[Federal Register Volume 78, Number 120 (Friday, June 21, 2013)]
[Rules and Regulations]
[Pages 37468-37474]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2013-14914]
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ENVIRONMENTAL PROTECTION AGENCY
40 CFR Part 180
[EPA-HQ-OPP-2012-0177; FRL-9387-3]
Cyproconazole; Pesticide Tolerances
AGENCY: Environmental Protection Agency (EPA).
ACTION: Final rule.
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SUMMARY: This regulation establishes tolerances for residues of
cyproconazole in or on peanut and peanut, hay. Syngenta Crop
Protection, LLC. requested these tolerances under the Federal Food,
Drug, and Cosmetic Act (FFDCA).
DATES: This regulation is effective June 21, 2013. Objections and
requests for hearings must be received on or before August 20, 2013,
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-2012-0177, 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: Shaunta Hill, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone
number: (703) 347-8961; 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 eCFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl. To access the OCSPP
test guidelines referenced in this document electronically, please go
to http://www.epa.gov/ocspp and select ``Test Methods and Guidelines.''
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-2012-0177 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
August 20, 2013. 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-2012-0177, 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 May 23, 2012 (77 FR 30481) (FRL-9347-8),
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 1F7956)
by Syngenta Crop Protection, LLC., P.O. Box 18300, Greensboro, NC
24719. The petition requested that 40 CFR 180.485 be amended by
establishing tolerances for residues of the fungicide cyproconazole, in
or on peanut, hay at 6.0 parts per million (ppm), and peanut, nutmeat;
peanut, meal; peanut, butter; and peanut, refined oil at 0.03 ppm. That
document referenced a summary of the petition prepared by Syngenta Crop
Protection, the registrant, which is available in the docket, http://www.regulations.gov. There were no substantive comments received in
response to the notice of filing.
Based upon review of the data supporting the petition, EPA has
modified the requested tolerance levels and crops for which tolerances
were needed. The reasons for these changes are explained in Unit IV.C.
III. Aggregate Risk Assessment and Determination of Safety
Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is reliable
information.'' This includes exposure through drinking water and in
residential settings, but does not include occupational exposure.
Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a
[[Page 37469]]
tolerance and to ``ensure that there is a reasonable certainty that no
harm will result to infants and children from aggregate exposure to the
pesticide chemical residue. . . .''
Consistent with FFDCA section 408(b)(2)(D), and the factors
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for cyproconazole including
exposure resulting from the tolerances established by this action.
EPA's assessment of exposures and risks associated with cyproconazole
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.
The acute studies demonstrate that cyproconazole is moderately
toxic by the oral, dermal, and inhalation routes. It is neither an eye
nor dermal irritant. Cyproconazole did not cause dermal sensitization.
Consistent with similar anti-fungal pesticide active ingredients in
this class (e.g., tetraconazole), the critical toxicological effects
for cyproconazole in mammals appear to be indicative of hepatotoxicity.
These effects include elevated levels of the liver enzymes lactate
dehydrogenase (LDH) and aspartate aminotransferase, increased liver
weight (relative and absolute), vacuolization, fatty changes,
hepatocytomegaly, hypertrophy, and single-cell necrosis. For both
subchronic and chronic durations, hepatotoxicity was observed in rats,
mice and dogs, and all of these species appeared to be equally
sensitive to cyproconazole toxicity with regards to the range of the
doses tested (~0.5 to 130 milligrams/kilogram/day (mg/kg/day)). Other
notable effects seen in rat subchronic oral feeding studies included
increased macrophages in the lung, increased white blood cell counts
and globulins, decreased spleen weights, histocytosis of the spleen,
and spleen micropathology.
There are two dermal toxicity studies submitted for cyproconazole,
both showing effects similar to the oral studies. In the 21-day study,
dermal exposure to cyproconazole resulted in decreased body-weight gain
and food consumption (males), increased aspartate aminotransferase
(males), increased creatinine (females), and increased cholesterol in
both sexes at the highest dose tested (1,250 mg/kg/day). In the 28-day
study, toxicity occurred at the mid-dose (100 mg/kg/day). These effects
included increased plasma globulin, protein and cholesterol, and
hemosiderin deposition in the spleen in females (1,000 mg/kg/day in
males), hypertrophy of the thyroid follicular epithelium in both males
and females, and increased incidences of centrilobular hepatocellular
hypertrophy in males (1,000 mg/kg/day in females).
The developmental studies indicate that cyproconazole causes
developmental toxicity. There are two developmental toxicity studies in
rabbits, which were more sensitive for developmental effects than the
rat. In the older study using chinchilla rabbits, the pups showed
increased susceptibility with toxicity occurring at the lowest dose
tested (2 mg/kg/day, the developmental no observed adverse effect level
(NOAEL) was not established). These effects included increased
incidences of hydrocephalus internus (abnormal accumulation of cerebral
spinal fluid in the ventricles of the brain). The maternal lowest
observed adverse effect level (LOAEL) was 10 mg/kg/day. This
developmental toxicity study was classified unacceptable and does not
satisfy the guideline requirement for a developmental toxicity study
(OPPTS Guideline 870.3700; OECD 414) in the rabbit because the
concentrations of test material were not within the acceptable range
(15% of nominal concentration) for the mid- and high-dose
suspensions immediately after preparation. In the most recent study
using New Zealand white rabbits, cyproconazole produced increased
incidences of malformed fetuses and litters with malformed fetuses
(hydrocephalus and kidney agenesis) at doses lower than the doses that
produced maternal toxicity (50 mg/kg/day for dams and 10 mg/kg/day for
fetuses). In rats, cyproconazole increased the incidences of
supernumerary ribs at the same doses at which maternal adverse effects
(decreased body-weight gain) were observed (12 mg/kg/day). There was no
evidence of reproductive toxicity in the 2-generation reproduction
toxicity study. The parental toxicity in the 2-generation reproduction
study was manifested as increased lipid storage and relative liver
weights in males and increased relative liver weights in females (8.29
mg/kg/day). No offspring toxicity was observed at any of the doses
tested.
Although there was evidence of carcinogenicity found in a mouse
study, EPA has determined that cyproconazole is ``not likely to be
carcinogenic to humans'' at doses that do not cause a mitogenic
response in the liver (Ref. 1). In contrast to rodent cells, there are
some limited data to suggest that constitutive androstane receptor
(CAR) activation does not stimulate cell proliferation or inhibit
apoptosis in human cells. However, the literature does not yet support
the conclusion that CAR activation is not biologically plausible in
humans. This conclusion is based on the weight of evidence that
supports a non-genotoxic mitogenic mode of action for cyproconazole.
The activation of the CAR receptor, the required initiating event,
leads to a cascade of key events resulting in liver tumor development
in mice. The data did not support: (1) Peroxisome proliferation, (2)
mutagenesis, or (3) cytotoxicity followed by sustained regenerative
proliferation as alternative modes of action. The quantification of
carcinogenic potential is not required. The current reference dose
(RfD) of 0.01 mg/kg/day is based on a 1-year dog study in which
hepatotoxicity and organ weight changes were seen at 3.2 mg/kg/day and
no adverse effects were observed at 1 mg/kg/day (NOAEL). This RfD would
be protective of any liver effects caused by cyproconazole in the mouse
toxicity studies or mode of action studies at higher doses.
There is no evidence of targeted neurotoxicity in the toxicity
database. There were no central nervous system (CNS) malformations
present in the developmental toxicity studies in rats and rabbits. In a
2-generation reproduction study in rats, there were no findings in pups
that were suggestive of changes in neurological development.
Additionally, there was no evidence of neurotoxicity in other studies.
Finally, there is no evidence that cyproconazole is an
immunotoxicant. Although there is no immunotoxicity study currently
available for cyproconazole, the available data indicate that
cyproconazole does not have immunotoxic effects. This is consistent
with the fact that the target organ is the liver, which is similar to
the other triazole fungicides, which do not have immunotoxic effects.
Specific information on the studies received and the nature of the
adverse effects caused by cyproconazole as well as the NOAEL and the
LOAEL from the toxicity studies can be found at http://www.regulations.gov in document ``Cyproconazole. Tolerance Petition for
[[Page 37470]]
Residues in/on Peanuts, Human-Health Risk Assessment'' in docket ID
number EPA-HQ-OPP-2012-0177.
B. Toxicological Points of Departure/Levels of Concern
Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern to use in evaluating the risk posed by human exposure to the
pesticide. For hazards that have a threshold below which there is no
appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which no adverse effects are observed (the NOAEL)
and the lowest dose at which adverse effects of concern are identified
(the LOAEL). Uncertainty/safety factors are used in conjunction with
the POD to calculate a safe exposure level--generally referred to as a
population-adjusted dose (PAD) or a reference dose (RfD)--and a safe
margin of exposure (MOE). For non-threshold risks, the Agency assumes
that any amount of exposure will lead to some degree of risk. Thus, the
Agency estimates risk in terms of the probability of an occurrence of
the adverse effect expected in a lifetime. For more information on the
general principles EPA uses in risk characterization and a complete
description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for cyproconazole used for
human risk assessment is shown in Table 1 of this unit.
Table 1--Summary of Toxicological Doses and Endpoints for Cyproconazole for Use in Human Health Risk Assessment
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Uncertainty/FQPA RfD, PAD, LOC for Study and
Exposure scenario POD SF risk assessment toxicological effects
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Acute Dietary (General N/A.............. N/A.............. N/A.............. A dose and endpoint
population, including infants attributable to a
and children). single dose were not
identified in the
database including
the developmental
toxicity studies.
Acute Dietary (Females 13-49 NOAEL = 2 mg/kg/ UFA = 10X........ aPAD = aRfD = Prenatal Developmental
years of age). day. UFH = 10X........ 0.02 mg/kg/day. toxicity Study--New
FQPA SF = 1X..... Zealand white rabbits
Developmental LOAEL =
10 mg/kg/day based on
increased incidence
of malformed fetuses
and litters with
malformed fetuses.
Chronic Dietary (All NOAEL = 1.0 mg/kg/ UFA = 10X........ cPAD = cRfD = Chronic oral toxicity
populations). day. UFH = 10X........ 0.01 mg/kg/day. study--dog
FQPA SF = 1X..... LOAEL = 3.2 mg/kg/day
based on liver
effects (P450
induction in females
and histopathology,
laminar eosinophilic
intrahepatocytic
bodies in males).
Short (1-30 days)- and NOAEL = 10 mg/kg/ UFA = 10X........ Residential LOC 28-Day Dermal Study--
Intermediate (1-6 months)-Term day. UFH = 10X........ for MOE = 100. rat
Dermal. FQPA SF = 1X..... LOAEL = 100 mg/kg/day,
based on increased
plasma globulin,
protein and
cholesterol, and
hemosiderin
deposition in the
spleen in females,
and hypertrophy of
the thyroid
follicular epithelium
in both males and
females.
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Cancer (oral, dermal, EPA has classified cyproconazole as ``not likely to be carcinogenic to
inhalation). humans'', according to EPA Proposed Guidelines for Carcinogen Risk Assessment
(April 10, 1996).
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FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
of concern. mg/kg/day = milligrams/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).
C. Exposure Assessment
1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to cyproconazole, EPA considered exposure under the
petitioned-for tolerances as well as all existing cyproconazole
tolerances in 40 CFR 180.485. EPA assessed dietary exposures from
cyproconazole in food as follows:
i. Acute exposure. Quantitative acute dietary exposure and risk
assessments are performed for a food-use pesticide, if a toxicological
study has indicated the possibility of an effect of concern occurring
as a result of a 1-day or single exposure. In conducting the acute
dietary exposure assessment, EPA used the food consumption data from
the U.S. Department of Agriculture's (USDA) National Health and
Nutrition Examination Survey, What We Eat in America, (NHANES/WWEIA).
This dietary survey was conducted from 2003 to 2008. As to residue
levels in food, an unrefined acute dietary exposure and risk analysis
was performed assuming tolerance-level residues, 100% crop treated,
DEEM (ver. 7.81) default processing factors.
ii. Chronic exposure. In conducting the chronic dietary exposure
assessment, EPA used the food consumption data from the USDA's NHANES/
WWEIA. This dietary survey was conducted from 2003 to 2008. An
unrefined chronic dietary exposure and risk analysis was performed
assuming tolerance-level residues, 100% crop treated, DEEM (ver. 7.81)
default processing factors.
iii. Cancer. Based on the data summarized in Unit III.A., EPA has
concluded that cyproconazole 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.
EPA did not use anticipated residue and/or PCT information in the
dietary assessment for cyproconazole. Tolerance-level
[[Page 37471]]
residues and 100% crop treated was assumed for all food commodities.
2. Dietary exposure from drinking water. The Agency used screening-
level water exposure models in the dietary exposure analysis and risk
assessment for cyproconazole in drinking water. These simulation models
take into account data on the physical, chemical, and fate/transport
characteristics of cyproconazole. 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) and
Screening Concentration in Ground Water (SCI-GROW) models, the
estimated drinking water concentrations (EDWCs) of cyproconazole for
acute exposures are estimated to be 113 parts per billion (ppb) for
surface water and 1.52 ppb for ground water. For chronic exposures for
non-cancer assessments are estimated to be 43 ppb for surface water and
1.52 ppb for ground water.
Modeled estimates of drinking water concentrations were directly
entered into the dietary exposure model. Since the EDWC estimates from
surface water were higher than those from ground water, EDWC estimates
in surface water were used in both acute and chronic dietary risk
assessments.
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).
Cyproconazole is not registered for any specific use patterns that
would result in residential handler exposure. Cyproconazole is proposed
for use on golf course turf, which may result in post-application
dermal exposure to golfers (both adults and children). No chemical-
specific data were available to assess potential short-term dermal
post-application exposures to adult and youth golfers. Therefore, a
series of assumptions and exposure factors served as the basis for
completing the residential post-application risk assessment. Each
assumption and factor is detailed in the 2012 Residential SOPs (http://www.epa.gov/pesticides/science/residential-exposure-sop.html). Post-
application oral and inhalation exposures, as well as residential
handler exposures, are not expected based on the current use patterns
for cyproconazole. 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.''
Cyproconazole is a member of the triazole-containing class of
pesticides. Although conazoles act similarly in plants by inhibiting
ergosterol biosynthesis, there is not necessarily a relationship
between their pesticidal activity and their mechanism of toxicity in
mammals. Structural similarities do not constitute a common mechanism
of toxicity. Evidence is needed to establish that the chemicals operate
by the same, or essentially the same, sequence of major biochemical
events (Ref. 2). In conazoles, however, a variable pattern of
toxicological responses is found; some are hepatotoxic and
hepatocarcinogenic in mice. Some induce thyroid tumors in rats. Some
induce developmental, reproductive, and neurological effects in
rodents. Furthermore, the conazoles produce a diverse range of
biochemical events including altered cholesterol levels, stress
responses, and altered DNA methylation. It is not clearly understood
whether these biochemical events are directly connected to their
toxicological outcomes. Thus, there is currently no evidence to
indicate that conazoles share common mechanisms of toxicity and EPA is
not following a cumulative risk approach based on a common mechanism of
toxicity for the conazoles. For information regarding EPA's procedures
for cumulating effects from substances found to have a common mechanism
of toxicity, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.
Cyproconazole is a triazole-derived pesticide. This class of
compounds can form the common metabolite 1,2,4-triazole and two
triazole conjugates (triazolylalanine and triazolylacetic acid). To
support existing tolerances and to establish new tolerances for
triazole-derivative pesticides, including cyproconazole, EPA conducted
a human health risk assessment for exposure to 1,2,4-triazole,
triazolylalanine, and triazolylacetic acid resulting from the use of
all current and pending uses of any triazole-derived fungicide. The
risk assessment is a highly conservative, screening-level evaluation in
terms of hazards associated with common metabolites (e.g., use of a
maximum combination of uncertainty factors) and potential dietary and
non-dietary exposures (i.e., high end estimates of both dietary and
non-dietary exposures). In addition, the Agency retained the additional
10X FQPA Safety Factor for the protection of infants and children. The
assessment includes evaluations of risks for various subgroups,
including those comprised of infants and children. The Agency's
complete risk assessment is found in the propiconazole reregistration
docket at http://www.regulations.gov, docket identification (ID) number
EPA-HQ-OPP-2005-0497.
An updated dietary exposure and risk analysis for the common
triazole metabolites 1,2,4-triazole (T), triazolylalanine (TA),
triazolylacetic acid (TAA), and triazolylpyruvic acid (TP) was
conducted and completed in August 2012, in association with a
registration request for the triazole fungicide, propiconazole. Residue
data demonstrated that there was no increase in exposure to the common
triazole metabolites with the proposed use. The tolerances for
cyproconazole in/on peanuts covered by this action are not expected to
change the risk of exposure to the triazoles determined in that risk
analysis. The document, titled ``Common Triazole Metabolites: Updated
Aggregate Human Health Risk Assessment to Address the Amended
Propiconazole Section 3 Registration to Add Use on Sugarcane'' may be
found in docket ID number EPA-HQ-OPP-2012-0427.
D. Safety Factor for Infants and Children
1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA Safety
Factor (SF). In applying this provision, EPA either retains the default
value of 10X, or uses a different additional safety factor when
reliable data available to EPA support the choice of a different
factor.
2. Prenatal and postnatal sensitivity. There are no residual
uncertainties with regard to prenatal and postnatal toxicity, and the
database is complete for purposes of assessing prenatal and postnatal
toxicity. There is evidence that cyproconazole is a developmental
[[Page 37472]]
toxicant; however, the LOC is low since: (1) The effects in fetuses are
well-characterized with a clear NOAEL and (2) the developmental
toxicity study where increased susceptibility was observed is being
used for the acute dietary endpoint (females 13-49 years), which will
be protective of effects in infants and children. There is no evidence
of reproductive toxicity or neurotoxicity in the cyproconazole
database.
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF were reduced to 1X. That decision is based on the following
findings:
i. The toxicity database for cyproconazole is complete, except for
an immunotoxicity study. As noted in Unit III.A., the concern for the
lack of this study is low because there is no evidence that
cyproconazole causes immunotoxic effects. EPA does not believe that an
immunotoxicity study will result in a lower point of departure (POD)
than that which is currently in use for overall risk assessment. As
such, a database uncertainty factor is not necessary to account for the
lack of an immunotoxicity study.
ii. There is no indication that cyproconazole is a neurotoxic
chemical and there is no need for a developmental neurotoxicity study
or additional UFs to account for neurotoxicity.
iii. While there is evidence that exposure to cyproconazole results
in increased susceptibility in in utero rabbits, EPA does not believe
that the FQPA safety factor of 10X is necessary to protect infants and
children for the reasons stated in Unit III.D.2. above.
iv. There are no residual uncertainties identified in the exposure
databases. EPA made conservative (protective) assumptions in the ground
water and surface water modeling used to assess exposure to
cyproconazole in drinking water. These assessments will not
underestimate the exposure and risks posed by cyproconazole.
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, the acute dietary exposure from food and water
to cyproconazole will occupy 32% of the aPAD for females 13-49 years
old. The acute dietary exposure and risk analysis was conducted only
for females 13-49 years old since an endpoint of concern attributable
to a single dose for the general population was not identified.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
cyproconazole from food and water will utilize 28% of the cPAD for
infants (<1 years old), the population group receiving the greatest
exposure. There are no residential uses for cyproconazole.
3. Short-term risk. Short-term aggregate exposure is calculated by
aggregating short-term residential exposure plus chronic exposure to
food and water (considered to be a background exposure level). A short-
term adverse effect was identified; however, cyproconazole is not
currently registered for any use patterns that would result in short-
term residential exposure. In consideration of a pending turf use for
cyproconazole, a short-term aggregate assessment was completed. The
pending golf course use is the only use that may result in residential
exposure. The golfer exposure (dermal) represents the highest
residential exposure of all potential adult exposure scenarios.
Therefore, the short-term assessment is protective of all potential
exposures resulting from the pending golf course use. For the short-
term aggregate assessment, the short-term oral NOAEL of 1.5 mg/kg/day
(from the 90-day oral rat study) is compared to the total (dietary +
residential) exposure to calculate risk. Since the aggregate MOEs are
greater than 100, the calculated risks do not exceed the Agency's LOCs.
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). There are no residential scenarios that result in intermediate-
term exposure; therefore, an intermediate-term aggregate exposure and
risk assessment is not required.
5. Aggregate cancer risk for U.S. population. Although there was
evidence of carcinogenicity found in a mouse study, EPA has determined
that cyproconazole is ``not likely to be carcinogenic to humans'' at
doses that do not cause a mitogenic response in the liver (Ref. 1). As
a result, an aggregate cancer exposure and risk assessment is not
required, as cyproconazole 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 cyproconazole residues.
IV. Other Considerations
A. Analytical Enforcement Methodology
Adequate enforcement methodology (gas chromatograph/nitrogen-
phosphorus detection) is available to enforce the tolerance expression.
The method may be requested from: Chief, Analytical Chemistry Branch,
Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 20755-5350;
telephone number: (410) 305-2905; email address:
[email protected].
B. International Residue Limits
In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint United Nations
Food and Agriculture Organization/World Health Organization food
standards program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level. The Codex has not
established a MRL for cyproconazole.
C. Revisions to Petitioned-for Tolerances
The Agency is correcting the commodity terminology for peanut by
establishing a tolerance for peanut, rather than peanut, nutmeat. In
addition, the Agency has modified the levels for which tolerances are
being established for peanut (0.03 to 0.01 ppm). Based on an analysis
of the residue data using the OECD tolerance calculation procedures,
the tolerance for peanut is based on the limit of quantitation (0.01
ppm). Following exaggerated-rate applications of cyproconazole, average
residues of
[[Page 37473]]
cyproconazole were below the limit of quantitation in/on peanut, meal,
refined oil, and butter; therefore, processing factors could not be
calculated. Accordingly, separate tolerances for residues of
cyproconazole are not required for peanut, meal, refined oil, and
peanut butter.
Also, EPA has revised the tolerance expression for cyproconazole 40
CFR 180.485 to clarify:
1. That as provided in FFDCA section 408(a)(3), the tolerance
covers metabolites and degradates of cyproconazole.
2. That compliance with the specified tolerance levels is to be
determined by measuring only the specific compounds mentioned in the
tolerance expression.
V. Conclusion
Therefore, tolerances are established for residues of
cyproconazole, in or on peanut and peanut, hay at 0.01 and 6.0 ppm,
respectively.
VI. References
The following is a listing of the documents that are specifically
referenced in this rule.
1. J. Kidwell, et al., December 4, 2007. Cyproconazole: Fourth
Report of the Cancer Assessment Review Committee PC Code: 128993.
2. Environmental Protection Agency. January 14, 2002. Guidance on
Cumulative Risk Assessment of Pesticide Chemicals That Have a Common
Mechanism of Toxicity.
VII. 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).
VIII. 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: June 11, 2013.
Lois Rossi,
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. Section 180.485 is amended as follows:
0
a. Revise paragraph (a)(1) introductory text.
0
b. Add alphabetically the entries ``peanut'' and ``peanut, hay'' to the
table in paragraph (a)(1).
0
c. Revise paragraph (a)(2) introductory text.
0
d. Revise paragraph (a)(3) introductory text.
The amendments read as follows:
Sec. 180.485 Cyproconazole; tolerances for residues.
(a) * * * (1) Tolerances are established for residues of the free
and conjugated forms of the fungicide cyproconazole, including its
metabolites and degradates, in or on the commodities in the table
below. Compliance with the proposed tolerance levels specified below is
to be determined by measuring only cyproconazole ([alpha]-(4-
chlorophenyl)-[alpha]-(1-cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol)
in or on the following commodities:
------------------------------------------------------------------------
Parts per
Commodity million
------------------------------------------------------------------------
* * * * *
Peanut.................................................. 0.01
Peanut, hay............................................. 6.0
* * * * *
------------------------------------------------------------------------
* * * * *
(2) A tolerance is established for the combined residues of the
free and conjugated forms of the fungicide cyproconazole, including its
metabolites and degradates, in or on the commodity in the table below.
Compliance with the tolerance level specified below is to be determined
by measuring only the sum of cyproconazole ([alpha]-(4-chlorophenyl)-
[alpha]-(1-cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol) and its
metabolite [delta]-(4-chlorophenyl)-[beta],[delta]-dihydroxy-[gamma]-
methyl-1H-1,2,4-triazole-1-hexenoic acid, calculated as the
stoichiometric equivalent of cyproconazole, in or on the following
commodity:
* * * * *
[[Page 37474]]
(3) Tolerances are established for the combined residues of the
free and conjugated forms of the fungicide cyproconazole, including its
metabolites and degradates, in or on the commodities in the table
below. Compliance with the tolerance level specified below is to be
determined by measuring only the sum of cyproconazole ([alpha]-(4-
chlorophenyl)-[alpha]-(1-cyclopropylethyl)-1H-1,2,4-triazole-1-ethanol)
and its metabolite 2-(4-chlorophenyl)-3-cyclopropyl-1-[1,2,4]triazol-1-
yl-butane-2,3-diol, calculated as the stoichiometric equivalent of
cyproconazole, in or on the following commodities:
* * * * *
[FR Doc. 2013-14914 Filed 6-20-13; 8:45 am]
BILLING CODE 6560-50-P