[Federal Register Volume 79, Number 38 (Wednesday, February 26, 2014)]
[Rules and Regulations]
[Pages 10670-10678]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-04164]



40 CFR Part 180

[EPA-HQ-OPP-2012-0638; FRL-9906-70]

Fluxapyroxad; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.


SUMMARY: This regulation establishes tolerances for residues of 
fluxapyroxad in or on multiple commodities which are identified and 
discussed later in this document. BASF Corporation requested these 
tolerances under the Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective February 26, 2014. Objections and 
requests for hearings must be received on or before April 28, 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-2012-0638, 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

[[Page 10671]]

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. If OCSPP test 
guidelines are cited, insert the following: 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-2012-0638 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 
April 28, 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-2012-0638, 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.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 December 19, 2012 (77 FR 75082) (FRL-
9372-6), January 16, 2013 (78 FR 3377) (FRL-9375-4), and July 19, 2013 
(78 FR 43115) (FRL-9392-9), EPA issued notices pursuant to FFDCA 
section 408(d)(3), 21 U.S.C. 346a(d)(3), announcing the filing of a 
pesticide petitions (PP 2F8053, PP 2F8058 and PP 3F8161 by BASF 
Corporation, 26 Davis Drive, Research Triangle Park, NC 27709. The 
petitions requested that 40 CFR 180.666 be amended by establishing 
tolerances for residues of the fungicide fluxapyroxad, 3-
1H-pyrazole-4-carboxamide, in or on almond at 0.05 parts per million 
(ppm); almond, hulls at 4.0 ppm; berry, low growing, subgroup 13-07G at 
4.0 ppm; bushberry, subgroup 13-07B at 6.0 ppm; caneberry, subgroup 13-
07A at 6.0 ppm; fruit, small, vine climbing, except fuzzy kiwifruit, 
subgroup 13-07F at 2.0 ppm; grapes at 2.0 ppm; grapes, raisin at 5.7 
ppm; pecans at 0.05 ppm; rice, bran at 8.5 ppm; rice, grain at 5.0 ppm; 
rice, hulls strawberry at 4.0 ppm; sugarcane, cane at 3.0 ppm; 
vegetable, brassica leafy, group 5 at 3.0 ppm; vegetable, bulb, group 
3-07 at 0.8 ppm; vegetable, cucurbit, group 9 at 0.4 ppm; vegetable, 
leafy, except brassica, group 4 at 15.0 ppm; vegetable, root, except 
sugar beet, subgroup 1B at 0.7 ppm (PP 2F8053); nongrass animal feeds, 
group 18 at 0.5 ppm; mint at 0.05 ppm (PP 2F8058); and by amending the 
tolerance for fruit, stone, group 12 from 2.0 ppm to 3.0 ppm (PP 
3F8161). The documents referenced summaries of the petitions prepared 
by BASF Corporation, the registrant, which are available in dockets 
EPA-HQ-OPP-2012-0638 (PP 2F8053), EPA-HQ-OPP-2012-0924 (PP 2F8058), and 
EPA-HQ-OPP-2013-0477 (PP 3F8161), http://www.regulations.gov.
    Based on EPA's review of the data supporting the petitions, BASF 
Corporation revised their petition PP 2F8053 by proposing tolerances 
for fish-freshwater finfish; fish-shelfish, crustacean; and hog, meat 
byproducts; and by decreasing, increasing, or deleting previously 
proposed tolerances for various commodities, as follows: Almond at 0.02 
parts per million (ppm); almond, hulls at 4.0 ppm; berry, low growing, 
subgroup 13-07G at 4.0 ppm; bushberry, subgroup 13-07B at 7.0 ppm; 
caneberry, subgroup 13-07A at 5.0 ppm; fish-freshwater finfish at 0.01 
ppm; fish-shellfish, crustacean at 0.01 ppm; fruit, small, vine 
climbing, except fuzzy kiwifruit, subgroup 13-07F at 2.0 ppm; grape, 
raisin at 5.7 ppm; hog, meat byproducts at 0.01 ppm; pecan at 0.06 ppm; 
rice, bran at 8.5 ppm; rice, grain at 5.0 ppm; rice, hulls at 15.0 ppm; 
sugarcane, cane at 3.0 ppm; vegetable, brassica leafy, group 5 at 4.0 
ppm; vegetable, bulb, group 3-07 at 1.5 ppm; vegetable, cucurbit, group 
9 at 0.5 ppm; vegetable, leafy, except brassica, group 4 at 30.0 ppm; 
vegetable, root, except sugarbeet, subgroup 1B at 0.9 ppm. EPA issued a 
notice announcing the filing of the revised petition in the Federal 
Register of November 27, 2013 (78 FR 70906) (FRL-9902-87). That 
document referenced a summary of the revised petition prepared by BASF, 
which is available in docket EPA-HQ-OPP-2012-0638.
    Three comments were received on the notices of filing. EPA's 
response to the comments is discussed in Unit IV.C.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue. . . 
    Consistent with FFDCA section 408(b)(2)(D), and the factors 
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available 
scientific data

[[Page 10672]]

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 fluxapyroxad including exposure resulting from 
the tolerances established by this action. EPA's assessment of 
exposures and risks associated with fluxapyroxad 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 
    Fluxapyroxad is of low acute toxicity by the oral, dermal and 
inhalation routes, is not irritating to the eyes and skin, and is not a 
dermal sensitizer. The primary target organ for fluxapyroxad exposure 
via the oral route is the liver with secondary toxicity in the thyroid 
for rats only. Liver toxicity was observed in rats, mice, and dogs, 
with rats as the most sensitive species for all durations of exposure. 
In rats, adaptive effects of hepatocellular hypertrophy and increased 
liver weights and changes in liver enzyme activities were first 
observed. As the dose or duration of exposure to fluxapyroxad 
increased, clinical chemistry changes related to liver function also 
occurred, followed by hepatocellular necrosis, neoplastic changes in 
the liver, and tumors. Thyroid effects were observed only in rats. 
These effects were secondary to changes in liver enzyme regulation, 
which increased metabolism of thyroid hormone, resulting in changes in 
thyroid hormones, thyroid follicular hypertrophy and hyperplasia, and 
thyroid tumor formation. Tumors were not observed in species other than 
rats or in organs other than the liver and thyroid.
    Fluxapyroxad is classified as ``Not likely to be Carcinogenic to 
Humans'' based on convincing evidence that carcinogenic effects are not 
likely below a defined dose range. There is no mutagenicity concern 
from in vivo or in vitro assays. The hypothesized mode of action (i.e., 
a non-genotoxic) for treatment related tumors (i.e., the liver and 
thyroid) was supported by a full panel of in vitro and in vivo studies 
that showed no evidence of genotoxicity, together with mechanistic 
studies in the liver and thyroid of rats that satisfied stringent 
criteria for establishing tumorgenic modes of action. The studies 
clearly identified the sequence of key events, dose-response 
concordance and temporal relationship to the tumor types. The Agency 
has determined that the chronic population adjusted dose (PAD) will 
adequately account for all chronic effects, including carcinogenicity 
that could result from exposure to fluxapyroxad because the points of 
departure (POD) for the chronic population adjusted dose (cPAD) is 
based on the most sensitive endpoint, liver effects. Effects in the 
liver preceded liver tumors and the effects observed in the thyroid (in 
rats only) were believed to be secondary to the liver effects.
    No evidence of neurotoxicity was observed in response to repeated 
administration of fluxapyroxad. An acute neurotoxicity study showed 
decreased rearing and motor activity. This occurred on the day of 
dosing only and in the absence of histopathological effects or 
alterations in brain weights. This indicated that any neurotoxic 
effects of fluxapyroxad are likely to be transient and reversible due 
to alterations in neuropharmacology and not from neuronal damage. There 
were no neurotoxic effects observed in the subchronic dietary toxicity 
study. No evidence of reproductive toxicity was observed. Developmental 
effects observed in both rats and mice (thyroid follicular hypertrophy 
and hyperplasia in rats and decreased defecation, food consumption, 
body weight/body weight gain, and increased litter loss in rabbits) 
occurred at the same doses as those that caused adverse effects in 
maternal animals, indicating no quantitative susceptibility. Since the 
maternal toxicities of thyroid hormone perturbation in rats and 
systemic toxicity in rabbits likely contributed to the observed 
developmental effects there is low concern for qualitative 
susceptibility. An immunotoxicity study in mice showed no evidence of 
immunotoxic effects from fluxapyroxad.
    Subchronic oral toxicity studies in rats, developmental toxicity 
studies in rabbits, and in vitro and in vivo genotoxicity studies were 
performed for fluxapyroxad metabolites F700F001, M700F002, and 
M700F048. Like fluxapyroxad, no genotoxic effects were observed for any 
of these metabolites. All three metabolites displayed lower subchronic 
toxicity via the oral route than fluxapyroxad, with evidence of non-
specific toxicity (decreased body weight) observed only for M700F0048 
at the limit dose. Only M700F0048 exhibited developmental toxicity at 
doses similar to those that caused developmental effects in rabbits 
with fluxapyroxad treatment. However, these effects (abortions and 
resorptions) were of a different nature than for fluxapyroxad (paw 
hyperflexion) and are considered secondary to maternal toxicity. The 
Agency considers these studies sufficient for hazard identification and 
characterization and concludes that these metabolites do not have 
hazards that exceed those of fluxapyroxad in nature, severity, or 
    Specific information on the studies received and the nature of the 
adverse effects caused by fluxapyroxad as well as the no-observed-
adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-
level (LOAEL) from the toxicity studies can be found at http://www.regulations.gov in document, ``Human Health Risk Assessment for Use 
of Fluxapyroxad on Numerous Crops'' at pp. 52 in docket ID number EPA-

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological 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 the NOAEL and the LOAEL are identified. Uncertainty/safety 
factors are used in conjunction with the POD to calculate a safe 
exposure level--generally referred to as a 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 fluxapyroxad used for 
human risk assessment is shown in Table 1 of this unit.

[[Page 10673]]

 Table 1--Summary of Toxicological Doses and Endpoints for Fluxapyroxad for Use in Human Health Risk Assessment
                                        Point of departure and
          Exposure/Scenario               uncertainty/safety     RfD, PAD, LOC for risk         Study and
                                               factors                 assessment         toxicological effects
Acute dietary (General population      NOAEL = 125 mg/kg/day..  Acute RfD = 1.25 mg/kg/  Acute neurotoxicity
 including infants and children, and   UFA = 10x..............   day..                    study in rats.
 females 13-49 years of age).          UFH = 10x..............  aPAD = 1.25 mg/kg/day..  LOAEL = 500 mg/kg/day
                                       FQPA SF = 1x...........                            based on decreased
                                                                                          motor activity and
                                                                                          decreased rearing.
Chronic dietary (All populations)....  NOAEL = 2.1 mg/kg/day..  Chronic RfD = 0.021 mg/  Chronic toxicity/
                                       UFA = 10x..............   kg/day..                 carcinogenicity study
                                       UFH = 10x..............  cPAD = 0.021 mg/kg/day.   in rats.
                                       FQPA SF = 1x...........                           LOAEL = 11 mg/kg/day
                                                                                          based on non-
                                                                                          neoplastic changes in
                                                                                          the liver (foci,
Incidental oral short-term (1 to 30    NOAEL = 9 mg/kg/day....  LOC for MOE = 100......  28-day oral toxicity
 days).                                UFA = 10x..............                            study in rats.
                                       UFH = 10x..............                           LOAEL = 176 mg/kg/day
                                       FQPA SF = 1x...........                            based on changes in
                                                                                          thyroid hormones and
                                                                                          thyroid follicular
Dermal short- and intermediate-term                  No hazard identified                28-day dermal toxicity
 (1 day to 6 months).                                                                     study in rats.
                                                                                         LOAEL = Not observed.
Inhalation short-term (1 to 30 days).  NOAEL= 9 mg/kg/day.....  LOC for MOE = 100......  28-day oral toxicity
                                       UFA = 10x..............                            study in rats.
                                       UFH = 10x..............                           LOAEL = 176 mg/kg/day
                                       FQPA SF = 1x...........                            based on changes in
                                                                                          thyroid hormones and
                                                                                          thyroid follicular
Inhalation intermediate-term (1 to 6   Inhalation (or oral)     LOC for MOE = 100......  90-day dietary study in
 months).                               study NOAEL = 7.3 mg/                             rats.
                                        kg/day.                                          LOAEL = 35.1 mg/kg/day
                                       UFA = 10x..............                            based on thyroid
                                       UFH = 10x..............                            follicular hypertrophy/
                                       FQPA SF = 1x...........                            hyperplasia.
Cancer (Oral, dermal, inhalation)....       Classification: Not likely to be carcinogenic to humans at doses
                                        sufficient to induce liver and/or thyroid tumors. Quantification of risk
                                         using a non-linear approach (i.e., RfD) will adequately account for all
                                                      chronic toxicity, including carcinogenicity.
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
  of concern. mg/kg/day = milligram/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
  level. 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 fluxapyroxad, EPA considered exposure under the petitioned-
for tolerances as well as all existing fluxapyroxad tolerances in 40 
CFR 180.666. EPA assessed dietary exposures from fluxapyroxad 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. Such effects were identified 
for fluxapyroxad. In estimating acute dietary exposure, EPA used food 
consumption information from the United States Department of 
Agriculture (USDA) 2003-2008 National Health and Nutrition Examination 
Survey, What We Eat in America (NHANES/WWEIA). As to residue levels in 
food, EPA used tolerance level residues adjusted upward to account for 
metabolites of concern not included in the tolerance expression, 100 
percent crop treated (PCT) assumptions, and dietary exposure evaluation 
model (DEEM) default and empirical processing factors.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment, EPA used the food consumption data from the USDA 2003-2008 
NHANES/WWEIA. As to residue levels in food, a moderately refined 
chronic dietary exposure analysis was performed. An assumption of 100 
PCT and DEEM default and empirical processing factors were used for the 
chronic dietary analysis. Combined average field trial residues for 
parent and highest average field trial residues for metabolites of 
concern were used for all plant commodities. For livestock commodities 
tolerance level residues adjusted upward to account for metabolites of 
concern not included in the tolerance expression were used.
    iii. Cancer. Based on the data summarized in Unit III.A., EPA has 
concluded that a nonlinear RfD approach is appropriate for assessing 
cancer risk to fluxapyroxad. Cancer risk was assessed using the same 
exposure estimates as discussed in Unit III.C.1.ii., chronic exposure.
    iv. Anticipated residue and percent crop treated (PCT) information. 
Section 408(b)(2)(E) of FFDCA authorizes EPA to use available data and 
information on

[[Page 10674]]

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.
    2. Dietary exposure from drinking water. The Agency used screening 
level water exposure models in the dietary exposure analysis and risk 
assessment for fluxapyroxad in drinking water. These simulation models 
take into account data on the physical, chemical, and fate/transport 
characteristics of fluxapyroxad. 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 Tier 1 Rice Model and the Pesticide Root Zone Model 
Ground Water (PRZM GW), the estimated drinking water concentrations 
(EDWCs) of fluxapyroxad for acute exposures are estimated to be 127 
parts per billion (ppb) for surface water and 203 ppb for ground water. 
The EDWCs for chronic exposures for non-cancer assessments are 
estimated to be 127 ppb for surface water and 184 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 203 ppb was used to assess 
the contribution to drinking water. For chronic dietary risk 
assessment, the water concentration of value 184 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). Fluxapyroxad is 
registered for the following uses that could result in residential 
exposures: residential turf. EPA assessed residential exposure using 
the following assumptions: Residential handler exposures are expected 
to be short-term (1 to 30 days) via either the dermal or inhalation 
routes of exposures. Intermediate-term exposures are not likely because 
of the intermittent nature of applications by homeowners. Since no 
dermal hazard was identified for fluxapyroxad, MOEs were calculated for 
the inhalation route of exposure only.
    Both adults and children may be exposed to fluxapyroxad residues 
from contact with treated lawns. Adult postapplication exposures were 
not quantitatively assessed since no dermal hazard was identified for 
fluxapyroxad and inhalation exposures are typically negligible in 
outdoor settings. The exposure assessment for children included 
incidental oral exposure resulting from transfer of residues from the 
hands or objects to the mouth, and from incidental ingestion of soil. 
Post application hand-to-mouth and object-to-mouth exposures are 
expected to be short-term (1 to 30 days) in duration due to the 
intermittent nature of applications in residential environments. 
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 fluxapyroxad to share a common mechanism of 
toxicity with any other substances, and fluxapyroxad does not appear to 
produce a toxic metabolite produced by other substances. For the 
purposes of this tolerance action, therefore, EPA has assumed that 
fluxapyroxad 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 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 
    2. Prenatal and postnatal sensitivity. No evidence of quantitative 
susceptibility was observed in a reproductive and developmental 
toxicity study in rats or in developmental toxicity studies in rats and 
rabbits. Developmental toxicity data in rats showed decreased body 
weight and body weight gain in the offspring at the same dose levels 
that caused thyroid follicular hypertrophy/hyperplasia in parental 
animals. Effects in rabbits were limited to paw hyperflexion, a 
malformation that is not considered to result from a single exposure 
and that usually reverses as the animal matures. Developmental effects 
observed in both rats and rabbits occurred at the same doses as those 
that caused adverse effects in maternal animals, indicating no 
quantitative susceptibility. The Agency has low concern for 
developmental toxicity because the observed effects were of low 
severity, were likely secondary to maternal toxicity, and demonstrated 
clear NOAELs. Further, the NOAELs for these effects were at dose levels 
higher than the points of departure selected for risk assessment for 
repeat-exposure scenarios. Therefore, based on the available data and 
the selection of risk assessment endpoints that are protective of 
developmental effects, there are no residual uncertainties with regard 
to pre- and/or postnatal toxicity.
    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 
    i. The toxicity database for fluxapyroxad is complete. Although no 
subchronic inhalation data is available EPA has waived that data 
requirement based on, among other things, its conclusion that even if 
an additional 10x safety factor was applied, inhalation exposure would 
not raise a risk of concern.
    ii. There is no indication that fluxapyroxad is a neurotoxic 
chemical and there is no need for a developmental neurotoxicity study 
or additional UFs to account for neurotoxicity. Neither the acute or 
the subchronic neurotoxicity studies indicated specific neurotoxicity 
responses to fluxapyroxad. Because fluxapyroxad can disrupt thyroid

[[Page 10675]]

hormone levels, the Agency considered the potential for fluxapyroxad to 
cause developmental neurotoxicity as a result of thyroid hormone 
disruption, which is more sensitive endpoint than the endpoints used in 
a developmental neurotoxicity study. Based on its evaluation of thyroid 
hormone data submitted for fluxapyroxad and the ontogeny of thyroid 
hormone metabolism, the Agency has determined that adverse thyroid 
hormone disruptions in the young are unlikely to occur at dose levels 
as low as the points of departure chosen for risk assessment. The 
Agency has low concern for neurotoxic effects of fluxapyroxad at any 
life stage.
    iii. Based on the developmental and reproductive toxicity studies 
discussed in Unit III.D.2., there are no residual uncertainties with 
regard to prenatal and/or postnatal toxicity.
    iv. There are no residual uncertainties identified in the exposure 
databases. The dietary food exposure assessments were performed based 
on 100 PCT and tolerance-level residues or field trial residue data. 
The dietary risk assessment is based on reliable data, is conservative 
and will not underestimate dietary exposure to fluxapyroxad. EPA made 
conservative (protective) assumptions in the ground and surface water 
modeling used to assess exposure to fluxapyroxad in drinking water. EPA 
used similarly conservative assumptions to assess postapplication 
exposure of children as well as incidental oral exposure of toddlers. 
These assessments will not underestimate the exposure and risks posed 
by fluxapyroxad.

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 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 fluxapyroxad will occupy 12% of the aPAD for children 3-5 years old, 
the population group receiving the greatest exposure.
    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that chronic exposure to 
fluxapyroxad from food and water will utilize 64% of the cPAD for 
infants (< 1year 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 
fluxapyroxad 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). Fluxapyroxad 
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 fluxapyroxad. Using the exposure 
assumptions described in this unit for short-term exposures, EPA has 
concluded the combined short-term food, water, and residential 
exposures result in aggregate MOEs of 320 for adults and 560 for 
children. Because EPA's level of concern for fluxapyroxad 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 
level). An intermediate-term adverse effect was identified; however, 
fluxapyroxad 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. EPA classified 
fluxapyroxad as ``Not likely to be Carcinogenic to Humans'' based on 
convincing evidence that carcinogenic effects are not likely below a 
defined dose range. The Agency has determined that the quantification 
of risk using the cPAD for fluxapyroxad will adequately account for all 
chronic toxicity, including carcinogenicity, that could result from 
exposure to fluxapyroxad. The POD for the cPAD is based on the most 
sensitive endpoint, liver effects. Effects in the liver preceded liver 
tumors and the effects observed in the thyroid (in rats only) were 
believed to be secondary to the liver effects. As noted above, chronic 
exposure to fluxapyroxad from food and water will utilize 64% of the 
cPAD for infants (< 1year old) the population group receiving the 
greatest exposure.
    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 fluxapyroxad residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    A Liquid Chromatography-Mass Spectrometer/Mass Spectrometer (LC/MS/
MS) method is available as an enforcement method. This method uses 
reversed-phase High Pressure Liquid Chromatography (HPLC) with gradient 
elution, and includes 2 ion transitions to be monitored for the parent 
    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 MRLs for fluxapyroxad on the 
commodities subject in this notice.

C. Response to Comments

    Three anonymous public comments were received opposing 

[[Page 10676]]

of the requested tolerances. The first commenter alleges that there is 
already too much toxicity from pesticide chemicals in the U.S. and EPA 
should not allow more pesticide residues on food. The second commenter 
claims that a data gap exists for maximum residues of fluxapyroxad in 
wheat and for accumulation of fluxapyroxad residues in soil and argues 
that EPA should require testing of pesticides when combined with other 
pesticides. The third anonymous commenter states that the U.S. should 
no longer allow the importation of pet foods from China. The Department 
of Utility, City of Sacramento, California submitted a comment on the 
application by BASF to register fluxapyroxad for use on rice under the 
Federal Insecticide, Fungicide, and Rodenticide Act, 7 U.S.C. 136 et 
seq. Several issues in that comment pertain to EPA's risk assessment 
for the fluxapyroxad tolerance petition. The Department of Utility 
expresses concern with the potential human health effects of breakdown 
products (metabolites, degradates, transformations products) that occur 
both prior and subsequent to water treatment, the effects of water 
treatment on the removal of fluxapyroxad residues, and the potential 
synergistic effects from exposure to multiple rice pesticides in 
drinking water.
    The anonymous commenters either raise irrelevant or non-specific 
issues, make unsubstantiated claims, or are mistaken in their 
allegations. General claims regarding the toxicity of other pesticides 
and objections to the import of pet food from China do not raise safety 
concerns regarding EPA's assessment of the risk from aggregate exposure 
to fluxapyroxad. With regard to potential cumulative effects from the 
interaction of fluxapyroxad with other substances, EPA has addressed 
this issue in Unit III. C. 4., above. Finally, the commenter who claims 
there are data gaps is mistaken. The Agency determined that the 
available residue chemistry data for fluxapyroxad are sufficient to 
support the established tolerances for registered wheat uses. No data 
gaps were identified for wheat commodities or for rotational crop 
commodities. Additionally, the fluxapyroxad product label statements 
restrict crop rotation to commodities listed on the label.
    The remaining comments raised by Sacramento's Department of Utility 
express concerns with EPA's examination of breakdown products from 
fluxapyroxad, and fluxapyroxad residue removal through water treatment 
in a drinking water plant. EPA possesses a full complement of standard 
metabolism and environmental fate studies on fluxapyroxad, as specified 
under 40 CFR 158.1300 and 158.1410. These include hydrolysis (OCSPP 
Guideline 835.2120), aqueous photolysis (OCSPP Guideline 835.2240), 
aerobic soil metabolism, and aerobic aquatic metabolism studies (OCSPP 
Guidelines 835.4100/4200 and 835.4300/4400). While these studies 
provide general information on the fate of fluxapyroxad and its 
metabolites in the environment, they do not directly address the 
chemicals' fate during drinking water treatment, and were therefore 
used only for qualitative characterization of such effects. The studies 
show that fluxapyroxad is stable to hydrolysis and aquatic degradation, 
therefore the chemical is not expected to degrade during drinking water 
treatment, and/or subsequent delivery of treated water to the 
consumer's tap. Because fluxapyroxad is moderately to slightly mobile 
in soils, treatment methods such as sedimentation, flocculation, and 
activated carbon filtration are expected to have some effect at 
removing fluxapyroxad. Available studies also show that fluxapyroxad 
does not degrade via photolysis, therefore where ultraviolet light is 
used as a means of disinfection, enhanced degradation of fluxapyroxad 
is not expected to occur. The chemical structure of fluxapyroxad does 
not appear to include any moieties where oxidation due to water 
chlorination could result in the formation of an obviously more-toxic 
transformation product, such as an oxon. EPA possesses toxicity data on 
various fluxapyroxad metabolites and degradates. The data indicate that 
none of these metabolites are more toxic than parent fluxapyroxad, and 
they were therefore not considered as separate entities in dietary or 
drinking water risk assessments. In conclusion, based upon the 
available information, EPA believes that it has adequately taken 
drinking water treatment into account in addressing potential human 
health risks from fluxapyroxad. EPA does not routinely require data on 
the effects of water treatment processes on pesticides. Rather, in 
assessing risks, EPA generally employs (as it did with fluxapyroxad) 
estimates of pesticide concentrations in source (untreated) water as a 
surrogate for concentrations in consumed water. This approach is 
inherently conservative, and is therefore expected to be protective of 
public health.

D. Revisions to Petitioned-For Tolerances

    Based upon review of the data supporting the petitions, petition PP 
2F8058 was revised by decreasing the proposed tolerances for nongrass 
animal feeds, group 18 from 0.5 to 0.30 ppm; and mint from 0.05 to 0.01 
ppm. In addition, the Agency is amending the existing tolerance for 
grain, cereal, group 15, by adding ``except rice'' to the commodity 
definition. In lieu of the proposed tolerances for almonds and pecans, 
and since these are the representative commodities for the tree nut 
crop group, the Agency is establishing a tolerance for the tree nut 
crop group 14-12 at 0.06 ppm.
    The Agency concluded that based on the residue data these changes 
are required to support the proposed uses. The Agency analyzed the 
field trial data for the respective commodities using the Organization 
for Economic Cooperation and Development tolerance calculation 
procedures to determine the appropriate tolerances.

V. Conclusion

    Therefore, tolerances are established for residues of fluxapyroxad, 
1H-pyrazole-4-carboxamide, as requested in the revised petitions.

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 

[[Page 10677]]

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 
recordkeeping requirements.

    Dated: February 14, 2014.
Lois Rossi,
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.  180.666:
a. Revise the following commodities in the table in paragraph (a): 
``Grain, cereal, group 15, (except corn, field, grain; except corn, 
pop, grain; except corn, kernels plus cobs with husks removed; except 
wheat)'' and ``Fruit, stone, group 12.''
b. Add alphabetically 21 commodities to the table in paragraph (a).
c. Revise paragraph (d).
    The revisions and additions read as follows:

Sec.  180.666  Fluxapyroxad; tolerances for residues.

    (a) General. * * *

                                                              Parts per
                         Commodity                             million
Almond, hulls.............................................          4.0
                              * * * * * * *
Berry, low growing, subgroup 13-07G.......................          4.0
Bushberry, subgroup 13-07B................................          7.0
Caneberry, subgroup 13-07A................................          5.0
                              * * * * * * *
Fish-freshwater finfish...................................          0.01
Fish-shellfish, crustacean................................          0.01
                              * * * * * * *
Fruit, small, vine climbing, except fuzzy kiwifruit,                2.0
 subgroup 13-07F..........................................
                              * * * * * * *
Fruit, stone, group 12-12.................................          3.0
                              * * * * * * *
Grain, cereal, group 15, (except corn, field, grain;                3.0
 except corn, pop, grain; except corn, kernels plus cobs
 with husks removed; except rice; except wheat............
                              * * * * * * *
Grape, raisin.............................................          5.7
Hog, meat byproducts......................................          0.01
                              * * * * * * *
Nut, tree, group 14-12....................................          0.06
                              * * * * * * *
Rice, bran................................................          8.5
Rice, grain...............................................          5.0
Rice, hulls...............................................         15.0
                              * * * * * * *
Sugarcane, cane...........................................          3.0

[[Page 10678]]

                              * * * * * * *
Vegetable, brassica leafy, group 5........................          4.0
Vegetable, bulb, group 3-07...............................          1.5
Vegetable, cucurbit, group 9..............................          0.50
                              * * * * * * *
Vegetable, leafy, except brassica, group 4................         30
                              * * * * * * *
Vegetable, root, except sugarbeet, subgroup 1B............          0.90
                              * * * * * * *

* * * * *
    (d) Indirect or inadvertent residues. Tolerances are established 
for the combined indirect or inadvertent residues of the fungicide 
fluxapyroxad, including its metabolites and degradates, in or on the 
commodities listed in the table below. Compliance with the tolerance 
levels specified below is to be determined by measuring only 
fluxapyroxad, 3-(difluoromethyl)-1-methyl-N-(3',4',5'-trifluoro[1,1'-
biphenyl]-2-yl)-1H-pyrazole-4-carboxamide in or on the commodity.

                                                              Parts per
                         Commodity                             million
Nongrass animal feeds, group18............................          0.30
Peppermint, tops..........................................          0.01
Spearmint, tops...........................................          0.01

[FR Doc. 2014-04164 Filed 2-25-14; 8:45 am]