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 


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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–2012–0164 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– 

2012–0164, by one of the following 

methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the online 

instructions for submitting comments. 

Do not submit electronically any 

information you consider to be CBI or 

other information whose disclosure is 

restricted by statute. 

• Mail: OPP Docket, Environmental 

Protection Agency Docket Center (EPA/ 

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

NW., Washington, DC 20460–0001. 

• Hand Delivery: To make special 

arrangements for hand delivery or 

delivery of boxed information, please 

follow the instructions at http://

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

Additional instructions on 

commenting or visiting the docket, 

along with more information about 

dockets generally, is available at 

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

II. Summary of Petitioned-For 

Tolerance 

In the Federal Register of May 2, 2012 

(77 FR 25954) (FRL–9346–1), 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 1E7972) by DuPont Crop 

Protection, Stine Haskell Research 

Center, P.O. Box 30, Newark, DE 19714– 

0030. The petition requested that 40 

CFR 180.674 be amended by 

establishing tolerances for residues of 

the fungicide proquinazid, 6-Iodo-2- 

propoxy-3-propyl-3H-quinazolin-4-one, 

in or on imported commodities to 

include grape at 0.5 parts per million 

(ppm) and raisin at 1.0 ppm. That 

document referenced a summary of the 

petition prepared by DuPont Crop 

Protection., 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 

changed one of the requested 

commodity names from raisin; to grape, 

raisin; and added a significant figure to 

the numerical grape tolerance. The 

reasons for these changes are explained 

in Unit IV.C. 

III. Aggregate Risk Assessment and 

Determination of Safety 

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

allows EPA to establish a tolerance (the 

legal limit for a pesticide chemical 

residue in or on a food) only if EPA 

determines that the tolerance is ‘‘safe.’’ 

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

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

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ This includes 

exposure through drinking water and in 

residential settings, but does not include 

occupational exposure. Section 

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

give special consideration to exposure 

of infants and children to the pesticide 

chemical residue in establishing a 

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 proquinazid 

including exposure resulting from the 

tolerances established by this action. 

EPA’s assessment of exposures and risks 

associated with proquinazid 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. 

Proquinazid has no significant acute 

toxicity via the oral, dermal, or 

inhalation routes of exposure. It is not 

an eye or skin irritant and does not 

cause skin sensitization. Based on the 

results of a 28-day dermal study in rats 

(as well as the dermal lethal dose (LD) 

study), proquinazid is poorly absorbed 

through the skin. 


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The liver and thyroid are the primary 

target organs for proquinazid. In 

rodents, body weight/body weight gain 

reductions, increased liver and thyroid 

organ weights, hypertrophy/

hyperplasia, liver enzyme induction, 

and thyroid hormone changes were seen 

across varying durations and routes of 

exposure in rodents but not in dogs. In 

the 90-day oral rat study, the low dose 

effects of proquinazid are characterized 

primarily by altered thyroid hormones 

and associated follicular cell 

hypertrophy in the thyroid. Decrements 

in body weight and nutritional 

parameters, as well as histopathological 

changes in the liver (including 

hypertrophy) were observed at higher 

doses. In a 28-day oral rat study, 

hypertrophy of the thyroid and liver 

was completely reversible after a 6 week 

recovery period. In chronic rodent 

studies, non-neoplastic effects in both 

mice and rats included thyroid 

follicular hyperplasia and hypertrophy, 

with associated thyroid hormone 

changes (only investigated in rats), and 

some marked hepatic lesions, i.e., 

necrosis and hyperplasia (including 

oval cell hyperplasia in rats). In 

addition, chronic exposure in rats led to 

increases in the incidence of liver and 

thyroid tumors. The mode of action for 

the thyroid tumors in rats involves early 

changes in liver enzyme regulation that 

lead to dis-regulation of thyroid 

hormone homeostasis thyroid follicular 

hypertrophy/hyperplasia, and thyroid 

follicular adenoma formation. Mode of 

action data were submitted on the 

thyroid follicular cell tumors observed 

in male rats and the 

cholangiocarcinomas observed in female 

rats. The hypothesized mode of action 

(i.e., non-genotoxic) for each tumor type 

(i.e, the thyroid and 

cholangiocarcinoma) was supported by 

adequate studies that clearly identified 

the sequence of key events, doseresponse concordance, and temporal 

relationship to the tumor types. No 

treatment-related tumors were observed 

in male or female mice. The overall 

weight-of-evidence was considered 

sufficient to demonstrate that 

proquinazid thyroid follicular tumors 

are the result of an anti-thyroidal mode 

of action and that a carcinogenic 

response would not be expected at 

doses below the threshold for changes 

in liver enzyme regulation leading to 

dis-regulation of thyroid hormone 

homeostasis. The data also shows that 

rats are substantially more sensitive 

than humans to the development of 

thyroid follicular cell tumors in 

response to thyroid hormone imbalance. 

Proquinazid induced 

cholangiocarcinomas in female rats only 

at doses that produced marked liver 

toxicity and oval cell hyperplasia 

microscopically. In contrast, in both 

male and female rats, doses that 

produced less severe or no 

hepatotoxicity or oval cell proliferation 

did not produce chlolangiocarcinomas. 

Therefore, at high enough doses, 

proquinazid can cause these 

biochemical and histopathological 

effects in livers of rodents but is 

unlikely to be carcinogenic at doses 

below those causing these changes. In 

contrast, in both male and female rats, 

doses that produced less severe or no 

hepatoxicity or oval cell proliferation 

did not produce cholangiocarcinomas. 

Therefore, at high enough doses, 

proquinazid can cause these 

biochemical and histopathological 

effects in livers of rodents but is 

unlikely to be carcinogenic at doses 

below those causing these changes. 

Therefore, the Agency determined that 

quantification of risk using a non-linear 

approach (i.e., reference dose (RfD) will 

adequately protect for all chronic 

toxicity, including carcinogenicity, that 

could result from exposure to 

proquinazid. 

There is no mutagenicity concerns 

from in vivo or in vitro genetic toxicity 

assays. Proquinazid was not found to be 

immunotoxic. No evidence of increased 

quantitative or qualitative susceptibility 

was seen following in utero exposure to 

proquinazid with rats or rabbits in the 

prenatal developmental studies or in 

young rats in the 2-generation 

reproduction study. The 2-generation rat 

reproduction study resulted in no 

effects on reproduction or fertility. The 

offspring effects (decreases in F1 pup 

weight during lactation) occurred at the 

same dose which caused parental effects 

(thyroid hypertrophy, reduced body 

weight gain, and food consumption). 

Evidence of developmental delays were 

observed in developmental toxicity 

studies in rabbits and rats and were 

characterized by reduced fetal weight 

and an increased incidence of retarded 

ossification and patent ductus 

arteriosus, respectively. These 

developmental effects occurred in the 

presence of maternal toxicity and were 

considered of equal toxicity. 

There is limited evidence for 

neurotoxicity following oral exposures 

to proquinazid. Following a single 

exposure, evidence for neurotoxicity at 

the lowest observed adverse effect level 

(LOAEL) was limited to decreased 

motor activity in both sexes with no 

behavioral or neuropathology changes. 

At doses above the study LOAEL other 

effects including decreased grip strength 

and food splay were observed. 

Following repeated (dietary) exposures, 

there were no treatment-related clinical 

signs of neurotoxicity, behavioral 

changes or neuropathology. Specific 

information on the studies received and 

the nature of the adverse effects caused 

by proquinazid as well as the no 

observed adverse effect level (NOAEL) 

and the LOAEL from the toxicity studies 

can be found at http://

www.regulations.gov in document 

‘‘Proquinazid: Human Health Risk 

Assessment for the Tolerance on 

Imported Grapes’’ dated September 

2013 at pages 23 through 35 in docket 

ID number EPA–HQ–OPP–2012–0164. 

B. Toxicological Points of Departure/

Levels of Concern 

Once a pesticide’s toxicological 

profile is determined, EPA identifies 

toxicological points of departure (POD) 

and levels of concern to use in 

evaluating the risk posed by human 

exposure to the pesticide. For hazards 

that have a threshold below which there 

is no appreciable risk, the toxicological 

POD is used as the basis for derivation 

of reference values for risk assessment. 

PODs are developed based on a careful 

analysis of the doses in each 

toxicological study to determine the 

dose at which no adverse effects are 

observed (the NOAEL) and the lowest 

dose at which adverse effects of concern 

are identified (the LOAEL). Uncertainty/ 

safety factors are used in conjunction 

with the POD to calculate a safe 

exposure level—generally referred to as 

a population-adjusted dose (PAD) or a 

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 proquinazid used for 

human risk assessment is shown in 

Table 1. of this unit. Because only oral 

exposure are anticipated for imported 

grapes, no other endpoints are relevant 

such as dermal and inhalation 

exposures. 


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TABLE 1—SUMMARY OF TOXICOLOGICAL DOSES AND ENDPOINTS FOR PROQUINAZID 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).

NOAEL = 50 mg/kg/

bw UFA = 10x.

UFH = 10x 

FQPA SF = 10x 

UFDB

Acute RfD = aPAD = 

0.050 mg/kg/bw.

Acute Neurotoxicity Study-Rat. 

LOAEL = 100 mg/kg/bw based on decreased motor activity 

seen in females on day 1. 

Chronic dietary (All populations) NOAEL= 1.2 mg/kg/

day.

UFA = 13x 

UFH = 10x 

FQPA SF = 10x 

UFDB

Chronic RfD = cPAD 

= 0.004 mg/kg/day.

Chronic Toxicity/Carcinogenicity Study-Rat. 

LOAEL = 12 mg/kg/day based on increases in non-neoplastic 

liver lesions and changes in thyroid hormones and thyroid 

pathology. 

Cancer (Oral, dermal, inhalation).A non linear approach (i.e., RfD will adequately protect for all chronic toxicity, including carcinogenicity, that 

could result from exposure to proquinazid. The cPAD for proquinazid will protect for carcinogenic effects because it is below the level that caused changes in liver enzyme regulation and liver toxicity. 

FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest observed adverse effect level. mg/kg/bw = milligram/kilogram/body 

weight. 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). 

C. Exposure Assessment 

1. Dietary exposure from food and 

feed uses. In evaluating dietary 

exposure to proquinazid, EPA 

considered exposure under the 

petitioned-for tolerances as well as all 

existing proquinazid tolerances in 40 

CFR 180.674. EPA assessed dietary 

exposures from proquinazid 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 

proquinazid. 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/WWIA). As to 

residue levels in food, EPA used 

tolerance level residues and 100% 

percent crop treated (PCT). Default 

processing factors were used for grape 

juice. The Agency considers these to be 

highly conservative assessments. 

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, 

EPA used tolerance level residues and 

100% PCT. 

iii. Cancer. Quantification of risk 

using a non-linear approach (i.e., RfD 

will adequately protect for all chronic 

toxicity, including carcinogenicity, 

which could result from exposure to 

proquinazid. Cancer risk was assessed 

using the same exposure estimates as 

discussed in Unit III.C.1.ii., chronic 

exposure. 

iv. Anticipated residue and PCT 

information. EPA did not use 

anticipated residue and/or PCT 

information in the dietary assessment 

for proquinazid. Tolerance level 

residues and/or 100% CT were assumed 

for all food commodities. 

2. Dietary exposure from drinking 

water. There is no drinking water 

exposure in the U.S. associated with the 

establishment of an import tolerance. 

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). 

Proquinazid is not registered for any 

specific use patterns that would result 

in residential exposure. 

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 proquinazid to 

share a common mechanism of toxicity 

with any other substances, and 

proquinazid does not appear to produce 

a toxic metabolite produced by other 

substances. For the purposes of this 

tolerance action, therefore, EPA has 

assumed that proquinazid 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. 

No evidence of increased quantitative or 

qualitative susceptibility was seen 

following in utero exposure to 

proquinazid with rats or rabbits in the 

prenatal developmental studies or in 

young rats in the 2-generation 

reproduction study. The 2-generation rat 

reproduction study resulted in no 

effects on reproduction or fertility. The 


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offspring effects (decreases in F1 pup 

weight during lactation) occurred at the 

same dose which caused parental effects 

(thyroid hypertrophy, reduced body 

weight gain, and food consumption). 

Evidence of developmental delays were 

observed in developmental toxicity 

studies in rabbits and rats were 

characterized by reduced fetal weight 

and an increased incidence retarded 

ossification and paten ductus arteriosus, 

respectively. These developmental 

effects occurred in the presence of 

maternal toxicity. For the rats, the 

developmental effects were seen in the 

presence of clear maternal toxicity, 

including a marked reduction in body 

weight gain after adjustment for uterine 

contents and were considered to be of 

equal severity. 

3. Conclusion. In determining 

whether there are reliable data to amend 

or remove the presumptive 10X FQPA 

safety factor, EPA considered the 

following factors: 

i. The toxicity database for 

proquinazid required by 40 CFR Part 

158 is complete. However, there 

remains some uncertainty regarding the 

potential for proquinazid effects on the 

thyroid in the young. Effects on the 

thyroid (manifested as changes in 

hormones, weight, and histopathology) 

following proquinazid exposure were 

consistently observed in adult animals 

(rats) following subchronic and chronic 

exposures. Thyroid effects, however, 

were not assessed in studies involving 

neo- or postnatal animals, and EPA is 

lacking data showing the comparative 

effect of proquinazid on the thyroid in 

adult and neo- and postnatal animals. 

ii. There is only limited evidence that 

proquinazid is a neurotoxic chemical 

and there is no need for a 

developmental neurotoxicity study or 

additional UFs to account for 

neurotoxicity. There is limited evidence 

for neurotoxicity following oral 

exposures to proquinazid. Following a 

single exposure, evidence for 

neurotoxicity at the LOAEL was limited 

to decreased motor activity in both 

sexes with no behavioral or 

neuropathology changes. At doses above 

the study LOAEL other effects including 

decreased grip strength and foot splay 

were observed. Following repeated 

(dietary) exposures, there were no 

treatment-related clinical signs of 

neurotoxicity, behavioral changes, or 

neuropathology. 

iii. As discussed in Unit III.D.2., there 

is no evidence that proquinazid results 

in increased susceptibility with in utero 

rats or rabbits in the prenatal 

developmental studies or in young rats 

in the 2-generation reproduction study. 

iv. There are no residual uncertainties 

identified in the exposure databases. 

The dietary food exposure assessments 

were performed based on 100% CT and 

tolerance-level residues. Drinking water 

is not a factor because this is an import 

tolerance assessment. These 

assessments will not underestimate the 

exposure and risks posed by 

proquinazid. 

Despite the lack of any indication of 

sensitivity in the young and the very 

conservative exposure assessment, EPA 

has determined that it lacks reliable data 

to choose a FQPA safety factor other 

than the default value of 10X given (1) 

the absence of data on thyroid effects on 

the young, including comparative 

thyroid data on adults and the young, 

and (2) the fact that thyroid effects were 

the most sensitive effect seen in adult 

animals. At the same time, after 

considering all of the data on 

proquinazid toxicity and exposure, EPA 

has also determined that application of 

a FQPA safety factor of 10X, in 

conjunction with inter- and intraspecies 

safety factors, will result in a risk 

assessment that protects the safety of 

infants and children. Although there is 

some uncertainty as to whether the 

young might have greater sensitivity to 

proquinazid’s thyroid effects due to the 

absence of comparative thyroid data, 

two developmental studies and a 

reproduction study have otherwise 

shown no indication of sensitivity in the 

young to proquinazid. Additionally, the 

exposure assessment provides an extra 

margin of safety given that it is based on 

the conservative assumption that all 

grapes, and all food products derived 

from grapes (e.g., raisins, grape juice, 

wine), consumed in the United States 

bear residues of proquinazid at the 

appropriate tolerance level. This 

assumption is particularly conservative 

here because proquinazid is not 

registered for use in the United States. 

Taking into account all of these 

considerations, EPA concludes that no 

safety factor in addition to the inter- and 

intraspecies factors, and the default 

FQPA safety factor is needed to protect 

the safety of infants and children. 

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 dietary exposure from food to 

proquinazid will occupy 18% of the 

aPAD for children 1–2 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 proquinazid 

from food will utilize 47% of the cPAD 

for children 1–2 years old the 

population group receiving the greatest 

exposure. There are no residential uses 

for proquinazid. Based on the 

explanation in Unit III.C.3., regarding 

residential use patterns, chronic 

residential exposure to residues of 

proquinazid is not expected. 

3. Aggregate cancer risk for U.S. 

population. The cPAD of 0.004 mg/kg/ 

day will be protective of both noncancer and cancer effects, including rat 

tumors (liver, thyroid, and 

cholangiocarcinomas). As discussed in 

Unit III.E., aggregate exposure to 

proquinazid is below the cPAD. 

4. 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 proquinazid 

residues. 

IV. Other Considerations 

A. Analytical Enforcement Methodology 

Adequate enforcement methodology 

(gas chromatography with electron 

capture detection) is available to enforce 

the proposed tolerances for residues of 

proquinazid on grape commodities. 

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 


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Federal Register / Vol. 79, No. 65 / Friday, April 4, 2014 / Rules and Regulations 18815 

Organization food standards program, 

and it is recognized as an international 

food safety standards-setting 

organization in trade agreements to 

which the United States is a party. EPA 

may establish a tolerance that is 

different from a Codex MRL; however, 

FFDCA section 408(b)(4) requires that 

EPA explain the reasons for departing 

from the Codex level. 

The Codex has not established a MRL 

for proquinazid. However, the 

tolerances established in this rule are 

harmonized with Canadian MRLs. 

C. Revisions to Petitioned-For 

Tolerances 

The Agency is changing the proposed 

commodity definition for raisins from 

raisin to grape, raisin. The change in the 

commodity definition is to make the 

tolerance consistent with Agency 

naming-conventions for commodities 

and crop groups. No changes are 

recommended for the proposed 

tolerance levels, but the grape tolerance 

is being revised from 0.5 to 0.50 to 

correct the number of significant figures. 

V. Conclusion 

Therefore, tolerances are established 

for residues of proquinazid in or on 

grape at 0.50 ppm and grape, raisin 1.0 

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 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: March 25, 2014. 

Marty Marnell, 

Acting Director, 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. Add § 180.674 to read as follows: 

§ 180.674 Proquinazid; tolerances for 

residues. 

(a) General. Tolerances are 

established for residues of the fungicide, 

proquinazid, including its metabolites 

and degradates, in or on the 

commodities listed in the following 

table. Compliance with the tolerance 

levels specified in the following table is 

to be determined by measuring only 

proquinazid, [6-Iodo-2-propoxy-3- 

propyl-3H-quinazolin-4-one), in or on 

the following commodities: 

Commodity Parts per 

million 

Grape 1 ................................ 0 .50 

Grape, raisin 1 ..................... 1 .0 

1 No U.S. registrations for Proquinazid. 

(b) Section 18 emergency exemptions. 

[Reserved] 

(c) Tolerances with regional 

registrations. [Reserved] 

(d) Indirect or inadvertent residues. 

[Reserved] 

[FR Doc. 2014–07563 Filed 4–3–14; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2011–0110; FRL–9400–3] 

Imazapic; Pesticide Tolerances 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes a 

tolerance for residues of imazapic in or 

on soybean, seed. BASF Corporation 

requested this tolerance 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). 


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