23882 Federal Register / Vol. 76, No. 83 / Friday, April 29, 2011 / Rules and Regulations 

November 29, 2007, November 25, 2008, 

April 23, 2010 and November 19, 2010, 

to discontinue the vehicle inspection 

and maintenance (I/M) program in Clark 

and Floyd Counties. The submittal also 

includes Indiana’s demonstration that 

eliminating the I/M programs in Clark 

and Floyd Counties will not interfere 

with the attainment and maintenance of 

the ozone NAAQS and the fine 

particulate NAAQS and with the 

attainment and maintenance of other air 

quality standards and requirements of 

the CAA. We are further approving 

Indiana’s request to modify the SIP such 

that I/M is no longer an active program 

in these areas and is instead a 

contingency measure in this area’s 

maintenance plan. 

[FR Doc. 2011–10323 Filed 4–28–11; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2005–0308; FRL–8869–1] 

Metiram; Pesticide Tolerances 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes 

tolerances for residues of metiram in or 

on bananas and wine grapes. BASF 

Corporation requested these tolerances 

under the Federal Food, Drug, and 

Cosmetic Act (FFDCA). 

DATES: This regulation is effective April 

29, 2011. Objections and requests for 

hearings must be received on or before 

June 28, 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–2005–0308. 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: 

Andrew Ertman, Registration Division 

(7505P), Office of Pesticide Programs, 

Environmental Protection Agency, 1200 

Pennsylvania Ave., NW., Washington, 

DC 20460–0001; telephone number: 

(703) 308–9367; e-mail address: 

ertman.andrew@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://ecfr.gpoaccess.gov/cgi/t/

text/text-idx?c=ecfr&tpl=%2Findex.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–2005–0308 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 28, 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–2005–0308, 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 issue of 

November 30, 2005 (70 FR 71829) (FRL– 

7747–2), EPA issued a notice pursuant 

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

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

pesticide petition (PP 9E6006) by BASF 

Corporation, 26 Davis Dr., Research 

Triangle Park, NC 27709. The petition 

requested that 40 CFR part 180 be 

amended by establishing tolerances for 

residues of the fungicide metiram: A 

mixture of 5.2 parts by weight of 

ammoniates of 

ethylenebis(dithiocarbamato) zinc with 

1 part by weight 

ethylenebis(dithiocarbamic acid) 

bimolecular and trimolecular cyclic 

anhydrosulfides and disulfides, 

calculated as zinc 

ethylenebisdithiocarbamate in or on 


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imported bananas (whole fruit) at 5.0 

parts per million (ppm) and grapes at 

7.0 ppm. That notice referenced a 

summary of the petition prepared by 

BASF Corporation, the registrant, which 

is available in the docket, http:// 

www.regulations.gov. BASF 

subsequently revised their petition by 

requesting that the tolerances be set for 

banana at 3.0 ppm and for grape wine 

at 5.0 ppm. 

In the Federal Register issue of 

September 16, 2009, (74 FR 47507) 

(FRL–8431–4) in a document titled 

‘‘Mancozeb, Maneb, Metiram, and 

Thiram; Proposed Tolerance Actions,’’ 

EPA proposed: 

1. Revising the existing tolerances for 

apple and potato. 

2. Adding a tolerance for apple, 

pomace, wet. 

3. Revising the tolerance expression 

in § 180.217. The reasons for these 

changes are explained in Unit V.D. 

EPA did not receive comments on the 

Federal Register notice of November 30, 

2005, but comments were received on 

the Federal Register proposed rule of 

September 16, 2009. EPA’s response to 

these comments is discussed in Unit 

IV.C. 

III. Aggregate Risk Assessment and 

Determination of Safety 

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

allows EPA to establish a tolerance (the 

legal limit for a pesticide chemical 

residue in or on a food) only if EPA 

determines that the tolerance is ‘‘safe.’’ 

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

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

reasonable certainty that no harm will 

result from aggregate exposure to the 

pesticide chemical residue, including 

all anticipated dietary exposures and all 

other exposures for which there is 

reliable information.’’ This includes 

exposure through drinking water and in 

residential settings, but does not include 

occupational exposure. Section 

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

give special consideration to exposure 

of infants and children to the pesticide 

chemical residue in establishing a 

tolerance and to ‘‘ensure that there is a 

reasonable certainty that no harm will 

result to infants and children from 

aggregate exposure to the pesticide 

chemical residue * * *.’’ 

Consistent with FFDCA section 

408(b)(2)(D), and the factors specified in 

FFDCA section 408(b)(2)(D), EPA has 

reviewed the available scientific data 

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 metiram, 

including exposure resulting from the 

tolerances established by this action. 

Metiram is a member of the ethylene 

bisdithiocarbamate (EBDC) group of 

fungicides that also includes the related 

active ingredients mancozeb and maneb. 

Mancozeb, maneb, and metiram are all 

metabolized to ethylenethiourea (ETU) 

in the body and all degrade to ETU in 

the environment. Therefore, EPA has 

considered the aggregate or combined 

risks from food, water, and nonoccupational exposure resulting from 

metiram alone and ETU from all sources 

(i.e., the other EBDC fungicides) for this 

action. 

In response to the petitions submitted 

to establish tolerances for residues of 

metiram on bananas and grapes, EPA 

completed two risk assessments in 2007: 

A metiram risk assessment which 

considered all existing and proposed 

uses for metiram and an ETU risk 

assessment that considered exposure to 

ETU from all sources (mancozeb, 

maneb, and metiram) for all existing and 

proposed uses. 

Although the 2007 metiram review 

showed risks that were acceptable, the 

2007 ETU review demonstrated 

unacceptable cancer risks, therefore 

preventing the Agency from acting on 

the petition for bananas and grapes. The 

Agency worked to refine the cancer risk 

assessment for ETU. A refined cancer 

risk assessment for ETU from all sources 

has been completed and the Agency is 

now prepared to act on the proposed 

tolerances for bananas and wine grapes. 

Because the 2010 ETU review dealt 

strictly with refining the cancer risk, the 

Agency will be relying on three risk 

assessments to support this tolerance 

document. These assessments are as 

follows: 

• A 2007 risk assessment for metiram 

for acute, chronic, and cancer risk (refer 

to the risk assessment in docket ID 

number EPA–HQ–OPP–2005–0308 

titled ‘‘Metiram: Human Health Risk 

Assessment for PP#9E6006. Petition for 

the Establishment of Import Tolerances 

on Grapes and Bananas’’). 

• A 2007 risk assessment for ETU for 

acute, short-term, intermediate-term, 

and chronic risk (refer to the risk 

assessment in docket ID number EPA– 

HQ–OPP–2005–0308 titled 

‘‘Ethylenethiourea (ETU) from EBDCs: 

Health Effects Division (HED) Human 

Health Risk Assessment of the Common 

Metabolite/Degradate ETU’’). 

• A 2010 addendum to the 2007 ETU 

assessment for cancer risk (refer to the 

risk assessment in docket ID number 

EPA–HQ–OPP–2005–0308 titled 

‘‘Addendum to the Aggregate Human 

Health Risk Assessment of the Common 

Metabolite/Degradate Ethylene Thiourea 

(ETU) to Support New Tolerances on 

Imported Grapes and Bananas for 

Metiram and for New Tolerances for 

Mancozeb on Almonds, Broccoli, 

Cabbage, Lettuce, and Peppers’’). 

In the Federal Register issue of April 

16, 2010 (75 FR 19967) (FRL–8822–2), 

the voluntary cancellation of the last 

product containing maneb registered for 

use in the United States was announced 

by the Agency. Therefore, it is important 

to note that since all products for maneb 

have been cancelled and there are 

limited existing stocks for maneb still in 

the channels of trade, the risk 

assessments for ETU likely 

overestimates the exposures to this 

common metabolite. EPA’s assessment 

of exposures and risks associated with 

metiram and ETU 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. In addition to 

evaluating metiram, EPA also evaluated 

the risks of ETU, a contaminant, 

metabolite, and degradation product of 

metiram and the other EBDC group of 

fungicides, which includes the related 

active ingredients mancozeb and maneb. 

1. Metiram. Metiram is not acutely 

toxic via the oral, dermal, or inhalation 

routes of exposure, nor is it a skin or eye 

irritant. It is, however, a strong-to-severe 

skin sensitizer. The thyroid is a target 

organ for metiram. Thyroid effects 

observed in subchronic studies in rats 

include increased thyroid weights, 

increased thyroid stimulating hormone 

(TSH), and decreased T4 (serum 

thyroxin) values. Metiram degrades and/ 

or is metabolized to ETU. In oral rat 

metabolism studies with radiolabelled 

metiram and other EBDCs, an average 

7.5% in vivo metabolic conversion of 

EBDC to ETU occurred, on a weight-toweight basis. Metabolism data indicate 

metiram does not bio-accumulate. 

The nervous system is a target for 

metiram. Neurotoxic signs and 

neuropathology have been observed in 

subchronic studies in rats following oral 

dosing with metiram. Signs of 

neurotoxicity occurred after 2 weeks of 

dosing, including reduced forelimb grip 

strength, hind limb paralysis, muscle 

wasting, and ataxia. Neuropathology 

findings indicated decreased areas of 

myelinated axons in the sciatic, sural, 

and tibial nerves. 


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Metiram has been tested in a series of 

in vitro and in vivo genotoxicity assays. 

Metiram did not cause bacterial gene 

mutation, but there was evidence of 

mammalian gene mutation in two 

studies. The genotoxic effect was not 

considered to be related to the 

metabolism of metiram to ETU. 

Metiram degrades and/or metabolizes 

to ETU which causes thyroid tumors; 

therefore, EPA has historically 

attributed metiram’s potential for 

carcinogenicity to the formation of ETU, 

which is classified as a probable human 

carcinogen. The Agency has used the 

cancer potency factor (Q1*) of 0.0601 

(milligram/kilogram/day (mg/kg/ 

day) 1) for ETU (based on liver 

tumors in female mice) for risk 

assessment. 

Developmental toxicity was observed 

for metiram in the rat (increased 

incidence of post-implantation loss, 

decreased litter size, and decreased 

litter weight) at a dose level where 

minimal maternal toxicity (decreased 

body-weight gains) was observed. 

However, there is low concern for the 

qualitative susceptibility observed in 

the rat study since the dose response 

was well characterized; there was a 

clear NOAEL (no observed adverse 

effect level)/LOAEL (lowest observed 

adverse effect level) for maternal and 

developmental toxicity; and the doses 

selected for risk assessment were based 

on neurotoxicity and address concerns 

for developmental toxicity and thyroid 

toxicity, which occurred at higher 

doses. Additionally, in a rabbit 

developmental study, in which the 

maternal animals were adequately 

assessed, maternal toxicity observed 

included abortions and decreased bodyweight gains. 

2. ETU. The thyroid is a target organ 

for ETU; thyroid toxicity in subchronic 

and chronic rat, mouse, and dog studies 

included decreased levels of T4, 

increases or decreases in T3, 

compensatory increases in levels of 

TSH, increased thyroid weight, and 

microscopic thyroid changes, chiefly 

hyperplasia. Overt liver toxicity was 

observed in one chronic dog study. ETU 

is classified as a probable human 

carcinogen based on liver tumors in 

female mice. 

Developmental defects in the rat 

developmental study were similar to 

those seen with metiram, and included 

hydrocephaly and related lesions, 

skeletal system defects, and other gross 

defects. These defects showed increased 

susceptibility to fetuses because they 

occurred at a dose which only caused 

decreased maternal food consumption 

and body weight (BW) gain. 

Specific information on the studies 

received and the nature of the adverse 

effects caused by metiram as well as the 

NOAEL and the LOAEL from the 

toxicity studies can be found at http:// 

www.regulations.gov in the document 

titled ‘‘Metiram: Human Health Risk 

Assessment for PP#9E6006. Petition for 

the Establishment of Import Tolerances 

on Grapes and Bananas’’ on pages 18–21 

in docket ID number EPA–HQ–OPP– 

2005–0308. 

Additionally, specific information on 

the studies received and the nature of 

the toxic effects caused by ETU as well 

as the NOAEL and the LOAEL from the 

toxicity studies can be found at http:// 

www.regulations.gov in the document 

titled ‘‘Ethylenethiourea (ETU) from 

EBDCs: Health Effects Division (HED) 

Human Health Risk Assessment of the 

Common Metabolite/Degradate ETU’’ on 

pages 16–17 in docket ID number EPA– 

HQ–OPP–2005–0308. 

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 

LOAEL are identified. Uncertainty/ 

safety factors are used in conjunction 

with the POD to calculate a safe 

exposure level—generally referred to as 

a population-adjusted dose (PAD) or a 

reference dose (RfD)—and a safe margin 

of exposure (MOE). For non-threshold 

risks, the Agency assumes that any 

amount of exposure will lead to some 

degree of risk. Thus, the Agency 

estimates risk in terms of the probability 

of an occurrence of the adverse effect 

expected in a lifetime. For more 

information on the general principles 

EPA uses in risk characterization and a 

complete description of the risk 

assessment process, see http:// 

www.epa.gov/pesticides/factsheets/ 

riskassess.htm. 

A summary of the toxicological 

endpoints for metiram used for human 

risk assessment is shown in Table 1 of 

this unit. 

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

ASSESSMENT

Exposure/scenario 

POD and 

uncertainty/safety 

factors 

RfD, PAD, 

LOC for risk 

assessment 

Study and 

toxicological 

effects 

Acute dietary (General population 

including infants and children).

There was no appropriate endpoint attributable to a single dose in the available toxicity studies. 

Acute dietary (Females 13–50 

years of age).

NOAEL = 10 mg/kg/day ...............

UFA = 10x 

UFH = 10x 

FQPA SF = 10x UFDB

Acute RfD = 0.01 mg/kg/day ........

aPAD = 0.01 mg/kg/day 

Developmental Toxicity (Rabbit). 

LOAEL = 40 mg/kg/day, based on 

abortions. 

Chronic dietary (All populations) .... NOAEL = 0.4 mg/kg/day ..............

UFA = 10x 

UFH = 10x 

FQPA SF = 10x UFDB

Chronic RfD = 0.0004 mg/kg/day

cPAD = 0.0004 mg/kg/day 

Subchronic Oral Toxicity (Rat, 

bridging study). 

LOAEL = 6.7 mg/kg/day based on 

decreased forelimb grip 

strength. 


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

ASSESSMENT—Continued 

Exposure/scenario 

POD and 

uncertainty/safety 

factors 

RfD, PAD, 

LOC for risk 

assessment 

Study and 

toxicological 

effects 

Cancer (Oral, dermal, inhalation) .. Q1* = 6.01x10 2 (mg/kg/day) 1

Metiram is classified as Group B2 carcinogen (probable human carcinogen); use low-dose extrapolation for 

human risk assessment, based on ETU. Quantitative cancer risk assessments for metiram and other 

EBDCs are based on exposure to the ETU degradate. 

EBDC = ethylene bisdithiocarbamate. ETU = ethylenethiourea. FQPA SF = Food Quality Protection Act Safety Factor. LOC = level of concern. 

LOAEL = lowest observed adverse effect level. Mg/kg/day = milligram/kilogram/day. NOAEL = no observed adverse effect level. PAD = population adjusted dose (a = acute, c = chronic). POD = point of departure. Q1* = cancer potency factor. RfD = reference dose. 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). 

A summary of the toxicological 

endpoints for ETU used for human risk 

assessment is discussed in Unit IV.B. of 

the final rule published in the Federal 

Register issue of August 18, 2010 (75 FR 

50902) (FRL–8841–1). 

C. Exposure Assessment 

1. Dietary exposure from food and 

feed uses. In evaluating dietary 

exposure to metiram, EPA considered 

exposure under the petitioned-for 

tolerances as well as all existing 

metiram tolerances in 40 CFR 180.217. 

In evaluating dietary exposure to ETU, 

EPA considered exposure under the 

petitioned-for tolerances discussed in 

this document as well as all existing and 

proposed uses of the EBDC group of 

fungicides (mancozeb, maneb, and 

metiram,) including the uses for which 

there are maneb tolerances even though 

all maneb registrations have been 

cancelled. EPA assessed dietary 

exposures from metiram and ETU 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 metiram and ETU. In estimating 

acute dietary exposure, EPA used food 

consumption information from the 

United States Department of Agriculture 

(USDA) 1994–1996 and the 1998 

Nationwide Continuing Surveys of Food 

Intake by Individuals (CSFII). 

a. Metiram. The following 

assumptions were made for the acute 

exposure assessments: The Agency 

conducted a refined probabilistic 

assessment using a distribution of either 

field trial or monitoring data for 

commodities considered to be either 

non-blended or partially blended. 

Average field trial or monitoring 

residues were used for blended 

commodities. Maximum percent crop 

treated (PCT) and relevant processing 

factors were also included in the 

assessment. The PCT information is not 

available for the proposed import 

tolerances; however, percent imported 

factors were incorporated for wine 

grapes. It was assumed 100% of 

imported wine grapes would contain 

residues of metiram. EPA assumed 

100% of bananas are imported and 

would contain residues of metiram. 

b. ETU. The following assumptions 

were made for the acute exposure 

assessments: The Agency conducted a 

highly refined, probabilistic acute 

dietary assessment incorporating 

maximum PCT information for new and 

existing EBDC uses, field trial, or 

monitoring data for existing EBDC uses, 

and processing and cooking factors. It 

was assumed that PCT of total EBDCs 

could not exceed 100%; and if 

commodities were treated with more 

than one EBDC in a season, the 

combination of EBDC applications 

leading to the highest total exposure 

potential was assumed to occur. 

The PCT was estimated by summing 

the PCT for the individual EBDCs. For 

residue values, EPA used either market 

basket survey data or field trial data. For 

a few commodities mancozeb-derived 

ETU from mancozeb field trial data were 

used for both mancozeb and maneb 

because maneb field trial data were not 

available and application rates were 

sufficiently similar to estimate manebderived ETU values. 

ii. Chronic exposure. In conducting 

the chronic dietary exposure assessment 

EPA used the food consumption data 

from the USDA 1994–1996 and 1998 

CSFII. 

a. Metiram. To estimate chronic 

dietary exposure and risk to metiram 

per se, a refined assessment was 

conducted using average field trial or 

average monitoring residues. In 

addition, average PCT and relevant 

processing factors were included. The 

PCT information is not available for the 

proposed import tolerances; however, 

percent imported factors were 

incorporated for bananas and wine 

grapes. It was assumed 100% of 

imported wine grapes would contain 

residues of metiram. EPA assumed 

100% of bananas are imported and 

would contain residues of metiram. 

b. ETU. Chronic anticipated residues 

were calculated from field trial data on 

EBDCs or monitoring data for ETU. 

Averages of the field trial and market 

basket survey residues were used. EPA 

also used PCT data. 

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 

nonlinear approach is used and a cancer 

RfD is calculated based on an earlier 

non-cancer key event. If carcinogenic 

mode of action data are not available, or 

if the mode of action data determines a 

mutagenic mode of action, a default 

linear cancer slope factor approach is 

utilized. 

Metiram degrades and/or metabolizes 

to ETU which causes thyroid tumors; 

therefore, EPA has historically 

attributed metiram’s potential for 

carcinogenicity to the formation of ETU, 

which is classified as a probable human 

carcinogen. The Agency has used the 

Q1* of 0.0601 (mg/kg/day) 1 for ETU 

(based on liver tumors in female mice) 

for risk assessment. Therefore, cancer 

risk from exposure to metiram has been 

calculated by estimating exposure to 

metiram-derived ETU and using the Q1* 

for ETU. The same approach has been 

taken for the other EBDCs. EPA’s 

estimated exposure to metiram-derived 

ETU and ETU from other EBDCs 

included ETU residues found in food as 

well as ETU formed by metabolic 

conversion on parent metiram in the 

body (conversion rate of 0.075). 


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EPA relied on the same estimates 

used for the chronic exposure 

assessment in assessing cancer risk. 

iv. Anticipated residue and percent 

crop treated (PCT) information. Section 

408(b)(2)(E) of FFDCA authorizes EPA 

to use available data and information on 

the anticipated residue levels of 

pesticide residues in food and the actual 

levels of pesticide residues that have 

been measured in food. If EPA relies on 

such information, EPA must require 

pursuant to FFDCA section 408(f)(1) 

that data be provided 5 years after the 

tolerance is established, modified, or 

left in effect, demonstrating that the 

levels in food are not above the levels 

anticipated. For the present action, EPA 

will issue such data call-ins as are 

required by FFDCA section 408(b)(2)(E) 

and authorized under FFDCA section 

408(f)(1). Data will be required to be 

submitted no later than 5 years from the 

date of issuance of these tolerances. 

Section 408(b)(2)(F) of FFDCA states 

that the Agency may use data on the 

actual percent of food treated for 

assessing chronic dietary risk only if: 

• Condition a. The data used are 

reliable and provide a valid basis to 

show what percentage of the food 

derived from such crop is likely to 

contain the pesticide residue. 

• Condition b. The exposure estimate 

does not underestimate exposure for any 

significant subpopulation group. 

• Condition c. Data are available on 

pesticide use and food consumption in 

a particular area, the exposure estimate 

does not understate exposure for the 

population in such area. 

In addition, the Agency must provide 

for periodic evaluation of any estimates 

used. To provide for the periodic 

evaluation of the estimate of PCT as 

required by FFDCA section 408(b)(2)(F), 

EPA may require registrants to submit 

data on PCT. 

In the 2007 acute risk assessment for 

metiram, the Agency estimated the PCT 

for existing uses as follows: Apple, 25% 

and potatoes, 10%. 

In the 2007 chronic risk assessment 

for metiram the Agency estimated the 

PCT for existing uses as follows: Apple, 

15% and potatoes, 10%. 

In the 2007 acute risk assessment for 

ETU the Agency estimated the PCT for 

existing uses as follows: Apple, 65%; 

asparagus, 30%; barley, 2%; beans, 

dried, 2.5%; beets, sugar, 15%; Brussels 

sprouts, 32%; cantaloupe, 12.5%; carrot, 

2.5%; casaba, 12.5%; cauliflower, 15%; 

celery, 12%; chickpea, 2.5%; Chinese 

waxgourd, 15%; chive, 20%; collards, 

10%; corn, field, 2.5%; corn, sweet, 

17.5%; cottonseed, oil, 3.5%; cranberry, 

31%; cucumber, 40%; eggplant, 65%; 

fennel, Florence, 12%; fig, 1%; garlic, 

25%; grape, 81.5%; guar, seed, 1%; 

honeydew melon, 12.5%; kale, 5%; 

leek, 25%; mustard greens, 5%; oat, 2%; 

onion, dry bulb, 85%; peanut, 3.5%; 

pear, 55%; potato, 85%; pumpkin, 15%; 

rice, 2.5%; rye grain, 2%; squash, 

summer, 35%; squash, winter, 0%; 

tomato, fresh, 80%; tomato, processed, 

25%; turnip tops, 86%; walnut, 37.5%; 

watermelon, 55%; and wheat, grain, 

3.5%. 

For the 2007 chronic risk assessment 

for ETU the Agency estimated the PCT 

for existing uses as follows: Apple, 42%; 

asparagus, 21%; barley, 2%; beans, 

dried, 1%; beets, sugar, 6%; Brussels 

sprouts, 21%; cantaloupe, 6%; carrot, 

8%; casaba, 6%; cauliflower, 5%; 

celery, 12%; chickpea, 1%; Chinese 

waxgourd, 5%; chive, 10%; collards, 

10%; corn, field, 1%; corn, sweet, 11%; 

cottonseed, oil, 2%; cranberry, 31%; 

cucumber, 20%; eggplant, 45%; fennel, 

Florence, 12%; fig, 1%; garlic, 25%; 

grape, 60%; guar, seed, 1%; honeydew 

melon, 6%; kale, 5%; kohlrabi, 1%; 

leek, 10%; mustard greens, 5%; oat, 2%; 

onion, dry bulb, 60%; peanut, 2%; pear, 

40%; potato, 63%; pumpkin, 6%; rice, 

1%; rye grain, 2%; squash, summer, 

25%; squash, winter, 25%; tomato, 

fresh, 54%; tomato, processed, 54%; 

walnut, 31%; watermelon, 10%; and 

wheat, grain, 31%. 

For the 2010 ETU cancer risk 

assessment the Agency estimated the 

PCT for existing uses as follows: Apple, 

51%; asparagus, 15%; barley, 1%; 

beans, dried, 1%; beets, sugar, 3.5%; 

Brussels sprouts, 15%; cantaloupe, 

7.5%, carrot, 5%; cauliflower, 10%; 

chickpea, 1%; collards, 31%; corn, field, 

1%; corn, sweet, 6%; cottonseed, oil, 

11%; cranberry, 45%; cucumber, 30%; 

eggplant, 30%; fig, 5%; flaxseed, 11%; 

garlic, 25%; grape, 6%; guar, seed, 1%; 

kale, 73%; leek, 15%; mustard greens, 

22%; oat, 11%; onion, dry bulb, 75%; 

peanut, 2%; pear, 35%; potato, 67.5%; 

pumpkin, 20.5%; rice, 1%; rye grain, 

11%; safflower, oil, 11%; squash, 

summer, 57%; squash, winter, 26%; 

tomato, fresh, 30%; tomato, processed, 

30%; turnip tops, 36%; walnut, 36%; 

watermelon, 45%; and wheat, grain, 

11%. 

In most cases, EPA uses available data 

from USDA/National Agricultural 

Statistics Service (NASS), proprietary 

market surveys, and the National 

Pesticide Use Database for the chemical/ 

crop combination for the most recent 6– 

7 years. EPA uses an average PCT for 

chronic dietary risk analysis. The 

average PCT figure for each existing use 

is derived by combining available 

public and private market survey data 

for that use, averaging across all 

observations, and rounding to the 

nearest 5%, except for those situations 

in which the average PCT is less than 

one. In those cases, 1% is used as the 

average PCT and 2.5% is used as the 

maximum PCT. EPA uses a maximum 

PCT for acute dietary risk analysis. The 

maximum PCT figure is the highest 

observed maximum value reported 

within the recent 6 years of available 

public and private market survey data 

for the existing use and rounded up to 

the nearest multiple of 5%. 

Percent crop treated information is 

not available for the proposed import 

tolerances; however, percent imported 

factors were incorporated for wine 

grapes. 

In the 2007 acute risk assessment for 

metiram, the Agency estimated the 

percent imported factors for new uses as 

follows: Wine grape, 20%. 

In the 2007 chronic risk assessment 

for metiram, the Agency estimated the 

percent imported factors for new uses as 

follows: Wine grape, 20%. 

In the 2007 acute risk assessment for 

ETU the Agency estimated the percent 

imported for existing uses as follows: 

Wine grape, 81.5%. 

For the 2007 chronic risk assessment 

for ETU the Agency estimated the 

percent imported for existing uses as 

follows: Wine grape, 60%. 

For the 2010 ETU cancer risk 

assessment the Agency estimated the 

percent imported for existing uses as 

follows: Wine grape, 26%. 

EPA estimates the percent crop 

treated for new uses (PCTn) of a 

pesticide represent the upper bound of 

use expected during the pesticide’s 

initial 5 years of registration. The PCTn 

recommended for use in the chronic 

dietary assessment is calculated as the 

average PCT of the pesticide or 

pesticides that are the market leader or 

leaders, (i.e., the pesticides with the 

greatest PCT) on that site over the 3 

most recent years of available survey 

data. The PCTn recommended for use in 

the acute dietary assessment is the 

maximum observed PCT over the same 

period. Comparisons are only made 

among pesticides of the same pesticide 

types (e.g., the market leader for 

fungicides on the use site is selected for 

comparison with a new fungicide). The 

market leader included in the 

estimation may not be the same for each 

year since different pesticides may 

dominate at different times. 

Typically, EPA uses USDA/NASS as 

the source data because it is publicly 

available and directly reports values for 

PCT. When a specific use site is not 

reported by USDA/NASS, EPA uses 

proprietary data and calculates the PCT 

given reported data on acres treated and 


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acres grown. If no data are available, 

EPA may extrapolate PCTn from other 

crops, if the production area and pest 

spectrum are substantially similar. 

EPA refines PCTn estimates based on 

approaches other than the market leader 

approach if the previous PCTn estimates 

based on the market leader indicate that 

the chemical exposure potentially pose 

a risk of concern. EPA considers the 

pest or pest spectrum targeted by the 

chemical for the new uses and identifies 

other pesticides already registered on 

that crop that target the same pest or 

pest spectrum. The PCTn is calculated 

based on the data from the three most 

recently available pesticide usage 

surveys. If multiple chemicals are 

identified that target the same pest 

spectrum, then the one with the highest 

PCT is selected from each year/crop 

combination. Consideration is also 

given to the potential for the 

development of resistance for each 

chemical using data available from the 

Resistance Action Committees. 

EPA has considered all available 

relevant information and concludes that 

it is unlikely that the PCTn values will 

be exceeded during the next 5 years. 

The Agency believes that the three 

conditions discussed in Unit III.C.1.iv. 

have been met. With respect to 

Condition a, PCT estimates are derived 

from Federal and private market survey 

data, which are reliable and have a valid 

basis. The Agency is reasonably certain 

that the percentage of the food treated 

is not likely to be an underestimation. 

As to Conditions b and c, regional 

consumption information and 

consumption information for significant 

subpopulations is taken into account 

through EPA’s computer-based model 

for evaluating the exposure of 

significant subpopulations including 

several regional groups. Use of this 

consumption information in EPA’s risk 

assessment process ensures that EPA’s 

exposure estimate does not understate 

exposure for any significant 

subpopulation group and allows the 

Agency to be reasonably certain that no 

regional population is exposed to 

residue levels higher than those 

estimated by the Agency. Other than the 

data available through national food 

consumption surveys, EPA does not 

have available reliable information on 

the regional consumption of food to 

which metiram may be applied in a 

particular area. 

2. Dietary exposure from drinking 

water—i. Metiram. The Agency has 

determined that metiram is very shortlived in soil and water, and would not 

reach water used for human 

consumption whether from surface 

water or ground water. 

ii. ETU. ETU is highly water soluble, 

and may reach both surface and ground 

water under some conditions. The ETU 

surface water Estimated Drinking Water 

Concentrations (EDWCs) were generated 

using a combined monitoring/modeling 

approach. Results of a surface water 

monitoring study conducted by the ETU 

Task Force were used to refine the 

outputs of the Pesticide Root Zone 

Model/Exposure Analysis Modeling 

System (PRZM–EXAMS) models; the 

site/scenario modeled was application 

of an EBDC fungicide on peppers in 

Florida, and was chosen to produce the 

highest EDWC acute values. The ground 

water EDWC was detected in a Florida 

community water system intake in a 

targeted ground water monitoring study 

conducted by the EBDC Task Force from 

1999 to 2003. Both these surface and 

ground water values represent upperbound conservative estimates of the 

total ETU residual concentrations that 

might be found in surface water and 

ground water due to the use of the EBDC 

fungicides. 

Based on the PRZM/EXAMS and 

monitoring studies, the EDWCs of ETU 

acute and chronic exposures are 

estimated to be 25.2 parts per billion 

(ppb), and 0.1 ppb, respectively, for 

surface water. The EDWC for chronic 

exposure is estimated to be 0.21 ppb for 

ground water. 

Estimates of drinking water 

concentrations were directly entered 

into the dietary exposure model. For 

acute dietary risk assessment, the water 

concentration value of 25.2 ppb was 

used to assess the contribution to 

drinking water. For chronic dietary risk 

assessment of ETU, the water 

concentration of value 0.21 ppb was 

used to assess the contribution to 

drinking water. For cancer dietary risk 

assessment of ETU, the water 

concentration of value 0.21 ppb was 

used to assess the contribution to 

drinking water. 

3. From non-dietary exposure. The 

term ‘‘residential exposure’’ is used in 

this document to refer to nonoccupational, non-dietary exposure 

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

indoor pest control, termiticides, and 

flea and tick control on pets). 

i. Metiram. Metiram is not registered 

for any specific use patterns that would 

result in residential exposure. 

ii. ETU. ETU non-dietary exposure is 

expected as a result of the registered 

uses of mancozeb and the other EBDCs 

on home gardens, golf courses, and sod 

farms. For ETU, aggregate exposure 

sources include food, drinking water, 

home gardening activities, and golfing. 

The Agency has determined that it is 

appropriate to aggregate chronic 

exposure through food with short- and 

intermediate-term residential exposures 

to ETU. 

The three scenarios that were 

evaluated for ETU are as follows: The 

first is the Short/Intermediate-Term 

Home Garden Aggregate, which 

combines handler exposures (inhalation 

and dermal) and post application garden 

exposures (dermal) plus average daily 

food and drinking water exposure for 

adults and post application garden 

exposures (dermal) plus average daily 

food and drinking water exposure for 

youth. The second is the Short-Term 

Treated Turf Aggregate (Toddlers), 

which combines treated turf post 

application exposures (incidental oral 

and dermal) plus average daily food and 

drinking water exposure for toddlers. 

The third is the Short/IntermediateTerm Treated Turf Aggregate, which 

considers short-term residential 

exposures (dermal) plus average daily 

food and drinking water exposure for 

adults such as golfing on treated turf. 

This assessment is protective of adult 

and youth golfers. Although exposure to 

children golfing could be almost twice 

that of the adult golfer because of 

increased surface area (SA)/BW ratios, 

younger golfers are not expected to use 

the golf course for the same length of 

time as adolescents and adults. The 

shorter duration on the golf course for 

younger golfers offsets the higher SA/ 

BW; therefore, risks from short-term 

post-application exposures to young 

golfers are likely to be similar to risks 

for adult golfers. 

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.’’ 

As previously mentioned, the risk 

estimates summarized in this document 

are those that result only from the use 

of metiram, and ETU derived from 

metiram and the other EBDC chemicals, 

which are all dithiocarbamates. For the 

purposes of this action, EPA has 

concluded that metiram does not share 

a common mechanism of toxicity with 

other substances. The Agency reached 

this conclusion after a thorough internal 

review and external peer review of the 


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data on a potential common mechanism 

of toxicity. 

EPA concluded that the available 

evidence does not support grouping the 

dithiocarbamates based on a common 

toxic effect (neuropathology) occurring 

by a common mechanism of toxicity 

(related to metabolism to carbon 

disulfide (CS2)). After a thorough 

internal and external peer review of the 

existing data bearing on a common 

mechanism of toxicity, EPA concluded 

that the available evidence shows that 

neuropathology cannot be linked with 

CS2 formation. For more information, 

please see the December 19, 2001 

memo, ‘‘The Determination of Whether 

Dithiocarbamate Pesticides Share a 

Common Mechanism of Toxicity’’ on the 

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

oppsrrd1/cumulative/dithiocarb.pdf. 

D. Safety Factor for Infants and 

Children 

1. In general. Section 408(b)(2)(C) of 

FFDCA provides that EPA shall apply 

an additional tenfold (10X) margin of 

safety for infants and children in the 

case of threshold effects to account for 

prenatal and postnatal toxicity and the 

completeness of the database on toxicity 

and exposure unless EPA determines 

based on reliable data that a different 

margin of safety will be safe for infants 

and children. This additional margin of 

safety is commonly referred to as the 

Food Quality Protection Act Safety 

Factor (FQPA SF). In applying this 

provision, EPA either retains the default 

value of 10X, or uses a different 

additional safety factor when reliable 

data available to EPA support the choice 

of a different factor. 

2. Prenatal and postnatal sensitivity— 

i. Metiram. Developmental toxicity was 

observed in the rat (increased incidence 

of post-implantation loss, decreased 

litter size, and decreased litter weight) 

at a dose level where minimal maternal 

toxicity (decreased BW gains) was 

observed. However, there is low concern 

for the qualitative susceptibility 

observed in the rat study since the dose 

response was well characterized; there 

was a clear NOAEL/LOAEL for maternal 

and developmental toxicity; and the 

doses selected for risk assessment were 

based on neurotoxicity and address 

concerns for developmental toxicity and 

thyroid toxicity, which occurred at 

higher doses. In a rabbit developmental 

study, in which the maternal animals 

were adequately assessed, maternal 

toxicity observed included abortions 

and decreased BW gains. No qualitative 

or quantitative sensitivity was identified 

in the young in this study for the 

developmental effects assessed. 

Although many developmental effects 

were assessed, a new study was 

required because the study did not 

assess soft tissue and internal structures 

of the head. In a recently submitted 

developmental rabbit study with ETU, 

developmental effects in the brain were 

not observed at dose levels below those 

currently used for quantifying metiram 

risks, reducing concerns for these effects 

(see further description of study in this 

unit). 

ii. ETU. There was evidence of 

increased susceptibility of fetuses to 

ETU in the rat developmental studies 

because hydrocephaly occurred at doses 

below those causing maternal toxicity. 

Recently the Agency reviewed a new 

developmental study in rabbits. Effects 

seen in the pups (decreased BW, domed 

heads, and hydrocephaly) were 

observed in the presence of maternal 

toxicity. The incidence of domed heads 

and hydrocephaly is within the range of 

historical controls. In addition, these 

effects are observed at levels higher than 

the effects observed in the rat study. An 

acceptable reproductive study was not 

available for ETU. As a result, the 

Agency evaluated the level of concern 

for the effects observed when 

considered in the context of all available 

toxicity data. In addition, the Agency 

evaluated the database to determine if 

there were residual uncertainties after 

establishing toxicity endpoints and 

traditional uncertainty factors to be used 

in the ETU risk assessment. 

3. Conclusion—i. Metiram. Although 

there are no residual uncertainties for 

pre- and/or postnatal toxicity, the FQPA 

SF of 10X was retained due to database 

uncertainties for metiram. There are 

data gaps for a developmental 

neurotoxicity study (DNT), a 

developmental toxicity study in the 

rabbit and a 2-generation reproduction 

study in the rat. EPA determined that 

the FQPA SF must be retained to 

account for the lack of these studies, 

since the available data do not provide 

a basis to support reduction or removal 

of the factor. 

No additional FQPA SF is needed 

beyond the 10X database uncertainty 

factor that was applied to account for 

the data gaps for a developmental 

neurotoxicity study, a developmental 

toxicity study in the rabbit, and a 2- 

generation reproduction study in the rat 

with metiram. The reasons for this 

conclusion are: 

a. There are data gaps for studies that 

are critical for assessing effects on 

infants and children, but the Agency 

does have developmental toxicity (rat 

and rabbit) and reproduction data on 

metiram that provides some 

characterization of developmental and 

reproductive hazard. Although there 

was incomplete assessment of the fetal 

rabbit and there was incomplete 

measurement of some reproductive 

parameters in the reproduction study, 

the submitted studies provide a partial 

assessment of the effects of concern and 

sufficient information on pertinent toxic 

effects for EPA to conclude that a 10x 

database uncertainty factor is 

adequately protective. 

b. Pre- and/or postnatal susceptibility 

has been adequately characterized in 

one species (rat). 

c. The exposure assessment, although 

refined, is unlikely to underestimate 

potential exposures. 

d. Although there is a data gap for a 

developmental neurotoxicity study, 

since the available metiram database 

includes NOAELs for neurotoxicity and 

neuropathology (decreased grip strength 

at lower doses, demyelination at high 

doses) in adult animals upon which risk 

assessments are based, this information 

helps to characterize the dose range at 

which effects can be expected in the 

developmental neurotoxicity study and 

thus informs dose selection for that 

study. Selected doses would be in the 

range of the dose levels from the prior 

studies at the NOAEL and LOAEL levels 

(0.4 and 6.7 mg/kg/day, respectively). 

Significant toxic effects occurring at 

doses more than 10-fold below these 

levels are unlikely. 

ii. ETU. The toxicity database for ETU 

is not complete. EPA lacks the following 

studies: A DNT study, a 2-generation 

reproduction study, and a comparative 

thyroid study in adults and offspring. 

The Agency has recently received and 

evaluated a developmental toxicity 

study in rabbits. Given the remaining 

data gaps are for studies that directly 

assess the risk to the young, EPA does 

not have reliable data to remove or 

modify the presumptive 10X FQPA SF. 

No additional safety factor beyond 

10X is needed to account for the missing 

toxicity data for ETU for the following 

reasons: 

a. The teratogenic effects of ETU have 

been well characterized in numerous 

studies in the published literature, as 

well as in a guideline study submitted 

by the registrant. In addition, since 

metabolism studies have shown that 

approximately 7.5% of the EBDCs 

(mancozeb, maneb, and metiram,) 

convert to ETU in mammalian systems, 

the extensive toxicity database on the 

EBDCs on developmental effects 

provide information about the pre- and 

postnatal toxicity of ETU as well as the 

parent compound; 

b. There are clear NOAELs for 

developmental effects seen in the ETU 

developmental studies, and the doseVerDate Mar<15>2010 16:27 Apr 28, 2011 Jkt 223001 PO 00000 Frm 00028 Fmt 4700 Sfmt 4700 E:\FR\FM\29APR1.SGM 29APR1

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response relationships, although steep, 

are well characterized. 

c. The developmental endpoint with 

the lowest NOAEL was selected for 

deriving the acute PAD (aPAD). 

d. Thyroid toxicity was selected for 

deriving the chronic PAD (cPAD) as 

well as endpoints for non-dietary 

exposures (incidental oral, dermal, and 

inhalation). Since the available ETU 

database includes NOAELs for thyroid 

toxicity in adult animals upon which 

risk assessments are based, this 

information helps to characterize the 

dose range at which effects can be 

expected in the developmental 

neurotoxicity study and thus would 

inform dose selection for the 

comparative thyroid study; selected 

doses would be in the range of these 

dose levels (NOAEL of 0.2 mg/kg/day 

and LOAEL of 2 mg/kg/day). Significant 

toxic effects occurring at doses more 

than 10-fold below these levels are 

unlikely. 

e. Information on ETU gleaned from 

the extensive EBDC database on effects 

other than development effects also 

reduces, to a degree, the uncertainty 

arising from the significant data gaps for 

ETU. 

f. EPA has concluded that the 

exposure assessment, although refined, 

is unlikely to underestimate potential 

exposures especially considering 

exposure to maneb was included even 

though all maneb products have been 

canceled. In making this judgment, EPA 

has taken into account that it is relying 

on three separate reviews in this 

document: 

• A 2007 risk assessment for 

mancozeb for acute, short-term, 

intermediate-term, chronic, and cancer 

risk. 

• A 2007 risk assessment for ETU for 

acute, short-term, intermediate-term, 

and chronic risk. 

• A 2010 addendum to the 2007 ETU 

assessment for cancer risk—and that the 

PCT estimates differ slightly between 

reviews. 

In comparing the PCT information from 

2007 and 2010, there are some increases 

in usage for some crops, and there are 

decreases in usage for other crops. 

These differences appear to largely 

offset each other. Further, most of the 

increases are attributable to estimated 

increases in maneb usage but, as noted, 

maneb was canceled in 2010 and it is 

unlikely that existing stocks are 

sufficient to sustain prior usage levels 

much less any increased usage. An EPA 

sensitivity analysis of the main 

contributors to ETU exposure showed 

no significant increase in exposure from 

the changed PCT estimated. The PCT 

values used in these risk assessments 

are detailed in the memo titled 

‘‘Mancozeb. Discussion on Percent Crop 

Treated Values Used in Aggregate and 

Chronic Assessments’’ in docket ID 

number EPA–HQ–OPP–2005–0308. 

In any event, there are two other 

aspects of the exposure assessment that 

are likely to significantly overstate 

exposure to mancozeb and ETU. First, 

exposure estimates for some crops, 

including bananas, a high-consumption 

food, include the assumption that 

everything consumed in the United 

States has been treated. Second, the 

residue data used in the assessment for 

the proposed commodities and many 

other crops are based on crop field 

trials. Monitoring studies conducted for 

several crops have shown that residues 

on foods close to the point of 

consumption are much lower than the 

residues found in crop field trials. 

For all of these reasons, EPA 

concludes that it has not 

underestimated exposure to mancozeb 

and ETU. 

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 

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—i. Metiram. The 

metiram acute aggregate assessment 

considers acute exposure to metiram 

only and not ETU. Further, this 

assessment is based on residues of 

metiram in food only since residues of 

metiram are not expected in drinking 

water. Using the exposure assumptions 

discussed in this unit for acute 

exposure, the acute dietary exposure 

from food to metiram will occupy 22% 

of the aPAD for females 13–49 years of 

age, the only population group of 

concern. 

ii. ETU. Using the exposure 

assumptions discussed in this unit for 

acute exposure, the acute dietary 

exposure from food and water to ETU 

will occupy 87% of the aPAD for 

females 13–49 years of age, the only 

population group of concern. 

2. Chronic risk—i. Metiram. There are 

no long-term residential exposure 

scenarios for metiram and there is not 

likely to be residues of metiram in 

drinking water. Therefore, the long-term 

or chronic (non-cancer) aggregate risk 

for metiram includes contribution from 

food alone. Using the exposure 

assumptions described in this unit for 

chronic exposure, EPA has concluded 

that chronic exposure to metiram from 

food will utilize 70% of the cPAD for 

children 1–2 years of age, the 

population group receiving the greatest 

exposure. 

ii. ETU. The aggregate chronic risks 

were calculated using food and water 

exposure only because golfing and 

toddler transplanted turf exposure 

scenarios were considered to occur only 

on a short term basis. Using the 

exposure assumptions described in this 

unit for chronic exposure, EPA has 

concluded that chronic exposure to ETU 

from food and water will utilize 50% of 

the cPAD for children (1 to 2 years old), 

the population group receiving the 

greatest exposure. 

3. Short- and Intermediate-term risk— 

i. Metiram. Short- and intermediateterm aggregate exposure takes into 

account short- and intermediate-term 

residential exposure plus chronic 

exposure to food and water (considered 

to be a background exposure level). 

A short- and/or intermediate-term 

adverse effect was identified; however, 

metiram is not registered for any use 

patterns that would result in short- and/ 

or intermediate-term residential 

exposure. Short- and intermediate-term 

risk is assessed based on short- and/or 

intermediate-term residential exposure 

plus chronic dietary exposure. Because 

there is no short- or intermediate-term 

residential exposure and chronic dietary 

exposure has already been assessed 

under the appropriately protective 

cPAD (which is at least as protective as 

the POD used to assess short-term risk), 

no further assessment of short- and/or 

intermediate-term risk is necessary, and 

EPA relies on the chronic dietary risk 

assessment for evaluating short- and 

intermediate-term risk for metiram. 

ii. ETU. Short- and intermediate-term 

aggregate exposure takes into account 

short-term residential exposure plus 

chronic exposure to food and water 

(considered to be a background 

exposure level). 

Although there are no residential uses 

for metiram, the previous ETU aggregate 

assessment included residential 

exposures to other EBDCs. Mancozeb is 

currently registered for uses that could 

result in short- and intermediate-term 

residential exposure to ETU. The 2007 

ETU assessment also included products 

containing maneb which were expected 

to result in short- and intermediate-term 

exposure. As previously discussed, 

these products have since been 

cancelled. The Agency determined that 


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it was appropriate to aggregate chronic 

exposure through food with short- and 

intermediate-term residential exposures 

to ETU. The three scenarios that were 

evaluated for ETU are the following: 

a. ETU Short/Intermediate-Term 

Home Garden Aggregate. The ETU 

short/intermediate-term home garden 

aggregate MOEs are 13,000 and 17,000 

for adults and youth, respectively. For 

ETU EPA is concerned only with MOEs 

that are below 1,000, these MOEs do not 

raise a risk concern. 

b. ETU Short-Term Treated Turf 

Aggregate (Toddlers). The ETU shortterm treated turf aggregate MOE for 

toddlers is 1,100. For ETU EPA is 

concerned only with MOEs that are 

below 1,000; therefore, this MOE does 

not raise a risk concern. 

c. ETU Short/Intermediate-Term 

Treated Turf Aggregate. The ETU shortterm treated turf aggregate MOE for 

golfers is 6,100. For ETU EPA is 

concerned only with MOEs that are 

below 1,000; therefore, this MOE does 

not raise a risk concern. 

4. Aggregate cancer risk for U.S. 

population—Metiram and ETU. As 

noted earlier in this document, EPA has 

historically attributed metiram’s 

potential for carcinogenicity to the 

formation of ETU, which is classified as 

a probable human carcinogen (B2). 

The cancer risks were aggregated 

using the food and drinking water 

exposures for the general population 

and the food, water and recreational 

exposures for golfers, home gardeners 

and athletes. The average daily dose was 

used for food and water exposures and 

the lifetime average daily dose was used 

for the recreational exposures. The 

aggregate doses were multiplied times 

the potency factor for ETU, 0.0601 (mg/ 

kg/day)¥1 to determine the cancer risks. 

The risk is estimated to be 3 × 10¥6. 

EPA generally considers cancer risks 

(expressed as the probability of an 

increased cancer case) in the range of 

1 in 1 million (or 1 × 10¥6) or less to 

be negligible. The precision which can 

be assumed for cancer risk estimates is 

best described by rounding to the 

nearest integral order of magnitude on 

the logarithmic scale; for example, risks 

falling between 3 × 10¥7 and 3 × 10¥6

are expressed as risks in the range of 

10¥6. Considering the precision with 

which cancer hazard can be estimated, 

the conservativeness of low-dose linear 

extrapolation, and the rounding 

procedure described in this unit, cancer 

risk should generally not be assumed to 

exceed the benchmark level of concern 

of the range of 10¥6 until the calculated 

risk exceeds approximately 3 × 10¥6. 

This is particularly the case where some 

conservatism is maintained in the 

exposure assessment. Although the ETU 

exposure risk assessment is refined, it 

retains significant conservatism in that, 

for leafy greens, field trial data and not 

monitoring data on similar crops is used 

in estimating exposure. The leafy greens 

have tended to be among the top 

contributors to the aggregate risk (along 

with water and leaf lettuce). For other 

commodities, market basket data has 

shown reductions in residues one to two 

orders of magnitude lower than field 

trial data. Moreover, the only remaining 

EBDC registration for leafy greens 

(maneb) was canceled in 2010 but the 

exposure assessment does not take this 

into account. Additional conservatism is 

included in the exposure assessment by 

the assumption of 100 PCT for many 

commodities. Accordingly, EPA has 

concluded the aggregate cancer risk for 

all existing mancozeb and other EBDC 

uses and the uses associated with the 

tolerances established in this action fall 

within the range of 1 × 10¥6 and are 

thus negligible. 

5. 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 metiram 

and/or ETU residues. 

IV. Other Considerations 

A. Analytical Enforcement Methodology 

The available analytical methodology 

is considered adequate for tolerance 

enforcement. The Pesticide Analytical 

Manual (PAM) Vol. II lists Methods I, II, 

III, IV, and A for the determination of 

dithiocarbamate residues in or on plant 

commodities. The Keppel Colorimetric 

Method (PAM Method III) is the 

preferred method for tolerance 

enforcement. The Keppel Colorimetric 

Method determines EBDCs as a group by 

degradation to CS2. For determination of 

ETU residues, the Agency recommends 

the gas chromatography (GC) Method of 

Onley (Association of Analytical 

Communities (AOAC) 14th Edition 

29.119:554). 

The methods 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 is a joint United Nations 

Food and Agriculture Organization/ 

World Health Organization food 

standards program, and it is recognized 

as an international food safety 

standards-setting organization in trade 

agreements to which the United States 

is a party. EPA may establish a tolerance 

that is different from a CODEX MRL; 

however, FFDCA section 408(b)(4) 

requires that EPA explain the reasons 

for departing from the CODEX level. 

There are no established or proposed 

CODEX MRLs for residues of metiram 

per se; however, CODEX limits for 

dimethyldithiocarbamates fungicides 

are grouped under dithiocarbamates. 

There are CODEX MRLs for banana and 

grapes. 

Tolerances for the EBDC pesticides 

are expressed in terms of CS2, which is 

the same as the CODEX tolerance 

expression. The level of 5 ppm for wine 

grapes is the same as the CODEX MRL, 

although the CODEX MRL is for simply 

‘‘grapes.’’ The recommended tolerance 

for banana (3 ppm) cannot be 

harmonized with CODEX because 

residues in field trials exceeded the 

CODEX MRL of 2 ppm. 

C. Response to Comments 

As discussed in Unit II., EPA 

proposed tolerance actions for metiram 

in the Federal Register issue of 

September 16, 2009. EPA did receive 

comments on the proposed rule; 

however, none of these comments are 

related to the uses in this action. 

D. Revisions to Petitioned-For 

Tolerances 

EPA has revised the tolerance 

expression to clarify that: 

1. As provided in FFDCA section 

408(a)(3), the tolerance covers 

metabolites and degradates of metiram 

not specifically mentioned. 

2. Compliance with the specified 

tolerance levels is to be determined by 

measuring only the specific compounds 

mentioned in the tolerance expression. 

The change in the tolerance expression 

has resulted in the existing tolerances 

for apple and potato needing to be 

modified. These tolerances are being 

modified by this document. In addition, 

as a follow-up to recommendations 

made in the Metiram RED document, a 

tolerance is being added for apple, 

pomace, wet at 2 ppm. All of these 

revisions were proposed in the Federal 

Register issue of September 16, 2009. 


srobinson on DSKHWCL6B1PROD with RULES
Federal Register / Vol. 76, No. 83 / Friday, April 29, 2011 / Rules and Regulations 23891 

V. Conclusion 

Therefore, tolerances are established 

for residues of metiram (a mixture of 5.2 

parts by weight of ammoniates of 

[ethylenebis (dithiocarbamato)] zinc 

with 1 part by weight ethylenebis 

[dithiocarbamic acid] bimolecular and 

trimolecular cyclic anhydrosulfides and 

disulfides), including its metabolites 

and degradates, in or on banana at 3 

ppm and grape, wine at 5 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). 

Pursuant to the requirements of the 

Regulatory Flexibility Act (RFA) (5 

U.S.C. 601 et seq.), the Agency hereby 

certifies that this action will not have 

significant negative economic impact on 

a substantial number of small entities. 

Establishing a pesticide tolerance or an 

exemption from the requirement of a 

pesticide tolerance is, in effect, the 

removal of a regulatory restriction on 

pesticide residues in food and thus such 

an action will not have any negative 

economic impact on any entities, 

including small entities. 

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) (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: April 20, 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 180.217 is amended by 

revising the section heading and 

paragraph (a) to read as follows: 

§ 180.217 Metiram; tolerances for 

residues. 

(a) General. Tolerances are 

established for residues of a metiram (a 

mixture of 5.2 parts by weight of 

ammoniates of [ethylenebis 

(dithiocarbamato)] zinc with 1 part by 

weight ethylenebis [dithiocarbamic 

acid] bimolecular and trimolecular 

cyclic anhydrosulfides and disulfides), 

including its metabolites and 

degradates, in or on the commodities in 

the following table. Compliance with 

the tolerance levels specified in this 

paragraph is to be determined by 

measuring only those metiram residues 

convertible to and expressed in terms of 

the degradate carbon disulfide. 

Commodity Parts per 

million 

Apple ............................................. 0.5 

Apple, pomace, wet ...................... 2 

Banana 1 ....................................... 3 

Grape, wine 1 ................................ 5 

Potato ........................................... 0.2 

1There are no U.S. registrations on bananas and grape, wine as of April 29, 2011. 

* * * * * 

[FR Doc. 2011–10333 Filed 4–28–11; 8:45 am] 

BILLING CODE 6560–50–P 

ENVIRONMENTAL PROTECTION 

AGENCY 

40 CFR Part 180 

[EPA–HQ–OPP–2010–0266; FRL–8869–5] 

Pyrasulfotole; Pesticide Tolerances 

AGENCY: Environmental Protection 

Agency (EPA). 

ACTION: Final rule. 

SUMMARY: This regulation establishes or 

revises tolerances for residues of 

pyrasulfotole in or on grain sorghum, 

grass, and livestock commodities. Bayer 

CropScience LLC requested these 

tolerances under the Federal Food, 

Drug, and Cosmetic Act (FFDCA). 

DATES: This regulation is effective April 

29, 2011. Objections and requests for 

hearings must be received on or before 

June 28, 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–2010–0266. 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, 


srobinson on DSKHWCL6B1PROD with RULES