[Federal Register Volume 67, Number 176 (Wednesday, September 11, 2002)]
[Rules and Regulations]
[Pages 57521-57532]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-23086]


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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2002-0141 FRL-7187-2]


Iodosulfuron-Methyl-Sodium; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes a tolerances for residues of 
iodosulfuron-methyl-sodium, methyl 4-iodo-2-[3-(4-methoxy-6-methyl-
1,3,5 triazin-2-yl)ureidosulfonyl]benzoate, sodium salt, in or on corn, 
field, grain; corn, field, forage; and corn, field, stover. Aventis 
CropScience USA LP requested this tolerance under the Federal Food, 
Drug,

[[Page 57522]]

and Cosmetic Act, as amended by the Food Quality Protection Act of 
1996.

DATES: This regulation is effective September 11, 2002. Objections and 
requests for hearings, identified by docket ID number OPP-2002-0141 
must be received on or before November 12, 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-2002-0141 in the 
subject line on the first page of your response.

FOR FURTHER INFORMATION CONTACT: By mail: Joanne I. Miller, 
Registration Division (7505C), Office of Pesticide Programs, 
Environmental Protection Agency, 1200 Pennsylvania Ave., 
NW.,Washington, DC 20460; telephone number: (703) 305-6224; e-mail 
address: [email protected].

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 theFederal 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-2002-0141. 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 January 24, 2001 (66 FR 7644) (FRL-6758-
9), EPA issued a notice pursuant to section 408 of the Federal Food, 
Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a, as amended by the Food 
Quality Protection Act of 1996 (FQPA) (Public Law 104-170), announcing 
the filing of a pesticide petition (PP F6160) by Aventis CropScience 
USA LP, P.O. Box 12014, 2 T.W. Alexander Drive, Research Triangle Park, 
NC 27709. This notice included a summary of the petition prepared by 
Aventis CropScience, the registrant. There were no comments received in 
response to the notice of filing.
    The petition requested that 40 CFR 180.580 be amended by 
establishing tolerances for residues of the herbicide iodosulfuron-
methyl-sodium, methyl 4-iodo-2-[3-(4-methoxy-6-methyl-1,3,5 triazin-2-
yl)ureidosulfonyl]benzoate, sodium salt, in or on corn, field, grain at 
0.03 part per million (ppm); corn, field, forage at 0.05 ppm; and corn, 
field, stover at 0.05 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) 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 a tolerance for residues of iodosulfuron-methyl-sodium 
on corn, field, grain at 0.03 ppm; corn, field, stover at 0.05 ppm; and 
corn, field, forage at 0.05 ppm. EPA's assessment of exposures and 
risks associated with establishing the tolerance follows.

[[Page 57523]]

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 iodosulfuron-
methyl-sodium are discussed in the following Table 1 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 = 67 mg/kg/day in males, 74 mg/kg/day
                                          rodents-rat                 in females.
                                                                     LOAEL = 347 mg/kg/day in males, 388 mg/kg/
                                                                      day in females based on reduced body
                                                                      weight and overall body weight gains in
                                                                      both sexes
----------------------------------------------------------------------------------------------------------------
870.3100                                 90-Day oral toxicity        NOAEL = 119 mg/kg/day in males, Not
                                          rodents-mouse               observed in females
                                                                     LOAEL = 332 mg/kg/day in males, 139 mg/kg/
                                                                      day in females based on hepatotoxicity
----------------------------------------------------------------------------------------------------------------
870.3150                                 90-Day oral toxicity        NOAEL = 8.1 mg/kg/day in males, 8.4 mg/kg/
                                          nonrodents-dog              day infemales.
                                                                     LOAEL = 49 mg/kg/day in males, 51 mg/kg/day
                                                                      in females based on changes in hematology,
                                                                      microscopic pathology of the bone marrow
                                                                      and spleen (females), clinical chemistry
                                                                      (males)
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental in   Maternal: NOAEL = 315 mg/kg/day
                                          rodents-rat                LOAEL = 1,000 mg/kg/day based on increased
                                                                      salivation
                                                                     Developmental: NOAEL = 315 mg/kg/day
                                                                     LOAEL =1,000 mg/kg/day based on delayed
                                                                      ossification
----------------------------------------------------------------------------------------------------------------
870.3700                                 Prenatal developmental in   Maternal: NOAEL = 400 mg/kg/day (HDT)
                                          nonrodents-rabbit          LOAEL = Not observed
                                                                     Developmental: NOAEL = 400 mg/kg/day (HDT)
                                                                     LOAEL = Not observed
----------------------------------------------------------------------------------------------------------------
870.3800                                 Reproduction and fertility  Parental/Systemic NOAEL = 346 mg/kg/day in
                                          effects-rat                 males, 390 mg/kg/day in females (HDT).
                                                                     LOAEL = not established.
                                                                     Reproductive NOAEL = 346 mg/kg/day in
                                                                      males, 390 mg/kg/day in females (HDT).
                                                                     LOAEL = not established.
                                                                     Offspring NOAEL = 34.2 mg/kg/day in males,
                                                                      39.7 mg/kg/day in females.
                                                                     LOAEL = 346 mg/kg/day in males, 390 mg/kg/
                                                                      day in females (HDT) based on pup
                                                                      mortality.
----------------------------------------------------------------------------------------------------------------
870.4100                                  Chronic toxicity-dogs      NOAEL = 41.8 mg/kg/day in males, 7.25 mg/kg/
                                                                      day in females
                                                                     LOAEL = Not Established in males, 43.7 mg/
                                                                      kg/day in females based on gross and
                                                                      histopathologic changes observed in the
                                                                      hematopoietic system.
----------------------------------------------------------------------------------------------------------------
870.4300                                 Chronic/carcinogenicity-    NOAEL = 29.7 mg/kg/day in males, 39.1 mg/kg/
                                          rats                        day in females.
                                                                     LOAEL = 331 mg/kg/day in males and 452 mg/
                                                                      kg/day in females based on reduced body
                                                                      weight and body weight gains in males and
                                                                      on reduced body weight, body weight gains
                                                                      and food efficiency in females.
                                                                     No evidence of carcinogenicity.
----------------------------------------------------------------------------------------------------------------
870.4300                                 Carcinogenicity-mice        NOAEL = 54.2 mg/kg/day in males, 57.6 mg/kg/
                                                                      day in females.
                                                                     LOAEL = 279 mg/kg/day in males, 277 mg/kg/
                                                                      day in females based on increased liver
                                                                      weights and histopathological changes in
                                                                      the liver.
                                                                     No evidence of carcinogenicity at doses
                                                                      tested.
----------------------------------------------------------------------------------------------------------------
870.5100                                 Gene mutation               Non-mutagenic when tested up to 5000 ug/
                                                                      plate, in presence and absence of
                                                                      metabolic activation, in S. typhimurium
                                                                      strains TA98, TA100, TA1535 and TA1537 and
                                                                      E.coli strain WP2uvra.
----------------------------------------------------------------------------------------------------------------
870.5300                                  Gene mutation              Negative for induction of forward mutation
                                                                      at the HPRT locus in Chinese hamster V79
                                                                      lung fibroblasts, in the presence or
                                                                      absence of S9-activation at doses up to
                                                                      limit of solubility (2649 Fg/mL).
----------------------------------------------------------------------------------------------------------------
870.5375                                 Chromosome aberration       Did not induce structural chromosome
                                                                      aberration in Chinese hamster lung (V79)
                                                                      cell cultures in the presence and absence
                                                                      of activation up to cytotoxic
                                                                      concentrations.
----------------------------------------------------------------------------------------------------------------
870.5385                                 Chromosomal aberration      Non-mutagenic in NMRI mouse bone marrow
                                                                      micronucleus chromosomal aberrations assay
                                                                      up to the limit dose (2,000 mg/kg).
----------------------------------------------------------------------------------------------------------------

[[Page 57524]]

 
870.5550                                 Other genotoxicity          No evidence that unscheduled DNA synthesis
                                                                      was induced by iodosulfuron-methyl, as
                                                                      determined by radioactive tracer
                                                                      procedures nuclear silver grain counts.
                                                                      Iodosulfuron-methyl was tested up to
                                                                      cytotoxic concentrations ($3,000 [mu]g/
                                                                      mL). UDS activity was assessed at 0.01 to
                                                                      1,000 [mu]g/mL.
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism and              Total recovery of the administered dose was
                                          pharmacokinetics-rat        95.9-102.4% for all treatment groups. No
                                                                      radioactivity was detected in exhaled air
                                                                      or organic volatiles. Elimination of
                                                                      radioactivity occurred primarily in the
                                                                      urine, mostly within 24 hours of dosing,
                                                                      and was essentially complete within 3 days
                                                                      of dosing. Overall urinary excretion
                                                                      accounted for 78.5% and 85.8% of the dose
                                                                      for males and females, respectively, and
                                                                      fecal elimination accounted for 19.2% and
                                                                      10.1% of the dose, respectively. By 3 days
                                                                      post-dose, <=0.5% of the dose remained in
                                                                      the blood and tissues of both sexes of
                                                                      rats from the low- and high-dose groups.
                                                                     Rats excreted the majority of the dose as
                                                                      unchanged parent via the urine (48.7-86.3%
                                                                      dose) or feces (1.1-11.1% dose). Minor
                                                                      routes of metabolism for iodosulfuron-
                                                                      methyl included hydrolysis of the
                                                                      methylester to form 4-iodo-2-[3-(4-methoxy-
                                                                      6-methyl-1,3,5-triazin-2-
                                                                      yl)ureidosulfonyl] benzoic acid (AE
                                                                      F145740; 0.9-4.5% dose); O-demethylation
                                                                      of the triazine ring to form methyl 2-[3-
                                                                      (4-hydroxy-6-methyl-1,3,5-triazin-2-
                                                                      yl)ureidosulfonyl]-4-iodobenzoate (AE
                                                                      F148741; 1.5-8.2% dose); or hydroxylation
                                                                      of the methyl group on the triazine ring
                                                                      to form methyl 2-[3-(4-hydroxymethyl-6-
                                                                      methoxy-1,3,5-triazin-2-yl)ureidosulfonyl]-
                                                                      4-iodobenzoate (AE F168532; 0.3-6.6%
                                                                      dose). Each of these minor metabolites was
                                                                      present in both the urine and feces. The
                                                                      remaining metabolites each accounted for
                                                                      <3% of the dose.
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism and              Within 72 hours of oral dosing, 90-94% of
                                          pharmacokinetics-dog        the dosed radioactivity was recovered in
                                                                      the excrement and cage wash of both dose
                                                                      groups. Renal excretion accounted for 64-
                                                                      74% of the dose and elimination in the
                                                                      feces accounted for 14-17% of the
                                                                      radioactive dose. Most of the dose was
                                                                      excreted within 24 hours. Quantitative RP-
                                                                      HPLC analyses isolated up to 6 distinct
                                                                      radioactive components in urine and feces.
                                                                      The major isolated fraction was the
                                                                      parent: urine (54-61% dose) and feces (8-
                                                                      11%).
                                                                     In the rat, the major isolated fraction was
                                                                      also the parent, while the major
                                                                      metabolite was AE F145741. The metabolites
                                                                      identified in the dog were consistent with
                                                                      those identified in the rats.
----------------------------------------------------------------------------------------------------------------
870.7600                                 Dermal penetration-rat      For both the low- and high-dose groups,
                                                                      dermal penetration of radioactivity was
                                                                      low (< 2% dose) at exposure intervals up
                                                                      to 8 hours. Absorption increased slightly
                                                                      with duration of exposure in the low-dose
                                                                      group, increasing from 0.019% of the dose
                                                                      (0.043 Fg/cm2) at 3 hours to 0.69% of the
                                                                      dose (0.159 Fg/cm2) at 8 hours. However, a
                                                                      similar trend was not observed in the high-
                                                                      dose group, as the maximum absorption was
                                                                      observed at the 5-hour exposure (1.60%
                                                                      dose, 6.02 Fg/cm2).
----------------------------------------------------------------------------------------------------------------

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 
adverse effects of concern are identified 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 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 
acute or chronic Population Adjusted Dose (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 106 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 iodosulfuron-methyl-sodium used

[[Page 57525]]

for human risk assessment is shown in the following Table 2:

   Table 2.--Summary of Toxicological Dose and Endpoints for Iodosulfuron-Methyl-Sodium 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 for general population   NOAEL= 315 mg/kg/day     FQPA SF = 10x            Developmental Toxicity
                                       UF = 100...............  aPAD = 0.31 mg/kg/day..   in Rats
                                       aRfD = 3.15 mg/kg/day..                           Based on increased
                                                                                          salivation seen in
                                                                                          dams on day one and
                                                                                          throughout the dosing
                                                                                          period at the high
                                                                                          dose of 1,000 mg/kg/
                                                                                          day
                                                                                         (LOAEL, Maternal)
-----------------------------------------------------------------------------------------
Chronic dietary all populations        NOAEL = 7.3 mg/kg/day    FQPA SF= 10              Chronic Oral Toxicity
                                       UF = 100...............  cPAD = 0.007 mg/kg/day.   diet - dog
                                       cRfD = 0.073 mg/kg/day.                            Based on gross and
                                                                                          histopathologic
                                                                                          changes observed in
                                                                                          the hematopoietic
                                                                                          system seen at 1,200
                                                                                          ppm (LOAEL 43.7 mg/kg/
                                                                                          day)
-----------------------------------------------------------------------------------------
Incidental oral short-term (1-30       Oral NOAEL = 49 mg/kg/   FQPA SF= 10              Subchronic Oral
 days)                                  day                     LOC for MOE = 1,000....   Toxicity diet - dog
                                                                (residential)..........  Based on alterations in
                                                                                          hematological
                                                                                          parameters and changes
                                                                                          in clinical chemistry
                                                                                          seen at 4 week
                                                                                          observation period at
                                                                                          a dose level of 301 mg/
                                                                                          kg/day (HDT)
-----------------------------------------------------------------------------------------
Incidental oral, intermediate-term     Oral NOAEL= 8.1 mg/kg/   FQPA SF= 10              Subchronic Oral
 (30 days-6 months)                     day                     LOC for MOE = 1,000....   Toxicity diet - dog
                                                                (residential)..........  Based on changes in
                                                                                          hematology (males and
                                                                                          females), microscopic
                                                                                          pathology of the bone
                                                                                          marrow (males and
                                                                                          females) and spleen
                                                                                          (females), and
                                                                                          clinical chemistry
                                                                                          (males) seen at
                                                                                          termination at a dose
                                                                                          level of 49 mg/kg/day
                                                                                          (LOAEL)
-----------------------------------------------------------------------------------------
Dermal short-term (1-30 days)          Oral NOAEL= 49 mg/kg/    LOC for MOE = 1,000      Subchronic Oral
                                        day                     (residential)..........   Toxicity diet - dog.
                                       dermal absorption        LOC for MOE = 100......  Based on alterations in
                                        factor 2%.              (occupational).........   hematological
                                                                                          parameters and changes
                                                                                          in clinical chemistry
                                                                                          seen at 4 week
                                                                                          observation period at
                                                                                          a dose level of 301 mg/
                                                                                          kg/day (HDT)
-----------------------------------------------------------------------------------------
Dermal, intermediate-term (30 days-6   Oral NOAEL= 8.1 mg/kg/   LOC for MOE = 1,000      Subchronic Oral
 months)                                day                     (residential)..........   Toxicity diet - dog
                                       dermal absorption        LOC for MOE = 100......  Based on changes in
                                        factor 2%.              (occupational).........   hematology (males and
                                                                                          females), microscopic
                                                                                          pathology of the bone
                                                                                          marrow (males and
                                                                                          females) and spleen
                                                                                          (females), and
                                                                                          clinical chemistry
                                                                                          (males) seen at
                                                                                          termination at a dose
                                                                                          level of 49 mg/kg/day
                                                                                          (LOAEL)
-----------------------------------------------------------------------------------------
Dermal, long-term (6 months-life       Oral NOAEL= 7.3 mg/kg/   LOC for MOE = 1,000      Chronic Oral Toxicity
 time)                                  day                     (residential)..........   diet - dog
                                       dermal absorption        LOC for MOE = 100......  Based on gross and
                                        factor 2%.              (occupational).........   histopathologic
                                                                                          changes observed in
                                                                                          the hematopoietic
                                                                                          system seen at 1,200
                                                                                          ppm (LOAEL 43.7 mg/kg/
                                                                                          day)
-----------------------------------------------------------------------------------------
Inhalation, short-term (1-30 days)     Oral NOAEL= 49 mg/kg/    LOC for MOE = 1,000      Subchronic Oral
                                        day                     (residential)..........   Toxicity diet - dog
                                       inhalation absorption    LOC for MOE = 100......  Based on alterations in
                                        factor 100%.            (occupational).........   hematological
                                                                                          parameters and changes
                                                                                          in clinical chemistry
                                                                                          seen at 4 week
                                                                                          observation period at
                                                                                          a dose level of 301 mg/
                                                                                          kg/day (HDT)
-----------------------------------------------------------------------------------------
Inhalation, intermediate-term (30      Oral NOAEL= 8.1 mg/kg/   LOC for MOE = 1,000      Subchronic Oral
 days-6 months)                         day                     (residential)..........   Toxicity diet - dog
                                       inhalation absorption    LOC for MOE = 100......  Based on changes in
                                        factor 100%.            (occupational).........   hematology (males and
                                                                                          females), microscopic
                                                                                          pathology of the bone
                                                                                          marrow (males and
                                                                                          females) and spleen
                                                                                          (females), and
                                                                                          clinical chemistry
                                                                                          (males) seen at
                                                                                          termination at a dose
                                                                                          level of 49 mg/kg/day
                                                                                          (LOAEL)
-----------------------------------------------------------------------------------------
Inhalation, Long-term (6 months-life   Oral NOAEL= 7.3 mg/kg/   LOC for MOE = 1,000      Chronic Oral Toxicity
 time)                                  day                     (residential)..........   diet - dog
                                       inhalation absorption    LOC for MOE = 100......  Based on gross and
                                        factor 100%.            (occupational).........   histopathologic
                                                                                          changes ST observed in
                                                                                          the hematopoietic
                                                                                          system seen at 1,200
                                                                                          ppm (LOAEL 43.7 mg/kg/
                                                                                          day)
----------------------------------------------------------------------------------------------------------------
The reference to the FQPA Safety Factor refers to any additional safety factor retained due to concerns unique
  to the FQPA.


[[Page 57526]]

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. This is the first 
request for an iodosulfuron-methyl-sodium registration to establish 
tolerances for the residues of iodosulfuron-methyl-sodium, in or on a 
variety of raw agricultural commodities. Metsulfuron-methyl (registered 
active ingredient; PC code 122010) has been identified as a residue of 
concern in drinking water as a result of iodosulfuron-methyl-sodium 
application (metsulfuron-methyl was not identified as a residue of 
concern in cereal grains or livestock). Since metsulfuron-methyl had 
not undergone a full review by the EPA at the time the iodosulfuron-
methyl-sodium risk assessment was completed, it was assumed that the 
doses and endpoints identified for iodosulfuron-methyl-sodium were 
applicable to metsulfuron-methyl. This assumption was considered 
appropriate based on structural activity relationship (both are 
sulfonylureas), and the fact that metsulfuron-methyl is a predominant 
metabolite of iodosulfuron-methyl-sodium in soil in drinking water. 
Recently, metsulfuron-methyl has undergone a full review by EPA. In all 
instances, excluding short-term inhalation and incidental oral, the 
metsulfuron-methyl endpoints were greater than those identified for 
iodosulfuron-methyl-sodium. No acute dietary endpoint was selected for 
metsulfuron-methyl. Since metsulfuron-methyl was considered 
toxicologically equivalent to iodosulfuron-methyl-sodium for risk 
assessment purposes, the dietary and residential analyses included all 
registered and proposed uses for iodosulfuron-methyl-sodium and 
metsulfuron-methyl. Additionally, the iodosulfuron-methyl-sodium risk 
assessment incorporated a 10X FQPA safety factor (metsulfuron-methyl 
has a 1X FQPA safety factor). Therefore, this assessment is considered 
highly conservative. The nature of metsulfuron-methyl residues in/on 
cereal grains (residues of concern - metsulfuron-methyl and its 4 
hydroxy metabolite) and ruminants (residues of concern - metsulfuron-
methyl) have been determined and tolerances have been established in/on 
barley, grass, sugarcane, wheat, sorghum, milk and in the fat, meat, 
meat byproducts, and kidney of cattle, goats, hogs, horses, and sheep 
ranging from 0.05 - 20 ppm (40 CFR 180.428). Based on data from the 
ruminant and poultry metabolism studies, in which a cow and hens were 
dosed at 179x and 333x the MTDB, respectively, there is no reasonable 
expectation that finite residues of iodosulfuron-methyl-sodium will 
occur in livestock commodities (40 CFR 180.6(a)(3)). Therefore, 
livestock feeding studies and tolerances for livestock commodities were 
not performed. If the use of iodosulfuron-methyl-sodium is expanded in 
the future to include other livestock feed items, the need for feeding 
studies will be reevaluated. Risk assessments were conducted by EPA to 
assess dietary exposures from iodosulfuron-methyl-sodium 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 
(DEEMTM) 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: The acute analysis was performed 
for the general U.S. population and all population subgroups using 
existing and recommended tolerance level residues, 100% crop treated 
information, and DEEMTM default processing factors for all 
iodosulfuron-methyl-sodium and metsulfuron-methyl registered and 
proposed commodities.
    ii. Chronic exposure. In conducting this chronic dietary risk 
assessment the DEEMTM 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: 
The chronic analysis was performed for the general U.S. population and 
all population subgroups using existing and recommended tolerance level 
residues, 100% crop treated information, and DEEMTM default 
processing factors for all iodosulfuron-methyl-sodium and metsulfuron-
methyl registered and proposed commodities.
    iii. Cancer. The mouse carcinogenicity study was negative as was 
the carcinogenicity study conducted in rats. Iodosulfuron-methyl-sodium 
was negative for mutagenicity in various assays. Furthermore, 
registered sulfonyl urea compounds (structurally similar compounds) 
have been found to be non-carcinogenic. The maximum dose, however, was 
not achieved for the mouse cancer study for iodosulfuron-methyl-sodium; 
thus, EPA has requested a new carcinogenicity study in mice as 
confirmatory data.
    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for iodosulfuron-methyl-sodium 
and metsulfuron-methyl 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 iodosulfuron-methyl-
sodium and metsulfuron-methyl.
    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 Screening Concentrations in Ground Water (SCI-GROW) model is used 
to predict pesticide concentrations in shallow ground water. 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

[[Page 57527]]

residential uses. Since DWLOCs address total aggregate exposure to 
iodosulfuron-methyl-sodium and metsulfuron-methyl, they are further 
discussed in the aggregate risk sections see section E.
    Based on the PRZM/EXAMS and SCI-GROW models, the EECs of 
iodosulfuron-methyl-sodium and metsulfuron-methyl for acute exposures 
are estimated to be 1.43 parts per billion (ppb) for surface water and 
0.105 ppb for ground water. The EECs for chronic exposures are 
estimated to be 0.338 ppb for surface water and 0.105 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).
    Iodosulfuron-methyl-sodium is not registered for use on any sites 
that would result in residential exposure. However, metsulfuron-methyl 
is currently registered for use on the following residential non-
dietary site(s): Golf courses and residential turfgrass. Based on the 
use pattern, potential residential exposure scenarios include:
    [sbull] Golfer post-application exposure (adult and adolescent)
    [sbull] Non-dietary ingestion (toddler hand-to-mouth, object-to-
mouth, soil ingestion)
    [sbull] Dermal post-application exposure to turfgrass (adult and 
toddler)
    All MOEs calculated for residential post-application exposures do 
not exceed the HED's levels of concern for the respective exposure 
scenarios (MOEs<1,000).
    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 
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 iodosulfuron-methyl-sodium and metsulfuron-methyl have a common 
mechanism of toxicity with other substances or how to include these 
pesticides in a cumulative risk assessment. Unlike other pesticides for 
which EPA has followed a cumulative risk approach based on a common 
mechanism of toxicity, iodosulfuron-methyl-sodium and metsulfuron-
methyl do not appear to produce a toxic metabolite produced by other 
substances. For the purposes of this tolerance action, therefore, EPA 
has not assumed that iodosulfuron-methyl-sodium and metsulfuron-methyl 
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 margin of exposure 
(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. There is evidence for both 
quantitative and qualitative increased susceptibility in the multi-
generation rat reproduction study. While no parental toxicity was seen 
at the HDT (346 mg/kg/day), off-spring toxicity was manifested as 
reduced pup viability (death on Day 0 in F2, LOAEL 346 mg/
kg/day; NOAEL 34 mg/kg/day). Similarly, there is evidence for 
qualitative increase in susceptibility in the rat developmental 
toxicity study where delayed ossification was observed in the fetuses 
of dams that exhibited minimal maternal toxicity (salivation; maternal 
and developmental LOAEL 1,000 mg/kg/day and NOAEL 315 mg/kg/day). 
Maternal and developmental LOAELs were not established in the non-
rodent (rabbit) developmental toxicity study (HDT 400 mg/kg/day; study 
is classified as unacceptable/not upgradable due to inadequate dosing). 
Therefore, susceptibility of the offspring could not be addressed in 
this species.
    3. Conclusion. There is a complete toxicity data base for 
iodosulfuron-methyl-sodium. EPA concluded that the FQPA safety factor 
be retained at 10x for iodosulfuron-methyl-sodium for the following 
weight-of-evidence considerations: There is qualitative evidence of 
increased susceptibility following in utero exposure to iodosulfuron-
methyl-sodium in the rat developmental toxicity study; there is 
quantitative and qualitative evidence of increased susceptibility 
following prenatal/postnatal exposure to iodosulfuron-methyl-sodium in 
the 2-generation reproduction study in rats; susceptibility could not 
be assessed in the non-rodent (rabbit) developmental study since the 
doses tested in this study were considered to be inadequate (this study 
is classified as unacceptable); there is a data gap for an acute 
neurotoxicity study conducted in adult rats required to confirm and 
characterize the signs of neurotoxicity observed in the 90-day dog 
study and the rat developmental toxicity study; and the requirement for 
a developmental neurotoxicity study (DNT) with iodosulfuron-methyl-
sodium is ``reserved'' pending the results of the acute neurotoxicity 
study.

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 the Office of Water 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, OPP concludes with reasonable certainty that 
exposures to the pesticide in drinking water (when

[[Page 57528]]

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 
iodosulfuron-methyl-sodium and metsulfuron-methyl will occupy 1% of the 
aPAD for the U.S. population, <1% of the aPAD for females 13 years and 
older, 1% of the aPAD for all infants and 1% of the aPAD for children 
(1-6 years old). In addition, there is potential for acute dietary 
exposure to iodosulfuron-methyl-sodium and metsulfuron-methyl 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 the following Table 3:

   Table 3.--Aggregate Risk Assessment for Acute Exposure to Iodosulfuron-Methyl-Sodium and Metsulfuron-Methyl
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population subgroup                 aPAD (mg/      % aPAD     water EEC    water EEC   Acute DWLOC
                                                     kg)         (Food)       (ppb)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population--all seasons                           0.315            1         1.42        0.105       11,000
---------------------------------------------------------------------------
All Infants (<1 year old)                              0.315            1         1.42        0.105        3,100
---------------------------------------------------------------------------
Children (1-6 years old)                               0.315            1         1.42        0.105        3,100
---------------------------------------------------------------------------
Children (7-12 years old)                              0.315            1         1.42        0.105        3,100
---------------------------------------------------------------------------
Females (13-50 years old)                              0.315           <1         1.42        0.105        9,400
---------------------------------------------------------------------------
Males (13-19 years old)                                0.315            1         1.42        0.105       11,000
---------------------------------------------------------------------------
Males (20+ years old)                                  0.315           <1         1.42        0.105       11,000
---------------------------------------------------------------------------
Seniors (55+ years old)                                0.315           <1         1.42        0.105       11,000
----------------------------------------------------------------------------------------------------------------

    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
iodosulfuron-methyl-sodium and metsulfuron-methyl from food will 
utilize 10% of the cPAD for the U.S. population, 12% of the cPAD for 
all infants and 29% of the cPAD for children (1-6 years old). There are 
no residential uses for iodosulfuron-methyl-sodium and metsulfuron-
methyl that result in chronic residential exposure. Based on the use 
pattern, chronic residential exposure to residues of iodosulfuron-
methyl-sodium and metsulfuron are not expected. In addition, there is 
potential for chronic dietary exposure to iodosulfuron-methyl-sodium 
and metsulfuron-methyl 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 
the following Table 4:

     Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Iodosulfuron-Methyl-Sodium and
                                               Metsulfuron-Methyl
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population subgroup                cPAD mg/kg/     % cPAD     water EEC    water EEC     Chronic
                                                     day         (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                       0.0073           10        0.338        0.105          230
---------------------------------------------------------------------------
All Infants (<1 year old)                             0.0073           12        0.338        0.105           65
---------------------------------------------------------------------------
Children (1-6 years old)                              0.0073           29        0.338        0.105           52
---------------------------------------------------------------------------
Children (7-12 years old)                             0.0073           17        0.338        0.105           61
---------------------------------------------------------------------------
Females (13-50 years old)                             0.0073            7        0.338        0.105          200
---------------------------------------------------------------------------
Males (13-19 years old)                               0.0073           11        0.338        0.105          240
---------------------------------------------------------------------------
Males (20+ years old)                                 0.0073            7        0.338        0.105          240
---------------------------------------------------------------------------
Seniors (55+ years old)                               0.0073            6        0.338        0.105          240
----------------------------------------------------------------------------------------------------------------

    3. Short-term risk. Iodosulfuron-methyl-sodium is not registered 
for use on any sites that would result in residential exposure. 
However, for the purposes of this assessment, iodosulfuron-methyl-
sodium and metsulfuron-methyl are being considered toxicologically 
equivalent. Metsulfuron-methyl is currently

[[Page 57529]]

registered for use that could result in short-term residential 
exposure. Since a common toxicological effect was identified when 
assessing short-term oral and dermal exposures (alterations in 
hematology and clinical chemistry parameters), the aggregate short-term 
assessment considered exposure from food (chronic dietary), water, and 
residential uses (oral and dermal). The short-term oral and dermal 
endpoints were based on the same study, and therefore can be 
aggregated.
    Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded that food and residential exposures 
aggregated result in aggregate MOEs of 5.6e+05 for all U.S. 
populations, 2.5e+05 for all infants (<1 year old), 1.5e+05 for 
children (1-6 years old), 2.1e+05 for children (7-12 years old), 
7.7e+05 for females (13-50 years old), 5.1e+05 for males (13-19 years 
old), 7.4e+05 for males (20+ years old), and 8.4e+05 for seniors (55+ 
years old). These aggregate MOEs do not exceed the Agency's level of 
concern. In addition, short-term DWLOCs were calculated and compared to 
the EECs for average exposure of iodosulfuron-methyl-sodium and 
metsulfuron-methyl in ground and surface water. DWLOCs were then 
calculated using the following default body weights and drinking water 
consumption figures: 70 kg/2L (adult male), 60 kg/2L (adult female) and 
10 kg/1L (infant/child). After calculating DWLOCs and comparing them to 
the EECs for surface and ground water, EPA does not expect short-term 
aggregate exposure to exceed the Agency's level of concern, as shown in 
the following Table 5:

Table 5.--Aggregate Risk Assessment for Short-Term Exposure to Iodosulfuron-Methyl-Sodium and Metsulfuron-Methyl
----------------------------------------------------------------------------------------------------------------
                                                               Aggregate
                                                  Aggregate     level of     Surface       Ground     Short-term
              Population subgroup                MOE (Food +    concern     water EEC    water EEC   DWLOC (ppb)
                                                residential)     (LOC)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population--all                                 5.6e+05        1,000        0.338        0.105      1.7e+03
---------------------------------------------------------------------------
All infants (<1 year old)                            2.5e+05        1,000        0.338        0.105      4.7e+02
---------------------------------------------------------------------------
Children (1-6 years old)                             1.5e+05        1,000        0.338        0.105      4.6e+02
---------------------------------------------------------------------------
Children (7-12 years old)                            2.1e+05        1,000        0.338        0.105      4.7e+02
---------------------------------------------------------------------------
Females (13-50 years old)                            7.7e+05        1,000        0.338        0.105      1.5e+03
---------------------------------------------------------------------------
Males (13-19 years old)                              5.1e+05        1,000        0.338        0.105      1.7e+03
---------------------------------------------------------------------------
Males (20+ years old)                                7.4e+05        1,000        0.338        0.105      1.7e+03
---------------------------------------------------------------------------
Seniors (55+ years old)                              8.4e+05        1,000        0.338        0.105      1.7e+03
----------------------------------------------------------------------------------------------------------------

    4. Intermediate-term risk. Iodosulfuron-methyl-sodium is not 
registered for use on any sites that would result in residential 
exposure. However, for the purposes of this assessment, iodosulfuron-
methyl-sodium and metsulfuron-methyl are being considered 
toxicologically equivalent. Metsulfuron-methyl is currently registered 
for use that could result in intermediate-term residential exposure. 
Therefore, the aggregate intermediate-term assessment considered 
exposure from food (chronic dietary), water, and residential uses.
    Using the exposure assumptions described in this unit for 
intermediate-term exposures, EPA has concluded that food and 
residential exposures aggregated result in aggregate MOEs of 1.1e+04 
for all U.S. populations, 9.6e+03 and all infants (<1 year old), 
3.9e+03 for children (1-6 years old), 6.6e+03 for children (7-12 years 
old), 1.7e+04 for females (13-50 years old), 1.0e+04 for males (13-19 
years old), 1.7e+04 for males (20+ years old), and 2.0e+04 for seniors 
(55+ years old). These aggregate MOEs do not exceed the Agency's level 
of concern for food and residential uses. In addition, intermediate-
term DWLOCs were calculated and compared to the EECs for chronic 
exposure of iodosulfuron-methyl-sodium and metsulfuron-methyl in ground 
and surface water. DWLOCs were then calculated using the following 
default body weights and drinking water consumption figures: 70kg/2L 
(adult male), 60kg/2L (adult female) and 10kg/1L (infant/child). After 
calculating DWLOCs and comparing them to the EECs for surface and 
ground water, EPA does not expect intermediate-term aggregate exposure 
to exceed the Agency's level of concern, as shown in the following 
Table 6:

 Table 6.--Aggregate Aggregate Risk Assessment for Intermediate-Term Exposure to Iodosulfuron-Methyl-Sodium and
                                               Metsulfuron- Methyl
----------------------------------------------------------------------------------------------------------------
                                                             Aggregate
                                                Aggregate     level of     Surface       Ground    Intermediate-
             Population subgroup               MOE (Food +    concern     water EEC    water EEC     term DWLOC
                                              residential)     (LOC)        (ppb)        (ppb)         (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population--all                               1.1e+04        1,000        0.338        0.105       2.6e+02
-------------------------------------------------------------------------
All infants (<1 year old)                          9.6e+03        1,000        0.338        0.105       7.3e+01
-------------------------------------------------------------------------

[[Page 57530]]

 
Children (1-6 years old)                           3.9e+03        1,000        0.338        0.105       6.0e+01
-------------------------------------------------------------------------
Children (7-12 years old)                          6.6e+03        1,000        0.338        0.105       6.9e+01
-------------------------------------------------------------------------
Females (13-50 years old)                          1.7e+04        1,000        0.338        0.105       2.3e+02
-------------------------------------------------------------------------
Males (13-19 years old)                            1.0e+04         1000        0.338        0.105       2.6e+02
-------------------------------------------------------------------------
Males (20+ years old)                              1.7e+04        1,000        0.338        0.105       2.7e+02
-------------------------------------------------------------------------
Seniors (55+ years old)                            2.0e+04        1,000        0.338        0.105       2.7e+02
----------------------------------------------------------------------------------------------------------------

    5. Aggregate cancer risk for U.S. population. Given the available 
data, it is likely that iodosulfuron-methyl-sodium does not pose a 
cancer risk to humans. To date, cancer studies have proven negative and 
metsulfuron-methyl is classified as Group E (not likely human 
carcinogen) by Agency. Other registered sulfonyl urea compounds have 
also been found to be non-carcinogenic. There is some uncertainty here, 
however, due to the failure to test at a high enough dose in the mouse 
study. Nonetheless, given the following considerations, even assuming 
that the requested cancer study showed that iodosulfuron-methyl-sodium 
has some carcinogenic potential, EPA concludes that the cancer risk 
from exposure to iodosulfuron-methyl-sodium is negligible. First, 
cancer testing at relatively high doses has already had negative 
results, so the new study, at worst, could show iodosulfuron-methyl-
sodium to be a relatively weak carcinogen. Second, human exposure to 
iodosulfuron-methyl-sodium is expected to be basically non-existent. 
Field corn will be the only registered use, and field corn is only 
consumed by animals not humans. Studies have shown that there is no 
reasonable expectation that finite residues of iodosulfuron-methyl-
sodium will occur in livestock commodities as a result of livestock 
consuming iodosulfuron-methyl-sodium -treated corn. Finally, there are 
no residential uses for iodosulfuron-methyl-sodium.
    6. 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 iodosulfuron-methyl-sodium and metsulfuron-methyl residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    The analytical methods used to analyze the storage stability, field 
trial, and processing samples were adequately validated and are 
appropriate for data gathering purposes. The proposed tolerance 
enforcement method has been adequately validated by an independent 
laboratory and was forwarded to the Analytical Chemistry Laboratory 
(ACL) for petition method validation (PMV). The ACL concludes that this 
method using HPLC/MS, in general, meets the requirements for a residue 
analytical method for tolerance enforcement as defined in the Residue 
Chemistry Test Guidelines, 860.1340. The petitioner submitted data 
which indicated that iodosulfuron-methyl-sodium and metsulfuron-methyl 
are not adequately recovered when using FDA multiresidue method 
protocols. This information has been forwarded to the FDA.

B. International Residue Limits

    There is neither a Codex proposal, nor Canadian or Mexican limits, 
for residues of iodosulfuron-methyl-sodium in/on field corn. 
Harmonization is not an issue for this petition.

C. Conditions

    EPA is able to successfully validate the proposed field corn 
enforcement method and concludes that the toxicological, residue 
chemistry, and occupational/residential databases are sufficient for a 
conditional field corn registration. The following data are being 
required to confirm the results of the studies already reviewed by the 
Agency and/or to complete the database requirements prior to approval 
of an unconditional registration of iodosulfuron-methyl-sodium:
    i. Acute Neurotoxicity Study--to confirm the clinical signs of 
neurotoxicity.
    ii. 28-Day Inhalation Toxicity Study - for further characterization 
of inhalation hazard for risk assessment; the protocol for the existing 
90-day inhalation toxicity study (OPPTS 870.3465) should be followed 
with the exposure (treatment) ending after 28 days, instead of 90 days.
    iii. 21-Day Dermal Toxicity Study
    iv. Developmental Toxicity Study in Rabbits
    v. Carcinogenicity Study in Mice

V. Conclusion

    Therefore, the tolerance is established for residues of 
iodosulfuron-methyl-sodium, methyl 4-iodo-2-[3-(4-methoxy-6-methyl-
1,3,5 triazin-2-yl)ureidosulfonyl]benzoate, sodium salt, in or on corn, 
field, grain at 0.03 ppm; corn, field, forage at 0.05 ppm; and corn, 
field, stover at 0.05 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.

[[Page 57531]]

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 control number OPP-2002-0141 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 November 
12, 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 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.
    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-2002-0141 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: [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. 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). \1\This rule, 
however, has been repealed. 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

[[Page 57532]]

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: September 3, 2002.
James Jones,
Acting Director, 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 180.580 is added to read as follows:


Sec.  180.580  Iodosulfuron-Methyl-Sodium; tolerances for residues.

    (a) General. Tolerances are established for residues of the 
herbicide Iodosulfuron-Methyl-Sodium (methyl 4-iodo-2-[3-(4-methoxy-6-
methyl-1,3,5 triazin-2-yl)ureidosulfonyl]benzoate, sodium salt) in or 
on the following commodities:

------------------------------------------------------------------------
                 Commodity                        Parts per million
------------------------------------------------------------------------
Corn, field, forage.......................  0.05
Corn, field, grain........................  0.03
Corn, field, stover.......................  0.05
------------------------------------------------------------------------

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

[FR Doc. 02-23086 Filed 9-10-02; 8:45 am]
BILLING CODE 6560-50-S