Federal Register / Vol. 80, No. 145 / Wednesday, July 29, 2015 / Rules and Regulations 45073 

WEST VIRGINIA—2006 24-HOUR PM2.5 NAAQS—Continued 

[Primary and secondary] 

Designated area a

Designation Classification 

Date 1 Type Date 2 Type 

Webster County ................................................................................... ........................ Unclassifiable/Attainment. 

Wetzel County ..................................................................................... ........................ Unclassifiable/Attainment. 

Wirt County .......................................................................................... ........................ Unclassifiable/Attainment. 

Wood County ....................................................................................... ........................ Unclassifiable/Attainment. 

Wyoming County ................................................................................. ........................ Unclassifiable/Attainment. 

a Includes Indian Country located in each county or area, except as otherwise specified. 

1This date is 30 days after November 13, 2009, unless otherwise noted. 

2This date is July 2, 2014, unless otherwise noted. 

* * * * * 

[FR Doc. 2015–18532 Filed 7–28–15; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2012–0638; FRL–9930–73] 

Fluxapyroxad; Pesticide Tolerances 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes 

tolerances for residues of fluxapyroxad 

in or on cotton, gin byproducts and 

cotton, undelinted seed. BASF 

Corporation requested these tolerances 

under the Federal Food, Drug, and 

Cosmetic Act (FFDCA). 

DATES: This regulation is effective July 

29, 2015. Objections and requests for 

hearings must be received on or before 

September 28, 2015, 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), West William 

Jefferson Clinton Bldg., Rm. 3334, 1301 

Constitution Ave. NW., Washington, DC 

20460–0001. The Public Reading Room 

is open from 8:30 a.m. to 4:30 p.m., 

Monday through Friday, excluding legal 

holidays. The telephone number for the 

Public Reading Room is (202) 566–1744, 

and the telephone number for the OPP 

Docket is (703) 305–5805. Please review 

the visitor instructions and additional 

information about the docket available 

at http://www.epa.gov/dockets. 

FOR FURTHER INFORMATION CONTACT: 

Susan Lewis, Registration Division 

(7505P), Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave. NW., Washington, 

DC 20460–0001; main telephone 

number: (703) 305–7090; email address: 

RDFRNotices@epa.gov. 

SUPPLEMENTARY INFORMATION: 

I. General Information 

A. Does this action apply to me? 

You may be potentially affected by 

this action if you are an agricultural 

producer, food manufacturer, or 

pesticide manufacturer. The following 

list of North American Industrial 

Classification System (NAICS) codes is 

not intended to be exhaustive, but rather 

provides a guide to help readers 

determine whether this document 

applies to them. Potentially affected 

entities may include: 

• Crop production (NAICS code 111). 

• Animal production (NAICS code 

112). 

• Food manufacturing (NAICS code 

311). 

• Pesticide manufacturing (NAICS 

code 32532). 

B. How can I get electronic access to 

other related information? 

You may access a frequently updated 

electronic version of EPA’s tolerance 

regulations at 40 CFR part 180 through 

the Government Printing Office’s e-CFR 

site at http://www.ecfr.gov/cgi-bin/textidx?&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–2012–0638 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 September 28, 2015. 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 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.html. 

Additional instructions on 

commenting or visiting the docket, 

along with more information about 

dockets generally, is available at 

http://www.epa.gov/dockets. 

II. Summary of Petitioned-for Tolerance 

In the Federal Register of December 

17, 2014 (79 FR 75107) (FRL–9918–90), 

mstockstill on DSK4VPTVN1PROD with RULES

45074 Federal Register / Vol. 80, No. 145 / Wednesday, July 29, 2015 / Rules and Regulations 

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 4F8270) by BASF 

Corporation, 26 Davis Drive, Research 

Triangle Park, NC 27709. The petition 

requested that 40 CFR 180.666 be 

amended by establishing tolerances for 

residues of the fungicide fluxapyroxad 

(BAS 700 F), 3-(difluoromethyl)-1- 

methyl-N-(3′,4′,5′-trifluoro[1,1′- 

biphenyl]-2-yl)-1H-pyrazole-4- 

carboxamide, its metabolites, and 

degradates, in or on cotton, gin 

byproducts at 20 parts per million 

(ppm); cotton undelinted seed at 0.30 

ppm. That document referenced a 

summary of the petition prepared by 

BASF Corporation, the registrant, which 

is available in the docket, http://

www.regulations.gov. There were no 

comments received in response to the 

notice of filing 

III. Aggregate Risk Assessment and 

Determination of Safety 

Section 408(b)(2)(A)(i) of FFDCA 

allows EPA to establish a tolerance (the 

legal limit for a pesticide chemical 

residue in or on a food) only if EPA 

determines that the tolerance is ‘‘safe.’’ 

Section 408(b)(2)(A)(ii) of FFDCA 

defines ‘‘safe’’ to mean that ‘‘there is a 

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ This includes 

exposure through drinking water and in 

residential settings, but does not include 

occupational exposure. Section 

408(b)(2)(C) of FFDCA requires EPA to 

give special consideration to exposure 

of infants and children to the pesticide 

chemical residue in establishing a 

tolerance and to ‘‘ensure that there is a 

reasonable certainty that no harm will 

result to infants and children from 

aggregate exposure to the pesticide 

chemical residue. . . .’’ 

Consistent with 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 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 children. 

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 

potency. 

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 

mstockstill on DSK4VPTVN1PROD with RULES

Federal Register / Vol. 80, No. 145 / Wednesday, July 29, 2015 / Rules and Regulations 45075 

(NOAEL) and the lowest-observedadverse-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–HQ–OPP–2012–0638. 

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 nonthreshold 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 chemical name used for 

human risk assessment is shown in 

Table 1 of this unit. 

TABLE 1—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR FLUXAPYROXAD FOR USE IN HUMAN HEALTH RISK

ASSESSMENT

Exposure/scenario 

Point of departure 

and 

uncertainty/safety 

factors 

RfD, PAD, LOC for 

risk 

assessment 

Study and toxicological effects 

Acute dietary (General population including infants and 

children, and females 13–49 

years of age).

NOAEL = 125 mg/

kg/day.

UFA = 10× ...............

UFH = 10× ...............

FQPA SF = 1× .........

Acute RfD = 1.25 

mg/kg/day.

aPAD = 1.25 mg/kg/

day.

Acute neurotoxicity study in rats 

LOAEL = 500 mg/kg/day based on decreased motor activity 

and decreased rearing. 

Chronic dietary (All populations) NOAEL = 2.1 mg/kg/

day.

UFA = 10× ...............

UFH = 10× ...............

FQPA SF = 1× .........

Chronic RfD = 0.021 

mg/kg/day.

cPAD = 0.021 mg/

kg/day.

Chronic toxicity/carcinogenicity study in rats 

LOAEL = 11 mg/kg/day based on non-neoplastic changes in 

the liver (foci, masses). 

Incidental oral short-term (1 to 

30 days).

NOAEL = 9 mg/kg/

day.

UFA = 10× ...............

UFH = 10× ...............

FQPA SF = 1× .........

LOC for MOE = 100 28-day oral toxicity study in rats 

LOAEL = 176 mg/kg/day based on changes in thyroid hormones and thyroid follicular hypertrophy/hyperplasia. 

Inhalation short-term (1 to 30 

days).

NOAEL= 9 mg/kg/

day.

UFA = 10× ...............

UFH = 10× ...............

FQPA SF = 1× .........

LOC for MOE = 100 28-day oral toxicity study in rats 

LOAEL = 176 mg/kg/day based on changes in thyroid hormones and thyroid follicular hypertrophy/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). UFDB = to account for the absence of data or other data deficiency. UFH = potential variation in sensitivity among members of the human population (intraspecies). UFL = use 

of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term study for long-term risk assessment. 

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 fieldtrial residues for metabolites of concern 

were used for all plant commodities. For 

livestock commodities tolerance-level 

residues adjusted upward to account for 

mstockstill on DSK4VPTVN1PROD with RULES

45076 Federal Register / Vol. 80, No. 145 / Wednesday, July 29, 2015 / Rules and Regulations 

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 

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 nonoccupational, non-dietary exposure 

(e.g., for lawn and garden pest control, 

indoor pest control, termiticides, and 

flea and tick control on pets). 

Fluxapyroxad is currently 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. Postapplication hand-to-mouth and objectto-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 

Food Quality Protection Act Safety 

Factor (FQPA SF). In applying this 

provision, EPA either retains the default 

value of 10X, or uses a different 

additional safety factor when reliable 

data available to EPA support the choice 

of a different factor. 

2. Prenatal and postnatal sensitivity. 

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 findings: 

i. The toxicity database for 

fluxapyroxad is complete. Although no 

subchronic inhalation data is available, 

mstockstill on DSK4VPTVN1PROD with RULES

Federal Register / Vol. 80, No. 145 / Wednesday, July 29, 2015 / Rules and Regulations 45077 

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 nor the 

subchronic neurotoxicity studies 

indicated specific neurotoxicity 

responses to fluxapyroxad. Because 

fluxapyroxad can disrupt thyroid 

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 

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 

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 (< 1 year old). 

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 intermediateterm 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 

fluxapyroxad. 

5. Aggregate cancer risk for U.S. 

population. As discussed in Unit III.A., 

EPA has 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. 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 

fluxapyroxad. 

The method may be requested from: 

Chief, Analytical Chemistry Branch, 

Environmental Science Center, 701 

Mapes Rd., Ft. Meade, MD 20755–5350; 

telephone number: (410) 305–2905; 

email address: residuemethods@

epa.gov. 

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, 

mstockstill on DSK4VPTVN1PROD with RULES

45078 Federal Register / Vol. 80, No. 145 / Wednesday, July 29, 2015 / Rules and Regulations 

FFDCA section 408(b)(4) requires that 

EPA explain the reasons for departing 

from the Codex level. 

There is a Codex MRL for cotton, 

undelinted seed at 0.01 ppm. However, 

this MRL is based on seed treatment of 

cotton, and not foliar applications 

(which is the proposed use for the U.S. 

registration and which results in higher 

residues). Therefore, there is no ground 

for harmonization of U.S. tolerance and 

Codex MRL. 

V. Conclusion 

Therefore, tolerances are established 

for residues of fluxapyroxad [3- 

(difluoromethyl)-1-methyl-N-(3′,4′,5′- 

trifluoro[1,1′-biphenyl]-2-yl)-1Hpyrazole-4-carboxamide], including its 

metabolites and degradates, in or on 

cotton, gin byproducts at 20 ppm and 

cotton undelinted seed at 0.30 ppm. 

VI. Statutory and Executive Order 

Reviews 

This action amends existing 

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 action has been exempted from 

review under Executive Order 12866, 

this action 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 action 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 tolerances in this final rule, do not 

require the issuance of a proposed rule, 

the requirements of the Regulatory 

Flexibility Act (RFA) (5 U.S.C. 601 et 

seq.), do not apply. 

This action directly regulates growers, 

food processors, food handlers, and food 

retailers, not States or tribes, nor does 

this action alter the relationships or 

distribution of power and 

responsibilities established by Congress 

in the preemption provisions of 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 action. In addition, this action 

does not impose any enforceable duty or 

contain any unfunded mandate as 

described under Title II of the Unfunded 

Mandates Reform Act (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 

(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: July 22, 2015. 

Susan Lewis, 

Director, Registration Division, Office of 

Pesticide Programs. 

Therefore, 40 CFR chapter I is 

amended as follows: 

PART 180—[AMENDED] 

■ 1. The authority citation for part 180 

continues to read as follows: 

Authority: 21 U.S.C. 321(q), 346a and 371. 

■ 2. In § 180.666, revise the entries for 

‘‘Cotton, gin byproducts’’ and ‘‘Cotton, 

undelinted seed’’ in the table in 

paragraph (a) to read as follows: 

§ 180.666 Fluxapyroxad; tolerances for 

residues. 

(a) * * * 

Commodity Parts per million 

*******

Cotton, gin byproducts ....................................................................................................................................................................... 20 

Cotton, undelinted seed ..................................................................................................................................................................... 0 .30 

* * * * * * * 

* * * * * 

[FR Doc. 2015–18544 Filed 7–28–15; 8:45 am] 

BILLING CODE 6560–50–P 

mstockstill on DSK4VPTVN1PROD with RULES