is located, except as otherwise
prohibited by applicable Federal law.
Dated: December 5, 2008.
Lyle Laverty,
Assistant Secretary of the Interior for Fish
and Wildlife and Parks.
[FR Doc. E8–29249 Filed 12–9–08; 8:45 am]
BILLING CODE 4312–52–P
DEPARTMENT OF COMMERCE
Patent and Trademark Office
37 CFR Part 41
[Docket No.: PTO–P–2007–0006]
RIN 0651–AC12
Rules of Practice Before the Board of
Patent Appeals and Interferences in Ex
Parte Appeals; Delay of Effective and
Applicability Dates
dwashington3 on PROD1PC60 with RULES
AGENCY: United States Patent and
Trademark Office, Commerce.
ACTION: Final rule; delay of effective and
applicability dates.
SUMMARY: On June 10, 2008, the United
States Patent and Trademark Office
(Office) published the final rule that
amends the rules governing practice
before the Board of Patent Appeals and
Interferences (BPAI) in ex parte patent
appeals. The final rule states that the
effective date is December 10, 2008, and
that the final rule shall apply to all
appeals in which an appeal brief is filed
on or after the effective date. On June 9,
2008, the Office published a 60-Day
Federal Register Notice requesting the
Office of Management and Budget
(OMB) to establish a new information
collection for BPAI items in the final
rule and requesting public comment on
the burden impact of the final rule
under the provisions of the Paperwork
Reduction Act (PRA). On October 8,
2008, the Office published a 30-Day
Federal Register Notice stating that the
proposal for the collection of
information under the final rule was
being submitted to OMB and requesting
comments on the proposed information
collection be submitted to OMB. The
proposed information collection is
currently under consideration by OMB.
Since the review by OMB has not been
completed, the Office is hereby
notifying the public that the effective
and applicability date of the final rule
is not December 10, 2008. The effective
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and applicability dates will be
identified in a subsequent notice.
DATES: The effective date for the final
rule published at 73 FR 32938, June 10,
2008, is delayed, pending completion of
OMB review of the proposed
information collection under the PRA.
The Office will issue a subsequent
notice identifying a revised effective
date on which the final rule shall apply.
FOR FURTHER INFORMATION CONTACT:
Allen MacDonald, Administrative
Patent Judge, at (571) 272–9797, or
Kimberly Jordan, Chief Trial
Administrator, at (571) 272–4683, Board
of Patent Appeals and Interferences,
directly by phone, or by facsimile to
(571) 273–0043, or by mail addressed to:
Mail Stop Board of Patents Appeals and
Interferences, P.O. Box 1450,
Alexandria, VA 22313–1450.
SUPPLEMENTARY INFORMATION: On June
10, 2008, the United States Patent and
Trademark Office (Office) published the
final rule that amends the rules
governing practice before the Board of
Patent Appeals and Interferences (BPAI)
in ex parte patent appeals. See Rules of
Practice Before the Board of Patent
Appeals and Interferences in Ex Parte
Appeals; Final Rule, 73 FR 32938 (June
10, 2008), 1332 Off. Gaz. Pat. Office 47
(July 1, 2008) (hereinafter ‘‘BPAI final
rule 2008’’). The BPAI final rule 2008
states that the effective date is December
10, 2008, and that the final rule shall
apply to all appeals in which an appeal
brief is filed on or after the effective
date.
On June 9, 2008, the Office published
a new information collection request for
OMB to review several BPAI items in
the BPAI final rule 2008 as subject to
the PRA. See Board of Patent Appeals
and Interferences Actions; New
Collection, Comment Request, 73 FR
32559 (June 9, 2008) (hereinafter ‘‘60Day Notice’’). In addition to requesting
OMB to establish a new information
collection, the 60-Day Notice invited
comments from the public and other
Federal agencies on the burden impact
of the proposed information collection
under the provisions of the PRA. The
60-Day Notice specified that comments
were to be submitted on or before
August 8, 2008.
On October 8, 2008, the Office
published a notice that the proposed
information collection was being
submitted to OMB and public comments
on the proposed collection were to be
submitted to OMB on or before
November 7, 2008. See Submission for
OMB Review; Comment Request; 73 FR
58943 (October 8, 2008) (hereinafter
‘‘30-Day Notice’’). On October 9, 2008,
the Office filed a Supporting Statement
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with OMB (https://www.reginfo.gov/
public/do/PRAViewDocument?ref_nbr=
200809–0651–003). The Supporting
Statement included the Office’s
response to comments received
following the 60–Day Notice. The 30–
Day Notice requested public comments
be submitted to OMB on or before
November 7, 2008.
The proposed information collection
request is currently under consideration
for approval by OMB. The review by
OMB has not been completed.
Therefore, the effective and
applicability dates of the BPAI final rule
2008 will not be December 10, 2008.
The Office will notify the public when
the revised effective and applicability
dates are set. In the subsequent
notification, the Office will provide at
least a 30-day time period before the
BPAI final rule 2008 becomes effective.
On November 20, 2008, the Office
published a clarification notice on the
effective date provision. See
Clarification of the Effective Date
Provision in the Final Rule for Ex Parte
Appeals, 73 FR 70282 (November 20,
2008). As indicated in the clarification
notice, the Office will not hold an
appeal brief as non-compliant solely for
following the new format even though it
is filed before the effective date. Thus,
appeal briefs filed before the effective
date of the BPAI final rule 2008 (yet to
be determined) must either comply with
current 37 CFR 41.37 (which remains in
effect) or revised 37 CFR 41.37 (the
effective date of which has yet to be
determined). Furthermore, the Office
has posted a list of questions and
answers on the USPTO Web site (at
https://www.uspto.gov/web/offices/
dcom/bpai/rule.html) regarding the
implementation of the BPAI final rule
2008. These questions and answers will
be revised accordingly.
Dated: December 5, 2008.
Jon W. Dudas,
Under Secretary of Commerce for Intellectual
Property and Director of the United States
Patent and Trademark Office.
[FR Doc. E8–29297 Filed 12–9–08; 8:45 am]
BILLING CODE 3510–16–P
ENVIRONMENTAL PROTECTION
AGENCY
40 CFR Part 180
[EPA–HQ–OPP–2007–0672; FRL–8390–8]
Mefenpyr-diethyl and Metabolites;
Pesticide Tolerance
AGENCY: Environmental Protection
Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes
tolerances for residues of the herbicide
safener, mefenpyr-diethyl (CAS Reg. No.
135590–91–9), also known as 1-(2,4dichlorophenyl)-4,5-dihydro-5-methyl1H-pyrazole-3,5-dicarboxylic acid,
diethyl ester and its 2,4-dichlorophenylpyrazoline metabolites, applied at a rate
no greater than 0.053 pounds safener
per acre per growing season, in or on the
rotational crop commodities soybean
seed, soybean hay, soybean forage and
canola seed. Bayer CropScience
requested these tolerances under the
Federal Food, Drug, and Cosmetic Act
(FFDCA).
DATES: This regulation is effective
December 10, 2008. Objections and
requests for hearings must be received
on or before February 9, 2009, 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: EPA has established a
docket for this action under docket
identification (ID) number EPA–HQ–
OPP–2007– 0672. All documents in the
docket are listed in the docket index
available at https://www.regulations.gov.
Although listed in the index, some
information is not publicly available,
e.g., Confidential Business Information
(CBI) or other information whose
disclosure is restricted by statute.
Certain other material, such as
copyrighted material, is not placed on
the Internet and will be publicly
available only in hard copy form.
Publicly available docket materials are
available in the electronic docket at
https://www.regulations.gov, or, if only
available in hard copy, at the OPP
Regulatory Public Docket in Rm. S–
4400, One Potomac Yard (South Bldg.),
2777 S. Crystal Dr., Arlington, VA. The
Docket Facility is open from 8:30 a.m.
to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket
Facility telephone number is (703) 305–
5805.
FOR FURTHER INFORMATION CONTACT:
Karen Samek, Registration Division
(7505P), Office of Pesticide Programs,
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001; telephone number:
(703) 347-8825; e-mail address:
samek.karen@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. Potentially
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affected entities may include, but are
not limited to:
• Crop production (NAICS code 111).
• Animal production (NAICS code
112).
• Food manufacturing (NAICS code
311).
• Pesticide manufacturing (NAICS
code 32532).
This listing is not intended to be
exhaustive, but rather provides a guide
for readers regarding entities likely to be
affected by this action. Other types of
entities not listed in this unit could also
be affected. The North American
Industrial Classification System
(NAICS) codes have been provided to
assist you and others in determining
whether this action might apply to
certain entities. If you have any
questions regarding the applicability of
this action to a particular entity, consult
the person listed under FOR FURTHER
INFORMATION CONTACT.
B. How Can I Access Electronic Copies
of this Document?
In addition to accessing electronically
available documents at https://
www.regulations.gov, you may access
this Federal Register document
electronically through the EPA Internet
under the ‘‘Federal Register’’ listings at
https://www.epa.gov/fedrgstr. You may
also access a frequently updated
electronic version of 40 CFR part 180
through the Government Printing
Office’s e-CFR site at https://
www.gpoaccess.gov/ecfr. To access the
OPPTS Harmonized Guidelines
referenced in this document, go directly
to the guidelines at https://www.epa.gpo/
opptsfrs/home/guidelin.htm.
C. Can I File an Objection or Hearing
Request?
Under section 408(g) of 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. The EPA procedural
regulations which govern the
submission of objections and requests
for hearings appear in 40 CFR part 178.
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–2007–0672 in the subject line on
the first page of your submission. All
requests must be in writing, and must be
mailed or delivered to the Hearing Clerk
on or before February 9, 2009.
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 that does not
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contain any CBI for inclusion in the
public docket that is described in
ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2
may be disclosed publicly by EPA
without prior notice. Submit your
copies, identified by docket ID number
EPA–HQ–OPP–2007–0672, by one of
the following methods:
• Federal eRulemaking Portal: https://
www.regulations.gov. Follow the on-line
instructions for submitting comments.
• Mail: Office of Pesticide Programs
(OPP) Regulatory Public Docket (7502P),
Environmental Protection Agency, 1200
Pennsylvania Ave., NW., Washington,
DC 20460–0001.
• Delivery: OPP Regulatory Public
Docket (7502P), Environmental
Protection Agency, Rm. S–4400, One
Potomac Yard (South Bldg.), 2777 S.
Crystal Dr., Arlington, VA. Deliveries
are only accepted during the Docket
Facility’s normal hours of operation
(8:30 a.m. to 4 p.m., Monday through
Friday, excluding legal holidays).
Special arrangements should be made
for deliveries of boxed information. The
Docket Facility telephone number is
(703) 305–5805.
II. Petition for Tolerance
In the Federal Register of August 22,
2007 (72 FR 47008) (FRL–8145–1), EPA
issued a notice pursuant to section 408
of FFDCA, 21 U.S.C. 346a, as amended
by FQPA (Public Law 104–170),
announcing the filing of a pesticide
petition (PP 7E7224) by Bayer
CropScience, 2 T.W., Alexander Drive,
P.O. Box 12014, Research Triangle Park,
NC 27709. The petition requested that
40 CFR 180.509 be amended for the
herbicide safener, mefenpyr-diethyl, 1(2,4-dichlorophenyl)-4,5-dihydro-5methyl-1H-pyrazole-3,5-dicarboxylic
acid, diethyl ester and its 2,4dichlorophenyl-pyrazoline metabolites
by increasing the maximum allowable
seasonal use rate to 0.053 lb safener/
acre(A), as well as, establishing rotation
crop tolerances on soybean seed at 0.02
parts per million (ppm); soybean forage
at 0.1ppm; soybean hay at 0.1 ppm; and
canola seed at 0.02 ppm. That notice
referenced a summary of the petition
prepared by Bayer CropScience, the
registrant, which is available to the
public in the docket, https://
www.regulations.gov. There were no
comments received in response to the
Notice of Filing.
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
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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 section 408(b)(2)(D)
of FFDCA, and the factors specified in
section 408(b)(2)(D) of FFDCA, 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 the petitioned-for
tolerances for residues of the herbicide
safener, mefenpyr-diethyl, in or on
soybean seed at 0.02 ppm, soybean
forage at 0.1 ppm, soybean hay at 0.1
ppm, and canola seed at 0.02 ppm; as
well as the petitioned-for request to
increase the maxium allowable seasonal
use rate from 0.026 lb safener/A to 0.053
lb safener/A. EPA’s assessment of
exposures and risks associated with
establishing tolerances follows.
sensitivities of major identifiable
subgroups of consumers, including
infants and children.
Mefenpyr-diethyl has low acute
toxicity by the oral, dermal, and
inhalation routes of exposure. It is not
a dermal irritant but is a slight dermal
sensitizer and ocular irritant.
Metabolism studies indicate that
mefenpyr-diethyl is rapidly
metabolized, widely distributed, and
primarily excreted via the urine. Repeat
exposure via the dermal route did not
induce any treatment-related effects at
dose levels up to and including the limit
dose. Repeated exposure studies via the
oral route demonstrated that the target
organs are the liver and hematopoietic
system in dogs, mice, and rats.
Mefenpyr-diethyl was negative for
carcinogenicity in rats and mice, and
classified as ‘‘not likely to be
carcinogenic to humans.’’ Mefenpyrdiethyl did not show any genotoxic
potential. Developmental toxicity was
not observed in the rat at the limit dose
(1,000 milligrams/kilogram/day (mg/kg/
day)) but was observed in the rabbit
(abortions) at the same dose level
producing maternal toxicity. Mefenpyrdiethyl did not induce any signs of
reproductive toxicity or neurotoxic
potential. The developmental toxicity
studies in rats and rabbits, as well as the
reproductive toxicity study in rats, did
not demonstrate any prenatal or
postnatal sensitivity. There is a lack of
evidence of neurotoxicity in any study
on mefenpyr-diethyl and therefore there
is no concern for neurotoxicity resulting
from exposure to mefenpyr-diethyl.
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
B. Toxicological Endpoints
For hazards that have a threshold
below which there is no appreciable
risk, a toxicological point of departure
(POD) is identified as the basis for
derivation of reference values for risk
assessment. The POD may be defined as
the highest dose at which no adverse
effects are observed (the NOAEL) in the
toxicology study identified as
appropriate for use in risk assessment.
However, if a NOAEL cannot be
determined, the lowest dose at which
adverse effects of concern are identified
(the LOAEL) or a Benchmark Dose
(BMD) approach is sometimes used for
risk assessment. Uncertainty/safety
factors (UFs) are used in conjunction
with the POD to take into account
uncertainties inherent in the
extrapolation from laboratory animal
data to humans and in the variations in
sensitivity among members of the
human population as well as other
unknowns. Safety is assessed for acute
and chronic dietary risks by comparing
aggregate food and water exposure to
the pesticide to the acute population
adjusted dose (aPAD) and chronic
population adjusted dose (cPAD). The
aPAD and cPAD are calculated by
dividing the POD by all applicable UFs.
Aggregate short-, intermediate-, and
chronic-term risks are evaluated by
comparing food, water, and residential
exposure to the POD to ensure that the
margin of exposure (MOE) called for by
the product of all applicable UFs is not
exceeded. This latter value is referred to
as the Level of Concern (LOC).
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 greater than that 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/
pesticides/factsheets/riskassess.htm.
A summary of the toxicological
endpoints for mefenpyr-diethyl for
human risk assessment is shown in
Table 1 of this unit.
TABLE 1.—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR MEFENPYR-DIETHYL FOR USE IN DIETARY AND
NON-OCCUPATIONAL HUMAN HEALTH RISK ASSESSMENTS
Point of Departure and Uncertainty Factors
Exposure/Scenario
RfD, PAD, Level of Concern for Risk Assessment
Study and Toxicological Effects
No hazard was identified in any toxicity study for this duration of exposure.
Acute Dietary (Females 13–49
years of age)
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Acute Dietary (General population, including infants and
children)
No hazard was identified in any toxicity study for this duration of exposure.
Chronic Dietary (All populations)
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NOAEL = 51 mg/kg/day
UFA = 10x
UFH = 10x
FQPA SF = 1x
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Chronic RfD = 0.51 mg/kg/
day
cPAD = 0.51 mg/kg/day
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Chronic oral toxicity study (dog).
LOAEL = 260 mg/kg/day, based on increased
liver weight in both sexes, cholestasis, and
increased alkaline phosphates.
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TABLE 1.—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR MEFENPYR-DIETHYL FOR USE IN DIETARY AND
NON-OCCUPATIONAL HUMAN HEALTH RISK ASSESSMENTS—Continued
Exposure/Scenario
Point of Departure and Uncertainty Factors
Cancer
RfD, PAD, Level of Concern for Risk Assessment
Study and Toxicological Effects
Classification: Not likely to be carcinogenic to humans.
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Point of Departure = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of
extrapolation to determine risk associated with lower environmentally relevant human exposures. NOAEL = no observed adverse effect level.
LOAEL = lowest observed adverse effect level. UF=uncertainty factor. UFA = extrapolated from animal to human (interspecies). UFH = potential
variation in sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a = acute, c = chronic). RfD =
reference dose.
C. Exposure Assessment
1. Dietary exposure from food and
feed uses. In evaluating dietary
exposure to mefenpyr-diethyl, EPA
considered exposure under the
petitioned-for tolerances, as well as all
existing mefenpyr-diethyl tolerances in
40 CFR 180.509. The residue of concern
for both risk assessment and tolerance
setting purposes in plants and animals
is the parent compound, mefenpyrdiethyl, and its 2,4-dichlorophenylpyrazoline metabolites. EPA assessed
dietary exposures from mefenpyrdiethyl 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 mefenpyr-diethyl; therefore, a
quantitative acute dietary exposure
assessment is unnecessary.
ii. Chronic exposure. A highly
conservative chronic dietary risk
assessment was conducted for food and
drinking water for mefenpyr-diethyl. In
conducting the chronic dietary exposure
assessment EPA used the food
consumption data from the USDA 1994–
1996 and 1998 Continuing Survey of
Food Intake by Individuals. As to
residue levels in food, EPA assumed
that 100% of crops with requested uses
of mefenpyr-diethyl are treated and that
all treated crops contain residues at the
tolerance level.
No new magnitude of the residue
data, reflecting the new proposed
seasonal rate of 0.053 lb safener/A, were
submitted for the primary crop
commodities. It is, however, noted that
the field trial data that were previously
submitted in support of the petition to
establish tolerances for primary crops
were conducted at an exaggerated rate of
0.089 lb/safener/A. Therefore, the
Agency has determine that the
established tolerances for primary crop
commodities remain adequate to
support the proposed higher application
rate.
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iii. Cancer. Based on the results of
carcinogenicity studies in rats and mice,
EPA classified mefenpyr-diethyl as a
‘‘Not likely to be carcinogenic to
humans;’’ therefore, an exposure
assessment for assessing cancer risk is
unnecessary for this chemical.
iv. Anticipated residue and percent
crop treated (PCT) information. EPA did
not use anticipated residue or PCT
information in the dietary assessment
for mefenpyr-diethyl. 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 in the dietary
exposure analysis and risk assessment
for mefenpyr-diethyl in drinking water.
These simulation models take into
account data on the physical, chemical,
and fate/transport characteristics of
mefenpyr-diethyl. Further information
regarding EPA drinking water models
used in pesticide exposure assessment
can be found at https://www.epa.gov/
oppefed1/models/water/index.htm.
Based on the First Index Reservoir
Screening Tool (FIRST) and Screening
Concentration in Ground Water (SCIGROW) models, the estimated drinking
water concentrations (EDWCs) of
mefenpyr-diethyl and its transformation
products for chronic exposures for noncancer assessments are estimated to be
3 parts per billion (ppb) for surface
water and 4 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 4 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). No
products containing mefenpyr-diethyl
are available for sale in the residential
market because of the crops specified on
the applicable labels. As such, a
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residential risk assessment was not
conducted.
4. Cumulative effects. Unlike other
pesticides for which EPA has followed
a cumulative risk approach based on a
common mechanism of toxicity, EPA
has not made a common mechanism of
toxicity finding as to mefenpyr-diethyl
and any other substances and mefenpyrdiethyl does not appear to produce a
toxic metabolite produced by other
substances. For the purposes of this
tolerance action, therefore, EPA has not
assumed that mefenpyr-diethyl has 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 the policy statements
released by EPA’s Office of Pesticide
Programs concerning common
mechanism determinations and
procedures for cumulating effects from
substances found to have a common
mechanism on EPA’s website at https://
www.epa.gov/pesticides/cumulative/.
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
data available to EPA support the choice
of a different factor.
2. Prenatal and postnatal sensitivity.
The prenatal and postnatal toxicity
database for mefenpyr-diethyl includes
rat and rabbit developmental toxicity
studies and a two-generation
reproduction toxicity study in rats.
There was no evidence of increased
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Federal Register / Vol. 73, No. 238 / Wednesday, December 10, 2008 / Rules and Regulations
susceptibility of in utero rats or rabbits
in the prenatal developmental studies or
of young rats in the two-generation
reproduction study.
Developmental toxicity was not
observed in the rat at the limit dose
(1,000 mg/kg/day). The only effects
observed in the rat developmental
toxicity study were decreased bodyweight gain and food efficiency during
the first week of dosing and increased
spleen weights in the maternal animal
and a marginal decrease in fetal body
weight/body-weight gain during
lactation (postnatal study). In the rabbit
developmental toxicity study,
developmental toxicity (abortion) was
observed at the same dose level
producing maternal toxicity (250 mg/kg/
day).
In the reproduction study, parental
toxicity consisted of decreased body
weight and body-weight gain, and an
increase in spleen weight and in the
severity (not incidence) of splenic
extramedullary hematopoiesis in
females. In the pups, decreased body
weight and body-weight gains were
observed at the same dose levels as the
parental animals. The NOAEL is 82 mg/
kg/day (1,000 ppm) for both the parental
animal and offspring.
3. Conclusion. EPA has determined
that reliable data show the safety of
infants and children would be
adequately protected if the FQPA SF
were reduced to 1X. That decision is
based on the following findings:
i. The toxicity database for mefenpyrdiethyl is complete, with the exception
of immunotoxicity studies which are
new data requirements under the
revised Part 158 Toxicology Data
Requirements (40 CFR part 158). In the
absence of these studies, EPA has
evaluated the available toxicity data for
mefenpyr-diethyl and determined that
an additional database uncertainty
factor is not needed, based on the
following conclusions:
No acute and subchronic
Neurotoxcity studies are available,
however there is no evidence of
neurotoxicity in the toxicology database
on mefenpyr-diethyl, which includes
subchronic, chronic, developmental
toxicity, and reproduction studies
performed at dose of 250 mg/kg/day and
above. Therefore, based on the above
considerations, the Agency does not
believe that conducting acute and
subchronic neurotoxicity studies will
result in a NOAEL less than the NOAEL
of 51 mg/kg/day already set for
mefenpyr-diethyl; therefore additional
neurotoxicity studies are not necessary
and the 10x safety factor can be reduced
to 1x.
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Considering that the application of
mefenpyr-diethyl will be by either aerial
application or spray boom equipment,
the 28–day inhalation study is required
as confirmatory data. However, the
additional uncertainty factor for
database uncertainties does not need to
be applied since the MOE is >1,000 and
significant inhalation exposures of
concern are not anticipated.
EPA considered the entire toxicity
database for mefenpyr-diethyl for
potential adverse effects on the thymus
and spleen as indications of potential
immunotoxicity and noted enlarged
spleens; more severe hematopoiesis and
hemosiderin deposits and increased
spleen weights were observed in mice at
doses greater than the limit dose.
However, these were determined to be
non-specific changes not indicative of
immunotoxicity. Therefore, based on
the above considerations, EPA does not
believe that conducting a special series
(Harmonized Guideline 870.7800),
immunotoxicity study will result in a
NOAEL less than the NOAEL of 51 mg/
kg/day already set for mefenpyr-diethyl
and an additional uncertainty factor for
database uncertainties does not need to
be applied.
ii. There is no indication that
mefenpyr-diethyl 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
mefenpyr-diethyl results in increased
susceptibility in in utero rats or rabbits
in the prenatal developmental studies or
in young rats in the two-generation
reproduction study.
iv. There are no residual uncertainties
identified in the exposure databases.
The dietary food exposure assessments
were performed assuming 100 PCT and
tolerance-level residues. EPA made
conservative (protective) assumptions in
the ground and surface water modeling
used to assess exposure to mefenpyrdiethyl in drinking water. These
assessments will not underestimate the
exposure and risks posed by mefenpyrdiethyl.
E. Aggregate Risks and Determination of
Safety
EPA determines whether acute and
chronic pesticide exposures are safe by
comparing aggregate exposure estimates
to the aPAD and cPAD. The aPAD and
cPAD represent the highest safe
exposures, taking into account all
appropriate SFs. EPA calculates the
aPAD and cPAD by dividing the POD by
all applicable UFs. For linear cancer
risks, EPA calculates the probability of
additional cancer cases given the
PO 00000
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Fmt 4700
Sfmt 4700
estimated aggregate exposure. Short-,
intermediate-, and chronic-term risks
are evaluated by comparing the
estimated aggregate food, water, and
residential exposure to the POD to
ensure that the MOE called for by the
product of all applicable UFs is not
exceeded.
1. Acute risk. An acute aggregate risk
assessment takes into account exposure
estimates from acute dietary
consumption of food and drinking
water. No adverse effect resulting from
a single oral exposure was identified in
the toxicology studies for mefenpyrdiethyl and no acute dietary endpoint
was selected. Therefore, mefenpyrdiethyl is not expected to pose an acute
risk.
2. Chronic risk. Exposure to
mefenpyr-diethyl food and drinking
water results in an estimated risk
equivalent to <1% of the cPAD for the
general population and all regulated
subpopulations, including infants and
children as well.
There are no residential uses for
mefenpyr-diethyl, therefore the
aggregate risk assessments include the
contribution of risk from dietary (food
and water) sources only.
3. Aggregate cancer risk for U.S.
population. Mefenpyr-diethyl was
negative for carcinogenicity in rats and
mice and thus is not expected to pose
a cancer risk to humans.
4. 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 mefenpyrdiethyl residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
An enforcement method for plants
entitled ‘‘An Analytical Method for
Determination of Residues of AE
F107892 (mefenpyr-diethyl) and its
Metabolites in Wheat and Barley by Gas
Chromatography using Mass Selective
Detection (Report Supplement to EPA
MRID 45457401)’’ is available.
Radiovalidation and independent
laboratory validation (ILV) data have
been submitted for the plant method.
The Agency analytical lab has
concluded that this method is suitable
for food tolerance enforcement of
mefenpyr-diethyl and its 2,4dichlorophenyl-pyrazoline metabolites.
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.
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B. International Tolerances
No Codex, Canadian, or Mexican
maximum residue limits are established
for residues of mefenpyr-diethyl and its
metabolites in crop or livestock
commodities; therefore, there are no
issues with international harmonization
raised by this action.
V. Conclusions
Therefore, 40 CFR 180.509 is
amended for the herbicide safener,
mefenpyr-diethyl, 1-(2,4dichlorophenyl)-4,5-dihydro-5-methyl1H-pyrazole-3,5-dicarboxylic acid,
diethyl ester and its 2,4-dichlorophenylpyrazoline metabolites by increasing the
maximum allowable seasonal use rate to
0.053 lb safener/A, as well as rotation
crop tolerances are established for
residues of the herbicide safener,
mefenpyr-diethyl, 1-(2,4dichlorophenyl)-4,5-dihydro-5-methyl1H-pyrazole-3,5-dicarboxylic acid,
diethyl ester and its 2,4-dichlorophenylpyrazoline metabolites in or on soybean
seed at 0.02 ppm; soybean forage at 0.1
ppm; soybean hay at 0.1 ppm; and
canola seed at 0.02 ppm.
It should be noted that no new
magnitude of the residue data, reflecting
the new proposed seasonal rate of 0.053
lb safener/A, were submitted for the
primary crop commodities. However,
field trail data that were previously
submitted in support of the petition to
establish tolerances for primary crops
were conducted at an exaggerated rate of
0.089 lb safener/A. Therefore, the
Agency determined that the established
tolerances for primary crop
commodities remain adequate to
support the proposed higher application
rate.
dwashington3 on PROD1PC60 with RULES
VI. Statutory and Executive Order
Reviews
This final rule establishes tolerances
under section 408(d) of FFDCA 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 final rule
has been exempted from review under
Executive Order 12866, this final rule is
not subject to Executive Order 13211,
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 final rule does not contain any
information collections subject to OMB
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14:03 Dec 09, 2008
Jkt 217001
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 section 408(d) of FFDCA, 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 final rule 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 section 408(n)(4) of FFDCA. 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 final rule. In addition, this final
rule does not impose any enforceable
duty or contain any unfunded mandate
as described under Title II of the
Unfunded Mandates Reform Act of 1995
(UMRA) (Public Law 104–4).
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 of 1995
(NTTAA), Public Law 104–113, section
12(d) (15 U.S.C. 272 note).
VII. Congressional Review Act
The Congressional Review Act, 5
U.S.C. 801 et seq., generally provides
that before a rule may take effect, the
agency promulgating the rule must
submit a rule report to each House of
the Congress and to the Comptroller
General of the United States. 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
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74977
publication of this final rule in the
Federal Register. This final rule 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: December 2, 2008.
Donald R. Stubbs,
Acting Director, Registration Division, Office
of Pesticide Programs.
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. Section 180.509 is revised to read
as follows:
■
§ 180.509 Mefenpyr-diethyl; tolerance for
residues.
(a) General. Tolerances are
established for residues of the herbicide
safener, mefenpyr-diethyl, 1-(2,4dichlorophenyl)-4,5-dihydro-5-methyl1H-pyrazole-3,5-dicarboxylic acid,
diethyl ester and its 2,4-dichlorophenylpyrazoline metabolites, when applied at
a rate no greater than 0.053 pound
safener per acre per growing season in
or on the following raw agricultural
commodities:
Commodity
Barley, grain .........................
Barley, hay ............................
Barley, straw .........................
Canola, seed ........................
Cattle, meat byproducts .......
Goat, meat byproducts .........
Hog, meat byproducts ..........
Horse, meat byproducts .......
Sheep, meat byproducts ......
Wheat, forage .......................
Wheat, grain .........................
Wheat, hay ...........................
Wheat, straw .........................
Soybean forage ....................
Soybean, hay ........................
Soybean, seed ......................
Parts per million
0.05
0.2
0.5
0.02
0.1
0.1
0.1
0.1
0.1
0.2
0.05
0.2
0.5
0.1
0.1
0.02
(b) Section 18 emergency exemptions.
[Reserved]
(c) Tolerances with regional
registrations. [Reserved]
(d) Indirect or inadvertant residues.
[Reserved]
[FR Doc. E8–29112 Filed 12–9–08; 8:45 am]
BILLING CODE 6560–50–S
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Agencies
[Federal Register Volume 73, Number 238 (Wednesday, December 10, 2008)]
[Rules and Regulations]
[Pages 74972-74977]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-29112]
=======================================================================
-----------------------------------------------------------------------
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2007-0672; FRL-8390-8]
Mefenpyr-diethyl and Metabolites; Pesticide Tolerance
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
-----------------------------------------------------------------------
[[Page 74973]]
SUMMARY: This regulation establishes tolerances for residues of the
herbicide safener, mefenpyr-diethyl (CAS Reg. No. 135590-91-9), also
known as 1-(2,4-dichlorophenyl)-4,5-dihydro-5-methyl-1H-pyrazole-3,5-
dicarboxylic acid, diethyl ester and its 2,4-dichlorophenyl-pyrazoline
metabolites, applied at a rate no greater than 0.053 pounds safener per
acre per growing season, in or on the rotational crop commodities
soybean seed, soybean hay, soybean forage and canola seed. Bayer
CropScience requested these tolerances under the Federal Food, Drug,
and Cosmetic Act (FFDCA).
DATES: This regulation is effective December 10, 2008. Objections and
requests for hearings must be received on or before February 9, 2009,
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: EPA has established a docket for this action under docket
identification (ID) number EPA-HQ-OPP-2007- 0672. All documents in the
docket are listed in the docket index available at https://
www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at https://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.
FOR FURTHER INFORMATION CONTACT: Karen Samek, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 347-8825; e-mail address: samek.karen@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.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.
B. How Can I Access Electronic Copies of this Document?
In addition to accessing electronically available documents at
https://www.regulations.gov, you may access this Federal Register
document electronically through the EPA Internet under the ``Federal
Register'' listings at https://www.epa.gov/fedrgstr. You may also access
a frequently updated electronic version of 40 CFR part 180 through the
Government Printing Office's e-CFR site at https://www.gpoaccess.gov/
ecfr. To access the OPPTS Harmonized Guidelines referenced in this
document, go directly to the guidelines at https://www.epa.gpo/opptsfrs/
home/guidelin.htm.
C. Can I File an Objection or Hearing Request?
Under section 408(g) of 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. The EPA procedural regulations which
govern the submission of objections and requests for hearings appear in
40 CFR part 178. 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-2007-0672 in the subject line on the first page of
your submission. All requests must be in writing, and must be mailed or
delivered to the Hearing Clerk on or before February 9, 2009.
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 that does not contain any CBI for inclusion in the public
docket that is described in ADDRESSES. Information not marked
confidential pursuant to 40 CFR part 2 may be disclosed publicly by EPA
without prior notice. Submit your copies, identified by docket ID
number EPA-HQ-OPP-2007-0672, by one of the following methods:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW., Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.
II. Petition for Tolerance
In the Federal Register of August 22, 2007 (72 FR 47008) (FRL-8145-
1), EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C.
346a, as amended by FQPA (Public Law 104-170), announcing the filing of
a pesticide petition (PP 7E7224) by Bayer CropScience, 2 T.W.,
Alexander Drive, P.O. Box 12014, Research Triangle Park, NC 27709. The
petition requested that 40 CFR 180.509 be amended for the herbicide
safener, mefenpyr-diethyl, 1-(2,4-dichlorophenyl)-4,5-dihydro-5-methyl-
1H-pyrazole-3,5-dicarboxylic acid, diethyl ester and its 2,4-
dichlorophenyl-pyrazoline metabolites by increasing the maximum
allowable seasonal use rate to 0.053 lb safener/acre(A), as well as,
establishing rotation crop tolerances on soybean seed at 0.02 parts per
million (ppm); soybean forage at 0.1ppm; soybean hay at 0.1 ppm; and
canola seed at 0.02 ppm. That notice referenced a summary of the
petition prepared by Bayer CropScience, the registrant, which is
available to the public in the docket, https://www.regulations.gov.
There were no comments received in response to the Notice of Filing.
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
[[Page 74974]]
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 section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of FFDCA, 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 the petitioned-for
tolerances for residues of the herbicide safener, mefenpyr-diethyl, in
or on soybean seed at 0.02 ppm, soybean forage at 0.1 ppm, soybean hay
at 0.1 ppm, and canola seed at 0.02 ppm; as well as the petitioned-for
request to increase the maxium allowable seasonal use rate from 0.026
lb safener/A to 0.053 lb safener/A. EPA's assessment of exposures and
risks associated with establishing tolerances 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.
Mefenpyr-diethyl has low acute toxicity by the oral, dermal, and
inhalation routes of exposure. It is not a dermal irritant but is a
slight dermal sensitizer and ocular irritant. Metabolism studies
indicate that mefenpyr-diethyl is rapidly metabolized, widely
distributed, and primarily excreted via the urine. Repeat exposure via
the dermal route did not induce any treatment-related effects at dose
levels up to and including the limit dose. Repeated exposure studies
via the oral route demonstrated that the target organs are the liver
and hematopoietic system in dogs, mice, and rats. Mefenpyr-diethyl was
negative for carcinogenicity in rats and mice, and classified as ``not
likely to be carcinogenic to humans.'' Mefenpyr-diethyl did not show
any genotoxic potential. Developmental toxicity was not observed in the
rat at the limit dose (1,000 milligrams/kilogram/day (mg/kg/day)) but
was observed in the rabbit (abortions) at the same dose level producing
maternal toxicity. Mefenpyr-diethyl did not induce any signs of
reproductive toxicity or neurotoxic potential. The developmental
toxicity studies in rats and rabbits, as well as the reproductive
toxicity study in rats, did not demonstrate any prenatal or postnatal
sensitivity. There is a lack of evidence of neurotoxicity in any study
on mefenpyr-diethyl and therefore there is no concern for neurotoxicity
resulting from exposure to mefenpyr-diethyl.
B. Toxicological Endpoints
For hazards that have a threshold below which there is no
appreciable risk, a toxicological point of departure (POD) is
identified as the basis for derivation of reference values for risk
assessment. The POD may be defined as the highest dose at which no
adverse effects are observed (the NOAEL) in the toxicology study
identified as appropriate for use in risk assessment. However, if a
NOAEL cannot be determined, the lowest dose at which adverse effects of
concern are identified (the LOAEL) or a Benchmark Dose (BMD) approach
is sometimes used for risk assessment. Uncertainty/safety factors (UFs)
are used in conjunction with the POD to take into account uncertainties
inherent in the extrapolation from laboratory animal data to humans and
in the variations in sensitivity among members of the human population
as well as other unknowns. Safety is assessed for acute and chronic
dietary risks by comparing aggregate food and water exposure to the
pesticide to the acute population adjusted dose (aPAD) and chronic
population adjusted dose (cPAD). The aPAD and cPAD are calculated by
dividing the POD by all applicable UFs. Aggregate short-, intermediate-
, and chronic-term risks are evaluated by comparing food, water, and
residential exposure to the POD to ensure that the margin of exposure
(MOE) called for by the product of all applicable UFs is not exceeded.
This latter value is referred to as the Level of Concern (LOC).
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
greater than that 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/
pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for mefenpyr-diethyl for
human risk assessment is shown in Table 1 of this unit.
Table 1.--Summary of Toxicological Doses and Endpoints for Mefenpyr-diethyl for Use in Dietary and Non-
Occupational Human Health risk Assessments
----------------------------------------------------------------------------------------------------------------
RfD, PAD, Level of
Exposure/Scenario Point of Departure and Concern for Risk Study and Toxicological
Uncertainty Factors Assessment Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary (General population, No hazard was identified in any toxicity study for this duration of
including infants and children) exposure.
----------------------------------------------------------------------------------------------------------------
Acute Dietary (Females 13-49 years of No hazard was identified in any toxicity study for this duration of
age) exposure.
----------------------------------------------------------------------------------------------------------------
Chronic Dietary (All populations) NOAEL = 51 mg/kg/day Chronic RfD = 0.51 mg/ Chronic oral toxicity
UFA = 10x.............. kg/day study (dog).
UFH = 10x.............. cPAD = 0.51 mg/kg/day.. LOAEL = 260 mg/kg/day,
FQPA SF = 1x........... based on increased
liver weight in both
sexes, cholestasis,
and increased alkaline
phosphates.
----------------------------------------------------------------------------------------------------------------
[[Page 74975]]
Cancer Classification: Not likely to be carcinogenic to humans.
----------------------------------------------------------------------------------------------------------------
Point of Departure = A data point or an estimated point that is derived from observed dose-response data and
used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant
human exposures. NOAEL = no observed adverse effect level. LOAEL = lowest observed adverse effect level.
UF=uncertainty factor. UFA = extrapolated from animal to human (interspecies). UFH = potential variation in
sensitivity among members of the human population (intraspecies). PAD = population adjusted dose (a = acute, c
= chronic). RfD = reference dose.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to mefenpyr-diethyl, EPA considered exposure under the
petitioned-for tolerances, as well as all existing mefenpyr-diethyl
tolerances in 40 CFR 180.509. The residue of concern for both risk
assessment and tolerance setting purposes in plants and animals is the
parent compound, mefenpyr-diethyl, and its 2,4-dichlorophenyl-
pyrazoline metabolites. EPA assessed dietary exposures from mefenpyr-
diethyl 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 mefenpyr-diethyl;
therefore, a quantitative acute dietary exposure assessment is
unnecessary.
ii. Chronic exposure. A highly conservative chronic dietary risk
assessment was conducted for food and drinking water for mefenpyr-
diethyl. In conducting the chronic dietary exposure assessment EPA used
the food consumption data from the USDA 1994-1996 and 1998 Continuing
Survey of Food Intake by Individuals. As to residue levels in food, EPA
assumed that 100% of crops with requested uses of mefenpyr-diethyl are
treated and that all treated crops contain residues at the tolerance
level.
No new magnitude of the residue data, reflecting the new proposed
seasonal rate of 0.053 lb safener/A, were submitted for the primary
crop commodities. It is, however, noted that the field trial data that
were previously submitted in support of the petition to establish
tolerances for primary crops were conducted at an exaggerated rate of
0.089 lb/safener/A. Therefore, the Agency has determine that the
established tolerances for primary crop commodities remain adequate to
support the proposed higher application rate.
iii. Cancer. Based on the results of carcinogenicity studies in
rats and mice, EPA classified mefenpyr-diethyl as a ``Not likely to be
carcinogenic to humans;'' therefore, an exposure assessment for
assessing cancer risk is unnecessary for this chemical.
iv. Anticipated residue and percent crop treated (PCT) information.
EPA did not use anticipated residue or PCT information in the dietary
assessment for mefenpyr-diethyl. 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 in the dietary exposure analysis and risk
assessment for mefenpyr-diethyl in drinking water. These simulation
models take into account data on the physical, chemical, and fate/
transport characteristics of mefenpyr-diethyl. Further information
regarding EPA drinking water models used in pesticide exposure
assessment can be found at https://www.epa.gov/oppefed1/models/water/
index.htm.
Based on the First Index Reservoir Screening Tool (FIRST) and
Screening Concentration in Ground Water (SCI-GROW) models, the
estimated drinking water concentrations (EDWCs) of mefenpyr-diethyl and
its transformation products for chronic exposures for non-cancer
assessments are estimated to be 3 parts per billion (ppb) for surface
water and 4 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 4 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). No products
containing mefenpyr-diethyl are available for sale in the residential
market because of the crops specified on the applicable labels. As
such, a residential risk assessment was not conducted.
4. Cumulative effects. Unlike other pesticides for which EPA has
followed a cumulative risk approach based on a common mechanism of
toxicity, EPA has not made a common mechanism of toxicity finding as to
mefenpyr-diethyl and any other substances and mefenpyr-diethyl does not
appear to produce a toxic metabolite produced by other substances. For
the purposes of this tolerance action, therefore, EPA has not assumed
that mefenpyr-diethyl has 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 the policy statements
released by EPA's Office of Pesticide Programs concerning common
mechanism determinations and procedures for cumulating effects from
substances found to have a common mechanism on EPA's website at https://
www.epa.gov/pesticides/cumulative/.
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 data available to EPA support the choice of a different
factor.
2. Prenatal and postnatal sensitivity. The prenatal and postnatal
toxicity database for mefenpyr-diethyl includes rat and rabbit
developmental toxicity studies and a two-generation reproduction
toxicity study in rats. There was no evidence of increased
[[Page 74976]]
susceptibility of in utero rats or rabbits in the prenatal
developmental studies or of young rats in the two-generation
reproduction study.
Developmental toxicity was not observed in the rat at the limit
dose (1,000 mg/kg/day). The only effects observed in the rat
developmental toxicity study were decreased body-weight gain and food
efficiency during the first week of dosing and increased spleen weights
in the maternal animal and a marginal decrease in fetal body weight/
body-weight gain during lactation (postnatal study). In the rabbit
developmental toxicity study, developmental toxicity (abortion) was
observed at the same dose level producing maternal toxicity (250 mg/kg/
day).
In the reproduction study, parental toxicity consisted of decreased
body weight and body-weight gain, and an increase in spleen weight and
in the severity (not incidence) of splenic extramedullary hematopoiesis
in females. In the pups, decreased body weight and body-weight gains
were observed at the same dose levels as the parental animals. The
NOAEL is 82 mg/kg/day (1,000 ppm) for both the parental animal and
offspring.
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF were reduced to 1X. That decision is based on the following
findings:
i. The toxicity database for mefenpyr-diethyl is complete, with the
exception of immunotoxicity studies which are new data requirements
under the revised Part 158 Toxicology Data Requirements (40 CFR part
158). In the absence of these studies, EPA has evaluated the available
toxicity data for mefenpyr-diethyl and determined that an additional
database uncertainty factor is not needed, based on the following
conclusions:
No acute and subchronic Neurotoxcity studies are available, however
there is no evidence of neurotoxicity in the toxicology database on
mefenpyr-diethyl, which includes subchronic, chronic, developmental
toxicity, and reproduction studies performed at dose of 250 mg/kg/day
and above. Therefore, based on the above considerations, the Agency
does not believe that conducting acute and subchronic neurotoxicity
studies will result in a NOAEL less than the NOAEL of 51 mg/kg/day
already set for mefenpyr-diethyl; therefore additional neurotoxicity
studies are not necessary and the 10x safety factor can be reduced to
1x.
Considering that the application of mefenpyr-diethyl will be by
either aerial application or spray boom equipment, the 28-day
inhalation study is required as confirmatory data. However, the
additional uncertainty factor for database uncertainties does not need
to be applied since the MOE is >1,000 and significant inhalation
exposures of concern are not anticipated.
EPA considered the entire toxicity database for mefenpyr-diethyl
for potential adverse effects on the thymus and spleen as indications
of potential immunotoxicity and noted enlarged spleens; more severe
hematopoiesis and hemosiderin deposits and increased spleen weights
were observed in mice at doses greater than the limit dose. However,
these were determined to be non-specific changes not indicative of
immunotoxicity. Therefore, based on the above considerations, EPA does
not believe that conducting a special series (Harmonized Guideline
870.7800), immunotoxicity study will result in a NOAEL less than the
NOAEL of 51 mg/kg/day already set for mefenpyr-diethyl and an
additional uncertainty factor for database uncertainties does not need
to be applied.
ii. There is no indication that mefenpyr-diethyl 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 mefenpyr-diethyl results in
increased susceptibility in in utero rats or rabbits in the prenatal
developmental studies or in young rats in the two-generation
reproduction study.
iv. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed
assuming 100 PCT and tolerance-level residues. EPA made conservative
(protective) assumptions in the ground and surface water modeling used
to assess exposure to mefenpyr-diethyl in drinking water. These
assessments will not underestimate the exposure and risks posed by
mefenpyr-diethyl.
E. Aggregate Risks and Determination of Safety
EPA determines whether acute and chronic pesticide exposures are
safe by comparing aggregate exposure estimates to the aPAD and cPAD.
The aPAD and cPAD represent the highest safe exposures, taking into
account all appropriate SFs. EPA calculates the aPAD and cPAD by
dividing the POD by all applicable UFs. For linear cancer risks, EPA
calculates the probability of additional cancer cases 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 POD to ensure that the MOE called for
by the product of all applicable UFs is not exceeded.
1. Acute risk. An acute aggregate risk assessment takes into
account exposure estimates from acute dietary consumption of food and
drinking water. No adverse effect resulting from a single oral exposure
was identified in the toxicology studies for mefenpyr-diethyl and no
acute dietary endpoint was selected. Therefore, mefenpyr-diethyl is not
expected to pose an acute risk.
2. Chronic risk. Exposure to mefenpyr-diethyl food and drinking
water results in an estimated risk equivalent to <1% of the cPAD for
the general population and all regulated subpopulations, including
infants and children as well.
There are no residential uses for mefenpyr-diethyl, therefore the
aggregate risk assessments include the contribution of risk from
dietary (food and water) sources only.
3. Aggregate cancer risk for U.S. population. Mefenpyr-diethyl was
negative for carcinogenicity in rats and mice and thus is not expected
to pose a cancer risk to humans.
4. 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 mefenpyr-diethyl residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
An enforcement method for plants entitled ``An Analytical Method
for Determination of Residues of AE F107892 (mefenpyr-diethyl) and its
Metabolites in Wheat and Barley by Gas Chromatography using Mass
Selective Detection (Report Supplement to EPA MRID 45457401)'' is
available. Radiovalidation and independent laboratory validation (ILV)
data have been submitted for the plant method. The Agency analytical
lab has concluded that this method is suitable for food tolerance
enforcement of mefenpyr-diethyl and its 2,4-dichlorophenyl-pyrazoline
metabolites. 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; e-mail address:
residuemethods@epa.gov.
[[Page 74977]]
B. International Tolerances
No Codex, Canadian, or Mexican maximum residue limits are
established for residues of mefenpyr-diethyl and its metabolites in
crop or livestock commodities; therefore, there are no issues with
international harmonization raised by this action.
V. Conclusions
Therefore, 40 CFR 180.509 is amended for the herbicide safener,
mefenpyr-diethyl, 1-(2,4-dichlorophenyl)-4,5-dihydro-5-methyl-1H-
pyrazole-3,5-dicarboxylic acid, diethyl ester and its 2,4-
dichlorophenyl-pyrazoline metabolites by increasing the maximum
allowable seasonal use rate to 0.053 lb safener/A, as well as rotation
crop tolerances are established for residues of the herbicide safener,
mefenpyr-diethyl, 1-(2,4-dichlorophenyl)-4,5-dihydro-5-methyl-1H-
pyrazole-3,5-dicarboxylic acid, diethyl ester and its 2,4-
dichlorophenyl-pyrazoline metabolites in or on soybean seed at 0.02
ppm; soybean forage at 0.1 ppm; soybean hay at 0.1 ppm; and canola seed
at 0.02 ppm.
It should be noted that no new magnitude of the residue data,
reflecting the new proposed seasonal rate of 0.053 lb safener/A, were
submitted for the primary crop commodities. However, field trail data
that were previously submitted in support of the petition to establish
tolerances for primary crops were conducted at an exaggerated rate of
0.089 lb safener/A. Therefore, the Agency determined that the
established tolerances for primary crop commodities remain adequate to
support the proposed higher application rate.
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances under section 408(d) of
FFDCA 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 final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, 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 final rule 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 section 408(d) of FFDCA, 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 final rule 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 section 408(n)(4) of FFDCA. 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 final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Public Law 104-4).
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 of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
note).
VII. Congressional Review Act
The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. 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 this final rule in the Federal
Register. This final rule 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: December 2, 2008.
Donald R. Stubbs,
Acting Director, Registration Division, Office of Pesticide Programs.
0
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. Section 180.509 is revised to read as follows:
Sec. 180.509 Mefenpyr-diethyl; tolerance for residues.
(a) General. Tolerances are established for residues of the
herbicide safener, mefenpyr-diethyl, 1-(2,4-dichlorophenyl)-4,5-
dihydro-5-methyl-1H-pyrazole-3,5-dicarboxylic acid, diethyl ester and
its 2,4-dichlorophenyl-pyrazoline metabolites, when applied at a rate
no greater than 0.053 pound safener per acre per growing season in or
on the following raw agricultural commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
Barley, grain........................................... 0.05
Barley, hay............................................. 0.2
Barley, straw........................................... 0.5
Canola, seed............................................ 0.02
Cattle, meat byproducts................................. 0.1
Goat, meat byproducts................................... 0.1
Hog, meat byproducts.................................... 0.1
Horse, meat byproducts.................................. 0.1
Sheep, meat byproducts.................................. 0.1
Wheat, forage........................................... 0.2
Wheat, grain............................................ 0.05
Wheat, hay.............................................. 0.2
Wheat, straw............................................ 0.5
Soybean forage.......................................... 0.1
Soybean, hay............................................ 0.1
Soybean, seed........................................... 0.02
------------------------------------------------------------------------
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertant residues. [Reserved]
[FR Doc. E8-29112 Filed 12-9-08; 8:45 am]
BILLING CODE 6560-50-S