[Federal Register Volume 68, Number 43 (Wednesday, March 5, 2003)]
[Rules and Regulations]
[Pages 10377-10388]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-5192]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2003-0075; FRL-7296-2]


Folpet; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes a tolerance for residues of folpet 
(N-(trichloromethylthio)phthalimide) in or on hop, dried cones. 
Makhteshim-Agan of North America Inc. requested this tolerance under 
the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the 
Food Quality Protection Act of 1996 (FQPA).

DATES: This regulation is effective March 5, 2003. Objections and 
requests for hearings, identified by docket ID number OPP-2003-0075, 
must be received on or before May 5, 2003.

ADDRESSES: Written objections and hearing requests- may be submitted 
electronically, by mail, or through hand delivery/courier. Follow the 
detailed instructions as provided in Unit VI. of the SUPPLEMENTARY 
INFORMATION.

FOR FURTHER INFORMATION CONTACT: Richard P. Keigwin, Jr., Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW.,Washington, DC 20460-
0001; telephone number: (703) 305-7618; e-mail address: 
[email protected].

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:
    [sbull] Industry (NAICS 111), Crop production.
    [sbull] Industry (NAICS 112), Animal production.
    [sbull] Industry (NAICS 311), Food manufacturing.
    [sbull] Industry (NAICS 32532), Pesticide manufacturing.
    This listing is not intended to be exhaustive, but rather provides 
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 Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2003-0075. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public docket is the collection of materials 
that is available for public viewing at the Public Information and 
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The docket telephone number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/. A frequently updated 
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml__00/Title__40/40cfr180_(--
00.html, a beta site currently under development. To access the OPPTS 
Harmonized Guidelines referenced in this document, go directly to the 
guidelines at http://www.epa.gov/opptsfrs/home/guidelin.htm.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.

II. Background and Statutory Findings

    In the Federal Register of January 9, 2003 (68 FR 1182) (FRL-7287-
7), EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 
346a, as amended by FQPA (Public Law 104-170), announcing the filing of 
a pesticide petition (PP 2E6512) by Makhteshim-Agan of North America 
Inc., 551 Fifth Ave., Suite 1100 New York, NY 10176. That notice 
included a summary of the petition prepared by Makhteshim-Agan of North 
America Inc., the registrant. There were no comments received in 
response to the notice of filing.
    The petition requested that 40 CFR 180.191 be amended by 
establishing a tolerance for residues of the fungicide folpet, (N-
(trichloromethylthio)phthalimide), in or on hop at 120 parts per 
million (ppm).
    Section 408(b)(2)(A)(i) of the 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 the 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 the FFDCA requires EPA to give special 
consideration to

[[Page 10378]]

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....''
    EPA performs a number of analyses to determine the risks from 
aggregate exposure to pesticide residues. For further discussion of the 
regulatory requirements of section 408 of the FFDCA and a complete 
description of the risk assessment process, see the final rule on 
Bifenthrin Pesticide Tolerances (62 FR 62961, November 26, 1997) (FRL-
5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of the 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, consistent with section 
408(b)(2) of the FFDCA, for a tolerance for residues of folpet on hop, 
dried cones at 100 ppm. EPA's assessment of exposures and risks 
associated with establishing the tolerance 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. The nature of the toxic effects caused by folpet are 
discussed in Table 1 of this unit as well as the no-observed-adverse-
effect-level (NOAEL) and the lowest-observed-adverse-effect-level 
(LOAEL) from the toxicity studies reviewed.

                               Table 1.-- Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
             Guideline No.                       Study Type                            Results
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity        NOAEL = 160 milligrams/kilogram/day (mg/kg/
                                          rodents                     day)
                                                                     LOAEL = 500 mg/kg/day based on 5 percent
                                                                      decrease in body weight
----------------------------------------
870.3150                                 90-Day oral toxicity in     NOAEL = <790 mg/kg/day (lowest dose
                                          nonrodents                  tested)(LDT)
                                                                     LOAEL = 790 mg/kg/day based on decreased
                                                                      weight gain in males and females,
                                                                      testicular atrophy in males
----------------------------------------
870.3200                                 28-Day dermal toxicity      NOAEL = 1 mg/kg/day
                                                                     LOAEL = 10 mg/kg/day based on dermal
                                                                      irritation;systemic toxicity as reduced
                                                                      body weight gain occurred only at doses
                                                                      greater than 10 mg/kg/day
----------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 10 mg/kg/day
                                          rodents                    LOAEL = 60 mg/kg/day based on reduced body
                                         Crl: COBS-CD-(SD) BR         weight
                                          strain..                   Developmental NOAEL = 60 mg/kg/day
                                                                     LOAEL = 360 mg/kg/day based on possible
                                                                      incomplete ossification of one or both
                                                                      pubes and/or eschia
----------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 150 mg/kg/day
                                          rodents                    LOAEL = 550 mg/kg/day based on decreased
                                         CD Rats...................   body weight gain, soft feces
                                                                     Developmental NOAEL = <150 mg/kg/day (LDT)
                                                                     LOAEL = 550 mg/kg/day based on small
                                                                      fetuses, reduced ossification of
                                                                      interparietal bone as well as increase in
                                                                      angulated ribs
----------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 40 mg/kg/day
                                          nonrodents                 LOAEL = 160 mg/kg/day based on decrease in
                                         HY/CR Albino Rabbits......   body weight gain and food consumption
                                                                     Developmental NOAEL = 10 mg/kg/day
                                                                     LOAEL = 40 mg/kg/day based on delayed
                                                                      ossification of sternebrae and lack of
                                                                      ossification of caudal vertebrae distal to
                                                                      caudal vertebra 15.
----------------------------------------
870.3700                                 Prenatal developmental in   Maternal NOAEL = 10 mg/kg/day
                                          nonrodents                 LOAEL = 20 mg/kg/day based on decreased
                                         NZW Rabbits...............   food consumption & body weight gain during
                                                                      gestation. At 60 mg/kg/day, decreased food
                                                                      consumption & body weight gain,
                                                                      hydrocephalus and related skull
                                                                      malformations.
                                                                     Developmental NOAEL = 10 mg/kg/day
                                                                     LOAEL = 20 mg/kg/day based on Increased
                                                                      incidence of hydrocephalus & domed skull &
                                                                      irregularly shaped fontanelles
----------------------------------------
870.3800                                 Reproduction and fertility  Parental/Systemic NOAEL = 19.1 mg/kg/day in
                                          effects                     males; 22.5 mg/kg/day in females
                                         Charles River Rat.........  LOAEL = 112 mg/kg/day in males and 134 mg/
                                                                      kg/day in females based on diffuse
                                                                      hyperkeratosis of the non-glandular
                                                                      epithelium of in both sexes of both
                                                                      generations.
                                                                     Reproductive NOAEL = 370 mg/kg/day in
                                                                      males; 436 mg/kg/day in females highest
                                                                      dose tested (HDT)
                                                                     Offspring NOAEL = 112 mg/kg/day in males
                                                                      and 134 mg/kg/day in females
                                                                     LOAEL = 370 mg/kg/day in males and 565 mg/
                                                                      kg/day in females based on lower pup body
                                                                      weights primarily in the F1 litter
                                                                      generation
----------------------------------------

[[Page 10379]]

 
870.3800                                 Reproduction and fertility  Parental/Systemic NOAEL = 35 mg/kg/day
                                          effects                    LOAEL = 160 mg/kg/day based on decreased
                                         Sprague-Dawley Rat........   weight gain in F1 offspring.
                                                                     Reproductive NOAEL = 35 mg/kg/day
                                                                     LOAEL = 160 mg/kg/day based on decreased
                                                                      fertility in males
----------------------------------------
870.4100                                 Chronic toxicity rodents    NOAEL = 10 mg/kg/day
                                         Crl:CD(SD)BR albino rats..  LOAEL = 40 mg/kg/day based on ulceration/
                                                                      erosion, hyperkeratosis of stomach in
                                                                      males and females
----------------------------------------
870.4100                                 Chronic toxicity rodents    NOAEL = 25 mg/kg/day
                                         Fischer 344 Rat...........  LOAEL = 50 mg/kg/day based on
                                                                      hyperkeratosis of nonglandular epithelium
                                                                      of stomach in both sexes.
----------------------------------------
870.4100                                 Chronic toxicity rodents    NOAEL = 12 mg/kg/day in males; 15 mg/kg/day
                                                                      in females
                                                                     LOAEL = 81 mg/kg/day in males and 100 mg/kg/
                                                                      day in females based on an increase in
                                                                      incidence and severity of hyperkeratosis
                                                                      of the esophagus and non-glandular
                                                                      epithelium of the stomach.
----------------------------------------
870.4100                                 Chronic toxicity dogs       NOAEL = 10 mg/kg/day
                                                                     LOAEL = 60 mg/kg/day based on decreased
                                                                      food consumption & body weight gain;
                                                                      decreased serum cholesterol and serum
                                                                      proteins
----------------------------------------
870.4200                                 Carcinogenicity rats        NOAEL = Not achieved.
                                         Crl:CD(SD)BR albino rats..  LOAEL = 10 mg/kg/day on increased incidence
                                                                      of C-cell adenoma & carcinoma of thyroid
                                                                      in males & intrietical cell tumors of
                                                                      testes
----------------------------------------
870.4200                                 Carcino-genicity rats       NOAEL =50 mg/kg/day
                                         Fischer 344 Rat...........  LOAEL = 100 mg/kg/day on increased benign
                                                                      fibroepithelial tumor of the mammary
                                                                      glands & C-cell adenoma of the thyroid
                                                                     No evidence of carcinogenicity
----------------------------------------
870.4200                                 Carcinogenicity mice        NOAEL = Not achieved.
                                         B6C3F1 Strain.............  LOAEL = 150 mg/kg/day based on duodenal
                                                                      carcinoma and stomach papilloma both
                                                                      sexes; malignant lymphoma in high dose
                                                                      females only
                                                                     Evidence of carcinogenicity
----------------------------------------
870.4200                                 Carcinogenicity mice        NOAEL = Not achieved.
                                         CD-1 Mice.................  LOAEL = 150 mg/kg/day based on a dose
                                                                      related increase in incidence of
                                                                      intestinal adenomas and adenocarcinomas in
                                                                      both sexes
                                                                     Evidence of carcinogenicity
----------------------------------------
870.5195                                 Mutagenic-Lymphoma          Positive for forward mutations in L5178Y/TK
                                          Mutation in L5178Y/TK       mouse lymphoma cells. Higher concentration
                                          mouse lymphoma cells        necessary in the presence of S-9 fraction
----------------------------------------
870.5275                                 Mutagenic-Sex Link          Positive for sex linked recessive lethals
                                          Recessive in Drosophilia
----------------------------------------
870.5300                                 Mutagenic-In vivo           No effect on the incidence of coat color
                                          Cytogenetic toxicity in     spots - negative for mutations.
                                          Mouse                       Significant pup mortality at all doses
                                                                      levels. Decreased survival of pups during
                                                                      lactation. Increased melanocyte toxicity
                                                                      in pups at 4310 ppm, decreased weight gain
                                                                      in dams at 4310.
----------------------------------------
870.5300                                 Mutagenic-In Vivo           Decreases in the number and percentage of
                                          Cytogenetic in Mouse        live born pups; maternal weight gain
----------------------------------------
870.5375                                 Mutagenic-Chromosome        Not a clastogen at the HDT. No measure of
                                          Aberration in Rats          cytotoxicity in bone marrow. Dose used not
                                                                      supported by evidence that the HDT was a
                                                                      maximum tolerated dose.
----------------------------------------
870.5380                                 Cytogenetics Chromosome     Folpet was tested up to toxicity in non-
                                          Aberration in Chinese       activated (2.5 [mu]g/mL) & activated
                                          hamster ovary cells         Chinese hamster ovary cells (CHO) (25.7 &
                                                                      75.0 [mu]g/mL) in 10 & 20 hour assays.
                                                                     Results: There was a 10-30 fold difference
                                                                      in toxicity sensitivity. The test article
                                                                      induced chromosomal aberrations at
                                                                      marginally cytotoxic concentrations of
                                                                      0.75 [mu]g/mL in the non-activated system,
                                                                      and 0.26 [mu]g/mL in the 10 hour activ.
                                                                      assay, but required 25.0 [mu]g/mL in the
                                                                      20 hour activation assay.
----------------------------------------
870.5395                                 Mutagenic Micronucleus      No evidence of mutagenicity.
                                          Assay in the Mouse (CD-1)
----------------------------------------
870.5450                                 Mutagenic-Dominant Lethal   Negative for mutation
                                          Test in the Mouse
----------------------------------------

[[Page 10380]]

 
870.5500                                 Mutagenic-Reverse Mutation  Positive direct acting mutagen. Both
                                                                      batches tested were equally mutagenic.
                                                                      Effect of metabolic activation not
                                                                      assessed.
----------------------------------------
870.5500                                 Mutagenic-DNA Repair Test   Positive for DNA damage without metabolic
                                                                      activation.
----------------------------------------
870.5550                                 Unscheduled DNA Synthesis   Positive in the presence of metabolic
                                          in WI 38 Fibroblasts:       activation only.
----------------------------------------
870.5500                                 Reverse Mutation            Positive for reverse mutations in
                                                                      Salmonella TA100, TA1535 & TA1538, & in E.
                                                                      coli WP2.
                                                                     Rat liver S-9 had no effect on mutagenicity
----------------------------------------
870.5575                                 Mutagenic-Recomb/Convers    Positive for recombinants with/without
                                          Assay                       metabolic activity.
----------------------------------------
870.6200                                 Acute neurotoxicity         Not available.
                                          screening battery
----------------------------------------
870.6200                                 Subchronic neurotoxicity    Not available.
                                          screening battery
----------------------------------------
870.6300                                 Developmental               Not available.
                                          neurotoxicity
----------------------------------------
870.7485                                 Metabolism and              Doses: 50 and 5,000 ppm.
                                          pharmacokinetics           Results: The 5,000 ppm level had been shown
                                                                      to cause the tumors in mice but not in
                                                                      rats. The studies suggested that folpet
                                                                      was tumorigenic in the mouse and not in
                                                                      the rat because: Greater intake in the
                                                                      mouse and greater target tissue exposure
                                                                      to active metabolites that the mouse could
                                                                      not detoxify; greater local effects on
                                                                      mouse upper gastrointestinal tract; and
                                                                      greater reliance by the mouse on
                                                                      glutathione for detoxification of folpet.
----------------------------------------
870.7485                                 Metabolism and              C\14\-Folpet was administered orally to
                                          pharmacokinetics            Sprague-Dawley rats in 3 studies:
                                                                     1. Single dose of 10 mg/kg;
                                                                     2. Single dose of 500 mg/kg; and
                                                                     3. On day 15, 10 mg/kg of C\14\-Folpet
                                                                      after 14 consecutive days of unlabeled
                                                                      folpet at 10 mg/kg. Samples were examined
                                                                      for radioactivity for up to 120 hours post
                                                                      C\14\-dosing.
                                                                     Results:
                                                                     1. Single C\14\-Folpet at 10 mg/kg was
                                                                      absorbed > 90% of the dose, there was
                                                                      rapid urinary excretion and by 120 hours,
                                                                      there was little detactable radioactivity.
                                                                     2. Single C\14\-Folpet at 500 mg/kg was
                                                                      about 60% absorbed with the urinary
                                                                      excretion rate being slower that after the
                                                                      10 mg/kg dose (possibly due to rate-
                                                                      limiting absorption).
                                                                     3. Single C\14\-Folpet at 10 mg/kg
                                                                      following 14 daily non-labeled doses of 10
                                                                      mg/kg yielded results similar to those
                                                                      observed after a single c\14\ dose.
                                                                     4. No accumulation of folpet was detected
                                                                      during the 5 days after dosing;
                                                                      concentrations of radioactivity in
                                                                      measured tissues were generally below the
                                                                      limit of detection at 10 mg/kg or were
                                                                      detected at very low levels at 500 mg/kg.
                                                                     5. Phthalamic acid was determined to be the
                                                                      single active metabolite found in urine &
                                                                      it was suggested that its formation from
                                                                      Folpet may have been by trichloro-
                                                                      methylthio groups loss and hydrolytic
                                                                      cleavage of the maleimide ring.
                                                                     At 10 mg/kg,the major fecal metabolite was
                                                                      phthalamic acid and at 500 mg/kg, the
                                                                      radioactivity was primarily associated
                                                                      with unchanged C\14\-folpet (assumed to be
                                                                      unabsorbed test article).
----------------------------------------
870.7600                                 Dermal penetration          Doses: C\14\-Folpet was administered
                                                                      dermally to male doses of 10, 1, 0.1, and
                                                                      0.01 mg/rat (200 uL volume of test
                                                                      suspension to 18.9 cm2 of clipped skin)
                                                                      for up to 24 hours.
                                                                     Blood, urine, feces, carcass and skin
                                                                      radioactivity was measured (up to 24 hrs).
                                                                     Results:
                                                                     1. Rapid absorption into the skin and
                                                                      carcass;
                                                                     2. Low blood levels;
                                                                     3. Primary excretion by urine with rate
                                                                      apparently inversely related to quantity
                                                                      applied; and
                                                                     4. Minor bile involvement in excretion as
                                                                      little in feces.
----------------------------------------------------------------------------------------------------------------


[[Page 10381]]

B. Toxicological Endpoints

    The dose at which the NOAEL from the toxicology study identified as 
appropriate for use in risk assessment is used to estimate the 
toxicological level of concern (LOC). However, the lowest dose at which 
the LOAEL is sometimes used for risk assessment if no NOAEL was 
achieved in the toxicology study selected. An uncertainty factor (UF) 
is applied to reflect uncertainties inherent in the extrapolation from 
laboratory animal data to humans and in the variations in sensitivity 
among members of the human population as well as other unknowns. An UF 
of 100 is routinely used, 10X to account for interspecies differences 
and 10X for intra species differences.
    For dietary risk assessment (other than cancer) the Agency uses the 
UF to calculate an acute or chronic reference dose (acute RfD or 
chronic RfD) where the RfD is equal to the NOAEL divided by the 
appropriate UF (RfD = NOAEL/UF). Where an additional safety factors 
(SF) is retained due to concerns unique to the FQPA, this additional 
factor is applied to the RfD by dividing the RfD by such additional 
factor. The acute or chronic Population Adjusted Dose (aPAD or cPAD) is 
a modification of the RfD to accommodate this type of FQPA SF.
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for interspecies differences and 10X for intraspecies 
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to 
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and 
compared to the LOC.
    The linear default risk methodology (Q*) is the primary method 
currently used by the Agency to quantify carcinogenic risk. The Q 
approach assumes that any amount of exposure will lead to some degree 
of cancer risk. A Q* is calculated and used to estimate risk which 
represents a probability of occurrence of additional cancer cases 
(e.g., risk is expressed as 1 x 10-\6\ or one in a million). 
Under certain specific circumstances, MOE calculations will be used for 
the carcinogenic risk assessment. In this non-linear approach, a 
``point of departure'' is identified below which carcinogenic effects 
are not expected. The point of departure is typically a NOAEL based on 
an endpoint related to cancer effects though it may be a different 
value derived from the dose response curve. To estimate risk, a ratio 
of the point of departure to exposure (MOEcancer = point of 
departure/exposures) is calculated. A summary of the toxicological 
endpoints for folpet used for human risk assessment is shown in Table 2 
of this unit:

        Table 2.--Summary of Toxicological Dose and Endpoints for Folpet for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                 FQPA SF* and Level of
          Exposure Scenario               Dose Used in Risk         Concern for Risk     Study and Toxicological
                                            Assessment, UF             Assessment                Effects
----------------------------------------------------------------------------------------------------------------
Acute Dietary (Females 13-50 years of  NOAEL = 10 mg/kg/day     FQPA SF = 1X             Developmental Toxicity
 age)                                  UF = 100...............  aPAD = acute RfD/FQPA     Study in Rabbits
                                       Acute RfD = 0.1 mg/kg/    SF.                     LOAEL = 20 mg/kg/day
                                        day.                    = 0.1 mg/kg/day........   based on an increased
                                                                                          number of fetuses and
                                                                                          litters with
                                                                                          hydrocephaly and
                                                                                          related skull
                                                                                          malformations
--------------------------------------
Chronic Dietary (All populations)      NOAEL = 9 mg/kg/day      FQPA SF = 1X             Chronic Toxicity Study
                                       UF = 100...............  cPAD = chronic RfD/FQPA   in Rat
                                       Chronic RfD = 0.09 mg/    SF.                     LOAEL = 35 mg/kg/day
                                        kg/day.                 = 0.09 mg/kg/day.......   based on
                                                                                          hyperkeratosis/
                                                                                          acanthosis and
                                                                                          ulceration/erosion of
                                                                                          non-glandular stomach
                                                                                          epithelium in both
                                                                                          sexes
--------------------------------------
Short-Term Dermal (1 to 7 days)        oral study NOAEL=        LOC for MOE =            Developmental Toxicity
 (Residential)                         10 mg/kg/day (dermal     100 (Residential)......   Study in Rabbits
                                        absorption rate =                                LOAEL = 20 mg/kg/day
                                        2.7%).                                            based on an increased
                                                                                          number of fetuses and
                                                                                          litters with
                                                                                          hydrocephaly and
                                                                                          related skull
                                                                                          malformations
--------------------------------------
Intermediate-Term Dermal (1 week to    oral study NOAEL =       LOC for MOE =            Developmental Toxicity
 several months) (Residential)         10 mg/kg/day (dermal     100 (Residential)......   Study in Rabbits
                                        absorption rate = 2.7%.                          LOAEL = 20 mg/kg/day
                                                                                          based on an increased
                                                                                          number of fetuses and
                                                                                          litters with
                                                                                          hydrocephaly and
                                                                                          related skull
                                                                                          malformations
--------------------------------------
Short-Term Inhalation (1 to 7 days)    oral study NOAEL=        LOC for MOE =            Developmental Toxicity
 (Residential)                         10 mg/kg/day             100 (Residential)......   Study in Rabbits
                                        (inhalation absorption                           LOAEL = 20 mg/kg/day
                                        rate = 100%).                                     based on an increased
                                                                                          number of fetuses and
                                                                                          litters with
                                                                                          hydrocephaly and
                                                                                          related skull
                                                                                          malformations
--------------------------------------
Intermediate-Term Inhalation (1 week   oral study NOAEL =       LOC for MOE =            Developmental Toxicity
 to several months) (Residential)      10 mg/kg/day             100 (Residential)......   Study in Rabbits
                                        (inhalation absorption                           LOAEL = 20 mg/kg/day
                                        rate = 100%).                                     based on an increased
                                                                                          number of fetuses and
                                                                                          litters with
                                                                                          hydrocephaly and
                                                                                          related skull
                                                                                          malformations
--------------------------------------
Cancer (oral, dermal, inhalation)      Cancer potency factor                             Based on increased
                                        (Q1*) is 1.86 x 10-                               incidences of adenomas
                                        \3\.                                              and carcinomas in the
                                                                                          duodenum of male and
                                                                                          female mice in two
                                                                                          strains
----------------------------------------------------------------------------------------------------------------
*The reference to the FQPA SF refers to any additional SF retained due to concerns unique to the FQPA.


[[Page 10382]]

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances have been 
established (40 CFR 180.191) for the residues of folpet, in or on a 
variety of raw agricultural commodities. Risk assessments were 
conducted by EPA to assess dietary exposures from folpet in food as 
follows:
    i. Acute exposure. Acute dietary 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 one day 
or single exposure. The Dietary Exposure Evaluation Model-Food 
Commodity Intake Database (DEEM-FCID\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) and accumulated exposure to the chemical for each 
commodity. The following assumptions were made for the acute exposure 
assessments: Anticipated residues for most commodities and percent crop 
treated for many commodities. For hop, the dietary exposure analysis 
assumed tolerance level residues and 100 percent crop treated.
    ii. Chronic exposure. In conducting this chronic dietary risk 
assessment the Dietary Exposure Evaluation Model Food Commodity Intake 
Database (DEEM FCID\ \) 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) and 
accumulated exposure to the chemical for each commodity. The following 
assumptions were made for the chronic exposure assessments: Anticipated 
residues for most commodities and percent crop treated for many 
commodities. For hop, the dietary exposure analysis assumed tolerance 
level residues and 100 percent crop treated.
    iii. Cancer. In conducting this cancer dietary risk assessment the 
Dietary Exposure Evaluation Model Food Commodity Intake Database (DEEM-
FCID\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) and 
accumulated exposure to the chemical for each commodity. The following 
assumptions were made for the chronic exposure assessments: Anticipated 
residues for most commodities and percent crop treated for many 
commodities. For hop, the dietary exposure analysis assumed tolerance 
level residues and 100 percent crop treated.
    iv. Anticipated residue and percent crop treated (PCT) information. 
Section 408(b)(2)(E) of the 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 chemicals that have been 
measured in food. If EPA relies on such information, EPA must require 
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. Following the initial data 
submission, EPA is authorized to require similar data on a time frame 
it deems appropriate. As required by section 408(b)(2)(E) of the FFDCA, 
EPA will issue a data call-in for information relating to anticipated 
residues to be submitted no later than 5 years from the date of 
issuance of this tolerance.
    The Agency did use anticipated residue calculations in conducting 
its risk assessment. These calculations are based upon submitted field 
trial data and could be further refined through the use of monitoring 
data.
    Section 408(b)(2)(F) of the FFDCA states that the Agency may use 
data on the actual percent of food treated for assessing chronic 
dietary risk only if the Agency can make the following findings: 
Condition 1, that 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 such pesticide residue; Condition 2, that the exposure estimate 
does not underestimate exposure for any significant subpopulation 
group; and Condition 3, if 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 section 408(b)(2)(F) of the FFDCA, EPA may require registrants to 
submit data on PCT.
    The Agency used PCT information as follows. The only registered 
food use of folpet in the United States is avocados grown in Florida. 
According to data available from the United States Department of 
Agriculture's National Agricultural Statistics Service, California 
accounted for 89 percent of avocado production in the United States, 
followed by Florida at nearly 11 percent and Hawaii at approximately 
0.1 percent. Therefore, the Agency has assumed that only 11 percent of 
the U.S. avocado crop is treated with folpet. As stated earlier, for 
the hop use, the Agency assumed 100 percent crop treated even though 
imports of hop accounted for less than 50 percent of the crop consumed 
in the United States, based upon data available from the Hop Growers of 
American 2001 Statistical Report. For all other commodities (except 
hops and avocados), the Agency assumed a maximum percent crop treated 
value of 1% for each commodity (i.e., apple, cranberry, cucumber, 
grape, lettuce, melon, onion, strawberry, and tomato) based upon 
information derived through an analysis of import and domestic 
production data available from the United States Department of 
Agriculture for the years 1995 through 1999 and adjusted for the 
countries in which folpet is registered.
    The Agency believes that the three conditions listed in Unit III. 
have been met. With respect to Condition 1, PCT estimates are derived 
from Federal and private market survey data, which are reliable and 
have a valid basis. In using these data, the Agency also took into 
account the specific countries where folpet is registered. In the case 
of avocados, the Agency based its PCT estimate on the volume of the 
avocado crop grown in the United States, utilizing data from the U.S. 
Department of Agriculture. For all potentially-treated commodities, EPA 
used estimated maximum PCT assumptions in conducting both the acute and 
chronic dietary exposure assessments. The exposure estimates resulting 
from this approach reasonably represent the highest levels to which an 
individual could be exposed, and are unlikely to underestimate an 
individual's acute dietary exposure. The Agency is reasonably certain 
that the percentage of the food treated is not likely to be an 
underestimation. As to Conditions 2 and 3, 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 information on the regional consumption of food to 
which

[[Page 10383]]

folpet may be applied in a particular area.
    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for folpet in drinking water. 
Because the Agency does not have comprehensive monitoring data, 
drinking water concentration estimates are made by reliance on 
simulation or modeling taking into account data on the physical 
characteristics of folpet.
    The Agency uses the First Index Reservoir Screening Tool (FIRST) or 
the Pesticide Root Zone/Exposure Analysis Modeling System (PRZM/EXAMS), 
to produce estimates of pesticide concentrations in an index reservoir. 
The SCI-GROW model is used to predict pesticide concentrations in 
shallow groundwater. For a screening-level assessment for surface water 
EPA will use FIRST (a tier 1 model) before using PRZM/EXAMS (a tier 2 
model). The FIRST model is a subset of the PRZM/EXAMS model that uses a 
specific high-end runoff scenario for pesticides. While both FIRST and 
PRZM/EXAMS incorporate an index reservoir environment, the PRZM/EXAMS 
model includes a percent crop area factor as an adjustment to account 
for the maximum percent crop coverage within a watershed or drainage 
basin.
    None of these models include consideration of the impact processing 
(mixing, dilution, or treatment) of raw water for distribution as 
drinking water would likely have on the removal of pesticides from the 
source water. The primary use of these models by the Agency at this 
stage is to provide a coarse screen for sorting out pesticides for 
which it is highly unlikely that drinking water concentrations would 
ever exceed human health levels of concern.
    Since the models used are considered to be screening tools in the 
risk assessment process, the Agency does not use estimated 
environmental concentrations (EECs) from these models to quantify 
drinking water exposure and risk as a %RfD or %PAD. Instead drinking 
water levels of comparison (DWLOCs) are calculated and used as a point 
of comparison against the model estimates of a pesticide's 
concentration in water. DWLOCs are theoretical upper limits on a 
pesticide's concentration in drinking water in light of total aggregate 
exposure to a pesticide in food, and from residential uses. Since 
DWLOCs address total aggregate exposure to folpet they are further 
discussed in the aggregate risk sections in Unit III.E..
    Based on the FIRST and SCI-GROW models the estimated environmental 
concentrations (EECs) of folpet for acute exposures are estimated to be 
309 parts per billion (ppb) for surface water and 0.83 ppb for ground 
water. The EECs for chronic exposures are estimated to be 0.62 ppb for 
surface water and 0.83 ppb for ground 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).
    Folpet is currently registered for use as an additive in paints and 
stains for use both occupationally and by the homeowner. Four major 
exposure scenarios for homeowner handlers using folpet containing 
paints and stains labeled for pesticidal use and three major scenarios 
for homeowners using folpet containing products not labeled for 
pesticidal use were evaluated. The highest exposure level for combined 
inhalation and dermal exposures were based upon a homeowner applying a 
ready-to-use stain formulation with an airless sprayer. This exposure 
level was used to estimate the short- and intermediate-term risks for 
folpet.
    4. Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of the FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    EPA does not have, at this time, available data to determine 
whether folpet has a common mechanism of toxicity with other substances 
or how to include this pesticide in a cumulative risk assessment. 
Unlike other pesticides for which EPA has followed a cumulative risk 
approach based on a common mechanism of toxicity, folpet does not 
appear to produce a toxic metabolite produced by other substances. For 
the purposes of this tolerance action, therefore, EPA has not assumed 
that folpet has a common mechanism of toxicity with other substances. 
For information regarding EPA's efforts to determine which chemicals 
have a common mechanism of toxicity and to evaluate the cumulative 
effects of such chemicals, see the final rule for Bifenthrin Pesticide 
Tolerances (62 FR 62961, November 26, 1997).
    Captan and folpet share a common metabolite, thiophosgene, which 
the Agency believes to be responsible for the carcinogenic effects of 
these compounds. Thiophosgene is a highly reactive, short-lived 
compound. Studies indicate that thiophosgene causes local irritation of 
the site with which it comes in contact, and is believed to cause 
tumors through irritation of the duodenum. Because they are so short-
lived, thiophosgene residues cannot be quantified. Without measurable 
residues of the common metabolite, it is difficult to relate exposures 
of captan to those of folpet since the formation of thiophosgene may be 
different for both compounds. However, assuming that the carcinogenic 
effects observed in both pesticides are due solely to the metabolite 
thiophosgene, the Agency believes it is reasonable to add the estimate 
cancer risks from the individual aggregate risks from both folpet and 
captan to obtain a worst-case estimate.

D. Safety Factor for Infants and Children

    1. In general. Section 408 of the FFDCA provides that EPA shall 
apply an additional tenfold 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 data base on toxicity and exposure 
unless EPA determines that a different margin of safety will be safe 
for infants and children. Margins of safety are incorporated into EPA 
risk assessments either directly through use of a MOE analysis or 
through using uncertainty (safety) factors in calculating a dose level 
that poses no appreciable risk to humans.
    2. Prenatal and postnatal sensitivity. The data provided no 
indication of increased susceptibility in two prenatal developmental 
toxicity studies in rats following in utero or in the two (2) 2-
generation reproduction studies in rats. Two developmental toxicity 
studies in rabbits are also available. In a study with New Zealand 
rabbits, folpet caused an increase in the incidence of hydrocephalus in 
fetuses and with the associated dome skull and irregularly-shaped 
fontanelles at the mid and high dose groups in the presence of maternal 
toxicity. Both fetal and litter incidences of this malformation were 
increased in a dose-related manner. There were no toxicological effects 
noted on litter size, resorptions, sex ratio, or number of skeletal 
malformations. For maternal toxicity, the NOAEL was 10 mg/kg/day and 
the LOAEL was 20 mg/kg/day, based on decreased body weight gain and 
food consumption. For developmental toxicity, the NOAEL was

[[Page 10384]]

10 mg/kg/day and the LOAEL was 20 mg/kg/day, based upon an increase in 
the number of fetuses and litters with hydrocephaly and related skull 
malformations. Although the developmental malformations (hydrocephaly) 
and associated maternal toxicity occur at similar doses, such effects 
are toxic manifestations as a result of exposure.
     In order to determine the critical period of treatment for the 
occurrence of hydorcephaly and other treatment-related fetal anomalies 
observed in the above study, another developmental toxicity study was 
conducted with the same strain of rabbit with the highest dose group 
(60 mg/kg/day) receiving folpet on gestation days 7-9, 10-12, 13-15, or 
16-18. The incidence of hydrocephalus was higher than historical or 
concurrent controls, but lower than in the previous study. The maternal 
toxicity noted was a dose-related decreased food consumption and 
variable decrease in body weight gain. Significantly increased 
incidence of irregularly-shaped fontanelles and slightly increased 
incidences of angulated hyoid alae were noted in the 60 mg/kg/day dose 
group.
     In a second rabbit developmental toxicity study, HY/CR strain 
rabbits received folpet on gestation days 7 through 19. For maternal 
toxicity, the NOAEL was 40 mg/kg/day and the LOAEL was 160 mg/kg/day, 
based on decreased body weights and food consumption as well as 
clinical signs. For developmental toxicity, the NOAEL was 10 mg/kg/day 
and the LOAEL was 40 mg/kg/day, based on delayed ossification of the 
sternebrae. There was no evidence of hydrocephaly observed in this 
study at dose levels greater than in the previous study.
     In addition, the Agency examined the available studies for captan, 
the structural analog of folpet, and determined that there was no 
indication of increased susceptibility of rabbits or hamsters to pre- 
or post-natal exposure to captan. In prenatal developmental toxicity 
studies in rabbits and hamsters and reproduction studies in the rat, 
all conducted using captan as the test material, toxicity to the 
offspring occurred at equivalent or higher doses than maternal 
toxicity.
    3. Conclusion. i. There is a complete toxicity data base for folpet 
and exposure data are complete or are estimated based on data that 
reasonably accounts for potential exposures. The Agency has determined 
that the FQPA Safety Factor can be reduced to 1X based upon the 
following weight-of-the-evidence considerations:
    a. There was no evidence of quantitative or qualitative 
susceptibility in two developmental toxicity studies in the rat;
    b. There was no evidence of enhanced suspectibility to the pups in 
two different 2-generation reproduction studies in the rat;
    c. Folpet is not a cholinesterase inhibitor and, therefore, 
comments made at the June 26-27, 2002 Federal Insecticide, Fungicide, 
and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) meeting on 
the Determination of the Appropriate FQPA Safety Factor(s) in the 
Organophosphorous Pesticide Cumulative Risk Assessment: Susceptibility 
and Sensitivity to the Common Mechanism, Acetylcholinesterase 
Inhibition should not influence this uncertainty factor decision.
    d. There is inconsistency between the two available developmental 
toxicity studies in the rabbit. When tested at lower doses, there is a 
concern for hydrocephaly. However, when this study was repeated in the 
same strain of rabbit at higher dose levels, no evidence of 
hydrocephaly was observed. Nevertheless, for purposes of risk 
assessment, the Agency has selected the developmental NOAEL of 10 mg/
kg/day from the rabbit developmental study in which hydrocephaly was 
observed as the endpoint for evaluating acute risk.
    e. Other than the one rabbit developmental toxicity study, there 
are no other signs from the available toxicology database of a concern 
for neurotoxic effects.
    f. Furthermore, the Agency's exposure assumptions are conservative. 
The assessment assumes that all hops consumed in the United States are 
treated with folpet. In addition, the analysis presumes that all 
avocados grown in Florida are treated with this fungicide. The percent 
crop treated data for the imported commodities assumed that all crop 
exported to the U.S. from countries in which folpet is registered are 
treated with this chemical. Therefore, a figure of 1% crop treated was 
assumed for the following commodities: Apple, cranberry, cucumber, 
grape, lettuce, melon, onion, strawberry, and tomato.
    ii. The Agency has also determined that a developmental 
neurotoxicity study for folpet is not warranted based upon the 
following considerations:
    a. Although hydrocephalus was observed in one developmental 
toxicity study in the rabbit, it occurred at maternally toxic doses and 
was only seen in one species;
    b. No alterations to the fetal nervous system were seen in the 
developmental rat studies at the same doses that induce hydrocephaly in 
rabbits;
    c. Although there are no acute or subchronic neurotoxicity studies 
available, there is no evidence of neurotoxicity or neuropathology in 
adult animals in any of the studies;
    d. The available data indicate that the developmental neurotoxicity 
study would have to be tested at dose levels higher than 150 mg/kg/day 
because no developmental toxicity was observed in rats at 2,000 mg/kg/
day. In addition, given the results in the 2-generation reproduction 
study (NOAEL of 168 mg/kg/day), it is anticipated that in order to 
elicit any fetal nervous system abnormalities in the developmental 
neurotoxicity study, the selected dose levels would have to be higher 
than 160 mg/kg/day.
    e. Since the dose level selections for the developmental 
neurotoxicity study would be greater than 160 mg/kg/day, the resultant 
NOAEL would be either comparable to, or higher than, the doses 
currently used in the risk assessment. The NOAEL of 10 mg/kg/day 
selected for the acute reference dose and the residential exposure and 
risk assessments is seventeen times lower than the offspring NOAEL in 
the reproduction study. The NOAEL of 9 mg/kg/day selected for the 
chronic reference dose is nineteen times lower than the offspring NOAEL 
in the reproduction study. Therefore, it is unlikely that the 
developmental neurotoxicity study would change the current doses used 
for overall risk assessments.

E. Aggregate Risks and Determination of Safety

    To estimate total aggregate exposure to a pesticide from food, 
drinking water, and residential uses, the Agency calculates DWLOCs 
which are used as a point of comparison against the model estimates of 
a pesticide's concentration in water (EECs). DWLOC values are not 
regulatory standards for drinking water. DWLOCs are theoretical upper 
limits on a pesticide's concentration in drinking water in light of 
total aggregate exposure to a pesticide in food and residential uses. 
In calculating a DWLOC, the Agency determines how much of the 
acceptable exposure (i.e., the PAD) is available for exposure through 
drinking water [e.g., allowable chronic water exposure (mg/kg/day) = 
cPAD - (average food + residential exposure)]. This allowable exposure 
through drinking water is used to calculate a DWLOC.
    A DWLOC will vary depending on the toxic endpoint, drinking water 
consumption, and body weights. Default body weights and consumption 
values

[[Page 10385]]

as used by the Office of Water are used to calculate DWLOCs: 2 liter 
(L)/70 kg (adult male), 2L/60 kg (adult female), and 1L/10 kg (child). 
Default body weights and drinking water consumption values vary on an 
individual basis. This variation will be taken into account in more 
refined screening-level and quantitative drinking water exposure 
assessments. Different populations will have different DWLOCs. 
Generally, a DWLOC is calculated for each type of risk assessment used: 
Acute, short-term, intermediate-term, chronic, and cancer.
    When EECs for surface water and groundwater are less than the 
calculated DWLOCs, OPP concludes with reasonable certainty that 
exposures to the pesticide in drinking water (when considered along 
with other sources of exposure for which OPP has reliable data) would 
not result in unacceptable levels of aggregate human health risk at 
this time. Because OPP considers the aggregate risk resulting from 
multiple exposure pathways associated with a pesticide's uses, levels 
of comparison in drinking water may vary as those uses change. If new 
uses are added in the future, OPP will reassess the potential impacts 
of residues of the pesticide in drinking water as a part of the 
aggregate risk assessment process.
    1. Acute risk. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food to folpet 
will occupy <1 % of the aPAD for females 13 years and older. In 
addition, there is potential for acute dietary exposure to folpet in 
drinking water. After calculating DWLOCs and comparing them to the EECs 
for surface and ground water, EPA does not expect the aggregate 
exposure to exceed 100% of the aPAD, as shown in Table 3 of this unit:

                        Table 3.--Aggregate Risk Assessment for Acute Exposure to Folpet
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                aPAD (mg/kg/    % aPAD     Water EEC    Water EEC   Acute DWLOC
                                                     day)        (Food)       (ppb)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
Females, 13-49 years old                                 0.1           <1          309         0.83        2,800
----------------------------------------------------------------------------------------------------------------

    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to folpet 
from food will utilize less than 1% of the cPAD for all population 
subgroups within the United States. Based the use pattern, chronic 
residential exposure to residues of folpet is not expected. In 
addition, there is potential for chronic dietary exposure to folpet in 
drinking water. After calculating DWLOCs and comparing them to the EECs 
for surface and ground water, EPA does not expect the aggregate 
exposure to exceed 100% of the cPAD, as shown in Table 4 of this unit:

                 Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Folpet
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                cPAD mg/kg/     % cPAD     Water EEC    Water EEC     Chronic
                                                     day         (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                         0.09          <1%         0.62         0.83        3,100
------------------------------------------------
All Infants                                             0.09          <1%         0.62         0.83          900
------------------------------------------------
Children, 1-2 years                                     0.09          <1%         0.62         0.83          900
------------------------------------------------
Females, 13-49 years                                    0.09          <1%         0.62         0.83        2,700
------------------------------------------------
Adults, 50+ years                                       0.09          <1%         0.62         0.83        3,100
----------------------------------------------------------------------------------------------------------------

    3. Short-term and intermediate-term risk. Short-term and 
intermediate-term aggregate exposures take into account residential 
exposure plus chronic exposure to food and water (considered to be a 
background exposure level).
    Folpet is currently registered for use that could result in short-
term and intermediate-term residential exposure and the Agency has 
determined that it is appropriate to aggregate chronic food and water 
and short-term and intermediate-term exposures for folpet.
     Using the exposure assumptions described in this unit for short-
term and intermediate-term exposures, EPA has concluded that food and 
residential exposures aggregated result in aggregate MOEs of 370. These 
aggregate MOEs do not exceed the Agency's level of concern for 
aggregate exposure to food and residential uses. In addition, short-
term and intermediate-term DWLOCs were calculated and compared to the 
EECs for chronic exposure of folpet in ground and surface water. After 
calculating DWLOCs and comparing them to the EECs for surface and 
ground water, EPA does not expect short-term or intermediate-term 
aggregate exposures to exceed the Agency's level of concern, as shown 
in Table 5 of this unit:

          Table 5.--Aggregate Risk Assessments for Short-Term and Intermediate-Term Exposures to Folpet
----------------------------------------------------------------------------------------------------------------
                                                               Aggregate
                                                  Aggregate     Level of     Surface       Ground
              Population Subgroup                MOE (Food +    Concern     Water EEC    Water EEC   DWLOC (ppb)
                                                Residential)     (LOC)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
Females, 13-49 years                                     370          100         0.62         0.83        2,200
----------------------------------------------------------------------------------------------------------------


[[Page 10386]]

     4. Aggregate cancer risk for U.S. population. The aggregate cancer 
risk (food plus residential) from exposure to folpet is estimated to be 
7.2 x 10-\8\. Assuming a negligible risk level of 1.0 x 
10-\6\, the cancer DWLOC would be 15 ppb. Based on the FIRST 
and SCI-GROW models the EECs for chronic exposures to folpet are 
estimated to be 0.62 ppb for surface water and 0.83 ppb for ground 
water, significantly lower than the DWLOC.
     As discussed in Unit III.C.4., captan and folpet share a common 
metabolite, thiophosgene, which the Agency believes to be responsible 
for the carcinogenic effects of these compounds. Thiophosgene is a 
highly reactive, short-lived compound. Studies indicate that 
thiophosgene causes local irritation of the site with which it comes in 
contact, and is believed to cause tumors through irritation of the 
duodenum. Because they are so short-lived, thiophosgene residues cannot 
be quantified. Without measurable residues of the common metabolite, it 
is difficult to relate exposures of captan to those of folpet since the 
formation of thiophosgene may be different for both compounds. However, 
assuming that the carcinogenic effects observed in both pesticides are 
due solely to the metabolite thiophosgene, the Agency believes it is 
reasonable to add the estimate cancer risks from the individual 
aggregate risks from both folpet and captan to obtain a worst-case 
estimate.
     For captan, the estimated cancer risk for the U.S. population from 
exposure to food only is 1.26 x 10-\7\. As discussed above, 
the estimate cancer risk (food only) from exposure to folpet is 7.2 x 
10-\8\. If these two risk estimates are added together, the 
total estimated cancer risk is 2.0 x 10-\7\. Assuming a 
negligible cancer risk in the range of 1.0 x 10-\6\ to 3.0 x 
10-\6\, the smallest cancer DWLOC would be 11 ppb. Based on 
the FIRST and SCI-GROW models the EECs for chronic exposures to folpet 
are estimated to be 0.62 ppb for surface water and 0.83 ppb for ground 
water. The EECs for chronic exposure to captan are estimated to be 4 
ppb for surface water and 1 ppb for groundwater. The combined EECs for 
chronic exposure to captan plus folpet are 5 ppb for surface water and 
2 ppb for groundwater, both below the DWLOC of 11 ppb.
    5. Determination of safety. Based on these risk assessments, EPA 
concludes that there is a reasonable certainty that no harm will result 
to the general population, and to infants and children from aggregate 
exposure to folpet residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    An adequate gas chromatography/electron capture detector (GC/ECD) 
analytical method is available for enforcing tolerances of folpet in or 
on plant commodities. The method may be requested from: Chief, 
Analytical Chemistry Branch, Environmental Science Center, 701 Mapes 
Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; e-mail 
address: [email protected].

B. International Residue Limits

    No CODEX MRLs exist for folpet on hop.

V. Conclusion

    Therefore, the tolerance is established for residues of folpet, (N-
(trichloromethylthio)phthalimide), in or on hop, dried cones at 120 
ppm.

VI. Objections and Hearing Requests

    Under section 408(g) of the FFDCA, as amended by the FQPA, any 
person may file an objection to any aspect of this regulation and may 
also request a hearing on those objections. The EPA procedural 
regulations which govern the submission of objections and requests for 
hearings appear in 40 CFR part 178. Although the procedures in those 
regulations require some modification to reflect the amendments made to 
the FFDCA by the FQPA, EPA will continue to use those procedures, with 
appropriate adjustments, until the necessary modifications can be made. 
The new section 408(g) of the FFDCA provides essentially the same 
process for persons to ``object'' to a regulation for an exemption from 
the requirement of a tolerance issued by EPA under new section 408(d) 
of FFDCA, as was provided in the old sections 408 and 409 of the FFDCA. 
However, the period for filing objections is now 60 days, rather than 
30 days.

A. What Do I Need to Do to File an Objection or Request a Hearing?

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2003-0075 in the subject line on the 
first page of your submission. All requests must be in writing, and 
must be mailed or delivered to the Hearing Clerk on or before May 5, 
2003.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900C), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Rm.104, Crystal Mall 2, 1921 
Jefferson Davis Hwy., Arlington, VA. The Office of the Hearing Clerk is 
open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Office of the Hearing Clerk is 
(703) 603-0061.
    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters Accounting Operations Branch, Office 
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please 
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact James 
Tompkins by phone at (703) 305-5697, by e-mail at [email protected], 
or by mailing a request for information to Mr. Tompkins at Registration 
Division (7505C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.

[[Page 10387]]

    3. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit VI.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in Unit I.B.1. Mail your 
copies, identified by docket ID number OPP-2003-0075, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the 
PIRIB described in Unit I.B.1. You may also send an electronic copy of 
your request via e-mail to: [email protected]. Please use an ASCII 
file format and avoid the use of special characters and any form of 
encryption. Copies of electronic objections and hearing requests will 
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. 
Do not include any CBI in your electronic copy. You may also submit an 
electronic copy of your request at many Federal Depository Libraries.

B. When Will the Agency Grant a Request for a Hearing?

    A request for a hearing will be granted if the Administrator 
determines that the material submitted shows the following: There is a 
genuine and substantial issue of fact; there is a reasonable 
possibility that available evidence identified by the requestor would, 
if established resolve one or more of such issues in favor of the 
requestor, taking into account uncontested claims or facts to the 
contrary; and resolution of the factual issues(s) in the manner sought 
by the requestor would be adequate to justify the action requested (40 
CFR 178.32).

VII. Statutory and Executive Order Reviews

    This final rule establishes a tolerance under section 408(d) of the 
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 rule has been 
exempted from review under Executive Order 12866 due to its lack of 
significance, this rule is not subject to Executive Order 13211, 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). 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., or 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). 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); or OMB review or any Agency action under Executive 
Order 13045, entitled Protection of Children from Environmental Health 
Risks and Safety Risks (62 FR 19885, April 23, 1997). 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). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of the 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. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled Federalism 
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by State and local officials in the development of regulatory policies 
that have federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency 
has determined that this rule does not have any ``tribal implications'' 
as described in Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000). Executive Order 13175, requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by tribal officials in 
the development of regulatory policies that have tribal implications.'' 
``Policies that have tribal implications'' is defined in the Executive 
order to include regulations that have ``substantial direct effects on 
one or more Indian tribes, on the relationship between the Federal 
Government and the Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.'' 
This rule will not have substantial direct effects on tribal 
governments, on the relationship between the Federal Government and 
Indian tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian tribes, as specified in 
Executive Order 13175. Thus, Executive Order 13175 does not apply to 
this rule.

VIII. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement Fairness Act of 1996, generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report, which includes a copy of the rule, 
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: February 25, 2003.
Debra Edwards,
Acting Director, Registration Division, Office of Pesticide Programs.

    Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

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


[[Page 10388]]


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

    2. Section 180.191 is amended:
    i. By designating the existing text as paragraph (a) and adding a 
heading, and alphabetically adding a commodity to the table in newly 
designated paragraph (a); and
    ii. By adding and reserving with headings paragraphs (b), (c), and 
(d) to read as follows:


Sec.  180.191  Folpet; tolerances for residues.

    (a) General. * * *

------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------
                                * * * * *
Hop, dried cones                            120\1\
                               * * * * *
------------------------------------------------------------------------
1 There are no U.S. registrations on hop, dried cones as of February 14,
  2003

    (b) Section 18 emergency exemptions. [Reserved]
    (c) Tolerances with regional registrations. [Reserved]
    (d) Indirect or inadvertent residues. [Reserved]

[FR Doc. 03-5192 Filed 3-4-03; 8:45 am]
BILLING CODE 6560-50-S