[Federal Register: August 18, 2010 (Volume 75, Number 159)]
[Rules and Regulations]
[Page 50902-50914]
[DOCID:fr18au10-24]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2005-0541; FRL-8841-1]

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 multiple commodities which are identified and
discussed later in this document. The Interregional Research Project
Number 4 (IR-4) requested these tolerances under the Federal Food,
Drug, and Cosmetic Act (FFDCA). In addition, this action establishes a
time-limited tolerance for residues of mancozeb in or on walnuts in
response to the approval of a specific exemption under section 18 of
the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA)
authorizing the use of mancozeb on walnuts to control walnut blight.
This regulation establishes a maximum permissible level of residues of
mancozeb in walnuts. The time-limited tolerance on walnuts expires and
is revoked on December 31, 2013. Also, this action revises the
introductory text of paragraphs (a) and (b).

DATES: This regulation is effective August 18, 2010. Objections and
requests for hearings must be received on or before October 18, 2010,
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-2005-0541. 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:<PHONE_NUMBER>; e-mail address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to those
engaged in the following activities:
     Crop production (NAICS code 111).
     Animal production (NAICS code 112).
     Food manufacturing (NAICS code 311).
     Pesticide manufacturing (NAICS code 32532).
    This listing is not intended to be exhaustive, but rather to
provide a guide for readers regarding entities likely to be affected by
this action. Other types of entities not listed in this unit could also
be affected. The North American Industrial Classification System
(NAICS) codes have been provided to assist you and others in
determining whether this action might apply to certain entities. If you
have any questions regarding the applicability of this action to a
particular entity, consult the person listed under FOR FURTHER
INFORMATION CONTACT.

B. How Can I Get Electronic Access to Other Related Information?

    You may access a frequently updated electronic version of EPA's
tolerance regulations at 40 CFR part 180 through the Government
Printing Office's e-CFR site at http://www.gpoaccess.gov/ecfr

C. How Can I File an Objection or Hearing Request?

    Under 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-2005-0541 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
October 18, 2010. 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-2005-0541, 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<PHONE_NUMBER>.

II. Summary of Petitioned-For Tolerance

    In the Federal Register of March 15, 2006 (71 FR 13389) (FRL-7767-
3), EPA issued a notice pursuant to section 408(d)(3) of FFDCA, 21
U.S.C. 346a(d)(3), announcing the filing of pesticide petitions (PP
3E4173, 5E4570, 9E5054, and 9E5061) by the Interregional Research
Project Number 4 (IR-4), 681 US Highway No. 1 South, North Brunswick,
NJ 08902-3390. The petitions requested that 40 CFR 180.176 be amended
by establishing tolerances for residues of the fungicide mancozeb, zinc
manganese ethylenebis dithiocarbamate, in or on the following
commodities: (PP 3E4173) cucurbit vegetable crop group 9 at 4.0 parts
per million (ppm); (PP 5E4570) mango, star apple (caimito), canistel,
mamey sapote, sapodilla, and white sapote at 15.0 ppm; (PP 9E5054)
ginseng at 2.0 ppm; (PP 9E5061) sugar apple, cherimoya, atemoya,
custard apple, and sweetsop at 3.0 ppm. The notice included a summary
of the petitions prepared by Dow AgroSciences, the registrant. However,
in the Federal Register of September 16, 2009, (74 FR 47504) (FRL-8431-
4) in a document titled ``Mancozeb, Maneb, Metiram, and Thiram;
Proposed Tolerance Actions,'' EPA proposed establishing tolerances for
ginseng at 1.2 ppm, removing the existing tolerances for cucumber,
melon and summer squash and establish a tolerance for the vegetable,
cucurbit group 9 at 2.0 ppm, and revising the tolerance expression in
Sec.  180.176. The reasons why EPA determined the tolerances for
ginseng and cucurbit vegetable crop group 9 should be different from
the original IR-4 petition as well as the rationale for changing the
tolerance expression are explained in Unit V.D.
    EPA did not receive comments on the notice of March 15, 2006 but
comments were received on the proposed rule of September 16, 2009.
EPA's response to these comments is discussed in Unit V.C.
    EPA is not establishing a tolerance for sweetsop. The reason why is
explained in Unit V.D.
    Separate from the actions being taken in response to the IR-4
petitions, EPA is also establishing a time-limited tolerance for
residues of mancozeb in or on walnuts at 0.015 ppm in connection with
an emergency use of mancozeb approved under FIFRA. This tolerance
expires and is revoked on December 31, 2013.

III. Emergency Exemption for Mancozeb on Walnuts and FFDCA Tolerances

    Walnut blight is a bacterial disease caused by Xanthomonas
campestris pv.juglandis. It can result in severe economic losses due to
undeveloped walnuts or early walnut-drop when the pathogen is present
with free moisture during flowering and early nut development.
Historically, walnut blight was managed by the application of copper
products. Copper-resistant pathogens were found in some orchards and
walnut losses in these orchards increased. Maneb was found to
effectively manage walnut blight, and thus reduce walnut losses, where
copper-resistant populations occurred and EPA has allowed use of maneb
on walnut under an emergency exemption on a longstanding basis in the
State of California. However, registrants have requested all products
containing the active ingredient maneb be cancelled. Additionally, the
Agency has been notified by the EBDC Task Force that there are no
existing stocks of products containing maneb available for use on
walnuts during 2010. Therefore, for the 2009-2010 growing season, the
State of California requested an emergency exemption for use of
mancozeb. This is the first time that California has requested mancozeb
for this use. It represents an equivalent agricultural tool since
mancozeb and maneb are related compounds.
    After having reviewed the submission, EPA determined that an
emergency condition exists for California, and that the criteria for
approval of an emergency exemption are met. EPA has authorized a
specific exemption under FIFRA section 18 for the use of mancozeb on
walnuts for control of walnut blight in California.
    As part of its evaluation of the emergency exemption application,
EPA assessed the potential risks presented by residues of mancozeb in
or on walnuts. In doing so, EPA considered the safety standard in
section 408(b)(2) of FFDCA, and EPA decided that the necessary
tolerance under section 408(l)(6) of FFDCA would be consistent with the
safety standard and with FIFRA section 18. Consistent with the need to
move quickly on the emergency exemption in order to address an urgent
non-routine situation and to ensure that the resulting food is safe and
lawful, EPA is issuing this tolerance without notice and opportunity
for public comment as provided in section 408(l)(6) of FFDCA. Although
this time-limited tolerance expires on December 31, 2013, under section
408(l)(5) of FFDCA, residues of the pesticide not in excess of the
amounts specified in the tolerance remaining in or on walnuts after
that date will not be unlawful, provided the pesticide was applied in a
manner that was lawful under FIFRA, and the residues do not exceed a
level that was authorized by this time-limited tolerance at the time of
that application. EPA will take action to revoke this time-limited
tolerance earlier if any experience with, scientific data on, or other
relevant information on this pesticide indicate that the residues are
not safe.
    Because this time-limited tolerance is being approved under
emergency conditions, EPA has not made any decisions about whether
mancozeb meets FIFRA's registration requirements for use on walnuts or
whether permanent tolerances for this use would be appropriate. Under
these circumstances, EPA does not believe that this time-limited
tolerance decision serves as a basis for registration of mancozeb by a
State for special local needs under FIFRA section 24(c). Nor does this
tolerance by itself serve as the authority for persons in any State
other than California to use this pesticide on the applicable crops
under FIFRA section 18 absent the issuance of an emergency exemption
applicable within that State. For additional information regarding the
emergency exemption for mancozeb, contact the Agency's Registration
Division at the address provided under FOR FURTHER INFORMATION CONTACT.

IV. Aggregate Risk Assessment and Determination of Safety

    Section 408(b)(2)(A)(i) of FFDCA allows EPA to establish a
tolerance (the legal limit for a pesticide chemical residue in or on a
food) only if EPA determines that the tolerance is ``safe.'' Section
408(b)(2)(A)(ii) of FFDCA defines ``safe'' to mean that ``there is a
reasonable certainty that no harm will result from aggregate exposure
to the pesticide chemical residue, including all anticipated dietary
exposures and all other exposures for which there is

reliable information.'' This includes exposure through drinking water
and in residential settings, but does not include occupational
exposure. Section 408(b)(2)(C) of FFDCA requires EPA to give special
consideration to exposure of infants and children to the pesticide
chemical residue in establishing a tolerance and to ``ensure that there
is a reasonable certainty that no harm will result to infants and
children from aggregate exposure to the pesticide chemical
residue....''
    Consistent with section 408(b)(2)(D) of FFDCA, and the factors
specified in section 408(b)(2)(D) of FFDCA, EPA has reviewed the
available scientific data and other relevant information in support of
this action. EPA has sufficient data to assess the hazards of and to
make a determination on aggregate exposure for 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 ingredients
maneb and metiram. 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 non-occupational exposure resulting from
mancozeb alone and ETU from all sources (i.e., the other EBDC
fungicides) for this action.
    EPA completed the Reregistration Eligibility Decision (RED) for
mancozeb in September, 2005 (http://www.epa.gov/oppsrrd1/REDs/
mancozeb_red.pdf). The Agency determined that most uses for the active
ingredient mancozeb were eligible for reregistration provided that the
risk mitigation measures identified in the RED were adopted and labels
were amended to reflect these measures. Certain uses (foliar use on
cotton, use on pineapple seed pieces, use on residential lawns/turf,
use on athletic fields/turf, and use on pachysandra) were not eligible
for reregistration and have since been voluntarily canceled by mancozeb
registrants and deleted from all mancozeb labels.
    In assessing mancozeb risk for the RED, EPA included the uses
associated with the petitions submitted by IR-4 to establish tolerances
for residues of mancozeb on cucurbit vegetable crop group 9 (PP
3E4173), mango, star apple, canistel, mamey sapote, sapodilla, white
sapote (PP 5E4570), ginseng (PP 9E5054), sugar apple, cherimoya,
atemoya, custard apple, and sweetsop (PP 9E5061). Additionally, EPA
considered exposure to residues of mancozeb on walnut in connection
with a pending petition (PP 5F4582) submitted by the registrant. No
action was taken on these petitions until the mitigation measures
outlined in the RED were implemented and existing stocks for the
cancelled uses moved through the channels of trade. The registrant
later withdrew the petition request to establish tolerances for
mancozeb on walnuts.
    While these mitigation measures were being implemented several
things changed regarding the mancozeb/ETU risk profile. First, EPA
determined that it was appropriate to retain the 10X FQPA Safety Factor
for acute dietary risk due to lack of the developmental neurotoxicity
study. Second, the registrant submitted additional petitions in 2004
that were not considered in the RED to establish tolerances for
residues of mancozeb in or on almond (PP 4F4324), cabbage, leaf
lettuce, peppers and broccoli (PP 4F4333). Therefore, based on these
changes, EPA conducted an additional risk assessment in 2007 for
mancozeb which assessed all uses (refer to risk assessment in the
Docket EPA-HQ-OPP-2005-0541 titled ``Mancozeb: Human Health Risk
Assessment to Support Proposed New Uses on Broccoli, Cabbage, Lettuce,
Peppers and Almonds'').
    To date, EPA is still working to refine the risk assessment for ETU
which incorporates the pending new uses for mancozeb that were
submitted to EPA in 2004 (almond, cabbage, leaf lettuce, peppers and
broccoli). In the meantime, EPA is moving forward to establish a time-
limited tolerance on walnut to support the emergency exemption as well
as establish permanent tolerances for cucurbit vegetable group 9,
mango, star apple, canistel, mamey sapote, sapodilla, white sapote,
ginseng, sugar apple, cherimoya, atemoya, and custard apple. EPA is
relying on an assessment conducted for mancozeb in 2007 (refer to risk
assessment in the Docket EPA-HQ-OPP-2005-0541 titled ``Mancozeb: Human
Health Risk Assessment to Support Proposed New Uses on Broccoli,
Cabbage, Lettuce, Peppers and Almonds''), an assessment for ETU from
2007 (for short- and intermediate-term aggregate exposures; refer to
risk assessment in the Docket EPA-HQ-OPP-2005-0541 titled
``Ethylenethiourea (ETU) from EBDCs: Health Effects Division (HED)
Human Health Risk Assessment of the Common Metabolite/Degradate ETU''),
and the assessment completed in the RED for exposures to ETU since that
is still valid and accounts for exposure to all of the commodities
discussed in this rule (refer to risk assessment in the Docket EPA-HQ-
OPP-2005-0176 titled ``ETU from EBDCs: Health Effects Division (HED)
Human Health Risk Assessment of the Common Metabolite/Degradate ETU to
Support Reregistration''). Since the 2007 ETU assessment includes the
use on almond, cabbage, leaf lettuce, peppers and broccoli, uses for
which tolerances do not exist and are not being established at this
time, the estimates for short- and intermediate-term aggregate risk for
ETU are likely overestimates.
    It is also important to note that since most products for maneb
have been cancelled or will be shortly and there are limited existing
stocks for maneb still in the channels of trade, the risk assessments
for ETU likely overestimate the exposures to this common metabolite.
Additionally, the risk estimates for mancozeb include uses for which
tolerances do not exist and are not being established at this time, and
therefore, the numbers reported are an over estimate of the potential
risks.
    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 ingredients metiram and maneb.
    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 was 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 (injury to
peripheral nerves) microscopically with associated clinical signs
(abnormal gait and limited use of rear legs) and loss of muscle mass.
An acute neurotoxicity study with mancozeb has been completed and

reviewed since the last risk assessment; neuropathology was not
observed, and minimal effects upon motor activity were observed at high
doses. The Agency conducted a preliminary dietary assessment using a
point-of-departure from this study and found no risk concerns. 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 radiolabelled mancozeb and other EBDCs, an
average 7.5% in vivo metabolic conversion of EBDC to ETU occurred, on a
weight-to-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.
    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 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.
    Specific information on the studies received and the nature of the
toxic 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 www.regulations.gov
in the document titled ``Mancozeb: Human Health Risk Assessment to
Support Proposed New Uses on Broccoli, Cabbage, Lettuce, Peppers and
Almonds,'' pp. 13-15 in docket ID number EPA-HQ-OPP-2005-0541.
    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
document titled ``ETU from EBDCs: Health Effects Division (HED) Human
Health Risk Assessment of the Common Metabolite/Degraduate ETU to
Support Reregistration. Chemical ID No. 600016. DP Barcode No.
D305129,'' pp. 9-11 in docket ID number EPA-HQ-OPP-2004-0078.

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 and
          Exposure/Scenario               Uncertainty/Safety     RfD, PAD, LOC for Risk  Study and Toxicological
                                               Factors                 Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary                          NOAEL = 128 milligrams/  Acute RfD = 0.13 mg/kg/  Developmental Toxicity
(Females 13-50 years of age).........   kilograms/day (mg/kg/    day                      in the rat
                                        day)                    Acute PAD = 0.13 mg/kg/  LOAEL = 512 mg/kg/day
                                       UFA =10x...............   day.                     based on hydrocephaly
                                       UFH = 10x..............                            and other
                                       UFDB=10x...............                            malformations
----------------------------------------------------------------------------------------------------------------
Acute dietary                              No appropriate endpoint was identified from oral toxicity studies.
(General population including infants
 and children).
----------------------------------------------------------------------------------------------------------------

Chronic dietary                        NOAEL= 4.83 mg/kg/day    Chronic RfD = 0.005 mg/  Toxicity/
(All populations)....................  UFA = 10x..............   kg/day                   Carcinogenicity in the
                                       UFH = 10x..............  Chronic PAD = 0.005 mg/   rat
                                       UFDB=10x...............   kg/day.                 LOAEL = 30.9 mg/kg/day
                                                                                based thyroid toxicity
                                                                                (changes in thyroid
                                                                                hormone levels,
                                                                                microscopic thyroid
                                                                                changes and changes in
                                                                                thyroid weights)
----------------------------------------------------------------------------------------------------------------
Incidental oral short- or              NOAEL= 9.24 mg/kg/day    LOC for MOE = 1,000      Subchronic Toxicity
 intermediate term                     UFA = 10x..............                            Study in the rat
(1 to 30 days).......................  UFH = 10x..............                           LOAEL = 17.82 mg/kg/day
                                       UFDB=10x...............                            based on decreased T4
----------------------------------------------------------------------------------------------------------------
Dermal short- and intermediate term    Mancozeb has low dermal absorption. No systemic toxicity observed via the
(1 to 30 days).......................     dermal route at 1,000 mg/kg/day. Developmental effects were noted at
                                        doses much higher than those where systemic toxicity was observed in the
                                        maternal animals (in oral studies) indicating that developmental effects
                                            will not occur below 1,000 mg/kg/day the limit dose, from dermal
                                                                        exposure.
----------------------------------------------------------------------------------------------------------------
Dermal long-term                       Dermal (or oral) study   LOC for MOE = 1,000      Toxicity/
                                        NOAEL= 4.83 mg/kg/day                             Carcinogenicity in the
                                        (dermal absorption                                rat
                                        rate = 1%                                        LOAEL = 30.9 mg/kg/day
                                       UFA = 10x..............                            based on thyroid
                                       UFH = 10x..............                            toxicity (changes in
                                       UFDB=10................                            thyroid hormone
                                                                                levels, microscopic
                                                                                thyroid changes and
                                                                                changes in thyroid
                                                                                weights)
----------------------------------------------------------------------------------------------------------------
Inhalation short-, intermediate-, or   NOAEL = 0.079 mg/L       LOC for MOE = 1,000      Subchronic Inhalation
 long-term                              [equivalent to 21 mg/                             in the rat
                                        kg/day]                                          LOAEL = 0.326 mg/L
                                       UFA = 10x..............                            based on thyroid
                                       UFH = 10x..............                            hyperplasia and
                                       UFDB=10x...............                            decreased T4 (females)
----------------------------------------------------------------------------------------------------------------
Cancer                                  Mancozeb's potential for carcinogenicity is due to the formation of the
(Oral, dermal, inhalation)...........      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 provide a quantitative estimate of risk.
----------------------------------------------------------------------------------------------------------------
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
  of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term
  study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA
  SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD =
  reference dose. MOE = margin of exposure. LOC = level of concern.

     Table 2.--Summary of Toxicological Doses and Endpoints for ETU for Use in Human Health Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                        Point of Departure and
          Exposure/Scenario               Uncertainty/Safety     RfD, PAD, LOC for Risk  Study and Toxicological
                                               Factors                 Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute dietary                          NOAEL = 5 milligrams/    Acute RfD = 0.005 mg/kg/ Developmental Toxicity
 (Females 13-50 years of age)........   kilograms/day (mg/kg/    day                      in the rat (Khera
                                        day)                    Acute PAD = 0.005 mg/kg/  Study, MRID No.
                                       UFA = 10x..............   day.                     45937601)
                                       UFH = 10x..............                           LOAEL = 10 mg/kg/day
                                       UFDB=10x...............                            based on developmental
                                                                                defects of the brain
----------------------------------------------------------------------------------------------------------------
Acute dietary                             No appropriate endpoint attributable to a single exposure (dose) was
(General population including infants                                  identified.
 and children).
----------------------------------------------------------------------------------------------------------------
Chronic dietary                        NOAEL= 0.18 mg/kg/day    Chronic RfD = 0.0002 mg/ Chronic Oral Toxicity
(All populations)....................  UFA = 10x..............   kg/day                   in the dog.
                                       UFH = 10x..............  Chronic PAD = 0.0002 mg/ LOAEL = 1.99 mg/kg/day
                                       UFDB= 10x..............   kg/day.                  based on thyroid
                                                                                toxicity (increased
                                                                                thyroid weight and
                                                                                macroscopic changes in
                                                                                the thyroid -
                                                                                hypertrophy,
                                                                                follicular dilation)
----------------------------------------------------------------------------------------------------------------
Incidental Oral (Short- and            NOAEL= 7 mg/kg/day       Residential LOC = 1,000  4 week range-finding
 Intermediate-Term)                    UFA = 10x..............                            dog study
                                       UFH = 10x..............                           LOAEL = 34 mg/kg/day
                                       UFDB=10x...............                            based on thyroid
                                                                                toxicity (decreased
                                                                                levels of thyroid
                                                                                hormones, gross
                                                                                thyroid lesions)
----------------------------------------------------------------------------------------------------------------

Dermal (Short- and Intermediate-Term)  NOAEL = 5 mg/kg/day      LOC for MOE = 1,000      Developmental Toxicity
                                       DA = 26%...............                            in the rat (Khera
                                       UFA = 10x..............                            Study, MRID No.
                                       UFH = 10x..............                            45937601)
                                       UFDB= 10x..............                           LOAEL = 10 mg/kg/day
                                                                                based on developmental
                                                                                defects of the brain
----------------------------------------------------------------------------------------------------------------
Dermal (Long-Term)                     NOAEL = 0.18 mg/kg/day   LOC for MOE = 1,000      Chronic Oral Toxicity
                                       DA = 26%...............                            in the dog
                                       UFA = 10x..............                           LOAEL = 1.99 mg/kg/day
                                       UFH = 10x..............                            based on thyroid
                                       UFDB= 10x..............                            toxicity (increased
                                                                                thyroid weight and
                                                                                macroscopic changes in
                                                                                the thyroid -
                                                                                hypertrophy,
                                                                                follicular dilation)
----------------------------------------------------------------------------------------------------------------
Inhalation (Short- and Intermediate-   Inhalation (or oral)     LOC for MOE = 1,000      Developmental Toxicity
 Term)                                  study NOAEL= 5 mg/kg/                             in the rat (Khera
                                        day                                               Study, MRID No.
                                       UFA = 10x..............                            45937601)
                                       UFH = 10x..............                           LOAEL = 10 mg/kg/day
                                       UFDB= 10x..............                            based on developmental
                                       Inhalation toxicity is                             defects of the brain
                                        assumed to be
                                        equivalent to oral
                                        toxicity..
----------------------------------------------------------------------------------------------------------------
Inhalation (Long-Term)                 NOAEL = 0.18 mg/kg/day   LOC for MOE = 1,000      Chronic Oral Toxicity
                                       UFA = 10x..............                            in the dog
                                       UFH = 10x..............                           LOAEL = 1.99 mg/kg/day
                                       UFDB= 10x..............                            based on thyroid
                                       Inhalation toxicity is                             toxicity (increased
                                        assumed to be                                     thyroid weight and
                                        equivalent to oral                                macroscopic changes in
                                        toxicity..                                        the thyroid -
                                                                                hypertrophy,
                                                                                follicular dilation)
----------------------------------------------------------------------------------------------------------------
Cancer                                   Q1* = 6.01 x 10 -2 (mg/kg/day)-1ETU is classified as a probable human
(Oral, dermal, inhalation)...........        carcinogen. Cancer risk is quantitified with a linear low-dose
                                              extrapolation approach based on liver tumors in female mice.
----------------------------------------------------------------------------------------------------------------
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
  of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term
  study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA
  SF = Food Quality Protection Act Safety Factor. PAD = population adjusted dose (a = acute, c = chronic). RfD =
  reference dose. MOE = margin of exposure. LOC = level of concern. DA = Dermal Absorption.

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 discussed in this document including additional proposed
uses that the Agency is not establishing tolerances for at this point
(almonds, cabbage, lettuce, broccoli, and pepper) 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 (maneb, metiram, mancozeb). 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.
    The Dietary Exposure Evaluation Model (DEEM\(TM)\) analysis
evaluated the individual food consumption as reported by respondents in
the USDA 1994-1996 and 1998 Nationwide Continuing Surveys of Food
Intake by Individuals (CSFII).
    a. Mancozeb. The following assumptions were made for the acute
exposure assessments: The Agency conducted a highly refined,
probabilistic acute dietary assessment incorporating maximum percent
crop treated information for proposed uses that the Agency is not
establishing tolerances at this time (almonds, cabbage, lettuce,
broccoli, and pepper) and existing uses, field trial or monitoring
data, and processing and cooking factors.
    b. ETU. The following assumptions were made for the acute exposure
assessments: The Agency conducted a highly refined, probabilistic acute
dietary assessment incorporating maximum percent crop treated
information for new and existing uses, field trial or monitoring data,
and processing and cooking factors. It was assumed that commodities
would not be treated with more than one EBDC in a season, as there are
label restrictions regarding treatment with multiple EBDCs. Percent
crop treated was estimated by summing the percent crop treated 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 maneb-derived
ETU values.
    ii. Chronic exposure. In conducting the chronic dietary exposure
assessment EPA used the Dietary Exposure Evaluation Model software with
the Food Commodity Intake Database (DEEM-FCID\TM\), which incorporates
food consumption data as reported by respondents in the USDA 1994-1996
and 1998 Nationwide Continuing Surveys of Food Intake by Individuals
(CSFII).
    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 percent crop
treated data for proposed uses that the Agency is not

establishing tolerances at this time (almonds, cabbage, lettuce,
broccoli, and pepper) and existing uses, as well as processing and
cooking factors.
    b. ETU. Chronic anticipated residues were calculated from field
trial 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 food-use pesticide based on
the weight of the evidence from cancer studies and other relevant data.
Cancer risk is quantified using a linear or non-linear approach. If
sufficient information on the carcinogenic mode of action is available,
a threshold or non-linear approach is used and a cancer RfD is
calculated based on an earlier non-cancer key event. If carcinogenic
mode of action data 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.
    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).
    EPA relied on 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.
    For mancozeb the Agency estimated the PCT for existing uses as
follows:
    Cantaloupes 5%; pumpkins 5%; sugar beets 5%; tobacco 5%; cucumber
10%; garlic 10%; sweet corn 10%; grapes 15%; squash 15%; asparagus 20%;
eggplant 20%; tomatoes 25%; apples 30%; cranberries 30%; watermelons
35%; pears 40%; onions 50%; and potatoes 54%. Beans, green; carrots;
cherries; corn (field); cotton; oranges; peaches; peanuts; pecans;
prunes, plums; strawberries; walnuts; and wheat all average less than
1%.
    For ETU the Agency estimated the PCT for existing uses of mancozeb,
maneb and metiram.
    a. Mancozeb. For mancozeb, the PCT was identical to that listed in
this unit.
    b. Maneb. For maneb, the Agency estimated the PCT for existing uses
as follows:
    Almonds 10%; apples 1%; dry beans 1%; green beans 5%; broccoli 5%;
Brussels sprouts 21%; cabbage 15%; carrots 1%; cauliflower 5%; celery
5%; collards 10%; field corn 1%; eggplant 55%; garlic 25%; grapes 1%;
mustard greens 5%; kale 5%; lettuce 65%; onions; 10%; pears 1%; peppers
30%; potatoes 5%; pumpkins 5%; spinach 15%; squash 5%; sugar beets 1%;
sweet corn 1%; tomatoes 5%; walnuts 30%; watermelons 5%; wheat 5%.
    c. Metiram. For metiram, the Agency estimated the PCT for existing
uses as follows:
    Apples 15%; asparagus 1%; peaches 1%; potatoes 10%; squash 1%.
    The PCT estimates for mancozeb and maneb on walnuts reflect usage
of maneb on walnuts under an emergency exemption prior to the
cancellation of maneb products and establishment of the emergency
exemption use on walnuts for mancozeb. Going forward, EPA expects
mancozeb use on walnuts to replace maneb. However, for this present
action, EPA concludes it is reasonable to use the risk assessment that
relied upon the PCT estimates in this unit for walnuts because: EPA
does not expect mancozeb use on walnuts to be higher than the prior
maneb use; mancozeb residues on walnuts and the consumption level of
walnuts are insignificant compared to residue and consumption levels of
other mancozeb-treated commodities (e.g., melons and apples); and ETU
residues from maneb and macozeb are equivalent.
    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%.
    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
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 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. The values are listed in Table 3 of this unit.

                                   Table 3.-- Surface and Ground Water Values.
----------------------------------------------------------------------------------------------------------------
                                                Acute                   Chronic                   Cancer
----------------------------------------------------------------------------------------------------------------
Surface Water EDWC                     0.1 to 25.2 ppb          0.10 ppb                 0.10 ppb
----------------------------------------------------------------------------------------------------------------
Ground Water EDWC                      0.21 ppb                 0.21 ppb                 0.21 ppb
----------------------------------------------------------------------------------------------------------------

    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 non-occupational, non-dietary
exposure (e.g., for lawn and garden pest control, indoor pest control,
termiticides, and flea and tick control on pets).
    i. Mancozeb. Mancozeb is currently registered for use on the
following residential sites: Home gardens, golf courses, and sod farms
(potential exposure to mancozeb is from residues remaining on
transplanted turf). The Agency has determined that it is appropriate to
aggregate chronic exposure through food with short- and intermediate-
term residential exposures to mancozeb.
    The two scenarios that were evaluated for mancozeb are the Short/
Intermediate-Term Home Garden Aggregate (Adult) which considers
residential handler exposures (inhalation) to adult applicators
combined with average food exposures and the Short/Intermediate-Term
Treated Turf Aggregate (Toddler) which considers residential incidental
oral exposures to toddlers combined with average food exposures. The
only postapplication scenario for adults in contact with treated turf
(golf courses) is via the dermal route of exposure. Since no dermal
endpoints were selected for mancozeb, a quantitative risk assessment
for this scenario is not required.
    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
dietary 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 mancozeb.
    The three scenarios that were evaluated for ETU are 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 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 and the Short/Intermediate-Term
Treated Turf Aggregate (Adults ``Golfers'') which considers short-term
residential exposures (dermal) plus average daily food and drinking
water exposure for adults such as golfing on treated turf.
    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 in Unit IV., the risk estimates summarized
in this document are those that result only from the use of mancozeb,
and ETU derived from mancozeb and the other EBDC chemicals, which are
all 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 can not
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 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.
    ii. ETU. There was evidence of increased susceptibility of fetuses
to ETU in the rat developmental studies because hydrocephaly occurred
at doses below that causing maternal toxicity. Acceptable reproductive
and rabbit developmental toxicity studies were 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. Mancozeb. The toxicity database for mancozeb is
not complete. The new requirement for an immunotoxicity study has not
been met. The absence of an immunotoxicity study does not raise
significant uncertainty. In the absence of that study, the available
toxicity data for mancozeb have been thoroughly examined for any
information which suggests a potential for immunotoxicity. The analysis
did not reveal such information and the Agency does not believe that
conducting the immunotoxicity study will result in a point of departure
(POD) less than the currently selected PODs for risk assessment. A
developmental neurotoxicity (DNT) study has been submitted, and EPA has
recently completed a review of this study. Neurotoxicity was not
observed in the study, and the young animals did not show
susceptibility, as compared to the adults, for the slight toxicity that
was observed (reduced body weight gain). Since the review of the DNT
was completed after the most recent risk assessment was finished, EPA
has not had the opportunity to re-evaluate the need for an FQPA factor.
For this assessment, EPA has retained the presumptive 10X FQPA safety
factor for the protection of children, but will re-visit the need for
the safety factor for the next tolerance action.
    No additional FQPA Safety Factor is needed beyond the 10X database
uncertainty factor applied to account for the data gap for a
developmental neurotoxicity study with mancozeb. The reasons for this
conclusion are:
     a. There is a lack of evidence of pre- and/or postnatal
susceptibility resulting from exposure to mancozeb
    b. There are no residual uncertainties concerning toxicity, and
    c. The exposure assessment, although refined, is unlikely to under-
estimate potential exposures.
    ii. ETU. The toxicity database for ETU is not complete. EPA lacks
the following studies: A DNT study; a developmental study in rabbits; a
2-generaltion reproduction study; and a comparative thyroide study in
adults and offspring. Given these multiple datagaps for studies that
directly assess the risk to the young, EPA does not have reliable data
to remove or modify the presumptive 10X FQPA safety factor.
    No further safety factor to protect is needed for the following
reasons. First, the Agency determined that the degree of concern for
the susceptibility seen in ETU developmental studies was low. The
reasons for this conclusion are:
    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 mancozeb converts to ETU
in mammalian systems, the extensive toxicity database with mancozeb
provide extensive information about toxicity of ETU;
    b. There is a clear NOAEL for these effects and the dose-response
relationship, although steep, is well characterized in the numerous
developmental studies in rats.
    c. The developmental endpoint with the lowest NOAEL was selected
for deriving the acute RfD.
    d. The target organ toxicity (thyroid toxicity) was selected for
deriving the chronic RfD as well as endpoints for non-dietary exposures
(incidental oral, dermal, and inhalation). Since the ETU doses selected
for overall risk assessments will address the concern for developmental
and thyroid toxicity, there are no residual uncertainties with regard
to pre- and/or post-natal toxicity.
    Second, the information on ETU gleaned from the extensive mancozeb
database also reduces, to a degree, the uncertainty arising from the
significant datagaps for ETU.
    Third, EPA has concluded that the exposure assessment, although
refined, is unlikely to under-estimate potential exposures.

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 per se from food only since
residues of mancozeb per se are not expected in drinking water. Using
the exposure assumptions discussed in this unit for acute exposure, the
acute dietary exposure from food and water to mancozeb will occupy 6.9%
of the aPAD for females 13-49 years of age, the only population group
of concern.
    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 will occupy 87% 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
dietary (food only) exposure alone. Using the exposure assumptions
described in this unit for chronic exposure, EPA has concluded that

chronic exposure to mancozeb from food will utilize 3.3% of the cPAD
for children 1-2 years of age, the population group receiving the
greatest exposure.
    4. Chronic risk (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 58% of the cPAD for children (1 to 2
years old), the population group receiving the greatest exposure.
    5. Short-and intermediate-term risk (Mancozeb). Short- and
intermediate-term 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).
    Mancozeb is currently registered for uses that could result in
short- and intermediate-term residential exposure and the Agency has
determined that it is appropriate to aggregate chronic exposure through
food with short- and intermediate-term residential exposures to
mancozeb. The two scenarios that were evaluated for mancozeb are the
following:
    i. Short/Intermediate-Term Home Garden Aggregate (Adult). Since
there are no dermal endpoints selected for mancozeb, the home garden
aggregate risk assessment does not include dermal exposure. Further,
since residues of mancozeb are not expected in drinking water, only
mancozeb food residues are considered. This assessment combines
residential handler exposures (inhalation) to adult applicators plus
average food exposures. The exposure value used for food represents the
highest exposure found from all adult populations in the mancozeb
chronic dietary exposure assessment.
    The aggregate short/intermediate-term home garden MOEs for adults
are 110,000. Because for mancozeb EPA is concerned only with MOEs that
are below 1,000, this MOE does not raise a risk concern.
    ii. Short-Term Treated Turf Aggregate (Toddler). Since there are no
dermal endpoints selected for mancozeb and no likelihood of residues in
drinking water, the mancozeb short-term treated turf aggregate risk
assessment for toddlers combines residential incidental oral exposures
with average food residues. The exposure value used for food represents
the highest exposure found from all child populations in the mancozeb
chronic dietary exposure assessment.
    With a 5-day interval between application and transplant for the
sod farm use, which is now on the registered label, the mancozeb short-
term aggregate risk (MOE) for toddlers exposed to treated turf is
1,100. Because for mancozeb EPA is concerned only with MOEs that are
below 1,000, this MOE does not raise a risk concern.
    6. Short- and intermediate-term risk (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).
    Mancozeb and maneb are currently registered for uses that could
result in short- and intermediate-term residential exposure to ETU and
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
the following:
    i. ETU Short/Intermediate-Term Home Garden Aggregate. The ETU
short/intermediate-term home garden aggregate combines handler
inhalation and dermal exposures and post application garden dermal
exposures plus average daily food and drinking water for adults exposed
to ETU. For youth exposed to ETU, the assessment combines post
application garden dermal exposures with average food and drinking
water. Only mancozeb is registered for use in home garden settings.
Average food and drinking water exposure values reflect the most highly
exposed adult or youth subpopulation from the average daily dietary
assessment, and consider ETU derived from mancozeb, metiram, and maneb
applications. The existing and proposed food uses were included in the
food and drinking water exposure estimates.
    The ETU short/intermediate-term home garden aggregate MOEs for
adults is 13,000 and 17,000 for youth, respectively. Because for ETU
EPA is concerned only with MOEs that are below 1,000, this MOE does not
raise a risk concern.
    ii. ETU Short-Term Treated Turf Aggregate (Toddlers). The short-
term treated turf aggregate risk assessment combines treated turf post
application incidental oral and dermal exposures with average daily
food and drinking water exposure for toddlers. Maneb and mancozeb are
both registered for applications to sod farms. Average food and
drinking water exposure values, including all sources of ETU, reflect
the most highly exposed children's subpopulation from the chronic
dietary assessment.
    The ETU short-term treated turf aggregate MOE for toddlers is
1,100. Because for ETU EPA is concerned only with MOEs that are below
1,000, this MOE does not raise a risk concern.
    iii. ETU Short/Intermediate-Term Treated Turf Aggregate (Adults
``Golfers''). The short/intermediate-term treated turf aggregate risk
assessment combines dermal exposures for adults golfing on treated turf
exposed to ETU with average daily food and drinking water exposures.
Only mancozeb uses are relevant for this scenario.
    The ETU short-term treated turf aggregate MOE for adults
(``golfers'') is 6,100. Because for ETU EPA is concerned only with MOEs
that are below 1,000, this MOE does not raise a risk concern.
    7. Aggregate cancer risk for U.S. population (Mancozeb and ETU). As
noted earlier in Unit IV.C.iii., 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 (B2).
    The cancer risks were aggregated using the food and drinking water
doses for the general population and the food, water and recreational
doses 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 2.3 x 10-6.
    EPA generally considers cancer risks in the range of
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 log 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, 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 ETU exposure risk assessment is refined, it
retains significant conservatism in that, for leafy greens, field trial
data and not

market basket data on similar crops is used in estimating exposure.
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.
    8. 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.

V. 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 carbon disulfied
(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:<PHONE_NUMBER>; e-mail address:
<EMAIL_ADDRESS>
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 U.N. Food and
Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
    There are no established or proposed Codex maximum residue limits
for residues of mancozeb per se; however, Codex limits for
dimethyldithiocarbamates fungicides are grouped under dithiocarbamates.
There are Codex MRLs for cucumber (2 ppm), melons (0.5 ppm), pumpkins
(0.2 ppm), and summer squash (1 ppm).

C. Response to Comments

    As discussed in Unit II. of this document, in the Federal Register
of September 16, 2009, EPA proposed tolerance actions for mancozeb. EPA
did receive comments on the proposed rule; however, many of those
comments are not related to the uses proposed in this action.
Therefore, EPA is only responding to the comment received that directly
addresses issues that pertain to this action. EPA will respond to the
additional comments in a future rule.
    Comment. The Natural Resources Defense Council (NRDC) commented
about the FQPA Safety Factor and the risks to infants of low iodide
women. NRDC is concerned about the effects of the EBDC fungicides on
women of child-bearing age. All of the EBDC fungicides have shown
effects on the thyroid. They have noted that a decrease in thyroxine in
pregnant and lactating women, such as has been observed in laboratory
animals exposed to the EBDC fungicides, can result in neuro-
developmental problems in their children. NRDC has specifically
inquired whether the Agency considered the risks to the infants of low-
iodide women, and has recommended that the Agency retain the FQPA
factor of at least 10X, and possibly more.
    Agency Response. EPA agrees with NRDC that protection from adverse
effects in the thyroid in women of child-bearing age is important to
protect the developing fetus from adverse outcomes. An adverse effect,
even in the case of women with iodine deficiency, is not expected for
the following reasons.
    The mode of action for thyroid toxicity from the EBDCs is
understood. ETU, which is the common metabolite of the EBDCs, acts by
inhibiting thyroid peroxidase, an enzyme used in the synthesis of
thyroid hormone. This enzyme inhibition ceases when exposure to ETU is
removed and there is no subsequent change in enzyme function The other
thyroid effects (organ weight and microscopic changes), are secondary
to this enzyme inhibition as the body attempts to increase production
of thyroid hormone by stimulating the thyroid in compensation.
    People are protected from the enzyme inhibition because the EBDCs
are regulated from the NOAEL for thyroid effects, which is below the
dose at which there are thyroid effects in animals. Further, the EBDCs
were tested in rats, which are much more sensitive to thyroid
perturbations than are humans. Rats are more sensitive than humans
because the serum half-life of the thyroid hormone, thyroxine, is much
shorter in rats (less than 1 day) than in humans (5-9 days). The 10X
interspecies uncertainty factor applied to the EBDCs to account for the
possibility that humans are more sensitive than the test animals is
therefore more than adequate to protect humans. The 10X intraspecies
factor accounts for variability in sensitivity among species and gives
protection for women with iodine deficiency. The combination of these
factors is therefore expected to be protective for the fetus and
pregnant women with regard to possible iodine deficiencies. The Agency
has requested a comparative thyroid assay for ETU which will provide
additional information on the potential susceptibility of developing
organisms, including the developing fetus, to thyroid perturbation, and
has retained an FQPA safety factor of 10X to account for the
uncertainties associated with these missing data.

D. Revisions to Petitioned-For Tolerances

    EPA is not establishing a tolerance for sweetsop because it is the
same commodity as sugar apple. The Agency is establishing the tolerance
on sugar apple because it is the preferred term for this commodity.
    The ginseng tolerance is a reduction from the proposed 2.0 ppm to
1.2 ppm based on conclusions reached in the RED. The 2.0 tolerance
recommendation is on a mancozeb per se basis; however EPA is now
recommending for a tolerance on a carbon disulfide equivalents basis
thus resulting in a tolerance recommendation of 1.2 ppm.
    In regards to the cucurbit tolerance, based on available field
trial data that showed mancozeb residues as high as 2.1 ppm on
cucumber, 2.7 ppm on melons, and 1.75 ppm on summer squash, the Agency
determined that individual tolerances should be set at 3.0 ppm, 3.0
ppm, and 2 ppm, respectively, which when converted to carbon disulfide
equivalents using a rounded conversion factor of 0.6X is calculated as
1.8 ppm, 1.8 ppm, and 1.2 ppm, respectively. Because the
representatives for crop group 9 include cucumber, muskmelon, and
summer squash, EPA believes that these tolerances should be combined
into a single crop group tolerance and decreased from their current
individual

tolerance levels of 4 ppm to 2 ppm. EPA proposed these changes in the
Federal Register of September 16, 2009, in a document proposing
multiple changes to the mancozeb tolerances.

E. Revisions to Tolerance Expression

    EPA is also in this action changing the mancozeb tolerance
expression as proposed in the Federal Register of September 16, 2009.
Currently, tolerances for mancozeb are established in 40 CFR 180.176(a)
for residues of the fungicide mancozeb, a coordination product of zinc
ion and maneb (manganese ethylenebisdithiocarbamate) and calculated as
zinc ethylenebisdithiocarbamate (zineb). Mancozeb is a member of the
class of dithiocarbamates, whose decomposition releases CS2.
In order to allow harmonization of U.S. tolerances with Codex Maximum
Residue Limits (MRLs), the Agency determined that for the purpose of
tolerance enforcement, residues of mancozeb should be calculated as
carbon disulfide. Therefore, EPA is revising the introductory text
containing the tolerance expression in 40 CFR 180.176(a) and (b).

VI. Conclusion

    Therefore, tolerances are established for residues of mancozeb,
zinc manganese ethylenebis dithiocarbamate in or on cucurbit vegetable
crop group 9 at 2.0 ppm; mango, star apple, canistel, mamey sapote,
sapodilla, and white sapote at 15.0 ppm; ginseng at 1.2 ppm; sugar
apple, cherimoya, atemoya and custard apple at 3.0 ppm; and a time-
limited tolerance in or on walnut at 0.015 ppm.

VII. Statutory and Executive Order Reviews

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

VIII. 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: August 10, 2010.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

0
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. Section 180.176 is amended as follows.
    i. In paragraph (a), revise the introductory text;
    ii. In paragraph (a), in the table, remove the commodities
Cucumber, Melon, and Summer squash and alphabetically add the following
commodities;
    iii. In paragraph (b), revise the introductory text;
    iv. In paragraph (b), in the table, alphabetically add Walnut.
    The amendments read as follows:

Sec.  180.176  Mancozeb; tolerances for residues.

    (a) General. Tolerances are established for residues of mancozeb (a
coordination product of zinc ion and maneb (manganese
ethylenebisdithiocarbamate)), 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 mancozeb residues convertible to and expressed in
terms of the degradate carbon disulfide.

------------------------------------------------------------------------
                                                               Parts per
                          Commodity                             million
------------------------------------------------------------------------
                                * * * * *
Atemoya.....................................................         3.0
                                * * * * *
Canistel....................................................        15.0
                                * * * * *
Cherimoya...................................................         3.0
                                * * * * *
Custard apple...............................................         3.0

                                * * * * *
Ginseng.....................................................         1.2
                                * * * * *
Mango.......................................................        15.0
                                * * * * *
Sapodilla...................................................        15.0
Sapote, mamey...............................................        15.0
Sapote, white...............................................        15.0
                                * * * * *
Star apple..................................................        15.0
Sugar apple.................................................         3.0
                                * * * * *
Vegetable, cucurbit, group 9................................         2.0
------------------------------------------------------------------------

* * * * *
    (b) Section 18 emergency exemptions. Time limited tolerances are
established in connection with use of the pesticide under a section 18
emergency exemption granted by EPA for residues of mancozeb (a
coordination product of zinc ion and maneb (manganese
ethylenebisdithiocarbamate)), 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 mancozeb residues convertible to and expressed in
terms of the degradate carbon disulfide. The tolerances will expire and
are revoked on the dates specified in the following table.

----------------------------------------------------------------------------------------------------------------
                                                                                Expiration/revocation
                           Commodity                               Parts per million               date
----------------------------------------------------------------------------------------------------------------
                                                  * * * * * * *
Walnut........................................................                    0.015                 12/31/13
----------------------------------------------------------------------------------------------------------------

* * * * *

[FR Doc. 2010-20453 Filed 8-17-10; 8:45 am]
BILLING CODE 6560-50-S