PMEP Home Page --> Pesticide Active Ingredient Information --> Fungicides and Nematicides --> TCMTB (Busan) to zoxamide --> thiophanate-methyl (Topsin M) --> thiophanate-methyl (Topsin M) Pesticide Tolerance 7/02

thiophanate-methyl (Topsin M) Pesticide Tolerance 7/02


ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2002-0140; FRL-7192-1]


Thiophanate-methyl; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: This regulation establishes tolerances for residues of
thiophanate-methyl and its metabolite (methyl 2-benzimidazoyl carbamate
(MBC)) in or on grapes, pears, potatoes, canola and pistachios.
Cerexagri, Inc. and the Interregional Research Project Number 4 (IR-4)
requested these tolerances 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 August 28, 2002. Objections and
requests for hearings, identified by docket ID number OPP-2002-0140,
must be received on or before October 28, 2002.

ADDRESSES: Written objections and hearing requests may be submitted by
mail, in person, or by courier. Please follow the detailed instructions
for each method as provided in Unit VI. of the SUPPLEMENTARY
INFORMATION. To ensure proper receipt by EPA, your objections and
hearing requests must identify docket ID number OPP-2002-0140 in the
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Mary L. Waller, Registration
Division (7505C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW.,Washington, DC 20460;
telephone number: (703) 308-9354; e-mail address: waller.mary@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

    You may be affected by this action if you are an agricultural
producer, food manufacturer, or pesticide manufacturer. Potentially
affected categories and entities may include, but are not limited to:

------------------------------------------------------------------------
                                                          Examples of
           Categories                 NAICS Codes         Potentially
                                                       Affected Entities
------------------------------------------------------------------------
Industry                          111                 Crop production
                                  112                 Animal production
                                  311                 Food manufacturing
                                  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 the table could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether or not this action might apply to certain entities. If you have
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 Additional Information, Including Copies of this
Document and Other Related Documents?

    1. Electronically. You may obtain electronic copies of this
document, and certain other related documents that might be available
electronically, from the EPA Internet Home Page at http://www.epa.gov/.
To access this document, on the Home Page select ``Laws and
Regulations,'' ``Regulations and Proposed Rules,'' and then look up the
entry for this document under the ``Federal Register--Environmental
Documents.'' You can also go directly to 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.
    2. In person. The Agency has established an official record for
this action under docket ID number OPP-2002-0140. The official record
consists of the documents specifically referenced in this action, and
other information related to this action, including any information
claimed as Confidential
Business Information (CBI). This official record includes the documents
that are physically located in the docket, as well as the documents
that are referenced in those documents. The public version of the
official record does not include any information claimed as CBI. The
public version of the official record, which includes printed, paper
versions of any electronic comments submitted during an applicable
comment period is available for inspection in the Public Information
and Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2,
1921 Jefferson Davis Hwy., Arlington, VA, from 8:30 a.m. to 4 p.m.,
Monday through Friday, excluding legal holidays. The PIRIB telephone
number is (703) 305-5805.

II. Background and Statutory Findings

    In the Federal Register of August 8, 1997 (62 FR 42788) (FRL-5237-
6), 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 5F4550) by Cerexagri, Inc., 2000 Market
Street, Philadelphia, PA 19103. This notice included a summary of the
petition prepared by Cerexagri, Inc., the registrant. There were no
comments received in response to the notice of filing.
    The petition requested that 40 CFR 180.371 be amended by
establishing tolerances for residues of the fungicide thiophanate-
methyl in or on grapes at 5.0 part per million (ppm), and in or on
pears at 7.0 ppm.
    In the Federal Register of March 28, 2002 (67 FR 14944) (FRL-6829-
1), 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
pesticide petitions (PP 2E6355, 2E6367, and 2E6368) by the
Interregional Research Project Number 4 (IR-4), 681 U.S. Highway
1 South, North Brunswick, NJ, 08902-3390. This notice included
a summary of the petition prepared by IR-4. There were no comments
received in response to the notice of filing.
    The petitions requested that 40 CFR 180.371 be amended by
establishing tolerances for combined residues of the fungicide
thiophanate-methyl, (dimethyl [(1,2-phenylene)-
bis(iminocarbonothioyl)]
bis(carbamate), its oxygen analogue dimethyl-
4,4-o-phenylenebis(allophonate), and its benzimidazole-containing
metabolites (calculated as thiophanate-methyl), in or on potatoes at
0.05 ppm (PP 2E6367), on pistachios at 0.2 ppm (PP 2E6355), and on
canola at 0.1 ppm (PP 2E6368).
    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) 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)
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....''
    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 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), 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), for tolerances for residues of thiophanate-methyl and its
metabolite MBC, expressed as thiophanate-methyl on grapes at 5.0 ppm,
on pears at 3.0 ppm, on pistachios at 0.1 ppm, on potatoes at 0.1 ppm,
and on canola at 0.1 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 thiophanate-methyl
are discussed in Table 1 below. In addition, the nature of the toxic
effects caused by carbendazim or MBC are discussed in Table 2 below.
MBC which is also a pesticide is the primary metabolite and the
metabolite of concern for thiophanate-methyl. The tables also include
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 of Thiophanate-Methyl
Guideline No.
Study Type
Results
870.3100 90–Day oral toxicity in rodents NOAEL = 15.7 milligrams/kilograms/day (mg/kg/day)
LOAEL = 155.0 mg/kg/day, based on anemia, increased serum cholesterol and calcium
(males), increased liver and thyroid weights, increased kidney (males) weight
and increased incidence of thyroid hyperplasia/hypertrophy, liver swelling and lipofuscin deposition, and glomerulonephrosis (males) were observed
870.3150 90–Day oral toxicity in
dogs
NOAEL = 50 mg/kg/day
LOAEL = 200 mg/kg/day, based on thin/dehydrated appearance, tarry stools, decreased
body weight/weight gain, decreased food consumption, slight anemia, increased
serum cholesterol, decreased serum T3/T4 (females), increased liver and
thyroid weights, thyroid follicular cell hypertrophy and hyperplasia, hypoplasia/atrophy
of the prostate, thymic involution/atrophy (males) and depletion of spleen
lymphoid cells
870.3200 21–Day dermal toxicity in rabbits Systemic toxicity NOAEL = 100 mg/kg/day
Systemic toxicity LOAEL = 300 mg/kg/day, based on decreased food consumption in females
Slight dermal irritation was observed at all dose levels
870.3465 14–Day inhalation toxicity in rodents NOAEL = 0.00514 mg/Liter (L)
LOAEL = 0.0151 mg/L, based on increased incidence of alveolar macrophages,
pneumonocyte hyperplasia of the lung and nonsuppurative alveolitis
870.3700 Developmental toxicity in rodents Maternal NOAEL = 300 mg/kg/day
Maternal LOAEL = 1,000 mg/kg/day based on decreased body weight gain
Developmental NOAEL = 1,000 mg/kg/day
LOAEL > 1,000 mg/kg/day
870.3700 Developmental toxicity in
rodents
Maternal NOAEL = 18 mg/kg/day
Maternal LOAEL = 85 mg/kg/day based on decreased food consumption
Developmental NOAEL = 163 mg/kg/day (HDT)
Developmental LOAEL none established
870.3700 Developmental toxicity in
rabbits
Maternal NOAEL = 6 mg/kg/day
Maternal LOAEL = 20 mg/kg/day, based on transiently decreased body weight gain,
increased abortion/total litter loss
Developmental NOAEL = 20 mg/kg/day
Developmental LOAEL - none established
870.3700 Developmental toxicity in
rabbits
Maternal NOAEL = 10 mg/kg/day
Maternal LOAEL = 20 mg/kg/day, based on decreased body weight gain and food
consumption
Developmental NOAEL = 20 mg/kg/day
Developmental LOAEL = 40 mg/kg/day, based on increased supernumerary ribs and
decreased fetal weight
870.3800 Reproduction and fertility
effects
Parental systemic NOAEL < 13.7 mg/kg/day
Parental systemic LOAEL = 13.7 mg/kg/day based on hepatocellular hypertrophy
and thyroid hypertrophy/hyperplasia
Reproductive NOAEL = 138.9 mg/kg/day
Reproductive LOAEL > 138.9 mg/kg/day
Offspring NOAEL = 13.7 mg/kg/day
Offspring LOAEL = 43.3 mg/kg/day based on slightly reduced body weights of the
F2b offspring during lactation
870.3800 Reproduction and fertility
effects
Parental systemic/reproductive NOAEL = 32 mg/kg/day
Parental/systemic/reproductive LOAEL > 32 mg/kg/day
Offspring NOAEL = 8 mg/kg/day
Offspring LOAEL = 32 mg/kg/day based on slightly decreased mean litter weights
870.4100 Chronic toxicity dogs NOAEL = 8 mg/kg/day
LOAEL = 40 mg/kg/day based on decreased body weight/weight gain, markedly increased
serum TSH (1 male) and decreased T4 (males), increased serum cholesterol
(males), increased abs/rel thyroid weights (both sexes) and thyroid follicular
cell hypertrophy (females)
870.4100 Chronic toxicity dogs NOAEL = 23.7 mg/kg/day
LOAEL = 123.3 mg/kg/day based on hepatocellular hypertrophy in females
870.4100 Chronic toxicity in rodents NOAEL = 5.75 mg/kg/day
LOAEL = 24.3 mg/kg/day based on decreased body weight and body weight gain in
both sexes and increased incidence of thyroid and testicular microscopic effects in
males
870.4100
870.4200
Chronic toxicity/Carcinogenicity in rodents NOAEL = 8.8 mg/kg/day
LOAEL = 54.4 mg/kg/day based on decreased body weight/weight gain (males; marginal
in females), decreased food efficiency (males; marginal in females), sporadic
effects on circulating T3/T4 and TSH, increased serum cholesterol and creatinine,
decreased serum cholinesterase in females, increased liver, thyroid and kidney
weights, liver hypertrophy and lipofuscin accumulation, thyroid hypertrophy and
hyperplasia and lipofuscin accumulation in the kidney


                            
Table 2.--Subchronic, Chronic, and Other Toxicity of MBC
Guideline No.
Study Type
Results
870.3150 90–Day oral toxicity in dogs NOAEL = 11.3 mg/kg/day (F), 14.4 mg/kg/day (M)
LOAEL = 35 mg/kg/day (F), 40.7 mg/kg/day (M) based on histopathology changes in
liver 1/4 males and 1/4 females) and testes (@ males) and increased alkaline phosphatase,
cholesterol and serum glutamate pyruvate transaminase (SGPT). Liver
effects included hepatic cirrhosis (hepatic cell necrosis, tubular collapse, and increased
fibrous connective tissue around triads)
870.3700 Developmental toxicity in rodents Maternal NOAEL = 20 mg/kg/day
Maternal LOAEL = 90 mg/kg/day based on increased absolute liver weight
Developmental NOAEL = 10 mg/kg/day
Developmental LOAEL = 20 mg/kg/day based on decreased fetal body weight and
increases in skeletal variations and a threshold for malformations
870.3700 Developmental toxicity in
nonrodents
Maternal NOAEL = 20 mg/kg/day
Maternal LOAEL = 125 mg/kg/day based on abortions and decreased body weight
Developmental NOAEL = 10 mg/kg/day
Developmental LOAEL = 20 mg/kg/day based on decreased implantations and litter
size, and increased resorptions. Malformations (fused ribs, and malformed cervical
vertebrae) were noted at 125 mg/kg/day)
870.3800 Reproduction and fertility
effects
Reproductive NOAEL = 25 mg/kg/day
Reproductive LOAEL = 250 mg/kg/day based on toxic signs of decrased pup weight
noted at weaning
870.4100 Chronic toxicity in dogs NOAEL = 2.5 mg/kg/day
LOAEL = 12.5 mg/kg/day based on swollen, vacuolated hepatic cells, hepatic cirrhosis
and chronic hepatitis and biochemical alterations indicative of liver damage
(i.e., increased cholesterol, total protein, serum glutamate pyruvate transaminase
(SGPT) and alkaline phosphatase levels, and decreased A/G ratio)
870.4100 Chronic toxicity in dogs NOAEL = 6.43 mg/kg/day (200 ppm)
LOAEL = 16.54 mg/kg/day (500 ppm) based on possible transient increase in cholesterol
(males and females) consistent
870.4100
870.4200
Chronic toxicity/Carcinogenicity
in rodents
NOAEL = 25 mg/kg/day
LOAEL = 250 mg/kg/day based on statistically significant decreases in red blood cell
parameters (hematocrit, hemoglobin an red blood cells) in females and histological
lesions in the liver (cholangiohepatitis and pericholangitis) in males and females.
No evidence of carcinogenicity
870.4200 Carcinogenicity in rodents NOAEL (non-cancer systemic) = 75 mg/kg/day
LOAEL (non-cancer systemic) = 225 mg/kg/day based on liver toxicity
(hepatocellular necrosis and swelling), body weight decrease and lymphoid depletion.
In both sexes, there was an increased incidence of liver tumors In males,
hepatocellular carcinomas were noted at 225 mg/kg/day, while females exhibited
carcinomas and adenomas at all dose levels
870.4200 Carcinogenicity in mice NOAEL (non-cancer systemic) = 34.4–41.9 mg/kg/day
LOAEL (non-cancer systemic) = 522–648 mg/kg/day based on increases the
incidences of hepatic cell hypertrophy, clear cell foci and hepatocellular necrosis.
No increased incidence of carcinogenicity was noted
870.4200 Carcinogenicity in mice NOAEL = 45 mg/kg/day
LOAEL = 750 mg/kg/day based on hepatic alterations which included increased relative
liver weights in both sexes, increased number of foci of cellular alterations in
the liver in females, neoplastic nodules in females and hepatoblastomas in males
NA Single dose (gavage) rat
study
NOAEL: none observed
LOAEL: 50 mg/kg/day based on premature release of immature germ cells 2 days
post exposure, and atrophy of a few seminiferous tubules and significant decrease
in seminiferous tubule diameter 70 days post exposure

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 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
intraspecies differences.
    The Agency used a toxic equivalency factor (TEF) approach to sum
exposure and risk estimates from TM and MBC plus other metabolites of concern as
MBC equivalents. A TEF approach was used because both TM and MBC share
common toxicological effects (i.e., developmental and liver effects,
and liver tumors), and because individuals may be exposed to both
compounds simultaneously on food commodities, in drinking water and on
treated lawns. Using the TEF approach, all thiophanate-methyl dietary
exposure estimates were adjusted upwards to account for differences in
acute population adjusted doses (aPADs) and chronic population adjusted
doses (cPADs) between thiophanate-methyl and MBC.
    The Population Adjusted Dose (PAD) is the adjusted Reference Dose
(RfD) reflecting the retention or reduction of the FQPA safety factor
for all populations. The PAD is the RfD which is derived from an
exposure level at which there are no statistically or biologically
significant increases in the frequency or severity of adverse effects
between the exposed population and its appropriate control, along with
the application of uncertainty factors. The percent of the PAD is
calculated as the ratio of the exposure value to the PAD (exposure/PAD
x 100 = % PAD). A non-cancer TEF is derived based on a ratio of the MBC
PAD to the TM PAD.
    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 factor 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
aPAD or cPAD is a modification of the RfD to accommodate this type of
FQPA Safety Factor.
    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 thiophanate-methyl used for human risk assessment is
shown in the following Table 3. Table 4 summarizes the toxicological
endpoints for MBC.

  
Table 3.--Summary of Toxicological Dose and Endpoints for Thiophanate-methyl for Use in Human Risk Assessment
Exposure Scenario
Dose Used in Risk Assessment,
UF
FQPA SF* and/or Level of
Concern for Risk Assessment
Study and Toxicological Effects
Acute dietary, females 13–50 years NOAEL = 20 mg/kg/day
UF = 100
Acute RfD = 0.2 mg/kg/day
FQPA SF = 3
aPAD = acute RfD
FQPA SF = 0.067 mg/kg/
day
1997 Rabbit developmental study
LOAEL = 40 mg/kg/day based on supernumerary
ribs in fetuses of exposed dams
and decreased fetal weight
Acute dietary,
General population
NOAEL = 40 mg/kg/day
UF = 100
Acute RfD = 0.4 mg/kg/day
FQPA SF = 3
aPAD = acute RfD
FQPA SF = 0.13 mg/kg/day
Chronic oral toxicity dog study
LOAEL = 200 mg/kg/day based on tremors 2–4
hours post-dosing in 7 of 8 dogs
Chronic dietary NOAEL = 8 mg/kg/day
UF = 100
Chronic RfD = 0.08 mg/kg/day
FQPA SF = 3
cPAD = chronic RfD
FQPA SF = 0.027 mg/kg/day
Chronic oral toxicity dog study
LOAEL = 40 mg/kg/day based on thyroid effects and decreased body weight
Short- and intermediate-term - Incidental ingestion Oral NOAEL = 10 mg/kg/day LOC for MOE = 300 for all
residential populations
1997 Rabbit developmental study
LOAEL = 20 mg/kg/day based on decreased
maternal body weight and food consumption
Short- and intermediate term - dermal Dermal NOAEL = 100 LOC for MOE = 300 for all
residential populations
21–day rabbit dermal toxicity study
LOAEL = 300 mg/kg/day based on decreased
body weight (28%) and food consumption
(15%)
Short- and intermediate term -
inhalation**
Oral NOAEL = 10 mg/kg/
day (inhalation absorption rate
= 100% relative to oral
absorption)
LOC for MOE = 300 for all
residential populations
1997 Rabbit developmental study
LOAEL = 20 mg/kg/day based on decreased
maternal body weight and food consumption
Long-term dermal and
inhalation**
NOAEL = 8 mg/kg/day
(dermal absorption rate =
7% relative to oral absorption;
inhalation absorption rate =
100% relative to oral absorption)
LOC for MOE = 300 for all
residential populations
Chronic oral toxicity dog study
LOAEL = 40 mg/kg/day based on thyroid effects
and decreased body weight
Cancer** Q1* = 1.16 x 10–2 (mg/kg/
day)–1 (dermal absorption
rate = 7% relative to oral
absorption;
inhalation absorption rate =
100% relative to oral absorption)
Q1* = 1.16 x 10–2 (mg/kg/
day)–1
78–Week mouse study based on male mouse
liver adenoma and/or carcinoma and/or
hepatoblastoma combined tumor rates
* The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique to the FQPA.
**Since an oral value was selected, 7% dermal absorption factor and 100% inhalation absorption factor (equivalent to oral absorption) should
be used for route-to-route extrapolation.

         
Table 4.--Summary of Toxicological Dose and Endpoints for MBC for Use in Human Risk Assessment
Exposure Scenario
Dose Used in Risk Assessment,
UF
FQPA SF* and/or Level of
Concern for Risk Assessment
Study and Toxicological Effects
Acute dietary, females 13–50
years
NOAEL = 10 mg/kg/day
UF = 100
Acute RfD = 0.1 mg/kg/day
FQPA SF = 10
aPAD = acute RfD
FQPA SF = 0.01 mg/kg/day
Rat developmental study with MBC
LOAEL = 20 mg/kg/day based on decreased
fetal body weight and increases in skeletal
variations and a threshold for malformations
in fetuses of exposed dams
Acute dietary,
General population, including infants
and children
LOAEL = 50 mg/kg/day
UF = 300 acute RfD = 0.17
mg/kg/day
FQPA SF = 10 for infants
and children
FQPA SF = 1 general population
aPAD = acute RfD
FQPA SF = 0.017 mg/kg/
day (infants and children)
= 0.17 (general population)
Single dose rat study
LOAEL = 50 mg/kg/day based on adverse testicular
effects including sloughing (premature
release) of immature germ cells 2 days post
exposure, atrophy of a few seminiferous tubules in one testicle, significant decrease in
seminiferous tubule diameter, and slight abnormal growth of the efferent ductules at 70 days post exposure
Chronic dietary NOAEL = 2.5 mg/kg/day
UF = 100
Chronic RfD = 0.025 mg/kg/day
FQPA SF = 10 for children
and females 13–50 yrs
FQPA SF = 1 general population
cPAD = chronic RfD
÷FQPA SF
= 0.0025 mg/kg/day (children
and females) =
0.025 (general pop.)
2–year dog study with MBC
LOAEL = 12.5 mg/kg/day based on
histopathological lesions of the liver characterized
as swollen, vacuolated hepatic cells,
hepatic cirrhosis and chronic hepatitis in both
sexes
Short-term incidental ingestion Oral NOAEL = 10 mg/kg/day LOC for MOE = 1,000 for
all residential populations
1997 Rabbit developmental study with
thiophanate-methyl
LOAEL = 20 mg/kg/day based on decreased
maternal body weight and food consumption
Intermediate - term
Incidental ingestion
Oral NOAEL = 11 mg/kg/day
(rounded to 10 mg/kg/day)
LOC for MOE = 1,000 for
all residential populations
90–day dog feeding study with MBC
LOAEL = 35 mg/kg/day based on adverse liver
effects.
Short- and intermediate term
dermal**
Oral NOAEL = 10 mg/kg/
day (dermal absorption
rate = 3.5% relative to
oral absorption)
LOC for MOE = 1,000 for
children and females
(residential)
Rat developmental study with MBC
LOAEL = 20 mg/kg/day based on decreased
fetal body weight and increases in skeletal
variations and a threshold for malformations
in fetuses of exposed dams
Long-term dermal** Oral NOAEL = 2.5 mg/kg/day (dermal absorption rate = 3.5% relative to oral absorption) LOC for MOE = 1,000 for
children and females (residential)
2–year dog study with MBC
LOAEL = 12.5 mg/kg/day based on
histopathological lesions of the liver characterized
as swollen, vacuolated hepatic cells,
hepatic cirrhosis and chronic hepatitis in both
sexes of dogs
Short-, intermediate- and long term inhalation Inhalation NOAEL = 0.96
(10 mg/m3)
LOC for MOE = 1,000 for
children and females
(residential)
90–day rat inhalation study with benomyl
LOAEL = 4.8 mg/kg/day (50 mg/m3) based on
Olfactory degeneration in the nasal cavity
Cancer** Q1* = 2.39 x 10–3 (mg/kg/
day)–1 (dermal absorption
rate = 3.5% relative to
oral absorption;
inhalation absorption rate = 100% relative to oral absorption)
Q1* = 2.39 x 10–3 (mg/kg/
day)–1
2–Year mouse study with MBC based on
hepatocellular (adenoma and/or carcinoma)
tumors in female CD–1 mice
* The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique to the FQPA.
**Since an oral value was selected, 7% dermal absorption factor and 100% inhalation absorption factor (equivalent to oral absorption) should
be used for route-to-route extrapolation.

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Tolerances have been
established (40 CFR 180.371) for the residues of thiophanate methyl
(dimethyl [(1,2- phenylene)-bis(iminocarbonothioyl)]
bis[carbamate]),
its oxygen analogue dimethyl-4,4-o-phenylene bis (allophonate), and its
benzimidazole-containing metabolites (calculated as thiophanate-methyl)
in or on the following crops and commodities: Almonds, apples,
apricots, beans, celery, cherries, cucumbers, melons, nectarines,
onions, pecans, peaches, peanuts, plums, potatoes (seed pieces),
prunes, pumpkins, soybeans, squash, strawberries, sugar beets, wheat,
eggs, and the meat, meat-by-products, fat and liver of cattle, goats,
hogs, horses, and sheep. Emergency exemptions have been established for
the use of thiophanate-methyl on citrus and blueberries. The Agency is
modifying the tolerance expression so that the residues to be regulated
in plant and animal commodities for purposes of tolerance enforcement
will consist of the residues of thiophanate-methyl and its metabolite
(methyl 2-benzimidazolyl carbamate (MBC)), expressed as thiophanate-
methyl.
    Exposure from the use of benomyl, another pesticide which degrades
under environmental conditions to MBC was not included in this
assessment because the only basic registrant of benomyl requested
voluntary cancellation of all benomyl-containing products in April
2001. Product cancellations were effective in early 2001 with sales and
distribution of benomyl containing products ending by December 31,
2001. However, the Agency conducted a dietary assessment using USDA
Pesticide Data Program (PDP) monitoring data for benomyl, measured as
MBC to estimate residues of thiophanate-methyl because MBC is a common
metabolite of both benomyl and thiophanate-methyl. PDP data were
available for apples, bananas, beans, cucurbits, peaches and
strawberries. The PDP analytical method employs a hydrolysis step that
converts any benomyl present to MBC. MBC is then quantitated and
corrected for molecular weight, and results are measured as the sum of
benomyl and MBC. Therefore, using MBC data to estimate thiophanate-
methyl residues may be a conservative approach in that it may
overestimate thiophanate-methyl residues. Risk assessments were
conducted by EPA to assess dietary exposures from thiophanate-methyl
and MBC 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 1 day or
single exposure. The Dietary Exposure Evaluation Model (DEEM[reg])
analysis evaluated the individual food consumption as reported by
respondents in the USDA 1989-1992 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: Maximum percent crop treated (PCT) estimates and
anticipated residue estimates were used. The estimate of acute dietary
exposure to thiophanate-methyl for the most highly exposed population
subgroup of concern, (infants <1 year) is 25% of the aPAD at the 99.9th
percentile and the estimate for the general U.S. population is 10% of
the aPAD at the 99.9th percentile. The estimate of acute dietary
exposure to MBC + other metabolites from thiophanate-methyl for the
most highly exposed population subgroup of concern, (infants <1 year)
is 89% of the aPAD at the 99.9th percentile and the estimate for the
general U.S. population is 4% of the aPAD at the 99.9th percentile.
    In addition, acute dietary risk estimates for thiophanate-methyl
and MBC and other metabolites of concern were added together for
females (13-50 years) to account for the total acute dietary risk
estimate for developmental effects. Addition of acute dietary risk
estimates is appropriate since both chemicals have aPADs that are based
on developmental effects for females, and because individuals may
consume both residues simultaneously on a given food commodity. The
estimate of total acute dietary exposure to thiophanate-methyl and MBC
for the only population subgroup of concern, (females 13-50 years) is
51% of the aPAD.
    ii. Chronic exposure. In conducting this chronic dietary risk
assessment the DEEM[reg]
analysis evaluated the individual food consumption as reported by respondents in the USDA
1989-1992 nationwide CSFII and accumulated exposure to the chemical for
each commodity. The following assumptions were made for the chronic
exposure assessments: Average residues from field trial data and
average PCT estimates were used. The chronic dietary exposure estimates
for thiophanate-methyl are as follows: children (1-6 years) is 2.3% of
the cPAD; infants (<1 year) is 1.6% of the cPAD; children (7-12 years)
is 1.3% of the cPAD; general U.S. population is 0.8% of the cPAD;
females (13-50 years) and males (13-19 years) is 0.6% of the cPAD. The
chronic dietary exposure estimates for MBC and other metabolites from
thiophanate-methyl are as follows: children (1-6 years) is 26% of the
cPAD; children (7-12 years) is 16% of the cPAD; infants (<1 year) is
12% of the cPAD; females (13-50) is 8% of the cPAD; general U.S.
population and males (13-19 years) is 1% of the cPAD. The total chronic
dietary exposure estimates for thiophanate-methyl and MBC are as
follows: Children (1-6 years) is 28% of the cPAD; children (7-12 years)
is 17% of the cPAD; infants (<1 year) is 13% of the cPAD; females (13-
50 years) is 8.5% of the cPAD; general U.S. population is 1.7% of the
cPAD; and males (13-19 years) is 1.6% of the cPAD.
    iii. Cancer. Cancer risk estimates included existing uses, new
uses, and 1 year of citrus use under an emergency exemption amortized
over 70 years. The lifetime cancer risk estimate from thiophanate-
methyl using benomyl/MBC PDP data is 7.6 x 10-7. The
lifetime cancer risk estimate from MBC and other metabolites from
thiophanate-methyl is 9.3 x 10-8. The total lifetime
thiophanate-methyl and MBC dietary cancer risk estimate is 8.5 x
10-7. It is appropriate to add the cancer risk estimates
from TM and MBC because both chemicals cause mouse liver tumors, and
because both chemicals may be found concurrently on food items treated
with thiophanate-methyl.
    iv. Anticipated residue and PCT information. Section 408(b)(2)(E)
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), 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 these tolerances.
    Section 408(b)(2)(F) 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), EPA may require registrants to submit data on
PCT.
    The Agency used PCT information for almonds, apples, apricots,
beans (succulent or dried), green beans, bananas, blueberries, canola,
celery, cherries, citrus, cucurbits (cantaloupe, cucumbers, melons,
pumpkins, squash, watermelons), garlic, grapes, nectarines, onions
(bulb and green), peaches, peanuts, pears, pecans, pistachios, plums/
prunes, potatoes, soybeans, strawberries, sugar beets, and wheat. In
addition, when PCT estimates indicated no thiophanate-methyl use, a
default minimum assumption of 1% crop treated was applied. Where
residues were nondetectable, one-half the limit of quantitation was
assumed for treated commodities.
    The Agency believes that the three conditions listed above 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. EPA uses a weighted average PCT for chronic dietary
exposure estimates. This weighted average PCT figure is derived by
averaging State-level data for a period of up to 10 years, and
weighting for the more robust and recent data. A weighted average of
the PCT reasonably represents a person's dietary exposure over a
lifetime, and is unlikely to underestimate exposure to an individual
because of the fact that pesticide use patterns (both regionally and
nationally) tend to change continuously over time, such that an
individual is unlikely to be exposed to more than the average PCT over
a lifetime. For acute dietary exposure estimates, EPA uses an estimated
maximum PCT. 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 underestimated. 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 thiophanate-
methyl may be applied in a particular area.
    2. Dietary exposure from drinking water. Available environmental
fate data suggest that thiophanate-methyl rapidly degrades to MBC
following application to ornamentals, turf and agricultural crops. MBC
has a low potential to leach to ground water in measurable quantities
from most typical uses based on its high soil organic carbon partition
coefficient (Koc) of 2,100 L/kg. Available data indicate that the
primary metabolite of thiophanate-methyl, MBC, is less mobile and
significantly more persistent in many soils, especially under anaerobic
conditions. The MBC aerobic soil half-life is 320 days, while the
aerobic and anaerobic aquatic metabolism half lives are 61 and 743
days, respectively. The Agency concludes that MBC will probably not
reach ground water to any significant concentration due to its high
Koc.
    The Agency currently lacks sufficient monitoring data to complete a
quantitative drinking water exposure analysis and risk assessment for
thiophanate-methyl and MBC. Therefore, the Agency is presently relying
on water-quality models to estimate environmental concentrations (EECs)
of pesticides in ground and surface water in order to estimate drinking
water exposures to thiophanate-methyl and MBC. 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.
    EPA does not use these model estimates to quantify risk. Currently,
EPA uses a drinking water level of comparison (DWLOC) as a surrogate to
capture risk associated with exposure to pesticides in drinking water.
A DWLOC represents the concentration of a pesticide in drinking water
that would be acceptable as an upper limit in light of total aggregate
exposure to that pesticide from food, water, and residential uses (if
any). A DWLOC will vary depending on the residue level in foods, the
toxicity endpoint and the drinking water consumption patterns and body
weights for specific population subgroups. The calculated DWLOC is
compared to the model estimate (EEC), and if the model estimates are
below the DWLOC, the risks are not considered to be of concern.
    For estimating ground water concentrations of thiophanate-methyl
and MBC, EPA used the Screening Concentration in Ground Water (SCI-
GROW) model. The SCI-GROW is based on scaled ground water concentration
from ground water monitoring studies, and environmental fate properties
(aerobic soil half-lives and organic carbon partitioning coefficients-
Koc's). SCI-GROW provides a screening concentration which is an
estimate of likely ground water concentrations if the pesticide were
used at the maximum allowed label rate in areas with ground water
vulnerable to contamination. In most cases, a majority of the pesticide
use area will have ground water that is less vulnerable to
contamination than the areas used to derive the SCI-GROW estimate.
Using SCI-GROW, the acute and chronic ground water EEC for thiophanate-
methyl ranged from 0.033 part per billion (ppb) to 0.006 ppb, and the
acute and chronic EEC for MBC ranged from 0.51 ppb to 3.0 ppb.
    For estimating surface water concentrations of thiophanate-methyl
and MBC, EPA used a Tier II model, Pesticide Root Zone Model/Exposure
Analysis Modeling System (PRZM/EXAMS). PRZM (3.12)/EXAMS (2.97.5)
modeling uses an index reservoir and a percent crop area (PCA)
adjustment to estimate concentrations in surface water used as a source
of drinking water. The index reservoir represents a watershed that is
more vulnerable than most watersheds used as drinking water sources.
The index reservoir is used as a standard watershed that is combined
with local soils, weather, and cropping practices to represent a
vulnerable watershed for each crop that could support a drinking water
supply. If a community derives its drinking water from a large river,
the estimated exposure would likely be higher than the actual exposure.
Conversely, a community that derives its drinking water from smaller
bodies of water with minimal outflow would likely get higher drinking
water exposure than estimated using the index reservoir. Areas with a
more humid climate that use a similar reservoir and cropping patterns
would likely get more pesticides in their drinking water than predicted
levels.
    A single steady flow was used to represent the flow through the
reservoir. Discharge from the reservoir also removes chemicals so this
assumption will underestimate removal of the pesticide from the
reservoir during wet periods and overestimate removal during dry
periods. This assumption can both underestimate or overestimate the
concentration of pesticide in the reservoir depending upon the annual
precipitation pattern at the site. The index reservoir scenario uses
the characteristic of a single soil to represent all soils in the
basin. Soils can vary substantially across even small areas, thus, this
variation is not reflected in these simulations.
    The index reservoir scenario does not consider tile drainage. Areas
that are prone to substantial runoff are often tiled drained. This
assumption may underestimate exposure, particularly on a chronic basis.
However, the watershed used to model the EECs for thiophanate-methyl
and MBC had no documented tile drainage. Additionally, PRZM/EXAMS is
unable to easily model spring and fall turnover which would result in
complete mixing of a chemical through the water column during these
events. Because of this inability, the watershed used was simulated
without stratification. However, there is data that suggests that the
watershed used does stratify in the deepest parts of the lake at least
in some years, thereby adding to the conservativeness of the estimate.
    The EEC's for thiophanate-methyl and MBC were estimated based on
the new maximum agricultural application rate which was the proposed
new use on pears (2.8 pound active ingredient/Acre/season (lb./a.i./
acre)). The previous existing maximum label rate was reduced by half as
a result of risk mitigation. The EEC's using the new maximum rate are
as follows: The acute or peak (1 in 10 years) EEC for thiophanate-
methyl is 8.2 ppb and 23.5 ppb for MBC; the non-cancer chronic (1 in 10
years) EEC for thiophanate-methyl is 0.70 ppb and 14.0 ppb for MBC; and
the cancer chronic (mean 36-year annual concentration) EEC is 0.5 ppb
for thiophanate-methyl and 11.5 ppb for MBC.
    As a result of risk mitigation, the maximum nonagricultural
application rate (tees and greens of golf courses - 8.16 lb. a.i./acre)
was also substantially reduced. Using the mitigated rate (tees and
greens of golf courses - 8.16 lb. a.i./acre), the EEC's for
thiophanate-methyl and MBC are as follows: The acute EEC for
thiophanate-methyl is 22.7 ppb and 25 ppb for MBC; the non-cancer
chronic EEC for thiophanate-methyl is 0.92 ppb and 8.8 ppb for MBC; and
the cancer chronic EEC is 0.41 ppb and is 6.0 ppb for MBC.
    Since the chronic and cancer endpoints are based on the same
adverse effect, the thiophanate-methyl and MBC EECs are added together.
The total thiophanate-methyl plus MBC chronic EEC is 9.72 ppb and the
cancer EEC is 6.39 ppb.
    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). Thiophanate-methyl is
currently registered for use on the following residential non-dietary
sites: Lawns and home orchards. MBC is registered for use as an in-can
paint preservative which can be used in residential settings and as a
fungicide applied as a tree injection. The risk assessment was
conducted using the following residential exposure assumptions:
Potential residential or nonoccupational post-application exposure to
adults and children may occur as a result of residential application or
professional lawn care operator application of thiophanate-methyl
products to home lawns and golf courses.
    As a result of risk mitigation, application rates for
nonagricultural uses have been reduced, the use of thiophanate-methyl
by residents will be limited to granular products for broadcast turf
treatment and liquid treatments for ornamentals, and application using
a belly grinder or by hand will be removed from pesticide labels. In
addition, the Agency has negotiated a reduction in the rate of MBC used
as an in-can paint preservative. The following exposure
and risk estimates are based on the mitigated rates and label revisions
negotiated by the Agency.
    i. Chronic exposure and risk. The Agency estimated cancer risks
based on the number of years a person typically works in a home garden
(50 years) and lifetime (70 years) which are also the population
defaults used by the Agency. Therefore, cancer risks are based on 50
applications in a lifetime. A cancer risk assessment is considered
appropriate because thiophanate-methyl has been assessed as a
carcinogen using a model for carcinogenesis that assumes any exposure
at any point in time may result in carcinogenic effects. These
estimated risk do not exceed the Agency's level of concern.
    Lifetime cancer risk estimates for applying thiophanate-methyl
products once per year for 50 years (i.e., 50 times in a lifetime)
range from 4.7 x 10-9 to 2.8 x 10-8 for
ornamental treatment using a backpack sprayer and a ready to use hose-
end sprayer, respectively. Cancer risk estimates for the other
application methods are between these ranges.
    Lifetime cancer risk estimates for post-application exposure to
thiophanate-methyl ranged from 1.3 x 10-7 to 1.3 x
10-9 for adults. Cancer risk estimates were not calculated
for children as the exposure scenario was not applicable.
    ii. Short- and intermediate-term exposure and risk. All residential
exposures are considered to be short-term (1-30 days) for residential
handlers during the application of thiophanate-methyl products to turf
and ornamentals. Intermediate- and long-term exposures of residential
applicators were not anticipated based on the use pattern of
thiophanate-methyl and information from the registrant. Considering
toxicological criteria and potential for exposure, the Agency conducted
dermal and inhalation exposure assessments. The Agency only assessed
exposure to thiophanate-methyl because MBC risk from treated turf are
considered to be negligible relative to thiophanate-methyl risks (i.e.,
at least 10 fold lower) based on chemical-specific turf transferable
residue data.
    Residential application of thiophanate-methyl products to lawns and
ornamentals at the new maximum rate resulted in short-term risk
estimates that are below the Agency's level of concern (i.e., total MOE
<300). The inhalation MOE ranged from 140,000 to 620,000. The dermal
MOE ranged from 1,900 to 37,000. Total dermal and inhalation MOEs range
from 1,900 to 35,000.
    Short-term risk estimates for residential/recreational post-
application dermal exposure to adults resulted in estimates below the
Agency's level of concern. The dermal MOE for adults ranged from 1,700
to 49,000. Short-term risk estimates for children (1-6 years) are as
follows: MOE of 73,000 for incidental soil ingestion; MOE of 1,000 for
contact with treated turf; MOE of 990 for object to mouth exposure; MOE
of 250 for hand to mouth exposure; and MOE of 31 for incidental
granular ingestion. The MOEs below 300 exceed the Agency's level of
concern. However, the Agency believes that the exposure is
significantly lower than that estimated in this assessment because the
scenarios used to determine risk estimates are conservative and are
considered as a screening level for risk. Both the adult and toddler
transfer coefficients are upper percentile exposure duration values.
Where study data were used, the risk estimates were better refined, and
hence, less conservative. The dermal exposure estimates related to lawn
skin contact which were based on study data were more refined than the
estimates of incidental ingestion of thiophanate-methyl residues which
were based on standard defaults from Agency standard operating
procedures for residential exposure assessments. The registrant is
undertaking a study to refine the oral exposures. If these data do not
confirm that the Agency's estimates were overestimates, the registrant
has agreed to cancel the use on turf in residential areas.
    Inhalation exposures are thought to be negligible in outdoor post-
application scenarios relative to dermal and oral exposures because of
the low vapor pressure of thiophanate-methyl (1.3 x 10-5
milimeter mercury (mmHg)) and MBC (1 x 10-7 mmHg) and
because the uses (and primary exposures) are outdoors allowing for
significant dilution. As such, inhalation exposures were not considered
in the post-application exposure assessment.
    4. Cumulative exposure to substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) requires that, when considering
whether to establish, modify, or revoke a tolerance, the Agency
considers ``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 thiophanate-methyl and MBC have 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,
thiophanate-methyl and MBC do not appear to produce a toxic metabolite
produced by other substances. For the purposes of these tolerances
action, EPA has not assumed that thiophanate-methyl and MBC have 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).

D. Safety Factor for Infants and Children

    1. In general. FFDCA section 408 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 of thiophanate-methyl. In
assessing the potential for additional sensitivity of infants and
children to residues of thiophanate-methyl and MBC, EPA considered data
from developmental toxicity studies in the rat and rabbit and a 2-
generation reproduction study in the rat. The Agency determined that
the FQPA safety factor should be retained at 3X for assessing the risk
posed by thiophanate-methyl for the following reasons:
    (i). The toxicity data base is incomplete (acute and subchronic
neurotoxicity studies are required due to evidence of neurotoxicity)
and the requirement for a developmental neurotoxicity study has been
reserved.
    (ii). The Agency evaluated the new 1997 prenatal developmental
toxicity study in rabbits and classified this study as acceptable for
assessment of susceptibility.
    (iii). The Agency determined that the prenatal developmental
toxicity study in the rat was acceptable for assessment of
susceptibility.
    (iv). The Agency concluded that the available data provided no
indication of increased susceptibility for in utero exposure in the
developmental studies in rats and rabbits or following prenatal/postnatal exposure in the
multi-generation reproduction studies in rats.
    (v). The dietary (food and drinking water) and non-dietary exposure
assessments will not underestimate the potential exposures for infants
and children from the use of thiophanate-methyl.
    3. Prenatal and postnatal sensitivity of MBC. The Agency determined
that the FQPA Safety factor should be retained at 10X for assessing the
risk posed by MBC for the following reasons:
    (i). Evidence of increased susceptibility following in utero
exposure to MBC in the prenatal developmental toxicity in rats and
rabbits.
    (ii). The need for developmental neurotoxicity study in rats for
carbendazim.
    4. Conclusion. Based on the developmental and reproductive data on
thiophanate-methyl and MBC, EPA determined that an additional 3X safety
factor for thiophanate-methyl and that an additional 10X safety factor
for MBC for the protection of infants and children (as required by
FQPA) should be retained.

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 as used by EPA are used to calculate DWLOCs: 2L/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 ground water are less than the
calculated DWLOCs, EPA concludes with reasonable certainty that
exposures to the pesticide in drinking water (when considered along
with other sources of exposure for which EPA has reliable data) would
not result in unacceptable levels of aggregate human health risk at
this time. Because EPA 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, EPA 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. The thiophanate-methyl acute dietary risk estimate
uses 10% of the aPAD for the general U.S. population and 25% of the
aPAD for the most highly exposed population subgroup of concern,
infants, (<1 year). For MBC, the acute dietary risk estimate uses 4% of
the aPAD for the general U.S. population and 89% of the aPAD for the
population subgroup of concern, infants, (<1 year). The total
thiophanate-methyl plus MBC acute dietary risk estimate for the only
population subgroup of concern, females (13-50 years) uses 51% of the
aPAD. The DWLOC based on simultaneous dietary exposure to both MBC and
thiophanate-methyl which was converted to MBC equivalents resulted in
the following DWLOCs: Infants (<1 year) 18 ppb; children (1-6 years) 57
ppb; females (13-50 years) 150 - 170 ppb; and general U.S. population
5,700 ppb. The lowest DWLOC for the population subgroup, infants (<1
year) does not exceed the EEC for ground water (0.033 ppb); however,
the DWLOC does exceed the EEC for surface water (25 ppb). Although the
EEC is exceeded, the DWLOC is greatly inflated as 50% of the aPAD
percentage is consumed by citrus which is a 1-year registration only.
When citrus is removed from the DWLOC estimation, the DWLOC becomes 94
ppb which is well above the EEC of 25 ppb. The DWLOC is significantly
lowered by the addition of citrus because field trial data was used
which results in an overly conservative estimation.
    Another indication that the addition of citrus based on field trial
data results in an over estimation is the fact that benomyl PDP data
available for citrus indicated that there were zero hits out of 689
Florida samples of orange juice. These data were not used to refine the
DWLOC estimation as the benomyl application rate is somewhat lower than
the thiophanate-methyl rate approved in this year's emergency exemption
for thiophanate-methyl. However, the Agency believes that while most
growers used the benomyl rate as the emeregency exemption was approved
later in the use season and thus fewer applications than were
authorized were actually used. Furthermore, if the higher rate were
used, the impact would be lessened by the fact that juice is a blended
commodity. Therefore, although the DWLOC is exceeded, the acute dietary
risk from food and water does not exceed the Agency's level of concern.
    2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that exposure to
thiophanate-methyl and MBC will utilize the following percentages of
the RfD for the U.S. population: Thiophanate-methyl - 0.7%; MBC - 1.0%
and total thiophanate-methyl plus MBC - 1.7%. The major identifiable
subgroup with the highest aggregate exposure is children (1-6 years),
and EPA has concluded that aggregate dietary exposure to thiophanate-
methyl and MBC wil utilize the following percentages of the RfD:
thiophate-methyl - 2.3%; MBC - 26% and total thiophanate-methyl plus
MBC - 28%. EPA generally has no concern for exposures below 100% of the
RfD because the RfD represents the level at or below which daily
aggregate dietary exposure over a lifetime will not pose appreciable
risks to human health. The aggregate chronic DWLOCs are as follows: 858
ppb for the general U.S. population; 69 ppb for females (13-50 years);
22 ppb for infants (<1 year); and 18 ppb for children (1-6 years). The
aggregate surface water EEC for thiophanate-methyl is 0.7 ppb; 14 ppb
for MBC and 14.7 ppb for thiophanate-methyl plus MBC. Therefore, the
chronic aggregate risk to not exceed the Agency's level of concern.
    3. Short-term risk. Short-term aggregate exposure takes into
account residential exposure plus chronic exposure to food and water
(considered to be a background exposure level). Thiophanate-methyl and
MBC are currently registered for use that could result in short-term
residential exposure, and the Agency has determined that it is
appropriate to aggregate chronic food and water and short-term
exposures for thiophanate-methyl and MBC.
    All residential exposures are considered to be short-term. The
MOE's (converted to MBC equivalents) for
aggregate short-term exposure to thiophanate-methyl are as follows:
Oral exposure of children (1-6 years) is 670; dermal exposure of
children (1-6 years) is 1,000; and dermal exposure of females (13-50
years) is 1,315. The MOEs for aggregrate exposure to MBC from the use
of MBC as an in-can paint preservative are 670 for dermal exposure and
770 for exposure via inhalation. The MOEs (converted to MBC
equivalents) for the total thiophanate-methyl and MBC aggregate
exposure are as follows: 630 for oral and dermal exposure of children
(1-6 years); 770 for exposure via inhalation for females (13-50 years);
and 620 for oral and dermal exposure for females (13-50 years).
Although the MOEs below 1,000 exceed the Agency's level of concern,
when considering the conservative method of exposure estimation
previously discussed, and the negotiated risk mitigation whereby the
registrant has agreed to conduct hand-press studies to help refine this
assessment, the risks do not exceed the Agency's level of concern.
    4. Aggregate cancer risk for U.S. population. The total
thiophanate-methyl and MBC dietary cancer risk is 8.5 x 10-7
for existing and new uses. The cancer risk from non-occupational
residential exposure is 3.7 x 10-7. The aggregate cancer
risk is 1.2 x 10-6. This risk estimate includes cancer risk
from both thiophanate-methyl and MBC on food including all pending uses
and section 18 uses, thiophanate-methyl exposure from treating
ornamentals, thiophanate-methyl exposure from performing post-
application lawn activities, and exposure from applying paint
containing MBC. This is considered to be a high-end risk scenario since
it is not expected that someone would treat ornamentals, perform high
exposure post-application activities, and apply paint containing MBC
every year for 70 years. Therefore, this estimate is considered to be a
conservative estimate. Additionally, the cancer risk estimate based on
the highest EEC (thiophanate-methyl plus MBC EEC) is 9.6 x
10-7. This is also a very high-end risk estimate as it is
based on the maximum rate being applied every season for 70 years.
Thus, food plus water (assuming that the modeled surface water EEC is
equivalent to concentrations in finished drinking water) plus non-
occupational residential cancer risk is 2.2 x 10-6 which is
still within the range considered as negligible. In addition, the
cancer risk estimates using benomyl/MBC PDP monitoring data to estimate
thiophanate-methyl residues are below 1 x 10-6 for
thiophanate-methyl existing uses, new uses, and the amortized section
18 use on citrus. Therefore, the risks do not exceed the Agency's level
of concern.
    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 thiophanate-methyl and MBC residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology high pressure liquid
chromatography/ultra violet (HPLC/UV) is available to enforce the
tolerance expression. The method may be requested from: Calvin Furlow,
PRRIB, IRSD (7502C), Office of Pesticide Programs, Environmental
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460;
telephone number: (703) 305-5229; e-mail address:
furlow.calvin@epa.gov.

B. International Residue Limits

    The Codex Alimentarius Commission has established maximum residue
limits (MRLs) for thiophanate-methyl residues in/on various plant and
animal commodities. Codex MRLs for thiophanate-methyl are currently
expressed as MBC. The Codex MRL residue definition and the U.S.
tolerance definition are currently incompatible and will remain
incompatible even after the U.S. tolerance definition is revised, as
the revised tolerance definition will include both thiophanate-methyl
and MBC.

C. Conditions

    A 30-day plant back interval is required for crops without labeled
uses of thiophanate-methyl. Registrations for the use on canola will be
restricted to use in Minnesota, Montana and North Dakota (East of
Interstate 15).

V. Conclusion

    Therefore, the tolerances are established for residues of
thiophanate-methyl and its metabolite (methyl 2-benzimidazoyl carbamate
(MBC)), expressed as thiophanate-methyl in or on grapes at 5.0 ppm, on
pears at 3.0 ppm, on pistachios at 0.1 ppm, on potatoes at 0.1 ppm, and
on canola (restricted to use in Minnesota, Montana and North Dakota
(East of Interstate 15)) at 0.1 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 of 1996, EPA will continue to use those
procedures, with appropriate adjustments, until the necessary
modifications can be made. The new section 408(g) 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), as was provided in the old FFDCA sections 408 and 409.
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-2002-0140 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 October
28, 2002.
    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. You may also deliver your written 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 tompkins.jim@epa.gov,
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.
    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.
    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.2. Mail your
copies, identified by docket ID number OPP-2002-0140, 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.
In person or by courier, bring a copy to the location of the PIRIB
described in Unit I.B.2. You may also send an electronic copy of your
request via e-mail to: opp-docket@epa.gov. 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. Regulatory Assessment Requirements

    This final rule establishes a tolerance under FFDCA section 408(d)
in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this 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 FFDCA section 408(d), such as the tolerance in this
final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply. 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 FFDCA section 408(n)(4). 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. Submission to Congress and the Comptroller General

    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: July 3, 2002.
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:

    Authority: 21 U.S.C. 321(q), 346(a) and 374.

    2. Section 180.371 is amended as follows:
    i. By alphabetically adding entries for the commodities ``grape,''
``pear,'' and ``pistachio'' and revising the entry for ``potatoes, seed
treatment'' to read ``potato'' to the table in paragraph (a) as set
forth below.
    ii. By adding text and a table to paragraph (c):


Sec. 180.371  Thiophanate-methyl; tolerances for residues.

    (a) General. Thiophanate-methyl and its metabolite (methyl 2-
benzimidazoyl carbamate (MBC)), expressed as thiophanate-methyl

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
                      *      *      *      *      *
Grape................................................                5.0
                      *      *      *      *      *
Pear.................................................                3.0
                      *      *      *      *      *
Pistachio............................................                0.1
                      *      *      *      *      *
Potato...............................................                0.1
                      *      *      *      *      *
------------------------------------------------------------------------

* * * * *
    (c) Tolerances with regional registrations. Tolerances with
regional registration, as defined in Sec. 180.1(n), are established for
the residues of thiophanate-methyl and its metabolite (methyl 2-
benzimidazolyl carbamate (MBC)), expressed as thiophanate-methyl in or
on the following raw agricultural commodity:

------------------------------------------------------------------------
                      Commodity                        Parts per million
------------------------------------------------------------------------
Canola...............................................                0.1
------------------------------------------------------------------------

* * * * *
[FR Doc. 02-21678 Filed 8-27-02; 8:45 am]