[Federal Register Volume 79, Number 43 (Wednesday, March 5, 2014)]
[Rules and Regulations]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-04862]
ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
Triflumizole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
SUMMARY: This regulation establishes tolerances for residues of
triflumizole in or on multiple commodities which are identified and
discussed later in this document. Interregional Research Project Number
4 (IR-4) requested these tolerances under the Federal Food, Drug, and
Cosmetic Act (FFDCA).
DATES: This regulation is effective March 5, 2014. Objections and
requests for hearings must be received on or before May 5, 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-2012-0949, 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), EPA West 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: Lois Rossi, Registration Division
(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].
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.
C. How can I file an objection or hearing request?
Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2012-0949 in the subject line on
the first page of your submission. All objections and requests for a
hearing must be in writing, and must be received by the Hearing Clerk
on or before May 5, 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-2012-0949, 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
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.html.
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 February 15, 2013 (78 FR 11126) (FRL-
9378-4), EPA issued a document pursuant to FFDCA section 408(d)(3), 21
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP
2E8119) by IR-4, 500 College Road East, Suite 201W., Princeton, NJ
08540. The petition requested that 40 CFR 180.476 be amended by
establishing tolerances for residues of the fungicide triflumizole, 1-
imidazole, in or on berry, low growing, subgroup 13-07G at 2.0 parts
per million (ppm); fruit, pome, group 11-10 at 0.5 ppm; fruit, small,
vine climbing, except fuzzy kiwifruit, subgroup 13-07F at 2.5 ppm; and
tomato at 1.5 ppm. That document referenced a summary of the petition
prepared by Chemtura, the registrant, which is available in the docket,
http://www.regulations.gov. A comment was received on the notice of
filing. EPA's response to these comments is discussed in Unit IV.C.
In the Federal Register of October 25, 2013 (78 FR 63938) (FRL-
9901-96), EPA issued a document pursuant to FFDCA section 408(d)(3), 21
U.S.C. 346a(d)(3), which amended the notice of filing published on
February 15, 2013, for the pesticide petition (PP 2E8119) submitted by
IR-4, 500 College Road East, Suite 201W., Princeton, NJ 08540. The
modified petition requested that 40 CFR 180.476 be amended by
establishing tolerances for residues of the fungicide triflumizole, 1-
imidazole, in or on berry, low growing, subgroup, 13-07G at 2.0 ppm;
fruit, pome, group 11-10 at 0.5 ppm; fruit, small, vine climbing,
except fuzzy kiwifruit, subgroup 13-07F at 2.5 ppm; and tomato at 1.5
ppm. The petition also requested that EPA amend the existing tolerance
by modifying the vegetable, cucurbit, group 9 tolerance from 0.5 ppm to
0.8 ppm and, upon approval of the tolerances stated in this paragraph,
by removing established tolerances for apple at 0.5 ppm; grape at 2.5
ppm; pear at 0.5 ppm; and strawberry at 2.0 ppm.
Based upon review of the data supporting the petition summarized in
the Notices of Filing, EPA has modified the tolerance level needed for
the cucurbit vegetable group 9. The reason for this change is explained
in Unit IV.D.
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
Consistent with FFDCA section 408(b)(2)(D), and the factors
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for triflumizole including exposure
resulting from the tolerances established by this action. EPA's
assessment of exposures and risks associated with triflumizole 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
The liver is the primary target organ of triflumizole. Liver
effects were seen in rat and mouse subchronic and chronic/
carcinogenicity studies. Subchronic effects included increased absolute
and relative liver weights, accumulation of fat droplets, and slight
hepatocyte centrilobular swelling. With increased length of exposure,
the types of microscopic lesions noted increased in number and
severity. Chronic effects included hepatocyte fatty vacuolization;
hepatocyte hypertrophy, focal inflammation, and necrosis; fatty
degeneration; eosinophilic foci of hepatocyte alteration; hepatic
nodules; bile duct hyperplasia; and hyaline degeneration/fibrosis of
the bile duct. The dog was less sensitive to the effects of
triflumizole. In the dog chronic study, effects included increased
liver weights, increased serum alkaline phosphatase levels, and a
macroscopic hepatic lobular pattern and granular texture. A very mild,
macrocytic anemia was also noted and was most likely secondary to liver
Triflumizole is classified as not likely to be carcinogenic to
humans, based on a weight of evidence determination including the lack
of evidence of carcinogenicity in studies in rats and mice and the
absence of a mutagenicity concern.
The oral rat developmental study showed an increased qualitative
susceptibility of the fetus to triflumizole in utero. Decreased numbers
of viable fetuses, increased dead or resorbed fetuses, increased
numbers of late resorptions, decreased fetal body weight and increased
incidences of cervical ribs was seen in the fetuses at the same doses
at which maternal toxic effects were noted. In addition, increased
incidences of 14th rudimentary ribs were observed at the next highest
Maternal toxic effects in the rat were decreased body weight gain and
decreased food consumption, increased placental weight, and increased
maternal spleen and liver weights.
No increased susceptibility of the fetus was noted in utero in the
rabbit developmental study. Fetal effects included increased fetal and
litter incidences of lumbar ribs and decreased placental weights, which
was also included as a maternal toxic effect. Maternal toxic effects in
the rabbit included decreased body weight gain, decreased food
consumption, and decreased placental weights.
In the 3-generation reproductive toxicity study in the rat,
offspring effects included decreased pup weights, survival indices, and
litter sizes in both F3 litters, reduced litter size in the
F1a litter, increased total-litter mortality in the
F3a litter, and developmental effects in the F1b
and F2b progeny. Reproductive toxicity, manifested as
increased gestation length, was increased in the F0 dams
which were pregnant with F1 offspring. Increased gestation
length can be due to either effect in the dams and/or the offspring,
and this alteration in normal reproductive function can result in
adverse consequences in both dams and offspring. Accordingly, there is
no increased quantitative susceptibility of the fetus. There is
increased qualitative susceptibility in pups; however, a clear no-
observed-adverse-effect-level (NOAEL) for this effect was established
for these effects, and risk assessment endpoints and points of
departures (PODs) were selected which are protective for these effects.
In acute oral toxicity studies in the rat and mouse and an acute
inhalation study in the rat, animals developed neurotoxic signs within
30 to 60 minutes of administration, which resolved within 24 hours in
surviving animals. Signs included ataxia, hypotonia, ventral
positioning, urinary incontinence, decreased respiration and heart
rates, decreased locomotor movement, lacrimation, salivation, ptosis,
and/or rhinorrhea. No treatment-related histopathological effects were
found in surviving animals. In the chronic rat study, convulsions were
observed sporadically in all dosage groups, but the incidences were
significantly higher in the high-dose females. The majority of the
convulsions were noted within the first year. Cholinesterase activity
was also affected during the first year of the study, but not in a
consistent manner. High-dose males had decreased plasma and erythrocyte
cholinesterase activity while high-dose females had decreased plasma
cholinesterase activity only. There were no treatment-related effects
on cholinesterase activity in the brain in either sex at any dose and
no neuropathology was noted. No neurotoxic effects were observed in the
rat subchronic oral toxicity study or the mouse subchronic oral
toxicity and carcinogenicity studies.
The evidence does not support the need for a developmental
neurotoxicity (DNT) study. This conclusion is supported by lack of
neurotoxic signs noted in the rat subchronic study at any dose, and in
the adult or offspring in the developmental and reproductive toxicity
studies in the rat. In an immunotoxicity dietary study in female Bagg
Albino (BALB/c) mice, a significant decrease in the anti-sheep red
blood cells immunoglobulin M (anti-SRBC IgM) response was observed at a
dose level of 285.7 milligrams/kilograms/day (mg/kg/day). The NOAEL was
28.6 mg/kg/day. The results of the immunotoxicity study do not impact
the PODs selected for dietary and non-dietary exposure risk
Specific information on the studies received and the nature of the
adverse effects caused by triflumizole as well as the NOAEL and the
lowest-observed-adverse-effect-level (LOAEL) from the toxicity studies
can be found at http://www.regulations.gov in the document entitled
``Triflumizole: Human-Health Risk Assessment for the Proposed Uses on
Greenhouse-Grown Tomato and Cucumber; Pome Fruit Group 11-10, Small
Fruit Vine Climbing except Fuzzy Kiwifruit Subgroup 13-07F and Low
Growing Berry Subgroup 13-07G, Except Cranberry'' on pp. 33-36 in
docket ID number EPA-HQ-OPP-2012-0949.
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological PODs and levels of concern (LOCs) to use in
evaluating the risk posed by human exposure to the pesticide. For
hazards that have a threshold below which there is no appreciable risk,
the toxicological POD is used as the basis for derivation of reference
values for risk assessment. PODs are developed based on a careful
analysis of the doses in each toxicological study to determine the dose
at which no adverse effects are observed (the NOAEL) and the lowest
dose at which adverse effects of concern are identified (the LOAEL).
Uncertainty/safety factors (UF) 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 triflumizole used for
human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Triflumizole for Use in Human Health Risk Assessment
Point of departure
Exposure/scenario and uncertainty/ RfD, PAD, LOC for Study and toxicological effects
safety factors risk assessment
Acute dietary (Females 13-50 NOAEL = 10 mg/kg/day Acute RfD = 0.1 mg/ Developmental Toxicity Study--Rat.
years of age). UFA = 10x........... kg/day. Developmental LOAEL = 35 mg/kg/day
UFH = 10x........... aPAD = 0.1 mg/kg/ based on decreased numbers of
FQPA SF = 1x........ day. viable fetuses, increased dead or
resorbed fetuses, increased
numbers of late resorptions,
decreased fetal body weight, and
increased incidences of cervical
Acute dietary (General population NOAEL = 25 mg/kg/day Acute RfD = 0.25 mg/ Acute Neurotoxicity Study--Rat.
including infants and children). UFA = 10x........... kg/day. LOAEL = 100 mg/kg/day based on FOB
UFH = 10x........... aPAD = 0.25 mg/kg/ findings (neuromuscular
FQPA SF = 1x........ day. impairment) and decreased
Chronic dietary (All populations) LOAEL = 3.5 mg/kg/ Chronic RfD = 0.012 Combined Chronic.
day mg/kg/day. Toxicity/Carcinogenicity Study--
UFA = 10x........... cPAD = 0.012 mg/kg/ Rat.
UFH = 10x........... day. Based on liver toxicity
FQPA SF = 3x UFL.... (eosinophilic foci in male rats
and fatty vacuolation and
inflammation and necrosis in
Dermal short-term (1 to 30 days). Dermal (or oral) LOC for MOE = 100.. Multi-generation Reproduction
study NOAEL = 3.5 Study--Rat.
mg/kg/day (dermal LOAEL = 8.5 mg/kg/day based on
absorption rate = decreased pup body weight,
3.5%. mortality, reduced litter size,
UFA = 10x........... and increased incidence of
UFH = 10x........... hydroureter and space between the
FQPA SF = 1x........ body wall and organs were
observed at 8.5 mg/kg/day. In
addition, gestation length was
increased in the dams of F1a,
F2a, and F3a intervals at the
LOAEL of 8.5 mg/kg/day.
Inhalation short-term (1 to 30 Oral study NOAEL = LOC for MOE = 100.. Multi-generation Reproduction
days). 3.5 mg/kg/day. Study--Rat.
UFA = 10x........... LOAEL = 8.5 mg/kg/day based on
UFH = 10x........... decreased pup body weight,
FQPA SF = 1x........ mortality, reduced litter size,
and increased incidence of
hydroureter and space between the
body wall and organs were
observed at 8.5 mg/kg/day. In
addition, gestation length was
increased in the dams of F1a,
F2a, and F3a intervals at the
LOAEL of 8.5 mg/kg/day.
Cancer (Oral, dermal, inhalation) Classification: ``Not likely to be Carcinogenic to Humans'' based a weight of
evidence determination including the lack of evidence of carcinogenicity in
studies in rats and mice and the absence of a mutagenicity concern.
FOB = functional observational battery. FQPA SF = Food Quality Protection Act Safety Factor.
LOAEL = lowest-observed-adverse-effect-level. LOC = level of concern. mg/kg/day = milligram/kilogram/day. MOE =
margin of exposure. NOAEL = no-observed-adverse-effect-level. PAD = population adjusted dose (a = acute, c =
chronic). 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).
UFL = use of a LOAEL to extrapolate a NOAEL.
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to triflumizole, EPA considered exposure under the petitioned-
for tolerances as well as all existing triflumizole tolerances in 40
CFR 180.476. EPA assessed dietary exposures from triflumizole in food
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. Such effects were identified
for triflumizole and as noted in Table 1of this unit, separate acute
endpoints and PODs were selected for females of child-bearing age (13-
49) and the general population including infants and children. In
estimating acute dietary exposure, EPA used food consumption
information from the United States Department of Agriculture's (USDA's)
National Health and Nutrition Examination Survey, What We Eat in
America (NHANES/WWEIA). A conservative acute dietary assessment was
conducted using tolerance-level residues, and 100 percent crop treated
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the food consumption data from the USDA's NHANES/
WWEIA. As to residue levels in food, a partially refined chronic
dietary assessment was conducted using average residues from supervised
field trials, and PCT estimates for currently registered commodities.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has
concluded that triflumizole does not pose a cancer risk to humans.
Therefore, a dietary exposure assessment for the purpose of assessing
cancer risk is unnecessary.
iv. Anticipated residue and PCT information. Section 408(b)(2)(E)
of FFDCA authorizes EPA to use available data and information on the
anticipated residue levels of pesticide residues in food and the actual
levels of pesticide residues that have been measured in food. If EPA
relies on such information, EPA must require pursuant to FFDCA section
408(f)(1) that data be provided 5 years after the tolerance is
established, modified, or left in effect, demonstrating that the levels
in food are not above the levels anticipated. For the present action,
EPA will issue such data call-ins as are required by FFDCA section
408(b)(2)(E) and authorized under FFDCA section 408(f)(1). Data will be
required to be submitted no later than 5 years from the date of
issuance of these tolerances.
Section 408(b)(2)(F) of FFDCA 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 FFDCA section 408(b)(2)(F), EPA may require
registrants to submit data on PCT.
The Agency estimated the PCT for existing uses as follows:
Apple: 25%; cantaloupe: 10%; cherry: 25%; cucumber: 2.5%; filbert:
5%; grape: 5%; honeydew: 15%; pear: 45%; pumpkin: 5%; squash: 5%;
strawberry: 25%; and watermelon: 5%.
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 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 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 triflumizole may be applied in a particular area.
2. Dietary exposure from drinking water. The Agency used screening
level water exposure models in the dietary exposure analysis and risk
assessment for triflumizole in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of triflumizole. 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 Pesticide Root Zone Model/Exposure Analysis Modeling
System (PRZM/EXAMS) and Screening Concentration in Ground Water (SCI-
GROW) models, the estimated drinking water concentrations (EDWCs) of
triflumizole for acute exposures are estimated to be 98 parts per
billion (ppb) for surface water and 3.1 ppb for ground water and for
chronic exposures are estimated to be 22 ppb for surface water and 3.1
ppb for ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. For acute dietary risk
assessment, the water concentration value of 98 ppb was used to assess
the contribution to drinking water. For chronic dietary risk
assessment, the water concentration of value 22 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).
Triflumizole is currently registered for the following uses that
could result in residential exposures: As a foliar spray by home owner
and commercial applicators to landscape grown trees, shrubs, and vines
and also for use on residential/non-commercially grown trees/vines
bearing apples, pears and grapes.
EPA assessed residential exposure using the following assumptions:
For residential handlers, short-term dermal and inhalation exposures
are expected for triflumizole activities associated with use on
ornamental plants and bearing pome fruit trees. The dermal and
inhalation endpoints are based on the same toxicological effect for
triflumizole, and therefore the MOEs were combined to determine a total
risk estimates. For post-application, there is the potential for short-
term dermal exposure for adults and children (6-11 years old), exposed
as a result of being in an environment that has been previously treated
with triflumizole on landscape ornamentals. Post-application exposure
from triflumizole use on landscape ornamentals for children (1-2 years)
is expected to be negligible based on the following factors:
Children young enough to exhibit hand-to-mouth behavior
would not typically play in ornamental beds or tree plots.
If present, leaf to skin residue transfer would be
negligible because of the minimal frequency and duration of contact.
The residential handler exposure for adults from the back pack
sprayer broadcast use of triflumizole to gardens and trees represents
the highest estimated risk, and was therefore combined with the chronic
dietary exposure for adults (general U.S. population), to estimate the
highest aggregate exposure and risk.
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.''
EPA has not found triflumizole to share a common mechanism of
toxicity with any other substances, and triflumizole does not appear to
produce a toxic metabolite produced by other substances. For the
purposes of this tolerance action, therefore, EPA has assumed that
triflumizole does not have a common mechanism of toxicity with other
substances. For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see EPA's Web site at http://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 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. There is evidence of
increased qualitative susceptibility following in utero exposure to
rats in a developmental study. Developmental toxicity resulted in fetal
death as compared to maternal toxicity which included decreases in body
weight gain and food consumption and increases in placental, spleen,
and liver weights.
No quantitative or qualitative evidence of increased susceptibility
was seen following in utero exposure to rabbits in a developmental
study. In the developmental rabbit study, a cesarean section was
performed with evaluation of 24-hour fetal survival. At this interval,
fetal survival was decreased. EPA does not consider this finding to
indicate an adverse effect because a cesarean section with 24-hour
fetal survival is more an indicator of fetal endurance after being
removed from the womb than a measurement of treatment-related effects
on fetal viability and, thus, is not appropriate to use to ascertain
fetal susceptibility. For similar reasons, such an endpoint survival is
not a standard measurement in the guideline developmental toxicity
protocols. In addition, the decreased 24-hour fetal survival occurred
in isolation and only at a high dose level (100 mg/kg/day) which is 10-
fold higher than the NOAEL of 10 mg/kg/day selected for the acute
dietary (females 13-49 years of age) exposure scenario for which this
endpoint might be pertinent. Further, the 24-hour fetal survival was
not replicated in a second developmental rabbit guideline study.
Evidence of increased qualitative susceptibility in pups was
evident in the 3-generation reproductive toxicity study in the rat;
however, the use of the NOAEL of 3.5 mg/kg/day (offspring and
reproductive effects) for incidental oral scenarios and short-term
dermal and inhalation scenarios is protective of potential toxicity
(observed in the developmental and 2-generation reproductive toxicity
studies) following pre- and postnatal exposures.
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF for the acute risk assessment, and short-term dermal and
inhalation exposure scenarios is removed (1X), and for chronic risk
assessment is reduced to 3X. A 3X FQPA SF is retained for the chronic
RfD because it is derived from the use of a LOAEL established in the
combined chronic toxicity/carcinogenicity study in rats. A 3X rather
than a 10X is adequate for the FQPA SF for the reasons provided below:
For this chemical, the liver is the most sensitive target
organ and the histopathological lesions seen in the target organ is
used as the endpoint of concern.
The Agency is confident that the extrapolated NOAEL of 1.2
mg/kg/day (LOAEL of 3.5 mg/kg/day / 3 UFL (use of a LOAEL to
extrapolate a NOAEL) = 1.2 mg/kg/day) would be protective of liver
effects in this species because the observed liver effects were minimal
in severity and did not progress into malignancy (i.e., no liver tumors
were seen) even after 2 years of treatment in either sex of rats.
Retention of the 3X UFL results in an
extrapolated NOAEL of 1.2 mg/kg/day (LOAEL 3.5 mg/kg/day / 3
UFL= 1.2 mg/kg/day). This value, at a minimum, is
approximately 10-fold lower than all the NOAELs established in the
database with the other studies as shown in this unit.
The FQPA SF provides adequate protection of infants and children
based on the following findings:
i. The toxicity database for triflumizole is complete. Although no
subchronic inhalation data is available EPA has waived that data
requirement. In determining the need for a subchronic inhalation study,
EPA's weight of evidence decision process included both hazard and
exposure considerations as well as incorporation of a presumed 10X
Database Uncertainty Factor (UFdb) for the lack of this study.
Specifically, with regard to exposure considerations, the Agency's LOC
in the evaluating the need for the subchronic inhalation study is a MOE
of 1,000 for inhalation exposure, which includes the 10X inter-species
extrapolation factor, 10X intra-species variation factor, and the 10X
UFdb. For trifumizole, residential inhalation exposures resulted in
MOEs higher than the LOC of 1,000 when using an oral POD. This
indicates that the lack of an inhalation study does not reduce the
overall confidence in the risk assessment or result in an uncertainty
(i.e., the study will not provide a POD sufficiently low to result in a
risk of concern). Because EPA's decision to waive the subchronic
inhalation study essentially incorporates an additional 10X UFdb (i.e.,
the study was only waived because risks were at least 10X lower than
required by use of the inter- and intraspecies safety factors), a
second additional 10X FQPA SF is not being retained for the protection
of infants and children due to the absence of this study.
ii. Signs of neurotoxicity were seen in the acute oral and
inhalation studies in the rat and mouse. Signs of neurotoxicity
(neuromuscular impairment and decreased locomotor activity) were noted
in the acute neurotoxicity study at mid and high doses. As a result,
the endpoint from this study was used to assess acute dietary risks
from one-day exposures to triflumizole in the diet of the general
population. There were no treatment-related neuropathological findings
observed in either sex in the acute neurotoxicity study. No evidence of
neurotoxicity was seen in the submitted subchronic neurotoxicity study.
Likewise, neuropathological evaluation of study animals in the
subchronic neurotoxicity study did not reveal any treatment-related
histological effects of the central and peripheral nervous systems. A
DNT study is not required based on the lack of neurotoxicity in the rat
subchronic neurotoxicity study, and in the adult or offspring in the
developmental and reproductive toxicity studies in the rat.
iii. As noted in Unit III.D.2., there is evidence of increased
qualitative susceptibility following in utero exposure to rats in a
developmental study and pre- and or postnatal exposure in a 3-
generation reproductive toxicity study in the rat; however, there are
no residual uncertainties, and the use of associated RfDs will be
protective of the pre- and postnatal toxicity following an acute
dietary exposure, and short-term dermal and inhalation exposures.
No quantitative or qualitative evidence of increased susceptibility
was seen following in utero exposure to rabbits in a developmental
iv. There are no residual uncertainties identified in the exposure
databases. The acute dietary food exposure assessment utilizes
tolerance-level residues, Dietary Exsposure Evaluation Model (DEEM
7.81) default processing factors (where available), and 100 PCT
information for all commodities. By using these screening-level
assessments, actual exposures/risks will not be underestimated. The
food exposure assessment utilizes average field trial residues, and
percent crop treated information for established tolerances. Some
empirical processing factors were used in the chronic assessment along
with DEEM 7.81 default processing factors (where available). The
chronic assessment is partially refined; however, since it is based on
reliable, high-end data, it will not underestimate exposure/risk.
EPA made conservative (protective) assumptions in the ground and
surface water modeling used to assess exposure to triflumizole in
drinking water. EPA used similarly conservative assumptions to assess
post-application exposure of children 6-11 years old and expects post
application exposure for children below 6 years to be negligible. These
assessments will not underestimate the exposure and risks posed by
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. Using the exposure assumptions discussed in this
unit for acute exposure, EPA performed separate acute risk assessments
for females 13 to 49 years old and for the general population,
including infants and children, based on different endpoints and aPADs.
For females aged 13-49, acute dietary exposure to triflumizole from
food and water will occupy 66% of the aPAD chosen for that population
subgroup. For the general population and population subgroups other
than females aged 13-49, acute dietary exposure to triflumizole is
greatest for children 1-2 years old. That subgroup will occupy 40% of
the applicable aPAD.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
triflumizole from food and water will utilize 39% of the cPAD for
children 1-2 years old, the population group receiving the greatest
exposure. Based on the explanation in Unit III.C.3., regarding
residential use patterns, chronic residential exposure to residues of
triflumizole is not expected.
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).
Triflumizole is currently registered for uses that could result in
short-term residential exposure, and the Agency has determined that it
is appropriate to aggregate chronic exposure through food and water
with short-term residential exposures to triflumizole.
Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined worst case scenario
(adult handlers) for short-term food, water, and residential exposures
result in an aggregate MOE of 180 and an aggregate MOE of 600 for
children 6-11 years old. Because EPA's LOC for triflumizole is a MOE of
100 or below, these MOEs are not of concern.
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
An intermediate-term adverse effect was identified; however,
triflumizole is not registered for any use patterns that would result
in intermediate-term residential exposure. Intermediate-term risk is
assessed based on intermediate-term residential exposure plus chronic
dietary exposure. Because there is no intermediate-term residential
exposure and chronic dietary exposure has already been assessed under
the appropriately protective cPAD (which is at least as protective as
the POD used to assess intermediate-term risk), no further assessment
of intermediate-term risk is necessary, and EPA relies on the chronic
dietary risk assessment for evaluating intermediate-term risk for
5. Aggregate cancer risk for U.S. population. Based on the lack of
evidence of carcinogenicity in two adequate rodent carcinogenicity
studies, triflumizole 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 triflumizole residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (gas chromatography with nitrogen
phosphorous detector (GC/NPD); Method I in PAM Vol. II) is available to
enforce the tolerance expression.
B. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint United Nations
Food and Agriculture Organization/World Health Organization food
standards program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
The Codex has not established any MRLs for triflumizole.
C. Response to Comments
A comment was received that opposed the establishment of these
tolerances. Part of the comment opposed the manufacturing and selling
of this product due to potential effects on the environment. This is
considered irrelevant because the safety standard for approving
tolerances under FFDCA section 408 focuses on potential harms to human
health and does not permit consideration of effects on the environment.
Another part objected to the proposed tolerances because of the amounts
of pesticides/toxic chemicals already consumed and carried by the
American population. The Agency understands the commenter's concerns
and recognizes that some individuals believe that pesticides should be
banned completely. However, under the existing legal framework provided
by FFDCA section 408 EPA is authorized to establish pesticide
tolerances or exemptions where persons seeking such tolerances or
exemptions have demonstrated that the pesticide meets the safety
standard imposed by that statute.
D. Revisions to Petitioned-For Tolerances
Using the Organization for Economic Co-operation and Development
(OECD) tolerance calculation procedures, it was initially determined
that the existing cucurbit vegetable group 9 tolerance of 0.5 should be
increased to 0.8 ppm. However, if the crop group 9 tolerance
was to be increased to 0.8 ppm, the U.S. tolerance will be higher than
the Canadian MRL of 0.5 ppm. After re-examining the residue data, EPA
is confident that the 0.5 ppm level will be high enough to cover
residues from maximum use under the pesticide registration, and
therefore, in order to remain aligned with Canada, the existing
cucurbit vegetable group 9 tolerance will remain at 0.5 ppm.
Therefore, tolerances are established for residues of triflumizole,
imidazole, in or on berry, low growing, subgroup 13-07G at 2.0 ppm;
fruit, pome, group 11-10 at 0.5 ppm; fruit, small, vine climbing,
except fuzzy kiwifruit, subgroup 13-07F at 2.5 ppm; and. tomato at 1.5
ppm. In addition, due to the establishment of these tolerances, the
existing tolerances for apple, pear, grape, and strawberry are removed
VI. Statutory and Executive Order Reviews
This final rule establishes tolerances under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled ``Regulatory Planning and
Review'' (58 FR 51735, October 4, 1993). Because this 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 FFDCA section 408(d), such as the tolerance in this
final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.), do not apply.
This 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 FFDCA section 408(n)(4). As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled ``Federalism'' (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
``Consultation and Coordination with Indian Tribal Governments'' (65 FR
67249, November 9, 2000) do not apply to this 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
Dated: February 25, 2014.
Director, Registration Division, Office of Pesticide Programs.
Therefore, 40 CFR chapter I is amended as follows:
1. The authority citation for part 180 continues to read as follows:
Authority: 21 U.S.C. 321(q), 346a and 371.
2. In Sec. 180.476:
a. Remove the commodities ``Apple,'' ``Grape,'' ``Pear,'' and
``Strawberry'' from the table in paragraph (a)(1).
b. Add alphabetically the following commodities to the table in
The amendments read as follows:
Sec. 180.476 Triflumizole; tolerances for residues.
(a) * * *
(1) * * *
* * * * *
Berry, low growing, subgroup 13-07G, except cranberry... 2.0
* * * * *
Fruit, pome, group 11-10................................ 0.50
Fruit, small, vine climbing, except fuzzy kiwifruit, 2.5
* * * * *
* * * * *
* * * * *
[FR Doc. 2014-04862 Filed 3-4-14; 8:45 am]
BILLING CODE 6560-50-P