Document ID: EPA-HQ-OPP-2012-0628-0003
Agency: epa
Document Type: Rule
Title: Pesticide Tolerances: Mancozeb
Posted Date: 2013-07-24T04:00Z

[Federal Register Volume 78, Number 142 (Wednesday, July 24, 2013)]
[Rules and Regulations]
[Pages 44444-44455]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-17869]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2012-0628; FRL-9393-2]

Mancozeb; Pesticide Tolerances

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes tolerances for residues of 
mancozeb in or on walnuts and tangerines. United Phosphorus requested 
the tolerance for walnuts and Dow AgroSciences requested the tolerance 
for tangerines under the Federal Food, Drug, and Cosmetic Act (FFDCA).

DATES: This regulation is effective July 24, 2013. Objections and 
requests for hearings must be received on or before September 23, 2013, 
and must be filed in accordance with the instructions provided in 40 
CFR part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: The docket for this action, identified by docket 
identification (ID) number EPA-HQ-OPP-2012-0628, is available at http://www.regulations.gov or at the Office of Pesticide Programs Regulatory 
Public Docket (OPP Docket) in the Environmental Protection Agency 
Docket Center (EPA/DC), EPA West Bldg., Rm. 3334, 1301 Constitution 
Ave. NW., Washington, DC 20460-0001. The Public Reading Room is open 
from 8:30 a.m. to 4:30 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Public Reading Room is (202) 
566-1744, and the telephone number for the OPP Docket is (703) 305-
5805. Please review the visitor instructions and additional information 
about the docket available at http://www.epa.gov/dockets.

FOR FURTHER INFORMATION CONTACT: Lois Rossi, Registration Division 
(7505P), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave. NW., Washington, DC 20460-0001; telephone 
number: (703) 305-7090; email address: RDFRNotices@epa.gov.

SUPPLEMENTARY INFORMATION: 

I. General Information

A. Does this action apply to me?

    You may be potentially affected by this action if you are an 
agricultural producer, food manufacturer, or pesticide manufacturer. 
The following list of North American Industrial Classification System 
(NAICS) codes is not intended to be exhaustive, but rather provides a 
guide to help readers determine whether this document applies to them. 
Potentially affected entities may include:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).

B. How can I get electronic access to other related information?

    You may access a frequently updated electronic version of EPA's 
tolerance regulations at 40 CFR part 180 through the Government 
Printing Office's eCFR site at http://www.ecfr.gov/cgi-bin/text-idx?&c=ecfr&tpl=/ecfrbrowse/Title40/40tab_02.tpl.

C. How can I file an objection or hearing request?

    Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an 
objection to any aspect of this regulation and may also request a 
hearing on those objections. You must file your objection or request a 
hearing on this regulation in accordance with the instructions provided 
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify 
docket ID number EPA-HQ-

[[Page 44445]]

OPP-2012-0628 in the subject line on the first page of your submission. 
All objections and requests for a hearing must be in writing, and must 
be received by the Hearing Clerk on or before September 23, 2013. 
Addresses for mail and hand delivery of objections and hearing requests 
are provided in 40 CFR 178.25(b).
    In addition to filing an objection or hearing request with the 
Hearing Clerk as described in 40 CFR part 178, please submit a copy of 
the filing (excluding any Confidential Business Information (CBI)) for 
inclusion in the public docket. Information not marked confidential 
pursuant to 40 CFR part 2 may be disclosed publicly by EPA without 
prior notice. Submit the non-CBI copy of your objection or hearing 
request, identified by docket ID number EPA-HQ-OPP-2012-0628, by one of 
the following methods:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the online instructions for submitting comments. Do not submit 
electronically any information you consider to be CBI or other 
information whose disclosure is restricted by statute.
     Mail: OPP Docket, Environmental Protection Agency Docket 
Center (EPA/DC), (28221T), 1200 Pennsylvania Ave. NW., Washington, DC 
20460-0001.
     Hand Delivery: To make special arrangements for hand 
delivery or delivery of boxed information, please follow the 
instructions at http://www.epa.gov/dockets/contacts.htm.

Additional instructions on commenting or visiting the docket, along 
with more information about dockets generally, is available at http://www.epa.gov/dockets.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of May 2, 2012 (77 FR 25954) (FRL-9346-1), 
EPA issued a document pursuant to FFDCA section 408(d)(3), 21 U.S.C. 
346a(d)(3), announcing the filing of a pesticide petition (PP 1F7935) 
by United Phosphorus, Inc., 630 Freedom Business Center, King of 
Prussia, PA 19406. The petition requested that 40 CFR 180.176 be 
amended by establishing tolerances for residues of the fungicide 
mancozeb in or on walnuts at 0.75 parts per million (ppm). That 
document referenced a summary of the petition prepared by United 
Phosphorus, the registrant, which is available in the docket (EPA-HQ-
OPP-2012-0044), http://www.regulations.gov. There were no comments 
received in response to the notice of filing.
    In the Federal Register of September 28, 2012 (77 FR 59578) (FRL-
9364-6), EPA issued a document pursuant to FFDCA section 408(d)(3), 21 
U.S.C. 346a(d)(3), announcing the filing of a pesticide petition (PP 
2E8062) by Dow AgroSciences LLC, 9330 Zionsville Road, Indianapolis, IN 
46268. The petition requested that 40 CFR 180.176 be amended by 
establishing tolerances for residues of the fungicide mancozeb in or on 
tangerine at 10 ppm. The proposed tolerance supports imports of 
mandarins, tangerines, and clementines. That document referenced a 
summary of the petition prepared by Dow AgroSciences, the registrant, 
which is available in the docket (EPA-HQ-OPP-2012-0628) 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 the level at which the tolerance is being established for 
walnut. The reason for this change is explained in Unit IV.C.

III. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a 
reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of FFDCA requires EPA to give special 
consideration to exposure of infants and children to the pesticide 
chemical residue in establishing a tolerance and to ``ensure that there 
is a reasonable certainty that no harm will result to infants and 
children from aggregate exposure to the pesticide chemical residue. . . 
.''
    Consistent with FFDCA section 408(b)(2)(D), and the factors 
specified in FFDCA section 408(b)(2)(D), EPA has reviewed the available 
scientific data and other relevant information in support of this 
action. EPA has sufficient data to assess the hazards of and to make a 
determination on aggregate exposure for mancozeb including exposure 
resulting from the tolerances established by this action.
    Mancozeb is a member of the ethylene bisdithiocarbamate (EBDC) 
group of fungicides that also includes the related active ingredient 
metiram, the only other registered EBDC. A third EBDC, maneb, is no 
longer registered for use. Mancozeb and metiram are metabolized to 
ethylenethiourea (ETU) in the body and both degrade to ETU in the 
environment. Therefore, EPA has considered the aggregate or combined 
risks from food, water and non-occupational exposure resulting from 
mancozeb alone and ETU from all sources (i.e., the other EBDC 
fungicides) for this action. EPA's assessment of exposures and risks 
associated with mancozeb 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 mancozeb, EPA also evaluated the 
risks of ETU, a contaminant, metabolite and degradation product of 
mancozeb and the other EBDC group of fungicides, which includes the 
related active ingredient metiram.
    1. Mancozeb. Mancozeb is not acutely toxic via the oral, dermal or 
inhalation routes of exposure. Further, mancozeb is not a skin irritant 
nor is it a skin sensitizer, although it does cause mild eye 
irritation. The findings in multiple studies demonstrate that the 
thyroid is a target organ for mancozeb. Thyroid toxicity is manifested 
as alternations in thyroid hormones, increased thyroid weight, and 
microscopic thyroid lesions (mainly thyroid follicular cell 
hyperplasia). These effects are due to the ETU metabolite.
    In a subchronic study in the rat, neuropathology was seen 
microscopically (injury to peripheral nerves) with associated clinical 
signs (abnormal gait and limited use of rear legs) and loss of muscle 
mass. Decreased motor activity occurred in the acute neurotoxicity 
study. In the developmental neurotoxicity study, there was no maternal 
toxicity and pup effects were limited to decreased body weight. Other 
toxicity included increases in bilateral retinopathy in the chronic rat 
study. Elevated cholesterol and a mild, regenerative, anemia occurred 
in subchronic and chronic dog studies.
    Mancozeb is rapidly absorbed and eliminated in the urine. In oral 
rat metabolism studies with radiolabeled mancozeb and other EBDCs, an 
average 7.5% in vivo metabolic conversion of EBDC to ETU occurred, on a 
weight-to-

[[Page 44446]]

weight basis. Metabolism data indicate mancozeb does not bio-
accumulate. Mancozeb has been tested in a series of in vitro and in 
vivo genotoxicity assays, which have shown that it exhibits weak 
genotoxic potential.
    Thyroid follicular cell adenomas and carcinomas were increased in 
high-dose males and females in the combined rat toxicity/
carcinogenicity study with mancozeb. Doses in a mouse study were too 
low to assess carcinogenicity, and there were no treatment-related 
changes in tumor rates. Historically, mancozeb's potential for 
carcinogenicity has been based on its metabolite ETU, which is 
classified as a probable human carcinogen. However, since ETU is known 
to be the chemical causing the thyroid tumors observed, the cancer 
assessment has been done only for ETU rather than the parent compound.
    Developmental defects in the rat developmental toxicity study 
included hydrocephaly, skeletal system defects, and other gross defects 
which occurred at a dose causing maternal mortality and did not 
indicate increased susceptibility of offspring. Abortions occurred in 
the rabbit developmental toxicity study at the high dose which also 
caused maternal mortality, and there was no indication of enhanced 
susceptibility of offspring in the rabbit. There was no evidence of 
reproductive toxicity in the 2-generation reproduction study in rats. 
There was evidence of sensitivity in the developmental neurotoxicity 
study with mancozeb with decreased pup body weight observed in the 
absence of maternal toxicity; the selected endpoints are protective for 
these pup effects.
    An immunotoxicity study has been reviewed and mancozeb did not show 
any immunotoxicity potential.
    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 thyroxine (T4), increases or decreases in 
triiodothyronine (T3), compensatory increases in levels of 
thyroid stimulating hormone (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 mancozeb, 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 gain.
    An immunotoxicity study on ETU did not show any immunotoxicity 
potential.
    Specific information on the studies received and the nature of the 
adverse effects caused by mancozeb as well as the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level 
(LOAEL) from the toxicity studies can be found at http://www.regulations.gov in the document titled ``Mancozeb: Human Health 
Risk Assessment to Support Proposed New Section 3 Uses on Walnuts and 
Tolerances for Imported Tangerines'' on pages 70-75 in docket ID number 
EPA-HQ-OPP-2012-0628.
    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 www.regulations.gov in 
the document titled ``Ethylene Thiourea (ETU); Aggregate Human Health 
Risk Assessment of the Common Metabolite/Degradate Ethylene Thiourea 
(ETU) to Support Proposed New Section 3 Use on Walnuts and Tolerance 
for Imported Tangerines'' on pages 30-33 in docket ID number EPA-HQ-
OPP-2012-0628.

B. Toxicological Points of Departure/Levels of Concern

    Once a pesticide's toxicological profile is determined, EPA 
identifies toxicological points of departure (POD) and levels of 
concern to use in evaluating the risk posed by human exposure to the 
pesticide. For hazards that have a threshold below which there is no 
appreciable risk, the toxicological POD is used as the basis for 
derivation of reference values for risk assessment. PODs are developed 
based on a careful analysis of the doses in each toxicological study to 
determine the dose at which no adverse effects are observed (the NOAEL) 
and the lowest dose at which adverse effects of concern are identified 
(the LOAEL). Uncertainty/safety factors are used in conjunction with 
the POD to calculate a safe exposure level--generally referred to as a 
population-adjusted dose (PAD) or a 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 mancozeb and ETU used 
for human risk assessment is shown in Tables 1 and 2 of this unit.

   Table 1--Summary of Toxicological Doses and Endpoints for Mancozeb for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                    Point of departure                                            Study and
        Exposure/scenario            and  uncertainty/    RfD, PAD, LOC for risk assessment     toxicological
                                      safety factors                                               effects
----------------------------------------------------------------------------------------------------------------
Acute dietary (Adult Males,        NOAEL = 500 mg/kg/    Acute RfD = 5 mg/kg/day...........  Acute neurotoxicity
 Females > 49, and Children >= 6    day.                 aPAD = 5 mg/kg/day................   study in the rat.
 years).                           UFA = 10x...........                                      LOAEL 1,000 mg/kg/
                                   UFH = 10x...........                                       day based on
                                   FQPA SF = 1x........                                       decreased motor
                                                                                              activity.
Acute dietary (Children < 6        NOAEL = 500 mg/kg/    Acute RfD = 5 mg/kg/day...........  Acute neurotoxicity
 years).                            day.                 aPAD = 0.5 mg/kg/day..............   study in the rat.
                                   UFA = 10x...........                                      LOAEL 1,000 mg/kg/
                                   UFH = 10x...........                                       day based on
                                   FQPA SF UFDB = 10x..                                       decreased motor
                                                                                              activity.

[[Page 44447]]

 
Acute Dietary (Females 13-49       NOAEL = 1.28 mg/kg/   Acute RfD = 1.3 mg/kg/day.........  Developmental
 years).                            day.                 aPAD = 0.13 mg/kg/day.............   toxicity study in
                                   UFA = 10x...........                                       the rat.
                                   UFH = 10x...........                                      LOAEL = 512 mg/kg/
                                   FQPA SF UFDB = 10x..                                       day based on
                                                                                              hydrocephaly and
                                                                                              other
                                                                                              malformations.
Chronic dietary (Adult Males,      NOAEL = 4.83 mg/kg/   Chronic RfD = 0.16 mg/kg/day......  Toxicity/
 Females > 49, and Children >= 6    day.                 cPAD = 0.16 mg/kg/day.............   Carcinogenicity in
 years).                           UFA = 3x............                                       the rat.
                                   UFH = 10x...........                                      LOAEL = 30.9 mg/kg/
                                   FQPA SF = 1x........                                       day based on
                                                                                              thyroid toxicity.
Chronic dietary (Females 13-49     NOAEL = 4.83 mg/kg/   Chronic RfD = 0.16 mg/kg/day......  Toxicity/
 years and Children < 6 years).     day.                 cPAD = 0.016 mg/kg/day............   Carcinogenicity in
                                   UFA = 3x............                                       the rat.
                                   UFH = 10x...........                                      LOAEL = 30.9 mg/kg/
                                   FQPA SF UFDB = 10x..                                       day based on
                                                                                              thyroid toxicity.
Inhalation all durations (Adult    Inhalation study      LOC for MOE = 30..................  Subchronic
 Males, Females > 49 years, and     NOAEL = 0.079 mg/L                                        Inhalation in the
 Children >= 6 years).              (21 mg/kg/day).                                           rat.
                                   UFA = 3x............                                      LOAEL = 0.326 mg/L
                                   UFH = 10x...........                                       based on thyroid
                                   FQPA SF = 1x........                                       toxicity.
Inhalation all durations (Females  Inhalation study      LOC for MOE = 300.................  Subchronic
 13-49 years and Children < 6       NOAEL= 0.079 mg/L                                         Inhalation in the
 years).                            (21 mg/kg/day).                                           rat.
                                   UFA = 3x............                                      LOAEL = 0.326 mg/L
                                   UFH = 10x...........                                       based on thyroid
                                   FQPA SF UFDB = 10x..                                       toxicity.
                                  ------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)     Mancozeb's potential for carcinogenicity is due to the formation of the
                                        metabolite, ETU, which is classified as a probable human carcinogen.
                                      Mancozeb's cancer risk is calculated by estimating exposure to mancozeb-
                                     derived ETU and using the ETU cancer potency factor (Q1\*\) of 6.01 x 10-2
                                                          (mg/kg/day)-1 to quantitate risk.
----------------------------------------------------------------------------------------------------------------
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
  of concern. mg/kg/day = milligrams/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
  level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UF = uncertainty factor.
  UFA = extrapolation from animal to human (interspecies). UFDB = to account for the absence of data or other
  data deficiency. UFH = potential variation in sensitivity among members of the human population
  (intraspecies).

      Table 2--Summary of Toxicological Doses and Endpoints for ETU for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                    Point of departure
        Exposure/scenario            and uncertainty/     RfD, PAD, LOC for     Study and toxicological effects
                                      safety factors       risk assessment
----------------------------------------------------------------------------------------------------------------
Acute dietary (General population  A study with acute
 including infants and children).   toxicity applicable
                                    to the general
                                    population was not
                                    identified.
                                  ------------------------------------------------------------------------------
Acute Dietary (Females 13-49       NOAEL = 5 mg/kg/day.  Acute RfD = 0.05 mg/ Developmental Rat Toxicity.
 years).                           UFA = 10x...........   kg/day.             LOAEL = 10 mg/kg/day, based on
                                   UFH = 10x...........  aPAD = 0.005 mg/kg/   hydrocephaly and other
                                   FQPA SF UFDB = 10x..   day.                 malformations.

[[Page 44448]]

 
Chronic dietary (Adult Males,      NOAEL = 0.18 mg/kg/   Chronic RfD =        Dog Chronic Oral Toxicity.
 Females > 49, and Children >= 6    day.                  0.0018 mg/kg/day.   LOAEL = 1.99 mg/kg/day based on
 years).                           UFA = 10x...........  cPAD = 0.0018 mg/kg/  thyroid toxicity.
                                   UFH = 10x...........   day.
                                   FQPA SF = 1x........
Chronic dietary (Females 13-49     NOAEL = 0.18 mg/kg/   Chronic RfD =        Dog Chronic Oral Toxicity.
 years and Children < 6 years).     day.                  0.0018 mg/kg/day.   LOAEL = 1.99 mg/kg/day based on
                                   UFA = 10x...........  cPAD = 0.00018 mg/    thyroid toxicity.
                                   UFH = 10x...........   kg/day.
                                   FQPA SF UFDB = 10x..
Dermal short and intermediate-     Oral study..........  LOC for MOE = 1,000  4-Week Range-Finding Dog Study.
 term (Children < 6 years old).    NOAEL = 7 mg/kg/day                        LOAEL = 34 mg/kg/day based on
                                    (dermal absorption                         thyroid toxicity.
                                    rate = 26%).
                                   UFA = 10x...........
                                   UFH = 10x...........
                                   FQPA SF = 10x.......
Dermal short and intermediate-     Oral study..........  LOC for MOE = 100..  4-Week Range-Finding Dog Study.
 term (Adult Males, Females.       NOAEL = 7 mg/kg/day                        LOAEL = 34 mg/kg/day based on
 > 49 years, Children >= 6 years)   (dermal absorption                         thyroid toxicity.
                                    rate = 26%).
                                   UFA = 10x...........
                                   UFH = 10x...........
                                   FQPA SF = 1x........
Dermal short- and intermediate-    Oral study..........  LOC for MOE = 1,000  Developmental Rat Toxicity.
 term (Females 13-49 years old).   NOAEL = 5 mg/kg/day                        LOAEL = 10 mg/kg/day, based on
                                    (dermal absorption                         hydrocephaly and other
                                    rate = 26%).                               malformations.
                                   UFA = 10x...........
                                   UFH = 10x...........
                                   FQPA SF = 10x.......
Inhalation short- and              Oral study..........  LOC for MOE = 1,000  4-Week Range-Finding Dog Study.
 intermediate-Term (Children < 6   NOAEL = 7 mg/kg/day.                       LOAEL = 34 mg/kg/day based thyroid
 years of age).                    UFA = 10x...........                        toxicity.
                                   UFH = 10x...........
                                   FQPA SF UFDB = 10x..
Inhalation short- and              Oral study..........  LOC for MOE = 100..  4-Week Range-Finding Dog Study.
 intermediate-term (adult males,   NOAEL= 7 mg/kg/day..                       LOAEL = 34 mg/kg/day based thyroid
 females > 49 years, children >=   UFA = 10x...........                        toxicity.
 6 years).                         UFH = 10x...........
                                   FQPA SF = 1x........
Inhalation short- and              Oral study..........  LOC for MOE = 1,000  Developmental Rat Toxicity.
 intermediate-term (Females 13-49  NOAEL = 5 mg/kg/day.                       LOAEL = 10 mg/kg/day, based on
 years old).                       UFA = 10x...........                        hydrocephaly and other
                                   UFH = 10x...........                        malformations.
                                   FQPA SF = 10x.......
                                  ------------------------------------------------------------------------------
Cancer (Oral, dermal, inhalation)  ETU is classified as a probable human carcinogen. ETU's cancer potency factor
                                                        (Q1\*\) is 6.01 x 10-2 (mg/kg/day)-1.
----------------------------------------------------------------------------------------------------------------
FQPA SF = Food Quality Protection Act Safety Factor. LOAEL = lowest-observed-adverse-effect-level. LOC = level
  of concern. mg/kg/day = milligrams/kilogram/day. MOE = margin of exposure. NOAEL = no-observed-adverse-effect-
  level. PAD = population adjusted dose (a = acute, c = chronic). RfD = reference dose. UF = uncertainty factor.
  UFA = extrapolation from animal to human (interspecies). UFDB = to account for the absence of data or other
  data deficiency. UFH = potential variation in sensitivity among members of the human population
  (intraspecies).

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. In evaluating dietary 
exposure to mancozeb, EPA considered exposure under the petitioned-for 
tolerances as well as all existing mancozeb tolerances in 40 CFR 
180.176. In evaluating dietary exposure to ETU, EPA considered exposure 
under the petitioned-for tolerances discussed in this document as well 
as all existing uses of the EBDC group of fungicides

[[Page 44449]]

(mancozeb and metiram). EPA assessed dietary exposures from mancozeb 
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 mancozeb and ETU. In estimating acute dietary exposure for both 
mancozeb and ETU, EPA used food consumption information from the 2003-
2008 food consumption data from the U.S. Department of Agriculture's 
(USDA's) National Health and Nutrition Examination Survey, What We Eat 
in America, (NHANES/WWEIA).
    a. Mancozeb. The Agency conducted a highly refined, probabilistic 
acute dietary assessment incorporating field trial or monitoring data 
from the EBDC/ETU Market Basket Survey, percent crop treated (PCT) 
information, and processing study results to assess the established 
uses of mancozeb. The monitoring data were used for several commodities 
(corn, cucumber, onion, pumpkin, potato, squash, starfruit, tomato, 
meat, and milk). For evaluation of the proposed new uses and 
tolerances, field trial data, processing factors, PCT data based on 
section 18 usage for walnuts, and percent imported commodity in 
domestic consumption data on tangerines for mancozeb were used to 
refine residue estimates. The entire distributions of residue data from 
field trials or monitoring data were used to generate residue 
distribution files (RDFs) for commodities that are considered to be not 
blended or partially blended. For commodities considered to be blended, 
the average residues incorporating the likely maximum estimated PCT was 
used as a point estimate.
    b. ETU. The Agency conducted a highly refined, probabilistic acute 
dietary assessment incorporating field trial or monitoring data from 
the EBDC/ETU Market Basket Survey, PCT information, and processing 
study results to assess exposures to ETU from the established uses of 
mancozeb and metiram. The monitoring data were used for several 
commodities (corn, cucumber, onion, pumpkin, potato, squash, starfruit, 
tomato, meat, and milk). For evaluation of the proposed new uses and 
tolerances, field trial data, processing factors, PCT data based on 
section 18 usage for walnuts, and percent imported commodity in 
domestic consumption data on tangerines for mancozeb were used to 
refine residue estimates. The entire distributions of residue data from 
field trials or monitoring data were used to generate residue 
distribution files (RDFs) for commodities that are considered to be not 
blended or partially blended. For commodities considered to be blended, 
the average residues incorporating the likely maximum estimated PCT was 
used as a point estimate.
    ii. Chronic exposure. In conducting the chronic dietary exposure 
assessment for both mancozeb and ETU, EPA used food consumption 
information from the 2003-2008 food consumption data from the USDA 
NHANES/WWEIA.
    a. Mancozeb. The chronic dietary exposure and risk assessment for 
mancozeb (non-cancer and cancer) incorporated average values based 
either on field trial data or monitoring data and average PCT data for 
new and existing uses, as well as processing and cooking factors. 
Averages of the field trials were used for the walnuts and tangerines, 
while field trial and market basket survey data were used for 
established uses.
    b. ETU. Chronic anticipated residues were calculated using average 
values based either on field trial data or monitoring data and average 
PCT data or average projected PCT as well as processing and cooking 
factors. Averages of the field trials were used for the walnuts and 
tangerines, while field trial and market basket survey data were used 
for established uses.
    iii. Cancer. EPA determines whether quantitative cancer exposure 
and risk assessments are appropriate for a food-use 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 noncancer 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.
    The cancer risks were aggregated using the food and drinking water 
doses for the general population and the food, water and recreational 
doses for home gardeners (considered protective of other residential 
scenarios). 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.
    Mancozeb degrades and/or metabolizes to ETU which causes thyroid 
tumors; therefore, EPA has historically attributed mancozeb's 
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 (mg/kg/day) -1 for ETU 
(based on liver tumors in female mice) for risk assessment. Therefore, 
cancer risk from exposure to mancozeb has been calculated by estimating 
exposure to mancozeb-derived ETU and using the Q1* for ETU. 
The same approach has been taken for the other EBDCs. EPA's estimated 
exposure to mancozeb-derived ETU included ETU residues found in food as 
well as ETU formed by metabolic conversion on parent mancozeb in the 
body (conversion rate of 0.075).
    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.
    For mancozeb and ETU derived from mancozeb, the following maximum 
PCT

[[Page 44450]]

estimates were used in the acute dietary risk assessment for the 
following crops: Apples: 45%; asparagus: 30%; barley: 2.5%; 
cantaloupes: 15%; carrots: 2.5%; celery: 2.5%; corn: 2.5%; cranberries: 
20%; cucumbers: 50%; grapes: 20%; oats: 1%; onions: 70%; peanuts: 2.5%; 
pears: 50%; potatoes: 65%; pumpkins: 15%; rice: 2.5%; spinach: 2.5%; 
squash: 30%; sugar beets: 2.5%; sweet corn: 15%; tomatoes: 50%; 
watermelons: 50%; and wheat: 2.5%. A percent import value of 99% was 
used for banana.
    For mancozeb and ETU derived from mancozeb, the following average 
PCT estimates were used in the chronic and cancer dietary risk 
assessments for the following crops: Apples: 40%; asparagus: 15%; 
barley: 1%; cantaloupes: 5%; carrots: 1%; celery: 1%; cherries: 1%; 
corn: 1%; cranberries: 20%; cucumbers: 25%; grapes: 10%; oats: 1%; 
onions: 60%; peanuts: 2.5%; pears: 40%; potatoes: 55%; pumpkins: 10%; 
rice: 1%; spinach: 1%; squash: 20%; sugar beets: 1%; sweet corn: 5%; 
tomatoes: 25%; watermelons: 40%; and wheat: 1%. A percent import value 
of 99% was used for banana.
    As a further refinement, the commodity having the highest PCT 
results with livestock feed uses had these values applied to meat and 
milk (potato; 65% CT maximum for acute and 55% CT average for chronic).
    For ETU derived from metiram, the following maximum PCT estimates 
were used in the acute dietary risk assessment: apples: 15%; potatoes: 
10%. A 31% imported commodity in domestic consumption was used for wine 
grapes.
    For ETU derived from metiram, the following average PCT estimates 
were used in the chronic and cancer dietary risk assessment: Apples: 
10%; potatoes: 5%. A 31% imported commodity in domestic consumption was 
used for wine grapes.
    In most cases, EPA uses available data from United States 
Department of Agriculture/National Agricultural Statistics Service 
(USDA/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%.
    Also, for the acute risk assessment for mancozeb and ETU derived 
from mancozeb, the Agency estimated PCT for the following uses for 
mancozeb, which were recently approved in 2011: Almond, 25%; broccoli, 
6%; cabbage, 47%; cabbage, Chinese, 47%; head lettuce 75%; leaf lettuce 
66%; pepper, bell, 48%; pepper, non-bell, 48%. For the chronic risk 
assessment for mancozeb and ETU derived from mancozeb, the Agency 
estimated PCT as follows: Almond, 18%; broccoli, 5%; cabbage, 42%; 
cabbage, Chinese, 42%; head lettuce 67%; leaf lettuce 62%; pepper, 
bell, 44%; pepper, non-bell, 44%. Since metiram is not registered for 
use on these crops, all potential ETU exposure on these crops will 
result from use of mancozeb.
    EPA developed these refined PCT values based on a detailed 
chemical-specific analysis. EPA has considered all available relevant 
information and concludes that it is unlikely that the PCT values for 
these uses will be exceeded during the next 5 years. Further discussion 
of how these PCT values were derived can be found at 
www.regulations.gov in the document titled ``Percent Crop Treated for 
new Uses (PCTn) of Mancozeb on Almonds, Broccoli, Cabbage, Pepper, 
Pumpkin, and Winder Squash, PC Code: 014504; DP Barcode: 360397; 
Lettuce, both head and Other; PC Code: 014504; DP Barcode: 364745, NON 
PRIA, Parent DP: 635267; and Percent Crop Treated with Maneb for 
Collards, Mustard Greens, Turnip Greens, and Kale'' in docket ID number 
EPA-HQ-OPP-2012-0628.
    For mancozeb and ETU derived from mancozeb, a maximum PCT projected 
estimate of 50% for walnuts and a maximum percent import consumption 
value of 35% for tangerines were used in the acute dietary risk 
assessment. An average PCT estimate of 40% for walnuts as well as an 
average percent imported commodity in domestic consumption value of 29% 
for tangerines were used in the chronic and cancer dietary risk 
assessments.
    The walnut information is an amalgamation of the USDA/NASS and 
private pesticide market research data. The PCT values for walnuts are 
derived from survey data reported in 2006, 2010, and 2011. Only the 
state of California is represented in the survey data as 99% of the 
walnuts grown in the United States are grown in that state. The percent 
of imported fresh mandarin oranges in domestic consumption was 
calculated with data for the reporting period of 2008-2013 obtained 
from the Foreign Agricultural Service (FAS) USDA/Office of Global 
Analysis (FAS, 2013).
    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 mancozeb may be applied in a particular area.
    2. Dietary exposure from drinking water--i. Mancozeb. The Agency 
has determined that mancozeb is very short-lived 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 
water 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 water and ground water values represent

[[Page 44451]]

upper-bound 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 acute 
and 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 non-occupational, non-dietary 
exposure (e.g., for lawn and garden pest control, indoor pest control, 
termiticides, and flea and tick control on pets).
    1. Mancozeb. Mancozeb is currently registered for use on the 
following residential sites: Home gardens, golf courses, and sod farms 
(where treated sod could be transplanted to a residential setting). The 
Agency has determined that it is appropriate to aggregate chronic 
exposure through food with short-term residential exposures to 
mancozeb.
    The exposure scenario that was evaluated for mancozeb was the 
residential handler home garden use which considers residential handler 
exposures (inhalation) to adult applicators combined with average food 
exposures. Dermal exposure was not evaluated because no effects were 
observed in a mancozeb 28-day dermal toxicity study.
    For post-application, dermal exposure to home gardeners (adults and 
youth) harvesting vegetables from treated gardens and golfers (adults 
and youth) contacting mancozeb-treated turf after application is 
possible. However, as no dermal hazard was identified for mancozeb, a 
quantitative dermal post-application assessment (non-cancer/short-term 
and cancer) for the dermal exposure to home gardeners and golfers 
(adults and youth) was only performed for its metabolite, ETU.
    The previous mancozeb risk assessment had evaluated the short/
intermediate-term exposure of toddlers to treated turf from the sod 
farm use. In the most recent risk assessment, the Agency considered 
post-application exposure resulting from this scenario to be negligible 
for the following reasons: (1) Mancozeb has a post-harvest interval 
(PHI) of 5 days for sod; (2) it is unlikely that sod treated with 
mancozeb would be installed more than once per year; (3) transplanted 
sod requires constant and significant watering which will result in 
decreased mancozeb residues on the transplanted sod; and (4) it is 
unlikely that adults or children will spend any significant amount of 
time on recently transplanted sod until it is rooted which typically 
occurs around 2 weeks after transplanting. Therefore, dermal and 
incidental oral post-application scenarios were not quantitatively 
assessed for the sod farm use of mancozeb. There are no post-
application exposure risks of concern anticipated from the use of 
mancozeb on sod farms.
    ii. ETU. ETU non-dietary exposure is expected as a result of the 
registered uses of mancozeb, which is currently registered for use on 
the following residential sites: home gardens, golf courses, and sod 
farms (where treated sod could be transplanted to a residential 
setting). There are no uses of metiram that will result in exposure in 
residential settings. The Agency has determined that it is appropriate 
to aggregate chronic exposure through food with short-term residential 
exposures to ETU.
    The scenario that was evaluated for ETU was the residential home 
garden use, which considered handler garden exposures (inhalation and 
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 females 13-49 years old and youths.
    The previous risk assessment also considered treated turf (sod 
farm) post-application exposures to toddlers (incidental oral and 
dermal). This more recent risk assessment did not evaluate the sod farm 
use for the reasons outlined above in the mancozeb non-dietary exposure 
section.
    The previous risk assessment also calculated risks for adult and 
youth golfers from golfing on treated turf. The more recent assessment 
concluded that for residential post-application, the gardening 
scenarios represent the most conservative exposure estimates and are 
used in the aggregate assessment. The gardening scenarios result in 
higher estimated exposure than the golfing scenarios and are therefore 
protective of any golfer risk.
    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 mancozeb, and ETU 
derived from mancozeb and metiram, the other registered EBDC chemical, 
both of which are dithiocarbamates. For the purposes of this action, 
EPA has concluded that mancozeb 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 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). 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 carbon disulfide 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 FQPA Safety 
Factor (SF). In applying

[[Page 44452]]

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. Mancozeb. In the rat 
developmental study, developmental effects were observed in the 
presence of severe maternal effects, including maternal mortality and 
clinical signs. In the rabbit developmental study, developmental 
effects (spontaneous abortions) were observed at the same dose (80 mg/
kg/day) at which maternal effects included mortality and clinical 
signs. In the rat reproduction study, no effects were observed in 
offspring, while thyroid effects and body weight gain decrements 
occurred in adults. There was evidence of sensitivity in the 
developmental neurotoxicity study with mancozeb with decreased pup body 
weight occurring in the absence of maternal toxicity; risk assessment 
endpoints are protective for these pup effects.
    ii. ETU. There is evidence of increased susceptibility of fetuses 
to ETU. Fetal malformations occurred mainly in rats, although 
hydrocephaly and domed head were observed in a rabbit developmental 
study with ETU. The malformations in rats occurred throughout the body. 
Hydrocephaly occurred in the absence of maternal toxicity after 
treatment with a single dose of ETU. There was a steep dose-response 
for the malformations in rats. An acceptable reproductive toxicity 
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 for mancozeb. EPA is retaining the 10X FQPA safety 
factor for women of childbearing age and for children less than 6 years 
old but has determined that reliable data show the safety of children 
greater than 6 years of age would be adequately protected if the FQPA 
safety factor were reduced to 1X. That decision is based on the 
following findings:
    i. The toxicology database for mancozeb is complete, except that it 
lacks adequate data on the developing thyroid. Brain development is 
very sensitive to perturbations in thyroid hormones and it is possible 
that the developmental thyroid study (being conducted with ETU) could 
result in lower NOAELs for women of childbearing age (i.e., fetuses) 
and for children less than 6 years old. Results from the developmental 
thyroid study will not affect endpoints for children over 6 years of 
age (for whom the thyroid system is more developed) or adults as 
thyroid data for those populations are already available. Therefore, 
the FQPA safety factor is reduced to 1X for these populations.
    ii. There was some evidence of neurotoxicity for mancozeb as seen 
in the acute and subchronic neurotoxicity studies; however, no 
neurotoxicity occurred in the DNT. Additionally, there are clear NOAELs 
identified for the effects observed in the toxicity studies. The doses 
and endpoints selected for risk assessment are protective of all 
neurotoxicological effects observed in the database.
    iii. As noted above in Unit III.D.2., there was some evidence of 
increased susceptibility of rat pups to mancozeb exposure. Aside from 
the uncertainty resulting from the lack of adequate thyroid data (for 
which EPA is retaining the 10X FQPA safety factor), there are clear 
NOAELs for the offspring effects, and regulatory doses were selected to 
be protective of these effects.
    iv. There are no residual uncertainties identified in the exposure 
databases. The acute, chronic, and cancer dietary exposure assessments 
were refined and used PCT estimates and monitoring residue values for 
several commodities, including some major contributors to the dietary 
risk such as milk and corn commodities. Monitoring or modeling data 
were used to derive estimated drinking water concentrations. The 
drinking water concentrations that were derived from monitoring data 
reflect the highest value found in a community well monitoring program. 
The drinking water concentrations from modeling used conservative, 
health-protective, high-end estimates and are unlikely to be exceeded. 
The residential exposure assessment used residential SOPs, which are 
based on conservative high-end assumptions such as maximum application 
rates and day 0 exposures. Given the overall conservative nature of the 
exposure assumptions, the aggregate (food, water, and residential) 
exposure and risk estimates presented in this assessment are not 
expected to underestimate actual exposure and risk expected based on 
the current and proposed use patterns.
    4. Conclusion for ETU. EPA is retaining the 10X FQPA safety factor 
for women of childbearing age and for children less than 6 years old 
but has determined that reliable data show the safety of children 6 
years of age or older would be adequately protected if the FQPA safety 
factor were reduced to 1X. That decision is based on the following 
findings:
    i. The toxicology database for ETU is missing a developmental 
thyroid study, a reproduction study, and a developmental neurotoxicity 
(DNT) study. These data gaps are being addressed by an ongoing extended 
one-generation reproductive toxicity study. Because the developing 
brain is very sensitive to perturbations in thyroid hormones, it is 
possible that these studies could result in lower NOAELs for women of 
childbearing age (i.e., fetuses) and for children less than 6 years 
old; however, results from the developmental thyroid study will not 
affect points of departure for children greater than 6 years of age, 
who have a thyroid system similar to adults, adult females greater than 
49 years of age (assumed to be beyond typical child-bearing age), or 
adult males since thyroid data for those populations are already 
available. Additionally, endpoints from the other segments of the 
extended one-generation study will not affect these latter populations, 
and the FQPA safety factor is being reduced to 1X for these 
populations.
    ii. Although the ETU studies were inadequate in evaluating signs of 
neurotoxicity, there was no evidence of neurotoxicity seen in any study 
in the database. In any event, the Agency has determined that the 
selected endpoints would be protective of potential neurotoxicity. The 
basis for this is that the principal toxic effects occur in the 
thyroid; thyroid effects provide the most sensitive endpoint, which the 
Agency is regulating on. Although the extended 1-gen study being 
performed on ETU is evaluating the potential for effects on the 
developing brain, the Agency does not believe that a 10X FQPA safety 
factor is necessary to protect children 6 years old or older because: 
(1) The weight-of-evidence of the available data indicates that thyroid 
effects are the most sensitive effect of this chemical; (2) the Agency 
is regulating on the more sensitive thyroid effect; and (3) the Agency 
is retaining a 10X FQPA safety factor for the population most likely 
affected by the thyroid effects.
    iii. As noted in Unit III.D.2., there is evidence of increased 
quantitative and qualitative susceptibility following increased in 
utero exposure to ETU. The developmental study with the lowest NOAEL 
was selected for the acute endpoint for women of childbearing age and 
is therefore protective of the developmental malformations. The only 
remaining developmental uncertainties are related to effects on the 
developing fetus caused by perturbations in the

[[Page 44453]]

still-not-completely-developed thyroid in children younger than 6 years 
old. Brain development being very sensitive to perturbations in thyroid 
hormones, it is possible that the extended 1-generation reproductive 
toxicity test, in which developmental thyroid effects will be 
evaluated, will result in lower NOAELs for these populations than are 
presently being used to assess risk; therefore, the Agency is retaining 
the 10X FQPA safety factor for females 13-49 years of age and for 
children less than 6 years of age.
    iv. There are no residual uncertainties identified in the EBDC's 
(mancozeb or metiram) exposure databases for ETU assessment. The acute, 
chronic, and cancer dietary exposure assessments were refined and used 
PCT estimates and monitoring residue values for several commodities 
including some major contributors to the dietary risk such as milk and 
corn commodities. Monitoring or modeling data were used to derive 
estimated drinking water concentrations. The drinking water 
concentrations that were derived from monitoring data reflect the 
highest value found in a community well monitoring program. The 
drinking water concentrations from modeling used conservative, health-
protective, high-end estimates and are unlikely to be exceeded. The 
residential exposure assessment used residential SOPs, which are based 
on conservative high-end assumptions such as maximum application rates 
and day 0 exposures. Given the overall conservative nature of the 
exposure assumptions, the aggregate (food, water, and residential) 
exposure and risk estimates presented in this assessment are not 
expected to underestimate actual exposure and risk expected based on 
the current and proposed use patterns.

E. Aggregate Risks and Determination of Safety

    EPA determines whether acute and chronic dietary pesticide 
exposures are safe by comparing aggregate exposure estimates to the 
acute PAD (aPAD) and chronic PAD (cPAD). For linear cancer risks, EPA 
calculates the lifetime probability of acquiring cancer given the 
estimated aggregate exposure. Short-, intermediate-, and chronic-term 
risks are evaluated by comparing the estimated aggregate food, water, 
and residential exposure to the appropriate PODs to ensure that an 
adequate MOE exists.
    1. Acute risk. (mancozeb). The mancozeb acute aggregate assessment 
considers acute exposure to mancozeb only and not ETU. Further, this 
assessment is based on residues of mancozeb in food only since residues 
of mancozeb are not expected in drinking water. Using the exposure 
assumptions discussed in this unit for acute exposure, the acute 
dietary exposure from food to mancozeb will occupy 9.9% of the aPAD for 
children 1-2 years old, the population subgroup receiving the greatest 
exposure.
    2. Acute risk (ETU). Using the exposure assumptions discussed in 
this unit for acute exposure, the acute dietary exposure from food and 
water to ETU (from mancozeb and metiram) will occupy 60% of the aPAD 
for females 13-49 years of age, the only population group of concern.
    3. Chronic risk (mancozeb). There are no long-term residential 
exposure scenarios for mancozeb and there is not likely to be residues 
of mancozeb in drinking water. Therefore, the long-term or chronic 
(non-cancer) aggregate risk for mancozeb includes contribution from 
food alone. Using the exposure assumptions described in this unit for 
chronic exposure, EPA has concluded that chronic exposure to mancozeb 
from food will utilize 2.3% of the cPAD for children 1-2 years of age, 
the population group receiving the greatest exposure.
    4. Chronic risk (ETU). There are no long-term residential exposure 
scenarios for ETU; the aggregate chronic risks were calculated using 
food and water exposure only. Using the exposure assumptions described 
in this unit for chronic exposure, EPA has concluded that chronic 
exposure to ETU (from mancozeb and metiram) from food and water will 
utilize 58% of the cPAD for children (1 to 2 years old), the population 
group receiving the greatest exposure.
    5. Short-term risk (mancozeb). Short-term aggregate exposure takes 
into account short-term residential exposure plus chronic exposure to 
food and water (considered to be a background exposure level).
    Mancozeb is currently registered for uses that could result in 
short-term residential exposure and the Agency has determined that it 
is appropriate to aggregate chronic exposure through food with short-
term residential exposures to mancozeb. The scenario that was evaluated 
for mancozeb was the residential handler home garden use. The aggregate 
short-term home garden MOEs for adult males and females greater than 49 
years old is 99,000 and the MOE for adult females 13-49 years old is 
94,000. Because for mancozeb EPA is concerned only with MOEs that are 
below 30 (adult males and females greater than 49 years old) and 300 
(adult females 13-49 years old), these MOEs do not raise a risk 
concern.
    6. Short-term risk (ETU). Short-term aggregate exposure takes into 
account short-term residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level).
    Mancozeb is currently registered for uses that could result in 
short-term residential exposure to ETU. There are no residential uses 
for metiram. The Agency determined that it was appropriate to aggregate 
chronic exposure through food with short-term residential exposures to 
ETU. The ETU short-term handler home garden aggregate MOE for adult 
females 13-49 years old is 27,000 and for adult males (and females 
older than 49 years old) is 42,000. The ETU short-term post-application 
home garden aggregate MOE for adult females 13-49 years old is 2,600 
and for youths 11-16 years old is 3,100. Because for ETU EPA is 
concerned only with MOEs that are below 1,000 (adult females 13-49 
years old) and 100 (adult males, females >49 years old and youth 11-16 
years old), these MOEs do not raise a risk concern.
    7. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account intermediate-term residential exposure plus chronic 
exposure to food and water (considered to be a background exposure 
level).
    An intermediate-term adverse effect was identified; however, 
mancozeb is not registered for any use patterns that would result in 
intermediate-term residential exposure. Intermediate-term risk is 
assessed based on intermediate-term residential exposure plus chronic 
dietary exposure. Because there is no intermediate-term residential 
exposure and chronic dietary exposure has already been assessed under 
the appropriately protective cPAD (which is at least as protective as 
the POD used to assess intermediate-term risk), no further assessment 
of intermediate-term risk is necessary, and EPA relies on the chronic 
dietary risk assessment for evaluating intermediate-term risk for 
mancozeb.
    8. Aggregate cancer risk for U.S. population. As noted earlier in 
this document, mancozeb degrades and/or metabolizes to ETU which causes 
the same types of thyroid tumors as those seen when animals are dosed 
with mancozeb; therefore, EPA has historically attributed mancozeb's 
carcinogenicity to the formation of ETU, which is classified as a 
probable human carcinogen.
    The cancer aggregate risk estimates (home garden handler and post-
application scenarios) for the U.S.

[[Page 44454]]

population are 2 x 10-6 and 3 x 10-6, 
respectively.
    EPA generally considers cancer risks (expressed as the probability 
of an increased cancer case) in the range of 1 in 1 million (or 1 x 
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 x 10-7 and 3 x 
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 above, 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 x 
10-6. This is particularly the case where some conservatism 
is maintained in the exposure assessment. Although the mancozeb risk 
assessment is highly refined, the Agency believes there is some 
conservatism for the following reasons: (1) The linear low-dose 
extrapolation approach is conservative because it does not take into 
account certain human biological processes such as reversibility and 
repair; (2) the residential SOPs are based on conservative high-end 
assumptions such as maximum application rates and day 0 exposures; and 
(3) some food exposures are estimated based on tolerance-level 
residues. Accordingly, EPA has concluded the cancer risk for all 
existing mancozeb uses and the uses associated with the tolerances 
established in this action fall within the range of 1 x 10-6 
and are thus negligible.
    9. 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 mancozeb and/or ETU residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate methods are available for the enforcement of tolerances 
for the plant commodities which are the subject of this request. The 
Pesticide Analytical Method (PAM) Vol. II lists Methods I, II, III, IV, 
and A for the determination of dithiocarbamate residues in/on plant 
commodities. The Keppel colorimetric method (Method III) is the 
preferred method for tolerance enforcement. The Keppel method 
determines EBDCs as a group by degradation to CS2. The 
analytical methodology for ETU is based on the original method 
published by Olney and Yip (JAOAC 54:165-169).
    The method may be requested from: Chief, Analytical Chemistry 
Branch, Environmental Science Center, 701 Mapes Rd., Ft. Meade, MD 
20755-5350; telephone number: (410) 305-2905; email address: 
residuemethods@epa.gov.

B. International Residue Limits

    In making its tolerance decisions, EPA seeks to harmonize U.S. 
tolerances with international standards whenever possible, consistent 
with U.S. food safety standards and agricultural practices. EPA 
considers the international maximum residue limits (MRLs) established 
by the Codex Alimentarius Commission (Codex), as required by FFDCA 
section 408(b)(4). The Codex Alimentarius is a joint United Nations 
Food and Agriculture Organization/World Health Organization food 
standards program, and it is recognized as an international food safety 
standards-setting organization in trade agreements to which the United 
States is a party. EPA may establish a tolerance that is different from 
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain 
the reasons for departing from the Codex level.
    There is no Codex MRL established for mancozeb on walnuts.
    There is a MRL of 10 ppm established by Codex for the use of EBDC 
compounds on mandarins which is consistent with the 10 ppm tolerance on 
tangerine being established by this document.

C. Revisions to Petitioned-For Tolerances

    Based on the evaluation of the residue data, the Agency is modified 
the tolerance for walnuts from the proposed level of 0.75 ppm to 0.70 
ppm. EPA revised the tolerance levels based on analysis of the residue 
field trial data using the Organization for Economic Cooperation and 
Development (OECD) tolerance calculation procedures.

V. Conclusion

    Therefore, tolerances are established for residues of mancozeb, in 
or on walnut at 0.70 ppm and tangerine at 10 ppm.

VI. Statutory and Executive Order Reviews

    This final rule establishes tolerances under FFDCA section 408(d) 
in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled ``Regulatory Planning and 
Review'' (58 FR 51735, October 4, 1993). Because this final rule has 
been exempted from review under Executive Order 12866, this final rule 
is not subject to Executive Order 13211, entitled ``Actions Concerning 
Regulations That Significantly Affect Energy Supply, Distribution, or 
Use'' (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled 
``Protection of Children from Environmental Health Risks and Safety 
Risks'' (62 FR 19885, April 23, 1997). This final rule does not contain 
any information collections subject to OMB approval under the Paperwork 
Reduction Act (PRA) (44 U.S.C. 3501 et seq.), nor does it require any 
special considerations under Executive Order 12898, entitled ``Federal 
Actions to Address Environmental Justice in Minority Populations and 
Low-Income Populations'' (59 FR 7629, February 16, 1994).
    Since tolerances and exemptions that are established on the basis 
of a petition under FFDCA section 408(d), such as the tolerance in this 
final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.), do not apply.
    This final rule directly regulates growers, food processors, food 
handlers, and food retailers, not States or tribes, nor does this 
action alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of FFDCA section 408(n)(4). As such, the Agency has determined that 
this action will not have a substantial direct effect on States or 
tribal governments, on the relationship between the national government 
and the States or tribal governments, or on the distribution of power 
and responsibilities among the various levels of government or between 
the Federal Government and Indian tribes. Thus, the Agency has 
determined that Executive Order 13132, entitled ``Federalism'' (64 FR 
43255, August 10, 1999) and Executive Order 13175, entitled 
``Consultation and Coordination with Indian Tribal Governments'' (65 FR 
67249, November 9, 2000) do not apply to this final rule. In addition, 
this final rule does not impose any enforceable duty or contain any 
unfunded mandate as described under Title II of the Unfunded Mandates 
Reform Act of 1995 (UMRA) (2 U.S.C. 1501 et seq.).
    This action does not involve any technical standards that would 
require Agency consideration of voluntary consensus standards pursuant 
to section 12(d) of the National Technology

[[Page 44455]]

Transfer and Advancement Act of 1995 (NTTAA) (15 U.S.C. 272 note).

VII. Congressional Review Act

    Pursuant to the Congressional Review Act (5 U.S.C. 801 et seq.), 
EPA will submit a report containing this rule and other required 
information to the U.S. Senate, the U.S. House of Representatives, and 
the Comptroller General of the United States prior to publication of 
the rule in the Federal Register. This action is not a ``major rule'' 
as defined by 5 U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

    Environmental protection, Administrative practice and procedure, 
Agricultural commodities, Pesticides and pests, Reporting and 
recordkeeping requirements.

    Dated: July 16, 2013.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

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

0
2. In Sec.  180.176, add alphabetically the following commodities and 
the footnote to the table in paragraph (a) to read as follows:

Sec.  180.176  Mancozeb; tolerances for residues.

    (a) * * *

------------------------------------------------------------------------
                                                               Parts per
                          Commodity                             million
------------------------------------------------------------------------
 
                                * * * * *
Tangerine\1\................................................          10
 
                                * * * * *
Walnut......................................................        0.70
 
                                * * * * *
------------------------------------------------------------------------
\1\ There are no U.S. registrations for use of mancozeb on tangerine.

* * * * *
[FR Doc. 2013-17869 Filed 7-23-13; 8:45 am]
BILLING CODE 6560-50-P