Federal Register / Vol. 79, No. 65 / Friday, April 4, 2014 / Rules and Regulations 18805 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2013–0258; FRL–9907–67] 

Metaflumizone; Pesticide Tolerances 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes 

tolerances for residues of metaflumizone 

in or on eggplant, pepper, tomato, and 

tomato, paste. BASF Corporation 

requested these tolerances under the 

Federal Food, Drug, and Cosmetic Act 

(FFDCA). 

DATES: This regulation is effective April 

4, 2014. Objections and requests for 

hearings must be received on or before 

June 3, 2014, and must be filed in 

accordance with the instructions 

provided in 40 CFR part 178 (see also 

Unit I.C. of the SUPPLEMENTARY

INFORMATION). 

ADDRESSES: The docket for this action, 

identified by docket identification (ID) 

number EPA–HQ–OPP–2013–0258, 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: 

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. 

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–2013–0258 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 June 3, 2014. Addresses for mail 

and hand delivery of objections and 

hearing requests are provided in 40 CFR 

178.25(b). 

In addition to filing an objection or 

hearing request with the Hearing Clerk 

as described in 40 CFR part 178, please 

submit a copy of the filing (excluding 

any Confidential Business Information 

(CBI)) for inclusion in the public docket. 

Information not marked confidential 

pursuant to 40 CFR part 2 may be 

disclosed publicly by EPA without prior 

notice. Submit the non-CBI copy of your 

objection or hearing request, identified 

by docket ID number EPA–HQ–OPP– 

2013–0258, by one of the following 

methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the online 

instructions for submitting comments. 

Do not submit electronically any 

information you consider to be CBI or 

other information whose disclosure is 

restricted by statute. 

• Mail: OPP Docket, Environmental 

Protection Agency Docket Center (EPA/ 

DC), (28221T), 1200 Pennsylvania Ave. 

NW., Washington, DC 20460–0001. 

• Hand Delivery: To make special 

arrangements for hand delivery or 

delivery of boxed information, please 

follow the instructions at http://

www.epa.gov/dockets/contacts.htm. 

Additional instructions on 

commenting or visiting the docket, 

along with more information about 

dockets generally, is available at http:// 

www.epa.gov/dockets. 

II. Summary of Petitioned-for Tolerance 

In the Federal Register of June 5, 2013 

(78 FR 33785) (FRL–9386–2), 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 3E8146) by BASF 

Corporation, P.O. Box 13528, Research 

Triangle Park, NC 27790. The petition 

requested that 40 CFR 180.657 be 

amended by establishing tolerances for 

residues of the insecticide 

metaflumizone, (E and Z isomers; 2-[2- 

(4-cyanophenyl)-1-[3-(trifluoromethyl) 

phenyl]ethylidene]-N-[4- 

(trifluoromethoxy)phenyl] 

hydrazinecarboxamide), and its 

metabolite (4-{2-oxo-2-[3- 

(trifluoromethyl) phenyl]ethyl}- 

benzonitrile), in or on eggplant at 0.6 

parts per million (ppm); pepper at 0.6 

ppm; and tomato at 0.6 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. 

Based upon review of the data 

supporting the petition, EPA has 

determined that the tolerances for 

eggplant and pepper should each be 

established at 1.5 ppm, the tolerance for 

tomato should be established at 0.60 

ppm, and that an additional tolerance 

for tomato, paste should be established 

at 1.2 ppm. The reasons for these 

changes are explained in Unit IV.C. 

III. Aggregate Risk Assessment and 

Determination of Safety 

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

allows EPA to establish a tolerance (the 

legal limit for a pesticide chemical 

residue in or on a food) only if EPA 

determines that the tolerance is ‘‘safe.’’ 

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

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

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ This includes 

exposure through drinking water and in 

residential settings, but does not include 


TKELLEY on DSK3SPTVN1PROD with RULES
18806 Federal Register / Vol. 79, No. 65 / Friday, April 4, 2014 / Rules and Regulations 

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 metaflumizone 

including exposure resulting from the 

tolerances established by this action. 

EPA’s assessment of exposures and risks 

associated with metaflumizone 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. 

Hematotoxicity (toxicity of the blood) 

was the primary toxic effect of concern 

following subchronic or chronic oral 

exposures to metaflumizone. Splenic 

extramedullary hematopoiesis, 

increased hemosiderin, and anemia 

were the most common hematotoxic 

effects reported after repeated oral 

dosing with metaflumizone. Chronic 

oral (gavage) exposures to dogs resulted 

in slight decreases in mean corpuscular 

hemoglobin concentration and total 

hemoglobin, leading to increased 

plasma bilirubin, increased urinary 

urobilinogen, and increased 

hemosiderin in the liver. In a chronic 

toxicity/carcinogenicity study in mice, 

anemia was observed in the form of 

increased hemosiderin in the spleen, 

increased mean absolute reticulocyte 

count, decreased mean corpuscular 

volume, and mean corpuscular 

hemoglobin. 

The postulated pesticidal mode of 

action of metaflumizone involves 

inhibition of sodium channels in target 

insect species; however, in mammals 

(rats), there were only clinical signs of 

neurotoxicity (i.e., piloerection and 

body temperature variations) with no 

neuropathology in the presence of 

systemic toxicity (e.g., recumbency and 

poor general state) following acute or 

repeated exposures. Similarly, several 

immune system organs seem to be 

affected following metaflumizone 

administration via the oral, dermal, and 

inhalation routes (e.g., the presence of 

macrophages in the thymus, lymphocyte 

necrosis in the mesenteric lymph nodes, 

and diffuse atrophy of the mandibular); 

however, there was no evidence of any 

functional deficits at the highest dose 

tested in a recently submitted and 

reviewed guideline immunotoxicity 

study. Therefore, the clinical 

neurotoxicity signs and the effects on 

the immune system organs following 

metaflumizone administration are likely 

to be secondary to the hematotoxic 

effects. 

Metaflumizone induced an increased 

incidence of a missing subclavian artery 

at a relatively high dose that also caused 

severe maternal toxicity (e.g., late term 

abortions) in the developmental toxicity 

study in rabbits. There was no evidence 

(quantitative or qualitative) of increased 

susceptibility following in utero 

exposures to rats or rabbit and following 

pre- and post natal exposures. There 

was no evidence that metaflumizone is 

genotoxic and carcinogenicity studies 

with mice and rabbits were negative. 

Specific information on the studies 

received and the nature of the adverse 

effects caused by metaflumizone 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 

‘‘Metaflumizone: Human-Health Risk 

Assessment for Tolerances in/on 

Imported Tomato, Pepper, and 

Eggplant’’ in docket ID number EPA– 

HQ–OPP–2013–0258. 

B. Toxicological Points of Departure/

Levels of Concern 

Once a pesticide’s toxicological 

profile is determined, EPA identifies 

toxicological points of departure (POD) 

and levels of concern (LOCs) to use in 

evaluating the risk posed by human 

exposure to the pesticide. For hazards 

that have a threshold below which there 

is no appreciable risk, the toxicological 

POD is used as the basis for derivation 

of reference values for risk assessment. 

PODs are developed based on a careful 

analysis of the doses in each 

toxicological study to determine the 

dose at which no adverse effects are 

observed (the NOAEL) and the lowest 

dose at which adverse effects of concern 

are identified (the LOAEL). Uncertainty/ 

safety factors are used in conjunction 

with the POD to calculate a safe 

exposure level—generally referred to as 

a population-adjusted dose (PAD) or a 

reference dose (RfD)—and a safe margin 

of exposure (MOE). For non-threshold 

risks, the Agency assumes that any 

amount of exposure will lead to some 

degree of risk. Thus, the Agency 

estimates risk in terms of the probability 

of an occurrence of the adverse effect 

expected in a lifetime. For more 

information on the general principles 

EPA uses in risk characterization and a 

complete description of the risk 

assessment process, see http://

www.epa.gov/pesticides/factsheets/

riskassess.htm. 

A summary of the toxicological 

endpoints for metaflumizone used for 

human risk assessment is provided 

below: 

i. Acute dietary endpoint (general 

population including infants and 

children). An acute dietary endpoint 

was not established for this population 

group since an endpoint of concern 

(effect) attributable to a single dose was 

not identified in the database. Studies 

considered for this endpoint included 

the acute neurotoxicity study for which 

no toxicity was observed at any dose 

including the highest dose tested: The 

limit dose (1,000 mg/kg/day). 

ii. Acute dietary endpoint (females 

13–49 years old). This endpoint was 

established based on a developmental 

effect observed in the rabbit 

developmental toxicity study that can 

be potentially due to a single dose of 

metaflumizone. This effect consisted of 

an increased incidence of an absent 

subclavian artery in the offspring at the 

LOAEL of 300 mg/kg bw/day 

metaflumizone (NOAEL = 100 mg/kg 

bw/day). The rat developmental toxicity 

study was also considered for this 

endpoint; however, no developmental 

effects were observed in this study at 

the highest dose tested of 120 mg/kg 

bw/day metaflumizone. A combined 

uncertainty factor (UF) of 300 was 

applied to account for interspecies (10x) 

and intraspecies (10x) extrapolation. A 

Food Quality Protection Act (FQPA) 

safety factor (SF) of 3x was retained 

because the rabbit developmental 

toxicity study was performed via oral 

gavage dosing. In an absorption study 

submitted by the petitioner, dietary 

exposures (which are more relevant for 

human exposures) exhibited an 

approximately 2-fold greater absorption 

into the systemic circulation than oral 

gavage dosing and, thus, can potentially 

lead to toxicity at 2-fold lower levels of 

exposure. Thus, the acute population 

adjusted dose (aPAD) for females 13–49 

years old is estimated to be 0.33 mg/kg 

bw/day. 

iii. Chronic dietary endpoint. This 

endpoint was established based on the 

systemic toxicity observed in the 

chronic toxicity study with dogs. At the 

LOAEL of 30 mg/kg bw/day (NOAEL = 


TKELLEY on DSK3SPTVN1PROD with RULES
Federal Register / Vol. 79, No. 65 / Friday, April 4, 2014 / Rules and Regulations 18807 

12 mg/kg bw/day), the effects consisted 

of reduced general health condition, 

slight to severe ataxia, recumbency, and 

severe salivation, slight decreases in 

mean corpuscular hemoglobin 

concentration and total hemoglobin, 

increased plasma bilirubin, increased 

urinary urobilinogen, and increased 

hemosiderin in the liver. A combined 

UF of 300 was applied to account for 

interspecies (10x) and intraspecies (10x) 

extrapolation and an FQPA safety factor 

of 3x. The FQPA safety factor of 3x was 

retained because the chronic toxicity 

study was performed via capsule 

dosing, which is a bolus dose very 

similar to gavage dosing (this accounts 

for the 2-fold greater absorption 

observed in dietary versus oral gavage 

exposures, as described in Unit III.B.ii.). 

Thus, the chronic population adjusted 

dose (cPAD) is estimated to be 0.040 

mg/kg bw/day. 

iv. Incidental oral (short- and 

intermediate-term). This endpoint was 

selected on the basis of the maternal 

effects observed in the rat 2-generation 

reproductive toxicity study at the 

LOAEL of 50 mg/kg bw/day 

metaflumizone (NOAEL = 20 mg/kg bw/ 

day). Maternal toxicity consisted of poor 

general health and body weight deficits 

which were also associated with 

improper nursing behavior. Similar 

effects were also noted in a 

developmental neurotoxicity study 

(gavage, range finding) also considered 

for this endpoint. In this study, poor 

maternal health was also observed at the 

LOAEL of 120 mg/kg bw/day 

metaflumizone (NOAEL = 80 mg/kg bw/ 

day). Both studies considered for this 

endpoint achieved a clear maternal 

NOAEL for the offspring effects, but the 

NOAEL of 20 mg/kg bw/day for the 2- 

generation reproductive toxicity study is 

considered more protective. The 

Agency’s LOC for this scenario is 300 

based on a 10x intraspecies factor, a 10x 

interspecies factor, and an FQPA safety 

factor of 3x (to account for the 2-fold 

greater absorption observed in dietary 

versus oral gavage exposures, as 

described in Unit III.B.ii.). 

v. Dermal (short- and intermediateterm). This endpoint was based on a rat 

90-day dermal toxicity study in which 

deficits in body weight, body-weight 

gain and food consumption (in males 

and females); anogenital smearing; 

increased macrophages in the thymus; 

lymphocyte necrosis in the mesenteric 

lymph nodes; diffuse atrophy of the 

mandibular lymph node; and increased 

hemosiderin in the liver (females only) 

were observed at the LOAEL of 300 mg/ 

kg bw/day (NOAEL = 100 mg/kg bw/

day). The Agency’s LOC for this 

scenario is 100 based on a 10x 

interspecies factor and a 10x 

intraspecies factor. 

vi. Inhalation (short- and 

intermediate-term). There is a 28-day 

inhalation study that is adequate for 

both exposure durations. There was no 

NOAEL identified for female rats. At the 

LOAEL of 0.10 mg/L metaflumizone 

(NOAEL = 0.03 mg/L), histopathology of 

the nasal tissues, lungs, thymus, 

prostate, and adrenal cortex was 

observed in males. The LOAEL 

identified in females resulted in 

lymphocyte necrosis in the mesenteric 

lymph node. 

The methods and dosimetry equations 

described in EPA’s reference 

concentration (RfC) guidance (1994) are 

suited for calculating human-equivalent 

concentrations (HECs) based on the 

inhalation toxicity point of departure 

(NOAEL, LOAEL) for use in MOE 

calculations. The regional-depositeddose ratio (RDDR), which accounts for 

the particulate diameter (mass median 

aerodynamic diameter (MMAD) and 

geometric standard deviation [sg] of 

aerosols), can be used to estimate the 

different dose fractions deposited along 

the respiratory tract. The RDDR 

accounts for interspecies differences in 

ventilation and respiratory-tract surface 

areas. Thus, the RDDR can be used to 

adjust an observed inhalation 

particulate exposure of an animal to the 

predicted inhalation exposure for a 

human. For the subchronic inhalation 

toxicity study with metaflumizone, an 

RDDR was estimated at 2.81 based on 

systemic effects (lymphocyte necrosis in 

the mesenteric lymph node) in females 

at the LOAEL of 0.03 mg/L (no NOAEL 

established) and a MMAD of 1.7mm and 

sg of 2.7. 

For this action with metaflumizone, 

only residential handler scenarios are 

being assessed for which 2-hr/day 

inhalation exposures are assumed. 

Adjustment to shorter exposure 

scenarios relative to the animal toxicity 

study duration (e.g., 2 hr residential 

exposures) should only be made if there 

is time-course information that would 

support a shorter time-frame. Since 

there is no such information available 

for metaflumizone, the unadjusted 

animal POD was used for HEC 

estimation. The HEC equals the product 

of the LOAEL from the study and the 

RDDR or 0.084 mg/L. The FQPA SF of 

10x is being retained for lack of a 

NOAEL for females in the study. The 

standard interspecies extrapolation UF 

can be reduced from 10x to 3x due to 

the HEC calculation accounting for 

interspecies differences in 

pharmacokinetics (not 

pharmacodynamic). The intraspecies UF 

remains at 10x. Therefore, the LOC for 

this scenario is 300, which includes the 

FQPA SF of 10x, interspecies (3x), and 

intraspecies (10x) extrapolation. 

C. Exposure Assessment 

1. Dietary exposure from food and 

feed uses. In evaluating dietary 

exposure to metaflumizone, EPA 

considered exposure under the 

petitioned-for tolerances as well as all 

existing metaflumizone tolerances in 40 

CFR 180.657. EPA assessed dietary 

exposures from metaflumizone 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 metaflumizone. In estimating acute 

dietary exposure, EPA used food 

consumption information from the 

United States Department of Agriculture 

(USDA) National Health and Nutrition 

Examination Survey, What We Eat in 

America (NHANES/WWEIA). This 

dietary survey was conducted from 2003 

to 2008. As to residue levels in food, 

EPA assumed tolerance-level residues. It 

was further assumed that 100% of crops 

with the requested uses of 

metaflumizone were treated. 

ii. Chronic exposure. In conducting 

the chronic dietary exposure assessment 

EPA used the food consumption data 

from the USDA NHANES/WWEIA. As 

to residue levels in food, EPA assumed 

tolerance-level residues. It was further 

assumed that 100% of crops with the 

requested uses of metaflumizone were 

treated. 

iii. Cancer. Based on the data 

summarized in Unit III.A., EPA has 

concluded that metaflumizone does not 

pose a cancer risk to humans. Therefore, 

a dietary exposure assessment for the 

purpose of assessing cancer risk is 

unnecessary. 

iv. Anticipated residue and percent 

crop treated (PCT) information. EPA did 

not use anticipated residue or PCT 

information in the dietary assessment 

for metaflumizone. Tolerance level 

residues and/or 100% crop treated (CT) 

were assumed for all food commodities. 

2. Dietary exposure from drinking 

water. The Agency used screening level 

water exposure models in the dietary 

exposure analysis and risk assessment 

for metaflumizone in drinking water. 

These simulation models take into 

account data on the physical, chemical, 

and fate/transport characteristics of 

metaflumizone. Further information 

regarding EPA drinking water models 

used in pesticide exposure assessment 


TKELLEY on DSK3SPTVN1PROD with RULES
18808 Federal Register / Vol. 79, No. 65 / Friday, April 4, 2014 / Rules and Regulations 

can be found at http://www.epa.gov/

oppefed1/models/water/index.htm. 

Based on the Pesticide Root Zone 

Model/Exposure Analysis Modeling 

System (PRZM/EXAMS) and Screening 

Concentration in Ground Water (SCI– 

GROW) models, the estimated drinking 

water concentrations (EDWCs) of 

metaflumizone for acute exposures are 

estimated to be 1.14 parts per billion 

(ppb) for surface water and 0.00214 ppb 

for ground water. The EDWCs of 

metaflumizone for chronic exposures for 

non-cancer chronic assessments are 

estimated to be 0.597 ppb for surface 

water and 0.00214 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 1.14 ppb was 

used to assess the contribution of 

drinking water. For chronic dietary risk 

assessment, the water concentration 

value of 0.597 ppb was used to assess 

the contribution of 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). 

Metaflumizone is currently registered 

for the following uses that could result 

in residential exposures: As a fire ant 

bait for application to lawns, 

landscapes, golf courses, and other noncropland area; and as a fly bait for use 

around industrial buildings, commercial 

facilities, agricultural structures/

premises, and recreational facilities/

areas. 

EPA assessed residential exposure 

using the following assumptions: Fire 

ant bait applications to home lawns are 

expected to result in short-term, 

residential handler exposure to adults. 

Fire ant bait applications to lawns and 

golf-courses are expected to result in 

short-term, post-application dermal 

exposure to adults, children 11 to <16 

years old, and children 1 to <2 years 

old, and incident oral exposure for 

children 1 to <2 years old. For the fly 

bait product, residential handler 

exposure is not expected, because the 

product is applied by commercial 

handlers. The fly bait product is 

expected to result in short-term, postapplication dermal exposure to adults, 

children 11 to <16 years old, and 

children 1 to <2 years old, and incident 

oral exposure for children 1 to <2 years 

old. 

For residential handlers, dermal and 

inhalation exposures are combined 

since the endpoints are similar for these 

routes. For children (1- to <2-year-olds), 

post-application hand-to-mouth and 

dermal exposures are combined. Since 

the LOCs for the dermal, inhalation and 

incidental oral routes are not the same 

(dermal LOC = 100, inhalation LOC = 

300, and incidental oral LOC = 300), 

these routes were combined using the 

aggregate risk index approach. 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 metaflumizone to 

share a common mechanism of toxicity 

with any other substances, and 

metaflumizone does not appear to 

produce a toxic metabolite produced by 

other substances. For the purposes of 

this tolerance action, therefore, EPA has 

assumed that metaflumizone 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 factor. 

2. Prenatal and postnatal sensitivity. 

There is no evidence for increased 

qualitative or quantitative sensitivity/

susceptibility resulting from pre- and/or 

postnatal exposures. In the rat prenatal 

development toxicity study, there was 

no offspring toxicity reported at any 

dose tested whereas in the rabbit study 

a maltransformation based on an absent 

subclavian artery was noted to occur 

only in the presence of severe maternal 

toxicity. Similarly, offspring mortality 

in the 2-generation reproductive toxicity 

occurred only in the presence of a poor 

maternal health state. Thus, there is no 

evidence for increased susceptibility. 

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 from 10x to 3x for all oral 

exposure scenarios; retained at 10x for 

inhalation exposure scenarios; and 

reduced to 1x for dermal exposures. 

That decision is based on the following 

findings: 

i. The toxicity database for 

metaflumizone is complete. 

ii. There is no indication that 

metaflumizone directly affects the 

nervous system. Clinical signs 

consisting of piloerection and body 

temperature variations were observed 

only in the absence of neuropathology 

and in the presence of a poor general 

state. There is no need for a 

developmental neurotoxicity study or 

additional uncertainty factors to account 

for neurotoxicity. 

iii. There is no evidence that 

metaflumizone results in increased 

susceptibility in the prenatal 

developmental studies in rats and 

rabbits or in developing rats in the 2- 

generation reproduction study. 

iv. There are no residual uncertainties 

identified in the exposure databases. 

The dietary analyses assumed 

tolerance-level residues, 100% CT, and 

modeled drinking water estimates. 

Therefore, EPA concludes that while the 

submission of data/information by the 

petitioner addressing the residue 

chemistry deficiencies identified in a 

previous petition may conceivably 

result in adjustment of the maximum 

theoretical residue estimate, actual 

metaflumizone dietary exposure 

estimates will not be greater than those 

generated in the current risk assessment. 

EPA made conservative (protective) 

assumptions in the ground and surface 

water modeling used to assess exposure 

to metaflumizone 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 metaflumizone. 

v. Dietary exposures (which are more 

relevant for human exposures) exhibited 

an approximately 2-fold greater 

absorption into the systemic circulation 

as compared to oral gavage and, thus, 


TKELLEY on DSK3SPTVN1PROD with RULES
Federal Register / Vol. 79, No. 65 / Friday, April 4, 2014 / Rules and Regulations 18809 

can potentially lead to toxicity at 2-fold 

lower levels of exposure. Applying a 

FQPA SF of 3x for all oral exposure 

scenarios is adequate to protect against 

any greater toxicity that might occur in 

dietary exposures (absorption was noted 

to be 2-fold greater in dietary versus oral 

gavage studies). 

vi. The FQPA SF of 10x is being 

retained for inhalation exposure 

scenarios for the use of a LOAEL instead 

of a NOAEL (no NOAEL achieved) for 

histopathological lesions consisting of 

lymphocyte necrosis in the mesenteric 

lymph node. The FQPA SF of 10x is 

adequate because the effect (lymphocyte 

necrosis) is considered minimal to slight 

and does not exhibit a strong dose 

dependence. 

vii. The FQPA SF for dermal exposure 

scenarios is being reduced from 10x to 

1x since there is a route-specific study 

with a clear NOAEL. 

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 

metaflumizone will occupy 1.6% of the 

aPAD for females 13–49 years old. 

2. Chronic risk. Using the exposure 

assumptions described in this unit for 

chronic exposure, EPA has concluded 

that chronic exposure to metaflumizone 

from food and water will utilize 5.8% of 

the cPAD for children 1–2 years old, the 

population group receiving the greatest 

exposure. Based on the explanation in 

Unit III.C.3., regarding residential use 

patterns, chronic residential exposure to 

residues of metaflumizone 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). Metaflumizone 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 metaflumizone. Since the 

LOC and toxicological points of 

departure for the short-term dermal and 

oral routes of exposure differ, the 

aggregate risk index method was used to 

determine aggregate risk (aggregate risk 

indices >1 are not a risk of concern). 

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 

risk indices of 43 for the general 

population, and 27 for children 1–2 

years old. Because EPA’s LOC for 

metaflumizone is an aggregate risk 

index less than 1, the aggregate risks 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). 

Metaflumizone is currently registered 

for uses that could result in 

intermediate-term residential exposure; 

however, since the PODs for the shortand intermediate-term durations are the 

same for metaflumizone, the short-term 

aggregate assessment is protective of 

intermediate-term exposures. 

5. Aggregate cancer risk for U.S. 

population. Based on the lack of 

evidence of carcinogenicity in two 

adequate rodent carcinogenicity studies, 

metaflumizone is not expected to pose 

a cancer risk to humans. 

6. Determination of safety. Based on 

these risk assessments, EPA concludes 

that there is a reasonable certainty that 

no harm will result to the general 

population, or to infants and children 

from aggregate exposure to 

metaflumizone residues. 

IV. Other Considerations 

A. Analytical Enforcement Methodology 

Adequate enforcement methodology 

(liquid chromatograph/mass 

spectrometer/mass spectrometer (LC/

MS/MS) Method 531/0) is available to 

enforce the tolerance expression. The 

method may be requested from: Chief, 

Analytical Chemistry Branch, 

Environmental Science Center, 701 

Mapes Rd., Ft. Meade, MD 20755–5350; 

telephone number: (410) 305–2905; 

email address: 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, 

FFDCA section 408(b)(4) requires that 

EPA explain the reasons for departing 

from the Codex level. 

The Codex has established an MRL for 

metaflumizone in or on tomato at 0.6 

ppm. This MRL is the same as the 

tolerance established for metaflumizone 

in or on tomato in the United States. 

The Codex has established MRLs for 

metaflumizone in or on eggplant at 0.6 

ppm and pepper at 0.6 ppm. These 

MRLs are different than the tolerances 

established for metaflumizone in the 

United States. 

The currently established Codex 

MRLs are based on the 2009 Joint Food 

and Agricultural Organization/World 

Health Organization (FAO/WHO) 

Meeting on Pesticide Residues (JMPR) 

metaflumizone report, and this report 

was utilized in the Agency’s residue 

chemistry review. The difference in the 

United States tolerances and the Codex 

MRLs is thus due to the following 

issues: 

i. The United States metaflumizone 

tolerance expression for crops includes 

metaflumizone (E and Z isomers) and 

the metabolite M320I04. The Codex 

MRL expression differs in that it does 

not include M320I04. The Agency 

determined that M320I04 should be 

included as a residue of concern for risk 

assessment and tolerance enforcement 

purposes as it is identified at significant 

concentrations in the submitted 

metabolism study and is the primary 

residue in some processed commodities. 

ii. Harmonization with the Codex 

MRLs for pepper and eggplant is not 

appropriate because the U.S. residue 

data for pepper (and eggplant by 

translation) indicate maximum residues 

of in excess of 0.6 ppm. The 1.5 ppm 

tolerances for both pepper and eggplant 

are based on the Organisation for 

Economic Co-operation and 

Development (OECD) tolerancecalculation procedure. The current 

Codex MRLs were established using the 

North American Free Trade Agreement 

(NAFTA) tolerance-calculation 

procedure which allowed the 

establishment of tolerances less than the 


TKELLEY on DSK3SPTVN1PROD with RULES
18810 Federal Register / Vol. 79, No. 65 / Friday, April 4, 2014 / Rules and Regulations 

highest residues; the OECD tolerancecalculation procedure does not permit 

this. 

C. Revisions to Petitioned-for Tolerances 

For pepper and eggplant, the available 

data indicate that residues may be 

greater than the proposed 0.6 ppm 

tolerance. Using the OECD tolerancecalculation procedure, EPA determined 

that a tolerance of 1.5 ppm is 

appropriate for both pepper and 

eggplant. Based on the highest-average 

field-trial residue and an average tomato 

paste processing factor of 2.94x, the 

Agency concluded that a tomato, paste 

tolerance of 1.2 ppm should be 

established. 

V. Conclusion 

Therefore, tolerances are established 

for residues of metaflumizone, (E and Z 

isomers; 2-[2-(4-cyanophenyl)-1-[3- 

(trifluoromethyl)phenyl]ethylidene]-N- 

[4-(trifluoromethoxy)phenyl] 

hydrazinecarboxamide) and its 

metabolite 4-{2-oxo-2-[3- 

(trifluoromethyl)phenyl]ethyl}- 

benzonitrile, in or on eggplant at 1.5 

ppm; pepper at 1.5 ppm; tomato at 0.60 

ppm; and tomato, paste at 1.2 ppm. 

VI. Statutory and Executive Order 

Reviews 

This final rule establishes tolerances 

under FFDCA section 408(d) in 

response to a petition submitted to the 

Agency. The Office of Management and 

Budget (OMB) has exempted these types 

of actions from review under Executive 

Order 12866, entitled ‘‘Regulatory 

Planning and Review’’ (58 FR 51735, 

October 4, 1993). Because this final rule 

has been exempted from review under 

Executive Order 12866, this final rule is 

not subject to Executive Order 13211, 

entitled ‘‘Actions Concerning 

Regulations That Significantly Affect 

Energy Supply, Distribution, or Use’’ (66 

FR 28355, May 22, 2001) or Executive 

Order 13045, entitled ‘‘Protection of 

Children from Environmental Health 

Risks and Safety Risks’’ (62 FR 19885, 

April 23, 1997). This final rule does not 

contain any information collections 

subject to OMB approval under the 

Paperwork Reduction Act (PRA) (44 

U.S.C. 3501 et seq.), nor does it require 

any special considerations under 

Executive Order 12898, entitled 

‘‘Federal Actions to Address 

Environmental Justice in Minority 

Populations and Low-Income 

Populations’’ (59 FR 7629, February 16, 

1994). 

Since tolerances and exemptions that 

are established on the basis of a petition 

under FFDCA section 408(d), such as 

the 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 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: March 28, 2014. 

Lois Rossi, 

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 § 180.657: 

■ a. Add alphabetically the 

commodities to the table in paragraph 

(a). 

■ b. Add footnote 1 to the table in 

paragraph (a). 

The additions read as follows: 

§ 180.657 Metaflumizone; tolerances for 

residues. 

(a) General. * * * 

Commodity Parts per 

million 

* * * * * 

Eggplant 1 .................................. 1.5 

* * * * * 

Pepper 1 .................................... 1.5 

Tomato 1 .................................... 0.60 

Tomato, paste 1 ......................... 1.2 

1There are no U.S. registrations as of April 

4, 2014. 

* * * * * 

[FR Doc. 2014–07559 Filed 4–3–14; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2012–0164; FRL–9903–11] 

Proquinazid; Pesticide Tolerances 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes 

tolerances for residues of proquinazid in 

or on grape and raisin. DuPont Crop 

Protection requested these tolerances 

under the Federal Food, Drug, and 

Cosmetic Act (FFDCA). 

DATES: This regulation is effective April 

4, 2014. Objections and requests for 

hearings must be received on or before 

June 3, 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–2012–0164, 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 


TKELLEY on DSK3SPTVN1PROD with RULES