Federal Register / Vol. 76, No. 66 / Wednesday, April 6, 2011 / Rules and Regulations 18915 

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) (Pub. L. 104–4). 

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), Public Law 104–113, section 

12(d) (15 U.S.C. 272 note). 

VII. Congressional Review Act 

The Congressional Review Act, 5 

U.S.C. 801 et seq., generally provides 

that before a rule may take effect, the 

agency promulgating the rule must 

submit a rule report to each House of 

the Congress and to the Comptroller 

General of the United States. 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 this final rule in the 

Federal Register. This final rule 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 21, 2011. 

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. Section 180.176 is amended by 

alphabetically adding the following 

commodities to the table in paragraph 

(a) to read as follows: 

§ 180.176 Mancozeb; tolerances for 

residues. 

(a) * * * 

Commodity Parts per 

million 

Almond ...................................... 0 .1 

Almond, hulls ............................ 4 

* * * * * 

Broccoli ..................................... 7 

Cabbage ................................... 9 

* * * * * 

Lettuce, head ............................ 3 .5 

Lettuce, leaf .............................. 18 

* * * * * 

Pepper ...................................... 12 

* * * * * 

* * * * * 

[FR Doc. 2011–7461 Filed 4–5–11; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2009–0493; FRL–8863–1] 

Ethiprole; Pesticide Tolerances 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes 

permanent tolerances (without U.S. 

registrations) for residues of the 

insecticide ethiprole [5-amino-1-[2,6- 

dichloro-4-(trifluoromethyl)phenyl]-4- 

[(ethyl)-sulfinyl]-1H-pyrazole-3- 

carbonitrile], including its metabolites 

and degradate, in or on rice and tea. 

Bayer CropScience LP requested these 

tolerances under the Federal Food, 

Drug, and Cosmetic Act (FFDCA). 

DATES: This regulation is effective April 

6, 2011. Objections and requests for 

hearings must be received on or before 

June 6, 2011, 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: EPA has established a 

docket for this action under docket 

identification (ID) number EPA–HQ– 

OPP–2009–0493. All documents in the 

docket are listed in the docket index 

available at http://www.regulations.gov. 

Although listed in the index, some 

information is not publicly available, 

e.g., Confidential Business Information 

(CBI) or other information whose 

disclosure is restricted by statute. 

Certain other material, such as 

copyrighted material, is not placed on 

the Internet and will be publicly 

available only in hard copy form. 

Publicly available docket materials are 

available in the electronic docket at 

http://www.regulations.gov, or, if only 

available in hard copy, at the OPP 

Regulatory Public Docket in Rm. S– 

4400, One Potomac Yard (South Bldg.), 

2777 S. Crystal Dr., Arlington, VA. The 

Docket Facility is open from 8:30 a.m. 

to 4 p.m., Monday through Friday, 

excluding legal holidays. The Docket 

Facility telephone number is (703) 305– 

5805. 

FOR FURTHER INFORMATION CONTACT: 

Carmen Rodia, Registration Division, 

Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001; telephone number: 

(703) 306–0327; e-mail address: 

rodia.carmen@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. Potentially 

affected entities may include, but are 

not limited to, those engaged in the 

following activities: 

• Crop production (NAICS code 111). 

• Animal production (NAICS code 

112). 

• Food manufacturing (NAICS code 

311). 

• Pesticide manufacturing (NAICS 

code 32532). 

This listing is not intended to be 

exhaustive, but rather to provide a guide 

for readers regarding entities likely to be 

affected by this action. Other types of 

entities not listed in this unit could also 

be affected. The North American 

Industrial Classification System 

(NAICS) codes have been provided to 

assist you and others in determining 

whether this action might apply to 

certain entities. If you have any 

questions regarding the applicability of 

this action to a particular entity, consult 

the person listed under FOR FURTHER

INFORMATION CONTACT. 

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.gpoaccess.gov/ecfr. 

C. How can I file an objection or hearing 

request? 

Under section 408(g) of FFDCA, 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 


erowe on DSK5CLS3C1PROD with RULES
18916 Federal Register / Vol. 76, No. 66 / Wednesday, April 6, 2011 / Rules and Regulations 

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–2009–0493 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 6, 2011. 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 that does not 

contain any 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 a copy of 

your non-CBI objection or hearing 

request, identified by docket ID number 

EPA–HQ–OPP–2009–0493, by one of 

the following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the on-line 

instructions for submitting comments. 

• Mail: Office of Pesticide Programs 

(OPP) Regulatory Public Docket (7502P), 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001. 

• Delivery: OPP Regulatory Public 

Docket (7502P), Environmental 

Protection Agency, Rm. S–4400, One 

Potomac Yard (South Bldg.), 2777 S. 

Crystal Dr., Arlington, VA. Deliveries 

are only accepted during the Docket 

Facility’s normal hours of operation 

(8:30 a.m. to 4 p.m., Monday through 

Friday, excluding legal holidays). 

Special arrangements should be made 

for deliveries of boxed information. The 

Docket Facility telephone number is 

(703) 305–5805. 

II. Summary of Petitioned-For 

Tolerance 

In the Federal Register of August 19, 

2009 (74 FR 41898) (FRL–8426–7), EPA 

issued a notice pursuant to section 

408(d)(3) of FFDCA, 21 U.S.C. 

346a(d)(3), announcing the filing of a 

pesticide petition (PP 9E7550) by Bayer 

CropScience LP, P.O. Box 12014, 2 T.W. 

Alexander Dr., Research Triangle Park, 

NC 27709–2014. The petition requested 

that 40 CFR part 180 be amended by 

establishing permanent tolerances for 

residues of the insecticide ethiprole [5- 

amino-1-[2,6-dichloro-4- 

(trifluoromethyl)phenyl]-4-[(ethyl)- 

sulfinyl]-1H-pyrazole-3-carbonitrile], 

expressed as parent equivalent, in or on 

cattle, fat at 0.1 parts per million (ppm); 

cattle, liver at 0.1 ppm; cattle, meat at 

0.01 ppm; cattle, meat byproducts, 

except liver at 0.02 ppm; eggs at 0.05 

ppm; goat, fat at 0.1 ppm; goat, liver at 

0.1 ppm; goat, meat at 0.01 ppm; goat, 

meat byproducts, except liver at 0.02 

ppm; hog, fat at 0.1 ppm; hog, liver at 

0.1 ppm; hog, meat at 0.01 ppm; hog, 

meat byproducts, except liver at 0.02 

ppm; horse, fat at 0.1 ppm; horse, liver 

at 0.1 ppm; horse, meat at 0.01 ppm; 

horse, meat byproducts, except liver at 

0.02 ppm; milk at 0.01 ppm; poultry, fat 

at 0.1 ppm; poultry, meat at 0.01 ppm; 

poultry, meat byproducts at 0.05 ppm; 

rice, grain at 3.0 ppm; sheep, fat at 0.1 

ppm; sheep, liver at 0.1 ppm; sheep, 

meat at 0.01 ppm; sheep, meat 

byproducts, except liver at 0.02 ppm; 

and tea, dried at 50 ppm. That notice 

referenced a summary of the petition 

prepared by Bayer CropScience LP, 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 

modified a number of the petitioned-for 

tolerances for ethiprole. 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 section 408(b)(2)(D) 

of FFDCA, and the factors specified in 

section 408(b)(2)(D) of FFDCA, 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 ethiprole, 

including exposure resulting from the 

tolerances established by this action. 

EPA’s assessment of exposures and risks 

associated with ethiprole 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. 

Ethiprole has a low acute toxicity via 

the acute oral, dermal, and inhalation 

routes of exposure, and is not a skin 

sensitizer nor a skin or eye irritant. In 

the mammalian toxicology database, the 

critical effects of ethiprole are 

hepatoxicity and thyroid toxicity. The 

rat was the most sensitive species 

overall after administration of ethiprole. 

Evidence of hepatoxicity is seen in the 

28-day mouse and rat; 90-day rat and 

dog; chronic/carcinogenicity rat and 

mouse; 2–generation rat; developmental 

rat; and subchronic neurotoxicity rat 

studies, and was manifested as 

increased liver weight and 

hepatocellular hypertrophy. Other 

indicators of hepatotoxicity include: 

1. Increased prothrombin time as 

observed in the 28- and 90-day rat 

studies; and 

2. Changes in clinical chemistry such 

as increased alanine transaminase 

activity, increased alkaline phosphates 

activity, increased cholesterol, increased 

triglycerides, and increased total protein 

concentration. 

Liver toxicity was also observed 

within the mice chronic/carcinogenicity 

study. A statistically significant 

increased incidence (12%) of 

hepatocellular adenoma (HCA) was 

observed in females at the highest dose 

tested (HDT), when compared to 

controls (6/50 vs. 0/50). These benign 

tumors were only observed in high dose 

females where a reduced survival rate 

was also observed. Since no treatmentrelated HCA were reported at the lower 

dose levels, the dose-dependent effect 

could not be established. In addition, no 

hepatocellular carcinoma was noted in 

either sex. Given the lack of 

genotoxicity potential, the absence of 

carcinoma following a prolonged 

exposure to ethiprole, and the absence 

of any dose relationship, this increased 

incidence of HCA in high dose female 

mice was, therefore, considered to be 

due to a threshold mechanism with a 

probable phenobarbital-like action 

hepatocellular hypertrophy associated 


erowe on DSK5CLS3C1PROD with RULES
Federal Register / Vol. 76, No. 66 / Wednesday, April 6, 2011 / Rules and Regulations 18917 

with transient liver cell proliferation 

followed by a steady state. 

Thyroid toxicity was also observed in 

numerous studies throughout the 

ethiprole database. These studies 

include the 28- and 90-day rat; chronic/ 

carcinogenicity rat; 2-generation rat; and 

subchronic neurotoxicity rat studies. 

The results/observations of the 3 

mechanistic studies conducted in rats 

suggest that ethiprole exerts effect by 

inducing hepatic microsomal enzymes 

(e.g., T4-glucuronyl transferase). This 

mechanism can lower the circulating 

levels of thyroid hormones (T4 and T3), 

resulting in a release from negative 

feedback inhibition and a compensatory 

increased secretion of thyroid 

stimulating hormone (TSH) by the 

pituitary gland. This negative feedback 

loop results in increased TSH levels to 

compensate for the reduced T4 blood 

levels, since glucuronyl transferase in 

the liver is conjugating and removing T4 

via the bile. The chronic hypersecretion 

of TSH predisposes the sensitive rodent 

thyroid gland to develop an increased 

incidence of focal hyperplasic and 

neoplasic (adenomas) lesions by a 

secondary (epigenetic) mechanism. The 

thyroid toxicity observed in adult 

rodents was manifested as increased 

thyroid weight, thyroid follicular 

hyperthrophy along with higher TSH 

plasma levels, and reduced T4 

(thyroxine) plasma levels. A study that 

evaluates homeostasis and the 

developing nervous system in the young 

is not available. 

Based on a battery of mutagenicity 

studies, ethiprole is not considered to be 

genotoxic. In accordance with the EPA’s 

Final Guidelines for Carcinogen Risk 

Assessment (March 2005), ethiprole is 

classified as ‘‘Suggestive Evidence of 

Carcinogenic Potential.’’ This 

classification is based on benign liver 

tumors in female mice, and benign 

thyroid tumors in male rats. While the 

evidence from animal data is suggestive 

of carcinogenicity, a cancer risk to 

humans from dietary exposure to 

ethiprole is of low concern and the cRfD 

is deemed protective of any potential 

cancer risk based on the following 

weight-of-evidence considerations: 

1. The liver tumors in mice were 

benign with no progression to 

malignancy; 

2. The thyroid tumors in rats were 

also benign (with no progression to 

malignancy), and the increase in the 

tumor incidences at the high dose did 

not reach statistical significance when 

compared to controls; 

3. In both species (mice and rats), 

tumors were observed only at the HDT 

(i.e., there was a lack of evidence of a 

dose-response relationship); 

4. There is no concern for 

mutagenicity/genotoxicity; 

5. The no-observed-adverse-effectlevel (NOAEL) of 0.85 milligrams/ 

kilograms/day (mg/kg/day) used for 

deriving the cRfD is approximately 86- 

fold lower than the dose (73 mg/kg/day) 

that induced benign tumors in mice; 

and 

6. The retention of the 10x FQPA SF 

yields a chronic Population Adjusted 

Dose (cPAD) that provides even more 

protection for non-cancer dietary risk 

(i.e., the cPAD of 0.003 mg/kg/day is 

approximately 2,400-fold lower than the 

dose at which tumors were seen). 

Thus, for all these reasons, the 

Agency has determined that the cPAD 

will adequately account for all chronic 

effects, including carcinogenicity, likely 

to result from exposure to ethiprole. 

More detailed information on the 

studies received and the nature of the 

adverse effects caused by ethiprole as 

well as the NOAEL and the LOAEL from 

the toxicological studies can be found in 

the document entitled, ‘‘Ethiprole: 

Human Health Risk Assessment for 

Proposed Uses on Imported Rice and 

Tea,’’ dated December 1, 2010, by going 

to http://www.regulations.gov. The 

referenced document is available in the 

docket established by this action, which 

is described under ADDRESSES. Locate 

and click on the hyperlink for docket ID 

number EPA–HQ–OPP–2009–0493. 

Double-click on the document to view 

the referenced information on pages 13– 

20 of 60. 

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 (LOC) 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 

lowest-observed-adverse-effect-level 

(LOAEL). Uncertainty/safety factors are 

used in conjunction with the POD to 

calculate a safe exposure level— 

generally referred to as a populationadjusted 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. 

The acute and chronic dietary 

endpoints were not harmonized with 

Canada’s Pesticide Management 

Regulatory Agency (PMRA) due to 

policy differences. For both endpoints, 

PMRA chose the prenatal 

developmental toxicity study in rabbits 

as their POD. PMRA considered this 

endpoint to be protective of all 

populations, including pregnant women 

and their fetuses. EPA did not choose 

the prenatal developmental toxicity 

study in rabbits for the acute dietary 

endpoint as the observed increased 

incidence of abortions in the dams 

occurred from days 21 to 28 days of 

gestation, and was not considered to be 

a single dose (acute) effect since it did 

not occur within 1 to 2 days of dosing. 

In addition, EPA did not rely on the 

prenatal developmental toxicity in 

rabbits for the chronic dietary 

assessment since it is not a long-term 

study. Instead, EPA relied on the 

combined chronic/carcinogenicity oral 

(dietary) toxicity rat study in which 

thyroid and liver toxicity were observed 

at 3.21 mg/kg/day with a NOAEL of 0.85 

mg/kg/day. This chronic rat study is 

protective of the effects observed in the 

rabbit developmental study selected by 

Canada’s PMRA. A summary of the 

toxicological endpoints for ethiprole 

used for human health risk assessment 

is shown in the table of this unit. 


erowe on DSK5CLS3C1PROD with RULES
18918 Federal Register / Vol. 76, No. 66 / Wednesday, April 6, 2011 / Rules and Regulations 

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

ASSESSMENT

Exposure/scenario Point of departure and 

uncertainty/FQPA safety factors 

RfD, PAD, LOC for risk 

assessment Study and toxicological effects 

Acute Dietary (All Populations, 

including Infants, Children, 

and Females, 13–49 years of 

age).

NOAEL = 35 mg/kg/day ...........

UFA = 10x 

UFH = 10x 

FQPA SF = UFDB = 10x 

Acute RfD = 0.35 mg/kg/day ....

aPAD = 0.035 mg/kg/day 

Acute Neurotoxicity (dietary) in Rats. 

LOAEL = 250 mg/kg/day, based on increased tremors (females), decreased 

grooming (both sexes), decreased 

arousal alert (females), increased number of animals for which no assessment 

of gait was possible (females), increased eye closure (females), increased standing/sitting hunched (females), deceased activity and rearing 

counts (females), increased hindlimb 

and forelimb grip strength (males), decreased forelimb grip strength (day 8) 

(females), decreased splay (females, 

day 1), and increased splay (males, day 

8). 

Chronic Dietary (All Populations).NOAEL= 0.85 mg/kg/day .........

UFA = 3x 

UFH = 10x 

FQPA SF = UFDB = 10x 

Chronic RfD = 0.03 mg/kg/day

cPAD = 0.003 mg/kg/day 

Combined Chronic/Carcinogenicity Oral 

(dietary) Toxicity in Rats. LOAEL = 

3.21/4.40 mg/kg/day M/F, based on observed effects in the thyroid and/or liver 

(histopathologic changes, increased 

organ weights, and/or altered thyroid 

hormone or bilirubin levels). 

Cancer (Oral, Dermal, Inhalation).Suggestive Evidence of Carcinogenicity. Quantification of cancer risk using a cancer potency factor is not 

needed. The cRfD is protective of potential cancer risk. 

Point of Departure (POD) = A data point or an estimated point that is derived from observed dose-response data and used to mark the beginning of extrapolation to determine risk associated with lower environmentally relevant human exposures. UF = uncertainty factor. UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members of the human population (intraspecies). UFDB

= to account for the absence of key data (i.e., lack of a critical study). FQPA SF = FQPA Safety Factor. PAD = population adjusted dose (a = 

acute, c = chronic). 

More detailed information on the 

toxicological endpoints for ethiprole can 

be found in the document entitled, 

‘‘Ethiprole: Human Health Risk 

Assessment for Proposed Uses on 

Imported Rice and Tea,’’ dated 

December 1, 2010, by going to http:// 

www.regulations.gov. The referenced 

document is available in the docket 

established by this action, which is 

described under ADDRESSES. Locate and 

click on the hyperlink for docket ID 

number EPA–HQ–OPP–2009–0493. 

Double-click on the document to view 

the referenced information on page 21 of 

60. 

C. Exposure Assessment 

1. Dietary exposure from food and 

feed uses. In evaluating dietary 

exposure to ethiprole, EPA considered 

exposure under the petitioned-for 

tolerances. Acute and chronic dietary 

(food only) exposure and risk 

assessments were conducted using the 

Dietary Exposure Evaluation Model 

(DEEM–FCID TM), Version 2.03. The 

dietary assessments assumed that 100% 

of crops with the requested uses of 

ethiprole were treated and that all 

treated crops contained residues at 

tolerance-level residues for acute and 

chronic dietary exposure. In addition, 

empirical processing factors were 

assumed for the requested crop uses. 

EPA assessed dietary exposures from 

ethiprole 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. An unrefined, acute dietary 

exposure assessment using tolerancelevel residues, empirical processing 

factors and assuming 100 percent crop 

treated (PCT) for the proposed 

commodities was conducted for the 

general U.S. population and various 

population subgroups. 

ii. Chronic exposure. An unrefined 

chronic dietary risk analysis was 

conducted with the DEEM–FCID TM

model, assuming tolerance-level 

residues, empirical processing factors, 

and 100 PCT. 

iii. Cancer. EPA determines whether 

quantitative cancer exposure and risk 

assessments are appropriate for a fooduse pesticide based on the weight of the 

evidence from cancer studies and other 

relevant data. If quantitative cancer risk 

assessment is appropriate, cancer risk 

may be quantified using a linear or 

nonlinear approach. If sufficient 

information on the carcinogenic mode 

of action is available, a threshold or 

non-linear approach is used and a 

cancer RfD is calculated based on an 

earlier non-cancer key event. If 

carcinogenic mode of action data is not 

available, or if the mode of action data 

determines a mutagenic mode of action, 

a default linear cancer slope factor 

approach is utilized. Based on the data 

summarized in Unit III.A., EPA has 

determined that the cPAD will 

adequately account for all chronic 

effects, including carcinogenicity, likely 

to result from exposure to ethiprole. No 

separate exposure assessment pertaining 

to cancer risk was performed for 

ethiprole; rather, EPA relied on the 

chronic exposure assessment described 

in this Unit for assessing the risk of all 

chronic effects, including cancer. 

iv. Anticipated residue and PCT 

information. EPA did not use 

anticipated residue information in the 

dietary assessment for ethiprole. 

Tolerance-level residues and 100 PCT 

were assumed for all proposed food 

commodities. 

More detailed information on the 

acute and chronic dietary (food only) 


erowe on DSK5CLS3C1PROD with RULES
Federal Register / Vol. 76, No. 66 / Wednesday, April 6, 2011 / Rules and Regulations 18919 

exposure and risk assessment for 

ethiprole can be found in the document 

entitled, ‘‘Ethiprole: Acute and Chronic 

Dietary (Food Only) Exposure and Risk 

Assessment for Proposed Imported 

Tolerances on Rice and Tea,’’ dated 

December 1, 2010, by going to http:// 

www.regulations.gov. The referenced 

document is available in the docket 

established by this action, which is 

described under ADDRESSES. Locate and 

click on the hyperlink for docket ID 

number EPA–HQ–OPP–2009–0493. 

Double-click on the document to view 

the referenced information on pages 6– 

8 of 12. 

2. Dietary exposure from drinking 

water. Ethiprole and its degradates were 

not considered for drinking water 

assessment because ethiprole is not 

registered for use in the U.S.; therefore, 

exposure to drinking water is precluded. 

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). Ethiprole 

is not registered for any specific use 

patterns that would result in residential 

exposure. 

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.’’ 

Unlike other pesticides for which EPA 

has followed a cumulative risk approach 

based on a common mechanism of 

toxicity, EPA has not made a common 

mechanism of toxicity finding as to 

ethiprole and any other substances, and 

ethiprole does not appear to produce a 

toxic metabolite produced by other 

substances. For the purposes of this 

tolerance action; therefore, EPA has not 

assumed that ethiprole has 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 the policy statements released by 

EPA’s Office of Pesticide Programs 

concerning common mechanism 

determinations and procedures for 

cumulating effects from substances 

found to have a common mechanism on 

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 ten-fold (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 safer for infants 

and children. This additional margin of 

safety is commonly referred to as the 

FQPA SF. In applying this provision, 

EPA either retains the default value of 

10x, or uses a different additional safety 

factor when reliable data are available to 

EPA to support the choice of a different 

factor. 

2. Prenatal and postnatal sensitivity. 

Although no teratogenic effects were 

observed in the existing toxicology 

database, there is uncertainty regarding 

the potential impact of ethiprole on 

thyroid hormone homeostasis in the 

developing organism. Given the 

observations that thyroid hormones 

were affected in several studies 

throughout the ethiprole database and 

the critical role thyroid hormones play 

in the development of the nervous 

system, the Agency is requiring a 

developmental thyroid toxicity study to 

assess for more subtle effects that may 

not be identified in the available core 

guideline studies. 

3. Conclusion. Based on the hazard 

and exposure data, the Agency is 

retaining the 10x FQPA SF due to the 

lack of a developmental thyroid toxicity 

study in rats. As described previously, 

hormonal changes (decreased T4 plasma 

levels, increased TSH plasma levels and 

alteration in thyroid weights) were 

observed in several studies following 

oral administration of ethiprole. 

Therefore, there is concern that 

perturbation of thyroid homeostasis may 

lead to hypothyroidism, and possibly 

result in adverse effects on the 

developing nervous system. Since the 

developmental and reproductive studies 

do not assess the thyroid in the 

developing animals, EPA has required 

that a developmental thyroid assay be 

conducted to evaluate the impact of 

ethiprole on thyroid hormones, 

structure and/or thyroid hormone 

homeostasis during development. EPA’s 

determination on the FQPA SF is based 

on the following: 

i. The toxicological database for 

ethiprole is complete with the exception 

of a developmental thyroid toxicity 

study in juvenile rats, which is needed 

to address potential prenatal and 

perinatal thyroid toxicity. Thyroid 

toxicity was noted throughout the 

toxicological database; however, the 

thyroid toxicity was assessed in adult 

animals only. 

ii. In mammals, no neurotoxic effects 

were observed during the subchronic 

neurotoxicity study in which adverse 

effects of increased thyroid and liver 

weights were observed at 7.2/33 mg/kg/ 

day (LOAEL) in males and females, 

respectively. The acute neurotoxicity 

study yielded a LOAEL of 250 mg/kg/ 

day for decreased locomotor activity 

(both sexes, day 1) and FOB findings in 

both sexes on the day of treatment (4 

hours after dosing). The FOB findings 

include increased tremors (females), 

decreased grooming (both sexes), 

decreased arousal alert (females), 

increased number of animals for which 

no assessment of gait was possible 

(females), increased eye closure 

(females), increased standing/sitting 

hunched (females), decreased activity 

and rearing counts (females), increased 

hindlimb and forelimb grip strength 

(males), decreased forelimb grip 

strength (day 8) (females), decreased 

splay (females, day 1), and increased 

splay (males, day 8). The similarity in 

the NOAELs from the acute 

neurotoxicity and subchronic 

neurotoxicity studies are consistent 

with the metabolism data that suggests 

that ethiprole is not accumulated in the 

system. 

A developmental neurotoxicity (DNT) 

study is not required for ethiprole. In 

view of the fact that thyroid toxicity 

appears to be the most sensitive 

endpoint, and thyroid hormones play a 

critical role in the development of the 

nervous system, the Agency is requiring 

the developmental thyroid toxicity 

study in lieu of the DNT. 

iii. There is no evidence that ethiprole 

results in increased susceptibility in 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 

in the exposure database for ethiprole. 

Since the dietary exposure estimates 

were based on several conservative 

assumptions, the Agency does not 

believe that the exposure estimates are 

underestimated. 

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 aPAD and cPAD. For 

linear cancer risks, EPA calculates the 


erowe on DSK5CLS3C1PROD with RULES
18920 Federal Register / Vol. 76, No. 66 / Wednesday, April 6, 2011 / Rules and Regulations 

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. For this action, there is potential 

exposure to ethiprole from food only. 

1. Acute risk. An acute aggregate risk 

assessment takes into account acute 

exposure estimates from dietary 

consumption of food and drinking 

water. Using the exposure assumptions 

described in this unit for dietary and 

non-dietary acute exposures, EPA has 

concluded that acute exposure to 

ethiprole from food only will utilize 4% 

of the aPAD for the general U.S. 

population and 14% of the aPAD for all 

infants (<1 year old), the population 

group receiving the greatest exposure. 

There are no residential uses for 

ethiprole. Based on the explanation in 

Unit III.C.3., regarding residential use 

patterns, acute residential exposure to 

residues of ethiprole is not expected. 

2. Chronic risk. Using the exposure 

assumptions described in this unit for 

chronic exposure, EPA has concluded 

that chronic exposure to ethiprole from 

food only will utilize 22% of the cPAD 

for the general U.S. population and 42% 

of the cPAD for all infants (<1 year old), 

the population group receiving the 

greatest exposure. There are no 

residential uses for ethiprole. Based on 

the explanation in Unit III.C.3., 

regarding residential use patterns, 

chronic residential exposure to residues 

of ethiprole is not expected. 

3. Aggregate cancer risk for U.S. 

population. Based on the data 

summarized and referenced in Unit 

III.A., EPA has concluded that the cRfD/ 

cPAD for ethiprole is protective of the 

cancer effects. As noted in this Unit, the 

chronic exposure for the general U.S. 

population utilizes 22% of 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 U.S. 

population, or to infants and children, 

from aggregate exposure to ethiprole 

residues. 

IV. Other Considerations 

A. Analytical Enforcement Methodology 

The submitted data are adequate to 

satisfy residue analytical methods data 

requirements for tolerance enforcement 

purposes. The proposed High 

Performance Liquid Chromatography/ 

Multistage Mass Spectrometer (HPLC/ 

MS–MS) enforcement method, Method 

01128, is acceptable for determination 

of residues of ethiprole and its sulfone 

metabolite RPA097973 for data 

collection in plant commodities. The 

proposed Gas Chromatograph-Electron 

Capture Device (GC–ECD) method 

(Report No. B003572) is suitable for 

determining residues of parent ethiprole 

and its sulfone metabolite RPA097973 

in milk, eggs and tissues. The FDA 

multiresidue method testing study for 

ethiprole and its sulfone metabolite 

RPA097973 is adequate and indicates 

that PAM multiresidue methods are not 

suitable for enforcing maximum residue 

limits (MRLs) due to the thermolability 

of ethiprole. 

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 MRLs established by the 

Codex Alimentarius Commission 

(Codex), as required by section 408(b)(4) 

of FFDCA. The Codex Alimentarius is a 

joint U.N. 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, 

section 408(b)(4) of FFDCA requires that 

EPA explain the reasons for departing 

from the Codex level. 

There are currently no MRLs 

established by Codex for ethiprole. The 

tolerances established in this rule are 

identical to those being established in 

Canada. 

C. Revisions to Petitioned-for Tolerances 

There are currently no U.S. tolerances 

or MRLs in Canada for ethiprole and no 

uses for ethiprole are currently being 

proposed in the U.S. or Canada. As part 

of PP 9E7550, Bayer CropScience LP 

proposed harmonized tolerances/MRLs 

for ethiprole residues to allow for the 

importation of ethiprole-treated rice (3.0 

ppm) and tea (50 ppm) into the U.S. and 

Canada. In addition, Bayer CropScience 

LP proposed tolerances for the 

combined residues of the insecticide 

ethiprole in or on various livestock 

commodities. 

Adequate residue data are available 

from the rice field trials conducted in 

China, India and Thailand reflecting the 

critical use pattern for ethiprole on 

imported rice. The Agency’s Guidance 

for Setting Pesticide Tolerances Based 

on Field Trial Data was utilized for 

determining appropriate tolerance level 

for ethiprole residues in or on rice, 

grain. EPA has determined that these 

residue data indicate that the tolerance 

in or on rice, grain should be set at 1.7 

ppm. 

Adequate residue data are available 

from the tea field trials conducted in 

China reflecting the critical use pattern 

for ethiprole on imported tea. These 

residue data show that the highest 

average residues on plucked fresh tea 

leaves will be 11 ppm. Taking into 

account data from the tea processing 

study that shows that combined 

ethiprole residues concentrate by up to 

2.53x in dried tea (green and black), 

EPA determined that a tolerance of 30 

ppm for dried tea would be appropriate. 

EPA and PMRA are recommending 

the same tolerance values for rice and 

tea. In addition, EPA and PMRA are not 

establishing tolerances on livestock 

commodities since ethiprole is not 

registered in the U.S., and feedstuffs 

derived from rice are unlikely to be 

imported into the U.S. and Canada and 

fed to livestock. Further, based upon 

review of the available residue data 

supporting PP 9E7550, EPA has 

determined that the residue of concern 

in plant commodities (rice and tea) for 

both tolerance expression and risk 

assessment is only ethiprole. 

V. Conclusion 

Therefore, permanent tolerances 

(without U.S. registrations) are being 

established for residues of the 

insecticide ethiprole, including its 

metabolites and degradate, in or on the 

imported plant commodities listed in 

this Unit. Compliance with the 

tolerance levels specified in this Unit is 

to be determined by measuring only 

ethiprole [5-amino-1-[2,6-dichloro-4- 

(trifluoromethyl)phenyl]-4-[(ethyl)- 

sulfinyl]-1H-pyrazole-3-carbonitrile], in 

or on the following imported plant 

commodities: Rice, grain at 1.7 ppm; 

and tea, dried at 30 ppm. 

VI. Statutory and Executive Order 

Reviews 

This final rule establishes tolerances 

under section 408(d) of FFDCA 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 


erowe on DSK5CLS3C1PROD with RULES
Federal Register / Vol. 76, No. 66 / Wednesday, April 6, 2011 / Rules and Regulations 18921 

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 section 408(d) of FFDCA, 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 section 408(n)(4) of FFDCA. 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) (Pub. L. 104–4). 

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), Public Law 104–113, section 

12(d) (15 U.S.C. 272 note). 

VII. Congressional Review Act 

The Congressional Review Act, 5 

U.S.C. 801 et seq., generally provides 

that before a rule may take effect, the 

agency promulgating the rule must 

submit a rule report to each House of 

the Congress and to the Comptroller 

General of the United States. 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 this final rule in the 

Federal Register. This final rule 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, 2011. 

Steven Bradbury, 

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. Section 180.652 is added to read as 

follows: 

§ 180.652 Ethiprole; tolerances for 

residues. 

(a) General. Tolerances (without U.S. 

registrations) are established for 

residues of the insecticide ethiprole, 

including its metabolites and degradate, 

in or on the following commodities 

listed in the table. Compliance with the 

tolerance levels specified in the table is 

to be determined by measuring only 

ethiprole [5-amino-1-[2,6-dichloro-4- 

(trifluoromethyl)phenyl]-4-[(ethyl)- 

sulfinyl]-1H-pyrazole-3-carbonitrile], in 

or on the following commodities: 

Commodity Parts per 

million 

Rice, grain 1 ............................ 1 .7 

Tea, dried 1 ............................. 30 

1There are no U.S. registrations for rice and 

tea. 

(b) Section 18 emergency exemptions. 

[Reserved] 

(c) Tolerances with regional 

registrations. [Reserved] 

(d) Indirect or inadvertent residues. 

[Reserved] 

[FR Doc. 2011–8024 Filed 4–5–11; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 268 

[EPA–HQ–RCRA–2010–0851; FRL–9290–6] 

Land Disposal Restrictions: Nevada 

and California; Site Specific Treatment 

Variances for Hazardous Selenium 

Bearing Waste 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Direct final rule. 

SUMMARY: EPA is taking direct final 

actions to both issue a site-specific 

treatment variance to U.S. Ecology 

Nevada (USEN) in Beatty, Nevada and 

to withdraw an existing site-specific 

treatment variance issued to Chemical 

Waste Management, Inc. (CWM) in 

Kettleman Hills, California. These 

actions pertain to the treatment of a 

hazardous waste generated by the 

Owens-Brockway Glass Container 

Company in Vernon, California that is 

unable to meet the concentration-based 

treatment standard for selenium 

established under the Land Disposal 

Restrictions program. The site-specific 

treatment variance issued to USEN 

provides an alternative treatment 

standard of 59 mg/L for selenium as 

measured by the Toxicity Characteristic 

Leaching Procedure. EPA has 

determined that the treatment 

performed by USEN provides the best 

demonstrated treatment available for 

this waste by reducing the potential 

amount of selenium released to the 

environment, while minimizing the 

total volume of hazardous waste land 

disposed. 

DATES: This direct final rule will be 

effective June 6, 2011 without further 

notice, unless EPA receives adverse 

written comment by May 6, 2011. If EPA 

receives adverse comments, EPA will 

publish a timely withdrawal in the 

Federal Register informing the public 

that the direct final rule will not take 

effect. 

ADDRESSES: Submit your comments, 

identified by Docket ID No. EPA–HQ– 

RCRA–2010–0851, by one of the 

following methods: 

• http://www.regulations.gov: Follow 

the on-line instructions for submitting 

comments. 

• E-mail: rcra-docket@epa.gov and 

miller.jesse@epa.gov. Attention Docket 

ID No. EPA–HQ–RCRA–2010–0851. 

• Fax: 202–566–9744. Attention 

Docket ID No. EPA–HQ–RCRA–2010– 

0851. 

• Mail: RCRA Docket (28221T), U.S. 

Environmental Protection Agency, 1200 


erowe on DSK5CLS3C1PROD with RULES