[Federal Register Volume 79, Number 209 (Wednesday, October 29, 2014)]
[Rules and Regulations]
[Pages 64322-64330]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-25732]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2013-0659; FRL-9917-30]
Prallethrin; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of the
insecticide prallethrin, including its metabolites and degradates, in
or on all food commodities from use of prallethrin in food handling
establishments where food and food products are held, processed,
prepared and/or served, or as a wide-area mosquito adulticide at 1.0
part per million (ppm). McLaughlin Gormley King Company requested these
tolerances under the Federal Food, Drug and Cosmetic Act (FFDCA).
DATES: This regulation is effective October 29, 2014. Objections and
requests for hearings must be received on or before December 29, 2014,
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-2013-0659, is available at http://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 http://www.epa.gov/dockets.
FOR FURTHER INFORMATION CONTACT: Daniel J. Rosenblatt, Registration
Division (RD) (7505P), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave. NW., Washington, DC 20460-
0001; 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 http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.
[[Page 64323]]
C. How 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. 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-2013-0659 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
December 29, 2014. 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-2013-0659, by one of
the following methods:
Federal eRulemaking Portal: http://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 http://www.epa.gov/dockets/contacts.htm. Additional
instructions on commenting or visiting the docket, along with more
information about dockets generally, is available at http://www.epa.gov/dockets.
II. Summary of Petitioned-For Tolerance
In the Federal Register of October 25, 2013 (78 FR 63938) (FRL-
9901-96), EPA issued a document pursuant to section 408(d)(3) of FFDCA,
21 U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
2F8090) by McLaughlin Gormley King Company, 8810 Tenth Avenue,
Minneapolis, MN 55427. The petition requested that 40 CFR 180.545 be
amended by establishing a tolerance of 1.0 ppm for residues of the
insecticide prallethrin, including its metabolites and degradates, in
or on all raw agricultural commodities and processed food, and food
products in food handling establishments where food and food products
are held, processed, prepared and/or served, or as a wide-area mosquito
adulticide. That document referenced a summary of the petition prepared
by McLaughlin Gormley King Company, the registrant, which is available
in the docket, http://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 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 prallethrin including
exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with prallethrin
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.
Prallethrin is a member of the pyrethroid class of insecticides.
Pyrethroids have historically been classified into two groups, Type I
and Type II, based upon chemical structure and neurotoxicological
effect. Type I pyrethroids lack an alpha-cyano moiety and induce a
syndrome consisting of aggressive sparring, altered sensitivity to
external stimuli, and fine tremor progressing to whole-body tremor and
prostration in rats. These Type I pyrethroid-specific behaviors are
collectively described as the T-syndrome. Type II pyrethroids contain
an alpha-cyano moiety and produce a syndrome that includes pawing,
burrowing, salivation, and coarse tremors leading to choreoathetosis in
rats. These Type II pyrethroid-specific behaviors are collectively
described as the CS-syndrome (Verschoyle and Aldridge 1980; Lawrence
and Casida 1982). Prallethrin is structurally similar to Type I
pyrethroids. The adverse outcome pathway (AOP) shared by pyrethroids
involves the ability to interact with voltage-gated sodium channels
(VGSCs) in the central and peripheral nervous system, leading to
changes in neuron firing, and ultimately neurotoxicity.
Prallethrin has been evaluated for a variety of toxic effects in
experimental toxicity studies. Neurotoxicity was observed throughout
the database and is the most sensitive endpoint. Effects were seen
across species, sexes, and routes of administration. In the acute rat
neurotoxicity study, decreased exploratory behavior was seen at the
time of peak effect. Reduced motor activity and transient tremors were
also observed in the study. In the subchronic rat neurotoxicity study,
a higher arousal rate was observed in animals at the highest dose
tested. Clinical signs of neurotoxicity were also observed in other
toxicity studies (subchronic and chronic oral studies in dogs,
developmental toxicity studies in the rat and rabbit, 21-day dermal and
28-day inhalation studies in rats). No neurotoxic effects were observed
in rats in the chronic toxicity study.
Effects were also observed in the liver (rats, mice, and dogs),
heart (dogs), and thyroid gland (rats). Some effects were also seen in
the kidney (mice and rats). However, neurotoxicity was the most
sensitive endpoint in the toxicology database, and other effects were
generally seen in the presence of neurotoxicity and/or at higher doses.
Liver effects observed included increased weight, elevated serum
cholesterol and alkaline phosphatase
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activity, centrilobular hepatocyte vacuolation, histiocytic
infiltration, enlarged liver, and perilobular hepatocellular
hypertrophy. In dogs, myocardial fiber degeneration was seen in females
in the subchronic study at the highest dose tested. Heart effects were
also seen in one mid-dose female in the chronic study (hemorrhage and
red discoloration). However, there was no dose response for the
observed heart lesions in the study. Thyroid effects were observed in
rats and consisted of increases in the number of small follicles and
follicular cell hypertrophy and hyperplasia. The thyroid effects were
seen in short-term studies in the presence of liver effects. Kidney
effects observed were increased weights and histopathology.
Developmental and reproduction studies are available for
prallethrin. There was no evidence of increased quantitative or
qualitative susceptibility in any of the studies. In the developmental
studies, no toxic effects were noted in fetuses up to the highest doses
tested. Maternal effects in the studies included tremors, salivation,
exaggerated reflexes, and chromorhinorrhea. In the reproduction study,
decreased pup body weights were seen during the lactation period.
Effects seen in parental animals were decreased body weights and body
weight gains, increased liver weights and microscopic findings in the
liver, kidney, thyroid, and pituitary.
Prallethrin is classified as ``Not Likely to be Carcinogenic to
Humans.'' No tumors were observed in rat and mouse carcinogenicity
studies up to the highest doses tested. In both the rat and mouse
studies, the animals could have tolerated higher dose levels; however,
EPA determined that dose levels were adequate to assess potential
carcinogenicity.
Prallethrin tested negative in the majority of the genotoxicity
studies. It also tested negative in an in vitro chromosomal aberration
study in Chinese Hamster Ovary (CHO K1) cells without metabolic
activation, but tested positive at all doses with metabolic activation.
However, clastogenicity was not clearly dose-related, was seen at
nontoxic and slightly toxic doses, and was not expressed in in vivo
studies and structure-activity comparisons with the other pyrethroids
revealed no correlations with clastogenicity. Other gene mutation,
chromosomal aberration, and unscheduled DNA synthesis (UDS) studies
were negative; therefore, there is no concern for genotoxicity.
Acute lethality studies conducted with prallethrin indicate
moderate acute toxicity via the oral and inhalation routes of
administration (Category II) and low acute toxicity via the dermal
route (Categories IV). It is not irritating to the skin (Category IV)
but is minimally irritating to the eye (Category IV). It is not a
dermal sensitizer. The weight of evidence from the available guideline,
non-guideline, mechanism of action, and pharmacokinetics studies
supports characterizing the toxicological profile of pyrethroids,
including prallethrin, as being rapid in onset and associated with
acute, peak exposures. Also, there is no apparent increase in hazard
from repeated/chronic exposures to prallethrin.
Specific information on the studies received and the nature of the
adverse effects caused by prallethrin 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 in the document
titled ``Prallethrin: Human Health Risk Assessment for the Tolerance
Petition to Amend the Section 3 Mosquito Adulticide Registration to
Include Use of the Insecticide Over All Crops,'' dated September 15,
2014, by going to http://www.regulations.gov. The referenced document
is available in the docket established by this action, which is
described under ADDRESSES. Locate and click on the hyperlink for docket
ID number EPA-HQ-OPP- 2013-0659. Double-click on the document to view
the referenced information.
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 (LOC) to use in evaluating the risk posed by human exposure to
the pesticide. For hazards that have a threshold below which there is
no appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which no adverse effects are observed (the NOAEL)
and the lowest dose at which adverse effects 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 http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for prallethrin used for
human risk assessment are shown in Tables 1 and 2 of this unit. Based
on the proposed use patterns for prallethrin, endpoints and points of
departure were selected for dietary (acute only), dermal, inhalation,
and incidental oral exposures.
For oral exposures (acute dietary and incidental oral), the
endpoint and POD were selected from a chronic dog study in which
neurotoxicity was observed within 4 weeks of dosing and was considered
to have potentially resulted from a single dose, based on a weight-of-
the-evidence. For dermal assessment, the endpoint was selected from the
route-specific 21-day dermal study in the rat, in which clinical signs
were observed within 1 to 3 days of dosing. The endpoints being used to
assess oral and dermal exposures are the same (neurotoxicity);
therefore, risks from those routes of exposure were combined. Although
the LOAEL for inhalation is also based on neurotoxicity, derivation of
the human equivalent concentrations (HECs) used for inhalation risk
assessment shows that assessing inhalation exposure based on the
portal-of-entry effects is protective of the systemic endpoints,
including neurotoxicity. As a result, inhalation exposure was not
combined with either the dermal or the oral routes of exposure.
A chronic dietary risk assessment was not conducted for
prallethrin. Given what is known about pyrethroid toxicokinetics/
dynamics, in general, and as there is no apparent increase in hazard
from repeated/chronic exposures to prallethrin, the acute dietary
exposure assessment is protective of chronic dietary exposures. Based
on the toxicity profile, intermediate- or long-term exposure
assessments were not conducted for adults or children.
[[Page 64325]]
Table 1--Summary of Toxicological Doses and Endpoints for Prallethrin for Use in Dietary and Non-Occupational
Human Health Risk Assessments
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Point of departure
Exposure/scenario and uncertainty/FQPA RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
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Acute Dietary (Children >=6 years NOAEL = 2.5 mg/kg/ Acute RfD = 0.025 Chronic dog study (capsule). LOAEL
old and Adults). day. mg/kg/day. = 5 mg/kg/day based on clinical
UFA = 10x........... aPAD= 0.025 mg/kg/ signs of neurotoxicity.
UFH = 10x........... day..
FQPA SF = 1x........
Acute Dietary (Children <6 years NOAEL = 2.5 mg/kg/ Acute RfD = 0.025
old). day. mg/kg/day.
UFA = 10x........... aPAD= 0.008 mg/kg/
UFH = 10x........... day.
FQPA SF = 3x........
Incidental Oral Short-Term (1 to NOAEL = 2.5 mg/kg/ Residential LOC for
30 days). day. MOE = 300.
UFA = 10x...........
UFH = 10x...........
FQPA SF = 3x........
Dermal Short-term (1 to 30 days) Dermal NOAEL = 30 mg/ Residential LOC for 21-day Dermal Rat. LOAEL = 150 mg/
(Children <6 years old). kg/day. MOE = 300. kg/day based on observed clinical
UFA = 10x........... signs of toxicity (fixation,
UFH = 10x........... abnormal gait, tremors,
FQPA SF = 3x........ sensitivity to external stimuli,
vocalization, twitching and
writhing spasms), all beginning
between days 1 and 3 of a 21-day
dermal study in rats.
Dermal Short-term (1 to 30 days) Dermal NOAEL = 30 mg/ Residential LOC for
(Children >=6 years old and kg/day. MOE = 100.
Adults). UFA = 10x...........
UFH = 10x...........
FQPA SF = 1x........
Inhalation Short-term (1 to 30 Inhalation NOAEL = Residential LOC for 28-Day Inhalation Rat. LOAEL =
days) (Children <6 years old). 0.001 mg/L. MOE = 100. 0.0044 mg/L based on irregular
UFA = 3x............ respiration, decreased
UFH = 10x........... spontaneous activity, salivation,
FQPA SF = 3x........ incontinence, and nasal
HEC/HED calculations discharge.
used for risk
assessment (see
below).
Inhalation Short-term (1 to 30 Inhalation NOAEL = Residential LOC for
days) (Children >=6 years old 0.001 mg/L. MOE = 30.
and Adults). UFA = 3x............
UFH = 10x...........
FQPA SF = 1x........
HEC/HED calculations
used for risk
assessment.
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aPAD = acute population adjusted dose. FQPA SF = FQPA Safety Factor. HEC = human equivalent concentration. HED =
human equivalent dose. LOAEL = lowest observed adverse effect level. LOC = level of concern. MOE = margin of
exposure. NOAEL = no observed adverse effect level. Point of Departure (POD) = 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. RfD = reference dose. UF =
uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in
sensitivity among members of the human population (intraspecies).
Table 2--Summary of Toxicological Doses and Endpoints for Prallethrin for Use in Dietary and Non-Occupational
Human Health Risk Assessments
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Residential HECs HEDs
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Residential HECs and HEDs........ Handler/Outdoor Post- 0.00020 mg/L....... 0.006 mg/kg/day.
application.
Residential LOC for MOE = 100 Indoor Post- 0.00014 mg/L....... N/A.
(Children <6 years old). application without
air ventilation.
Residential LOC for MOE = 30 Indoor Post- Adults: 0.00004 mg/ N/A.
(Children >=6 years old and application with L.
Adults). air ventilation. Children: 0.00003
mg/L..
Bystander........... 0.00002 mg/L....... N/A.
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[[Page 64326]]
Cancer (Oral, dermal, inhalation) Classification: ``Not Likely to be Carcinogenic to Humans.''
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HEC = human equivalent concentration. HED = human equivalent dose. Kg = kilogram. LOC = level of concern. L =
Liter. Mg = milligram. MOE = margin of exposure. N/A = Not applicable.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to prallethrin, EPA considered exposure under the petitioned-
for tolerances as well as all existing prallethrin tolerances in 40 CFR
180.545. Acute and chronic aggregate dietary (food and drinking water)
exposure assessments were conducted using the Dietary Exposure
Evaluation Model software with the Food Commodity Intake Database
(DEEM-FCID) Version 3.16. This software uses 2003-2008 food consumption
data from the U.S. Department of Agriculture's (USDA's) National Health
and Nutrition Examination Survey, What We Eat in America, (NHANES/
WWEIA).
i. Acute exposure. The acute dietary risk assessment is partially
refined, and is based on the assumption that as a result of potential
use in food handling establishments (FHEs), most commodities will have
residues at one-half the limit of quantification (LOQ) of the
analytical method used in the FHE residue trials (0.05 ppm). It was
also based on the assumptions that all flour food forms will contain
residues at the highest level found in the FHE residue trials on flour,
and that tree nuts and peanuts will contain residues at the highest
level found in the FHE residue trials on peanuts. Based on residue
data, the highest residue value (0.0045 ppm) was used for all crops as
a result of treatment from the mosquito adulticide use.
The percent FHE value of 4.65% was applied to the FHE residue
values, and the adulticide residues were incorporated at a level of
100% (i.e., all foods could potentially have residues resulting from
the mosquito adulticide use). Residues from food handling (modified by
the % FHE estimate) and mosquito adulticide treatments were combined.
ii. Chronic exposure. A chronic dietary risk assessment was not
conducted. However, a chronic exposure assessment was conducted to
determine background levels of dietary exposure for estimating
aggregate risk. The exposure estimates are based on the highest residue
value from the FHE residue trials for tree nuts, peanuts, and all flour
food forms; and on the LOQ of the method used in the FHE trials (0.10
ppm). The data were treated in the same manner as the data in the acute
dietary risk assessment, with the exception that the average residue
value from the adulticide trials (0.0007 ppm) was used instead of the
highest residue value (0.0045 ppm).
For the chronic exposure assessment, EPA applied a percent FHE
value of 4.65% to the FHE residue values and assumed 100 percent crop
treated (PCT) for the proposed mosquito adulticide use, just as we have
done for the acute exposure assessment. This value is considered to be
an overestimate of the potential for the mosquito adulticide to drift
onto growing crops. Residues from the FHE and adulticide uses were then
combined. Processing factors were not used because the assumption was
made that foods in an FHE could be treated after processing.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has
concluded that prallethrin 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 percent crop treated (PCT) information.
Section 408(b)(2)(F) of FFDCA states that EPA to states that the Agency
may use data on the actual percent of food treated for assessing
chronic dietary risk only if:
Condition a: The data used are reliable and provide a
valid basis to show what percentage of the food derived from such crop
is likely to contain the pesticide residue.
Condition b: The exposure estimate does not underestimate
exposure for any significant subpopulation group.
Condition c: Data are available on pesticide use and food
consumption in a particular area, the exposure estimate does not
understate exposure for the population in such area. In addition, the
Agency must provide for periodic evaluation of any estimates used. To
provide for the periodic evaluation of the estimate of PCT as required
by section 408(b)(2)(F) of FFDCA, EPA may require registrants to submit
data on PCT.
In most cases, EPA uses available data from United States
Department of Agriculture/National Agricultural Statistics Service
(USDA/NASS), proprietary market surveys, and the National Pesticide Use
Database for the chemical/crop combination for the most recent 6-7
years. EPA uses an average PCT for chronic dietary risk analysis. The
average PCT figure for each existing use is derived by combining
available public and private market survey data for that use, averaging
across all observations, and rounding to the nearest 5%, except for
those situations in which the average PCT is less than one. In those
cases, 1% is used as the average PCT and 2.5% is used as the maximum
PCT. EPA uses a maximum PCT for acute dietary risk analysis. The
maximum PCT figure is the highest observed maximum value reported
within the recent 6 years of available public and private market survey
data for the existing use and rounded up to the nearest multiple of 5%.
The Agency estimates a maximum 4.65% probability that a food a
person consumes contains residues as a result of treatment in an FHE at
some point with any pesticide (i.e., it is not specific to
prallethrin). This value was derived by taking into account the daily
probability of treatment and the percent of expenditures resulting in
potential residues in restaurants, commercial kitchens, food
warehouses, and food processors. For both the acute and chronic
assessments, this value was used for the FHE component of the residue
for all commodities with the exception of drinking water.
The Agency believes that the three conditions discussed in Unit
III.C.1.iv. have been met. With respect to Condition a, PCT estimates
are derived from Federal and private market survey data, which are
reliable and have a valid basis. The Agency is reasonably certain that
the percentage of the food treated is not likely to be an
underestimation. As to Conditions b and c, regional consumption
information and consumption information for significant subpopulations
is taken into account through EPA's computer-based model for evaluating
the exposure of significant subpopulations including
[[Page 64327]]
several regional groups. Use of this consumption information in EPA's
risk assessment process ensures that EPA's exposure estimate does not
understate exposure for any significant subpopulation group and allows
the Agency to be reasonably certain that no regional population is
exposed to residue levels higher than those estimated by the Agency.
Other than the data available through national food consumption
surveys, EPA does not have available reliable information on the
regional consumption of food to which prallethrin may be applied in a
particular area.
Specific information on the methodology to estimate PCT can be
found in the document entitled ``Prallethrin: Upper Bound Estimate of
the Likelihood of Insecticide Residues on Food Resulting from Treatment
in Food Handling Establishments,'' dated September 7, 2014, by going to
http://www.regulations.gov.
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for prallethrin. These simulation models take into account
data on the physical, chemical, and fate/transport characteristics of
prallethrin. Further information regarding EPA drinking water models
used in pesticide exposure assessment can be found at http://www.epa.gov/oppefed1/models/water/index.htm.
Based on the First Index Reservoir Screening Tool (FIRST), Tier II
Pesticide Root Zone Model/Exposure Analysis Modeling System (PRZM/
EXAMS), and the Pesticide Flooded Application Model (PFAM), the surface
water estimated drinking water concentration (EDWC) value of 0.591
parts per billion (ppb) was used in the acute assessment and that the
annual average surface water EDWC value of 0.0375 ppb was used in the
chronic assessment.
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).
Prallethrin is currently registered for the following uses that
could result in residential exposures: A variety of residential pet,
indoor and outdoor uses for pests found on turf, and in homes and
commercial settings, including food handling establishments. However,
for purposes of this assessment, only registered residential products
and use sites with the highest application rates or percent active
ingredient (a.i.) were assessed because they are representative of the
worst case exposure scenarios for the exposed populations.
EPA assessed potential residential handler exposure scenarios
resulting from mixing/loading/applying sprays to lawns using hose-end
and backpack sprayers because exposure from treating lawns were higher
than from other application methods and sites. A quantitative
assessment was not required for handling of total release fogger
products since the labels state that the room/house must be vacated
immediately by the user once initiated.
EPA assessed post-application dermal exposure for adults and
children as well as incidental oral (i.e., hand-to-mouth) exposure for
children resulting from contact with residues deposited on turf and
indoor surfaces following application with aerial and truck-mounted
fogger mosquito vector control applications, hand-held spray
applications on turf and lawn, and indoor aerosol foggers,
respectively. Adult and child post-application inhalation exposure
resulting from both aerial and truck-mounted mosquito vector control
applications were also assessed. A quantitative post-application
inhalation exposure assessment was not performed for turf or indoor
aerosol foggers because inhalation exposure from these application
methods is anticipated to be negligible. Further information regarding
EPA standard assumptions and generic inputs for residential exposures
may be found at http://www.epa.gov/pesticides/trac/science/trac6a05.pdf.
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.''
The Agency has determined that the pyrethroids and pyrethrins share
a common mechanism of toxicity (go to http://www.regulations.gov and
search under document ID number EPA-HQ-OPP-2008-0489-0006). The members
of this group share the ability to interact with voltage-gated sodium
channels ultimately leading to neurotoxicity. The cumulative risk
assessment for the pyrethroids/pyrethrins was published on November 9,
2011, and is available at http://www.regulations.gov under EPA-HQ-OPP-
2011-0746. No cumulative risks of concern were identified, allowing the
Agency to consider new uses for pyrethroids. For information regarding
EPA's efforts to determine which chemicals have a common mechanism of
toxicity, and to evaluate the cumulative effects of this class of
chemicals, see EPA's Web site at http://www.epa.gov/oppsrrd1/reevaluation/pyrethroids-pyrethrins.html.
Prallethrin is included in the pyrethroids/pyrethrins cumulative
risk assessment. No dietary, residential or aggregate risk estimates of
concern have been identified in the single chemical assessment. In the
cumulative assessment, residential exposure was the greatest
contributor to the total exposure. An existing residential turf use for
prallethrin was evaluated to determine the potential contribution it
would have on the cumulative risk assessment. Although the turf use was
considered the main contributor for residential exposure, the turf
assessment indicated that exposure from turf would not impact the
residential component of the cumulative risk estimates for the
pyrethroids.
Therefore, since the proposed mosquito adulticide contributes far
less exposure than the registered turf uses, there will be no impact on
the residential component of the cumulative risk estimates.
Dietary exposures make a minor contribution to the total pyrethroid
exposure. The dietary exposure assessment performed in support of the
pyrethroid cumulative was much more highly refined than that performed
for prallethrin. In addition, for the prallethrin risk assessment, the
most sensitive apical endpoint in the prallethrin database was selected
to derive the POD. Further, the POD selected for prallethrin is
specific to prallethrin, whereas the POD selected for the cumulative
assessment was based on common mechanism of action data that are
appropriate for all 20 pyrethroids included in the cumulative
assessment. Dietary exposure to prallethrin residues resulting from the
proposed mosquito adulticide use over all crops will contribute very
little to the dietary exposure to prallethrin alone; therefore, the
proposed use will make an insignificant contribution to dietary risk to
the pyrethroids as a whole.
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,
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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 Food Quality Protection Act Safety Factor (FQPA 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 prallethrin toxicity
database includes developmental toxicity studies in the rat and rabbit,
and a reproduction study in the rat. No evidence of increased
qualitative or quantitative susceptibility was noted in any of these
studies. This lack of susceptibility is consistent with the results of
guideline developmental and reproduction studies with other pyrethroid
pesticides.
High-dose studies assessing what dose results in lethality to 50%
of the tested population (LD50) in the scientific literature
indicate that pyrethroid exposure can result in increased quantitative
sensitivity in the young, specifically in the form of neurotoxicity.
Examination of pharmacokinetic and pharmacodynamic data indicates that
the sensitivity observed at high doses is related to pyrethroid age-
dependent pharmacokinetics, which is the activity of enzymes associated
with the metabolism of pyrethroids. With otherwise equivalent
administered doses for adults and juveniles, predictive pharmacokinetic
models indicate that the differential adult-juvenile pharmacokinetics
will result in a 3x greater dose at the target organ in juveniles
compared to adults. No evidence of increased quantitative or
qualitative susceptibility was seen in the pyrethroid scientific
literature related to pharmacodynamics (the effect of pyrethroids at
the target tissue) both with regard to interspecies differences between
rats and humans and to differences between juveniles and adults.
Specifically, there are in vitro pharmacodynamic data and in vivo data
indicating similar responses between adult and juvenile rats at low
doses and data indicating that the rat is a conservative model compared
to the human based on species-specific pharmacodynamics of homologous
sodium channel isoforms in rats and humans.
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 3x for infants and children less than 6 years
of age. For the general population, including children greater than 6
years of age, EPA is reducing the FQPA SF to 1x. These decisions are
based on the following findings:
i. The toxicology database for prallethrin is considered complete
with respect to guideline toxicity studies for prallethrin; however,
the Agency lacks additional information to fully characterize the
potential for juvenile sensitivity to the neurotoxic effects of
pyrethroids. In light of the literature studies indicating a
possibility of increased sensitivity in juvenile rats at high doses,
EPA identified a need, and requested proposals for, additional non-
guideline studies to evaluate the potential for sensitivity in juvenile
rats. A group of pyrethroid registrants is currently conducting those
studies. Pending the results of those studies, however, the available
toxicity studies for prallethrin can be used to characterize toxic
effects including potential developmental and reproductive toxicity, as
well as neurotoxicity. Acceptable developmental toxicity studies in
rats and rabbits, reproduction studies in rats, neurotoxicity studies
(acute, subchronic, and developmental) in rats are available. In
addition, route-specific dermal and inhalation toxicity studies are
available. The Immunotoxicity study has been waived. As discussed in
Unit IV.D.2., EPA concludes that the 3x FQPA SF will be adequate for
protecting infants and children less than 6 years old.
ii. After reviewing the extensive body of data and peer-reviewed
literature on pyrethroids, the Agency has reached a number of
conclusions regarding fetal and juvenile sensitivity for pyrethroids,
including the following:
Based on an evaluation of over 70 guideline toxicity
studies for 24 pyrethroids submitted to the Agency, including prenatal
developmental toxicity studies in rats and rabbits, and pre- and
postnatal multi-generation reproduction toxicity studies and DNTs in
rats in support of pyrethroid registrations, there is no evidence that
pyrethroids directly impact developing fetuses. None of the studies
show any indications of fetal toxicity at doses that do not cause
maternal toxicity.
Increased susceptibility was seen in offspring animals in
the DNT study with the pyrethroid zeta-cypermethrin (decreased pup body
weights) and DNT and reproduction studies with another pyrethroid beta-
cyfluthrin (decreased body weights and tremors). However, the
reductions in body weight and the other non-specific effects occur at
higher doses than neurotoxicity, the effect of concern for pyrethroids.
The available developmental and reproduction guideline studies in rats
with zeta-cypermethrin did not show increased sensitivity in the young
to neurotoxic effects. Overall, findings of increased sensitivity in
juvenile animals in pyrethroid studies are rare. Therefore, the
residual concern for the postnatal effects is reduced.
High-dose LD50 studies (studies assessing what
dose results in lethality to 50% of the tested population) in the
scientific literature indicate that pyrethroids can result in increased
quantitative sensitivity to juvenile animals. Examination of
pharmacokinetic and pharmacodynamic data indicates that the sensitivity
observed at high doses is related to pyrethroid age-dependent
pharmacokinetics--the activity of enzymes associated with the
metabolism of pyrethroids. Furthermore, a rat physiologically-based
pharmacokinetic (PBPK) model predicts a 3-fold increase of pyrethroid
concentration in juvenile brain compared to adults at high doses.
In vitro pharmacodynamic data and in vivo data indicate
that adult and juvenile rats have similar responses to pyrethroids at
low doses and therefore juvenile sensitivity is not expected at
relevant environmental exposures. Further, data also show that the rat
is a conservative model compared to the human based on species-specific
pharmacodynamics of homologous sodium channel isoforms.
iii. There are no residual uncertainties with regard to dietary
exposure. The dietary exposure assessments are based on highly
conservative residue levels for the mosquito adulticide use and for the
FHE uses. Furthermore, conservative, upper-bound assumptions were used
to determine exposure through drinking water and residential sources,
such that these exposures have not been underestimated.
Taking all of this information into account, EPA has reduced the
FQPA SF for women of child-bearing age because there is no evidence in
the over 70 guideline toxicity studies submitted to the Agency that
pyrethroids directly impact developing fetuses. In addition, none of
the studies show any indications of fetal toxicity at doses that do not
cause maternal toxicity. Because there remains some uncertainty as to
juvenile sensitivity due to the findings in the high-dose
LD50 studies, EPA is retaining a 3x FQPA SF for infants and
children less than 6 years of age. By age 6, the metabolic system is
expected to be at or near adult levels thus reducing concerns for
potential age-dependent sensitivity related to pharmacokinetics;
therefore for children over 6, a 1x factor
[[Page 64329]]
is appropriate. Although EPA is seeking additional data to further
characterize the potential neurotoxicity for pyrethroids, EPA has
reliable data that show that reducing the FQPA SF to 3x will protect
the safety of infants and children less than 6 years old. These data
include:
a. Data from developmental and reproductive toxicity guideline
studies with prallethrin that show no sensitivity.
b. Data showing that the potential sensitivity at high doses is
likely due to pharmacokinetics.
c. A rat PBPK model predicting a 3-fold increase of pyrethroid
concentration in the juvenile brain compared to adults at high doses
due to age-dependent pharmacokinetics.
d. Data indicating that the rat is a conservative model compared to
the human based on species-specific pharmacodynamics of homologous
sodium channel isoforms.
iv. Although EPA has required additional data on transferable
residues from treated turf for prallethrin, EPA is confident that it
has not underestimated turf exposure due to the conservativeness of the
default turf transfer value and conservative assumptions in the short-
term turf assessment procedures (e.g., assuming residues do not degrade
over the thirty day assessment period and assuming high-end activities
on turf for every day of the assessment period). The additional data on
turf transferable residues have been required in case requirement of
exposure assessments is needed on the future, and to further EPA's
general understanding of the availability of pesticide residues on
turf.
For several reasons, EPA has determined that reliable data show
that a 3x factor is protective of the safety of infants and children
less than 6 years of age. First, it is likely that the extensive
guideline studies with pyrethroids, which indicate that increased
sensitivity in juvenile animals in pyrethroid studies is rare, better
characterize the potential sensitivity of juvenile animals than the
LD50 studies. The high doses that produced juvenile
sensitivity in the literature studies are well above normal dietary or
residential exposure levels of pyrethroids to juveniles and lower
levels of exposure anticipated from dietary and residential uses are
not expected to overwhelm the juvenile's ability to metabolize
pyrethroids, as occurred with the high doses used in the literature
studies. The fact that a greater sensitivity to the neurotoxicity of
pyrethroids is not found in guideline studies following in utero
exposures (based on more than 70 studies for 24 pyrethroids) supports
this conclusion, despite the relatively high doses used in the studies.
Second, in vitro data indicate similar pharmacodynamic response to
pyrethroids between juvenile and adult rats. Finally, as indicated,
pharmacokinetic modeling only predicts a 3x difference between
juveniles and adults. Therefore, the FQPA SF of 3x is protective of
potential juvenile sensitivity.
Specific information about the reevaluation of the FQPA SF for
pyrethroids may be found in document ID number EPA-HQ-OPP-2011-0746-
0011.
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. Acute aggregate risk from exposure to prallethrin
results from exposure to residues in food and drinking water alone. The
acute dietary exposure analysis included both food and drinking water;
therefore, acute aggregate risk estimates are equivalent to the acute
dietary risk estimates. The acute risk estimate for the general U.S.
population is 10% of the aPAD. The population subgroup with the highest
acute dietary risk estimate is children 1-2, which uses 76% of the
aPAD. Acute aggregate risk is not of concern for the general U.S.
population or any other population subgroup.
2. Chronic risk. Using the exposure assumptions described in this
unit, there is no increase in hazard with increasing dose duration;
therefore, the acute aggregate assessment is protective of potential
chronic aggregate exposures.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level). The short-
term aggregate risk assessments resulted in MOEs of 620 for children,
and 1,600 for adult females and the general U.S. population. The adult
and children's MOEs are greater than their respective LOCs of 100 and
300. As a result, the short-term aggregate risk estimates are not of
concern for the general U.S. population or any population subgroup.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level). Because no intermediate-term adverse effect was identified,
prallethrin is not expected to pose an intermediate-term risk.
5. Aggregate cancer risk for U.S. population. Based on the data
summarized in Units III.A. and III.C.1.iii., EPA has concluded that
prallethrin is not expected to pose a cancer risk to humans.
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 prallethrin residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
A method based on gas chromatography with electron capture
detection (GC/ECD), ID #262, is adequate for the enforcement of
tolerances for residues of prallethrin in or on crop commodities. The
reported limits of quantitation (LOQs) are 0.01 to 0.10 ppm, depending
on the commodity. The limits of detection (LODs) were reported to be
0.004 to 0.06 ppm, depending on the commodity. Multiresidue methods
testing for prallethrin have not been conducted, and is not required,
based on previous Agency discussions with the petitioner on November 3,
2010.
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 section
408(b)(4) of FFDCA. The Codex Alimentarius is a joint
[[Page 64330]]
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, section
408(b)(4) of FFDCA requires that EPA explain the reasons for departing
from the Codex level. The Codex has not established a MRL for
prallethrin.
V. Conclusion
Therefore, tolerances are established for residues of the
insecticide prallethrin, including its metabolites and degradates, in
or on all raw agricultural commodities and processed food from use of
prallethrin in food handling establishments where food and food
products are held, processed, prepared and/or served, or as a wide-area
mosquito adulticide at 1.0 part per million (ppm). Compliance with the
tolerance level specified is to be determined by measuring only
prallethrin, 2-methyl-4-oxo-3-(2-propyn-1-yl)-2-cyclopenten-1-yl-2,2-
dimethyl-3-(2-methyl-1-propen-1-yl)cyclopropanecarboxylate.
EPA is revising 40 CFR 180.545 to clarify the tolerance. EPA is
merging paragraphs (a)(1) and (2) together into a new paragraph (a).
EPA is removing paragraphs (a)(3) and (4) as they contain language that
is more appropriately regulated under the Federal Insecticide,
Fungicide, and Rodenticide Act (FIFRA) as use directions on the label.
VI. Statutory and Executive Order Reviews
This action 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, entitled ``Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use'' (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
``Protection of Children from Environmental Health Risks and Safety
Risks'' (62 FR 19885, April 23, 1997). This 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 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 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) (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 of 1995 (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: October 17, 2014.
Daniel J. Rosenblatt,
Acting Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
PART 180--[AMENDED]
0
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
0
2. Revise Sec. 180.545 to read as follows:
Sec. 180.545 Prallethrin; tolerances for residues.
(a) General. Tolerances are established for residues of the
insecticide prallethrin, including its metabolites and degradates, in
or on all raw agricultural commodities and processed food from use of
prallethrin in food handling establishments where food and food
products are held, processed, prepared and/or served, or as a wide-area
mosquito adulticide at 1.0 part per million (ppm). Compliance with the
tolerance level specified is to be determined by measuring only
prallethrin, 2-methyl-4-oxo-3-(2-propyn-1-yl)-2-cyclopenten-1-yl-2,2-
dimethyl-3-(2-methyl-1-propen-1-yl)cyclopropanecarboxylate.
(b) Section 18 emergency exemptions. [Reserved]
(c) Tolerances with regional registrations. [Reserved]
(d) Indirect or inadvertent residues. [Reserved]
[FR Doc. 2014-25732 Filed 10-28-14; 8:45 am]
BILLING CODE 6560-50-P