[Federal Register Volume 69, Number 67 (Wednesday, April 7, 2004)]
[Rules and Regulations]
[Pages 18263-18275]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-7864]


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

ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[OPP-2003-0296; FRL-7339-4]


Fosthiazate; Pesticide Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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

SUMMARY: This regulation establishes a tolerance for combined residues 
of

[[Page 18264]]

fosthiazate (O-ethyl S-(1-methylpropyl)(2-oxo-3-
thiazolidinyl)phosphonothioate and its metabolite O-ethyl S-(1-
methylpropyl)[2-(methylsulfonyl)ethyl] phosphoramidothioate (ASC-67131) 
in or on tomato. ISK Biosciences requested this tolerance under the 
Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Food 
Quality Protection Act of 1996 (FQPA). This tolerance will support the 
use of fosthiazate on tomatoes as a replacement for methyl bromide for 
the control of nematodes.

DATES: This regulation is effective April 7, 2004. Objections and 
requests for hearings, identified by docket ID number OPP-2003-0296, 
must be received on or before June 7, 2004.

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

FOR FURTHER INFORMATION CONTACT: Rita Kumar, Registration Division 
(7505C), Office of Pesticide Programs, Environmental Protection Agency, 
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone 
number: (703) 308-8291; e-mail address: [email protected].

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this Action Apply to Me?

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

B. How Can I Get Copies of this Document and Other Related Information?

    1. Docket. EPA has established an official public docket for this 
action under docket identification (ID) number OPP-2003-0296. The 
official public docket consists of the documents specifically 
referenced in this action, any public comments received, and other 
information related to this action. Although a part of the official 
docket, the public docket does not include Confidential Business 
Information (CBI) or other information whose disclosure is restricted 
by statute. The official public docket is the collection of materials 
that is available for public viewing at the Public Information and 
Records Integrity Branch (PIRIB), Rm. 119, Crystal Mall 2, 
1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open 
from 8:30 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The docket telephone number is (703) 305-5805.
    2. Electronic access. You may access this Federal Register document 
electronically through the EPA Internet under the ``Federal Register'' 
listings at http://www.epa.gov/fedrgstr/. A frequently updated 
electronic version of 40 CFR part 180 is available at http://www.access.gpo.gov/nara/cfr/cfrhtml_00/Title_40/40cfr180_00.html, a 
beta site currently under development. To access the OPPTS Harmonized 
Guidelines referenced in this document, go directly to the guidelines 
at http://www.epa.gov/opptsfrs/home/guidelin.htm.
    An electronic version of the public docket is available through 
EPA's electronic public docket and comment system, EPA Dockets. You may 
use EPA Dockets at http://www.epa.gov/edocket/ to submit or view public 
comments, access the index listing of the contents of the official 
public docket, and to access those documents in the public docket that 
are available electronically. Although not all docket materials may be 
available electronically, you may still access any of the publicly 
available docket materials through the docket facility identified in 
Unit I.B.1. Once in the system, select ``search,'' then key in the 
appropriate docket ID number.

II. Background and Statutory Findings

    In the Federal Register of November 21 2001 (66 FR 58477) (FRL-
6799-1), 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 a pesticide petition (PP 6F4662) by ISK Biosciences 
Corporation, 7470 Auburn Road, Suite A, Concord, OH 44077. That notice 
included a summary of the petition prepared by ISK Biosciences, the 
registrant. There were no comments received in response to the notice 
of filing.
    The petition requested that 40 CFR part 180 be amended by 
establishing a tolerance for combined residues of the insecticide 
fosthiazate, (O-ethyl S-(1-methylpropyl)(2-oxo-3-
thiazolidinyl)phosphonothioate) and its metabolite ASC-67131 (O-ethyl 
S-(1-methylpropyl)[2-(methylsulfonyl)ethyl] phosphoramidothioate), in 
or on tomatoes at 0.02 parts per million (ppm). Fosthiazate is a new 
organophosphate (OP) active ingredient (a.i.), that controls a broad 
spectrum of nematode species. It may be applied through drip (trickle) 
irrigation systems, as a band application under plastic mulch. 
Application is made once per season, either prior to or at planting/
transplanting of tomatoes. The United States Department of 
Agriculture's Interregional Research Project No. 4 has identified 
fosthiazate as a viable alternative to the use of methyl bromide for 
control of nematodes infesting tomato fields. Methyl bromide has been 
identified as a chemical that depletes the earth's ozone layer, and 
thus its use is being phased out. The United States is in the process 
of implementing a methyl bromide use reduction strategy leading to a 
complete ban for soil fumigation uses by the year 2005. Fosthiazate 
will provide growers with a pest management tool for use against 
nematode pest pressure.
    Section 408(b)(2)(A)(i) of the FFDCA allows EPA to establish a 
tolerance (the legal limit for a pesticide chemical residue in or on a 
food) only if EPA determines that the tolerance is ``safe.'' Section 
408(b)(2)(A)(ii) of the FFDCA defines ``safe'' to mean that ``there is 
a reasonable certainty that no harm will result from aggregate exposure 
to the pesticide chemical residue, including all anticipated dietary 
exposures and all other exposures for which there is reliable 
information.'' This includes exposure through drinking water and in 
residential settings, but does not include occupational exposure. 
Section 408(b)(2)(C) of the FFDCA requires EPA to give special 
consideration to 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

[[Page 18265]]

further discussion of the regulatory requirements of section 408 of the 
FFDCA and a complete description of the risk assessment process, see 
the final rule on Bifenthrin Pesticide Tolerances (62 FR 62961, 
November 26, 1997) (FRL-5754-7).

III. Aggregate Risk Assessment and Determination of Safety

    Consistent with section 408(b)(2)(D) of the FFDCA, EPA has reviewed 
the available scientific data and other relevant information in support 
of this action. EPA has sufficient data to assess the hazards of and to 
make a determination on aggregate exposure, consistent with section 
408(b)(2) of the FFDCA, for a tolerance for combined residues of the 
insecticide fosthiazate, (O-ethyl S-(1-methylpropyl)(2-oxo-3-
thiazolidinyl)phosphonothioate) and its metabolite ASC-67131 (O-ethyl 
S-(1-methylpropyl)[2-(methylsulfonyl)ethyl] phosphoramidothioate) on 
tomatoes at 0.02 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 fosthiazate are 
discussed in Table 1 of this unit as well as the no observed adverse 
effect level (NOAEL) and the lowest observed adverse effect level 
(LOAEL) from the toxicity studies reviewed.

                                Table 1.--Subchronic, Chronic, and Other Toxicity
----------------------------------------------------------------------------------------------------------------
             Guideline No.                       Study Type                            Results
----------------------------------------------------------------------------------------------------------------
870.3100                                 13-Week feeding study-rat   Systemic Toxicity LOAEL: 0.08 and 0.09 mg/
                                                                      kg/day for males and females,
                                                                      respectively, based on microscopic lesions
                                                                      in the adrenals (males) and increased ALT
                                                                      (females) levels. No NOAEL was
                                                                      established. At higher doses, the severity
                                                                      of vacuolation of cells in zona
                                                                      fasciculata (=1.07 ppm) and
                                                                      zona glomerulosa (=53.6 ppm) of
                                                                      the adrenals increased in a dose-dependent
                                                                      manner; at =53.6 ppm, the brain
                                                                      cholinesterase inhibition (ChEI) was also
                                                                      noted. In addition, there was increase in
                                                                      adrenal gland weight at 429 ppm
                                                                     LOAEL for ChEI: 10.7 ppm (0.77 and 0.89 mg/
                                                                      kg/day for males and females,
                                                                      respectively) based on plasma and RBC
                                                                      ChEI.
                                                                     NOAEL: 1.07 ppm (0.08 and 0.09 mg/kg/day
                                                                      for males and females, respectively)
----------------------------------------------------------------------------------------------------------------
--                                       4-Week range-finding        Systemic LOAEL: 400 ppm (equivalent to
                                          feeding study-rat           40.87 mg/kg/day in males and 43.52 mg/kg/
                                                                      day in females) based on fur loss, muscle
                                                                      tremor, enlarged pale spongiocytes in the
                                                                      adrenals, increased adrenal weights, and
                                                                      increased alkaline phosphatase and alanine
                                                                      aminotransferase levels.
                                                                     Systemic NOAEL: 100 ppm (equivalent to 9.69
                                                                      mg/kg/day in males and 10.67 mg/kg/day in
                                                                      females)
                                                                     LOAEL for ChEI: 5 ppm (equivalent to 0.48
                                                                      mg/kg/day in males and 0.5 mg/kg/day in
                                                                      females) based on decreased plasma butyryl-
                                                                       and acetyl-cholinesterase, and brain
                                                                      acetyl-cholinesterase in females, and
                                                                      erythrocyte acetyl-cholinesterase in males
                                                                     NOAEL: 1 ppm (equivalent to 0.10 mg/kg/day
                                                                      in males and females
----------------------------------------------------------------------------------------------------------------
--                                       28-Day feeding study-rat    NOAEL: 1,000 mg/kg/day, the highest dose
                                          with 2-butanesulfonic       tested.
                                          acid (BSA)
----------------------------------------------------------------------------------------------------------------
--                                       4-Week range-finding        LOAEL: 400 ppm (males: 68.99 and females:
                                          feeding study-mice          82.38 mg/kg/day) based on increased
                                                                      tubular basophilia in the kidney
                                                                     NOAEL: 100 ppm (equivalent to 17.59 mg/kg/
                                                                      day in males and 21.43 mg/kg/day in
                                                                      females)
----------------------------------------------------------------------------------------------------------------
870.3150                                 13-Weeks subchronic         Systemic Toxicity
                                          toxicity-dog               LOAEL: 0.11 mg/kg/day, based on
                                                                      histopathological changes in the adrenal
                                                                      glands
                                                                     NOAEL: 0.054 mg/kg/day
                                                                     LOAEL for plasma ChEI: 0.11 mg/kg/day in
                                                                      females and 0.54 mg/kg/day in males
                                                                     NOAEL: 0.054 mg/kg/day in females and 0.11
                                                                      mg/kg/day in males.
----------------------------------------------------------------------------------------------------------------

[[Page 18266]]

 
870.3200                                 21-Day repeated dermal      Systemic LOAEL: 250 mg/kg/day for males and
                                          toxicity-rat                females based on mortality, clinical signs
                                                                      (emaciation, torpor lethargy or dullness,
                                                                      tremor, hunched posture, hypothermia,
                                                                      gasping, hypersensitivity to noise, pallor
                                                                      paleness, tachypnea labored breathing, and
                                                                      piloerection), decreased body weight
                                                                      gains, and histopathology of the adrenal
                                                                      cortex observed in both sexes; increased
                                                                      food conversion factor and hematology
                                                                      findings were observed in males only
                                                                     Systemic NOAEL: 25 mg/kg/day
                                                                     LOAEL for ChEI: 25 mg/kg/day in males and
                                                                      2.5 mg/kg/day in females based on
                                                                      inhibition of plasma, erythrocyte, and
                                                                      brain cholinesterase (ChE) in both sexes
                                                                     NOAEL for ChEI: 2.5 mg/kg/day in males and
                                                                      0.5 mg/kg/day in females
----------------------------------------------------------------------------------------------------------------
870.3700                                 Developmental toxicity-rat  Maternal Toxicity
                                                                     LOAEL = 10 mg/kg/day, based on reduced body
                                                                      weight gain
                                                                     NOAEL = 5 mg/kg/day
                                                                     Developmental Toxicity
                                                                     LOAEL = Not determined
                                                                     NOAEL = 10 mg/kg/day
                                                                     Although data were not provided on clinical
                                                                      signs in the dams during or after dosing
                                                                      no cholinergic signs were seen in
                                                                      neurotoxicity studies at the same dose.
                                                                      Therefore, the study classification is
                                                                      upgraded to acceptable/guideline
----------------------------------------------------------------------------------------------------------------
870.3700                                 Developmental toxicity-     Maternal
                                          rabbit                     LOAEL: 2 mg/kg/day based on weight loss,
                                                                      abortion, and cholinergic clinical signs
                                                                      noted in the range finding study (MRID
                                                                      41381110)
                                                                     NOAEL: 1.5 mg/kg/day.
                                                                     Developmental toxicity
                                                                     LOAEL: Not determined
                                                                     NOAEL: 2 mg/kg/day
                                                                     No developmental toxicity was observed at
                                                                      any dose tested in the definitive prenatal
                                                                      developmental toxicity study. No
                                                                      developmental toxicity was observed at
                                                                      doses up to 2.5 mg/kg in a range-finding
                                                                      study
----------------------------------------------------------------------------------------------------------------
870.3800                                 2-Generation reproduction-  Parental Toxicity
                                          rat                        LOAEL = 100 ppm (equivalent to 9.32 and
                                                                      7.21 mg/kg/day in females, and males,
                                                                      respectively) based on increased
                                                                      incidences of adrenal zona glomerulosa
                                                                      hypertrophy, centriacinar hepatocytic
                                                                      vacuolation and liver inflammation in F0
                                                                      females and periacinar hepatocytic
                                                                      hypertrophy in F0 males
                                                                     NOAEL: 30 ppm (equivalent to 2.6 and 2.09
                                                                      mg/kg/day) in females and males,
                                                                      respectively). in F0 females and in males
                                                                     Reproductive Toxicity
                                                                     LOAEL = >100 ppm
                                                                     NOAEL = 100 ppm
                                                                     Offspring Toxicity
                                                                     LOAEL = 30 ppm based on decreased litter
                                                                      size and decreased pup weight and
                                                                      viability index during lactation
                                                                     NOAEL = 10 ppm
----------------------------------------------------------------------------------------------------------------
870.4100                                 1-Year chronic oral         Systemic LOAEL: 0.5 mg/kg/day in males
                                          toxicity-dog                based on increased alanine
                                                                      aminotransferase and 5 mg/kg/day in
                                                                      females based on microscopic lesions in
                                                                      the adrenal gland
                                                                     NOAEL: 0.1 mg/kg/day in males and 0.5 mg/kg/
                                                                      day in females
                                                                     LOAEL for ChEI: 0.5 mg/kg/day based on
                                                                      plasma acetyl- and butyryl-cholinesterase
                                                                      activity in males/females
                                                                     NOAEL: 0.1 mg/kg/day based on plasma acetyl-
                                                                       and butyryl-cholinesterase activity
                                                                     The erythrocyte and brain ChE activity
                                                                      LOAELs were not observed. The erythrocyte
                                                                      and brain cholinesterase NOAELs are 5 mg/
                                                                      kg/day
----------------------------------------------------------------------------------------------------------------

[[Page 18267]]

 
870.4200                                 Carcinogenicity-mouse       Systemic LOAEL: 10.43 mg/kg/day (100 ppm)
                                                                      for females, based on increased adrenal
                                                                      cortico-medullary pigmentation and 30.51
                                                                      mg/kg/day (300 ppm) for males, based on
                                                                      decreased body weights and non-neoplastic
                                                                      lesions in the adrenals, pituitary and
                                                                      kidney. At 300 ppm, increase in
                                                                      cholinergic signs (ataxia, hunched
                                                                      posture, tremors) was observed
                                                                     NOAEL: 3.20 mg/kg/day (30 ppm) and 10.32 mg/
                                                                      kg/day (100 ppm) for females and males,
                                                                      respectively. The test material was not
                                                                      carcinogenic at the doses tested
----------------------------------------------------------------------------------------------------------------
870.4300                                 Combined chronic/           Systemic
                                          carcinogenicity-rat        LOAEL: 50 ppm (2.45 mg/kg/day) for females,
                                                                      based on decreased RBC parameters (packed
                                                                      cell volume, hemoglobin, and RBC count),
                                                                      and increased incidence of atrophy and
                                                                      foamy interstitial cells in the ovaries
                                                                      and 200 ppm (8.34 mg/kg/day) for males,
                                                                      based on increased incidences of retinal
                                                                      atrophy, skeletal degenerative myopathy
                                                                      and non-neoplastic lesions in the adrenal
                                                                      and pituitary glands
                                                                     NOAEL: 10 ppm (0.50 mg/kg/day) and 50 ppm
                                                                      (1.94 mg/kg/day) for female and male rats,
                                                                      respectively. The test material was not
                                                                      carcinogenic at the doses tested
                                                                     LOAEL for ChEI: 10 ppm for male rats (0.38
                                                                      mg/kg/day) and 1 ppm for female rats
                                                                      (0.051 mg/kg/day) based on inhibition of
                                                                      plasma and RBC ChE activity
                                                                     NOAEL: 1 ppm for male rats (0.039 mg/kg/
                                                                      day) and a NOAEL was not established for
                                                                      female rats
----------------------------------------------------------------------------------------------------------------
870.5100                                 Gene mutation salmonella/   Negative in salmonella strains with or
                                          mammalian activation gene   without S-9 activation. No cytotoxicity
                                          mutation assay with BSA     response up to the limit dose
----------------------------------------------------------------------------------------------------------------
870.5265                                 Gene mutation salmonella/   Negative for mutagenic effects at dose
                                          mammalian activation gene   levels up to 5,000 [mu]g/plate with or
                                          mutation assay              without metabolic activation
----------------------------------------------------------------------------------------------------------------
870.5300                                 In vitro gene mutation-     No evidence of increased mutation frequency
                                          mouse lymphoma assay        at the thymidine locus in cells treated
                                                                      upto cytotoxic concentration with or
                                                                      without S-9. Cytotoxicity was evident at
                                                                      =640 [mu]g/ml (-S9) and =160 [mu]g/mL (+S9)
----------------------------------------------------------------------------------------------------------------
870.5300                                 In vitro mammalian gene     No evidence of increased mutation frequency
                                          mutation - mouse lymphoma   in cells treated up to the limit dose with
                                          assay with BSA              or without S-9
----------------------------------------------------------------------------------------------------------------
 870.5375                                In vitro cytogenetics       No effects at concentrations up to 200
                                          (CHO) assay                 [mu]g/ml (without S9) or 750 [mu]g/mL
                                                                      (with S9). Cytotoxicity was evident at =50 [mu]g/mL (-S9)and =93.75 [mu]g/mL (+S9)
----------------------------------------------------------------------------------------------------------------
870.5395                                 In vivo mammalian           No evidence of clastogenic or aneugenic
                                          cytogenetics assay          effect at doses tested. Negative for
                                                                      induction of micronuclei at a dose
                                                                      approaching oral MTD, 50 mg/kg
----------------------------------------------------------------------------------------------------------------
870.5395                                 In vivo mammalian           No evidence of clastogenic or aneugenic
                                          cytogenetics micronucleus   effect at doses tested. Negative for
                                          assay with BSA              induction of micronuclei
----------------------------------------------------------------------------------------------------------------
870.5500                                 In vitro DNA repair test    Negative in the DNA repair test.
                                                                      Fosthiazate did not induce any clear
                                                                      differences in the diameter of growth
                                                                      inhibitory zones between H17 (rec+) and M
                                                                      45 (rec-), either in the presence or
                                                                      absence of metabolic activation
----------------------------------------------------------------------------------------------------------------
870.6100                                 Acute delayed               Six hens treated with IKI-1145 (fosthiazate
                                          neurotoxicity (ADNT)        technical) died within 6 days; 2 had
                                          study-hen                   relapses and progressed to moribundity on
                                                                      days 13 and 26; 9 hens survived. No
                                                                      abnormal neuropathological changes were
                                                                      observed except for a minimal case of
                                                                      focal gliosis in the lumbar sacral area of
                                                                      one of the two relapsing hens. IKI-1145
                                                                      did not cause ADNT
----------------------------------------------------------------------------------------------------------------

[[Page 18268]]

 
870.6200                                 Acute neurotoxicity         Neurotoxicity
                                          screening battery          LOAEL: 10 mg/kg/day based on decreased
                                                                      forelimb grip strength in females. No
                                                                      abnormal neuropathological changes were
                                                                      observed
                                                                     NOAEL: 0.4 mg/kg/day
                                                                     LOAEL for ChEI: 10 mg/kg/day based on
                                                                      inhibition of plasma. Erythrocyte, and
                                                                      brain 3 hrs postdosing (plasma ChEI was
                                                                      reversible)
                                                                     NOAEL: 0.4 mg/kg/day
----------------------------------------------------------------------------------------------------------------
--                                       Special cholinesterase      LOAEL: 4.0 mg/kg/day based on plasma ChEI
                                          inhibition study-rat       NOAEL: 0.4 mg/kg/day
                                                                     Decrease plasma ChE activity was noted in
                                                                      the male and female rats 3 hours after a
                                                                      single dose at 4.0 mg/kg body weight.
                                                                      Brain and RBC ChE activities were
                                                                      unaffected
----------------------------------------------------------------------------------------------------------------
870.6200                                 Subchronic neurotoxicity    Systemic
                                          screening battery           LOAEL: 2.5 mg/kg/day based on decreased
                                                                      hind limb grip strength (21%; p<0.01) in
                                                                      females. No abnormal neuropathological
                                                                      changes were observed
                                                                     NOAEL: 0.5 mg/kg/day.
                                                                     LOAEL for ChEI: 0.5 mg/kg/day based on
                                                                      significant inhibition of plasma,
                                                                      erythrocyte and brain ChE in females at
                                                                      weeks 5 and/or 9 and 14
                                                                     NOAEL: 0.05 mg/kg/day
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism-rat              IKI-1145 (fosthiazate technical) was
                                                                      rapidly absorbed and widely distributed
                                                                      with only >5% detected in the tissues. No
                                                                      sex-related differences noted in the
                                                                      absorption and distribution; absorption
                                                                      was not dose dependent. Peak concentration
                                                                      in the blood was at 0.33 hr in both sexes.
                                                                      Only one metabolite, BESxP, represented
                                                                      >10% of the administered dose. Test
                                                                      material was rapidly eliminated primarily
                                                                      in the urine (57%-72%) within 24 hrs.
                                                                      Unacceptable/Guideline due to lack of
                                                                      identification of metabolites in fecal
                                                                      radioactivity (accounted for 9-15% of the
                                                                      administered dose). Mean recovery was 95%-
                                                                      99%. IKI-1145 was metabolized by multiple
                                                                      processes including hydrolysis, oxidation,
                                                                      methylation and glutathione conjugation
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism-rat              IKI-1145 was rapidly and extensively
                                                                      absorbed independent of dose; rapidly
                                                                      metabolized and excreted in the urine
                                                                      (>65%), expired air (>10%) and in feces
                                                                      (<9%). Elimination was biphasic with first
                                                                      phase elimination half-life (t1/2) of 5-6
                                                                      hrs and second phase of 85-112 hrs.
                                                                      Metabolism and excretion was rapid within
                                                                      24 hrs. IKI-1145 was metabolized by
                                                                      multiple processes including hydrolysis,
                                                                      oxidation, methylation and glutathione
                                                                      conjugation. Female rats tended to excrete
                                                                      a metabolite containing a
                                                                      methylsulfinylethyl group while male rats
                                                                      excreted more containing a sulfoethyl
                                                                      group
----------------------------------------------------------------------------------------------------------------
870.7485                                 Metabolism-rat with BSA     Recovery was 100-108%. BSA was rapidly
                                                                      eliminated unchanged following dosing via
                                                                      the iv (approx. 100% in the urine) or oral
                                                                      (63%-89% in the urine and 10%-28% in
                                                                      feces) routes. Tissue burden was low
----------------------------------------------------------------------------------------------------------------

B. Toxicological Endpoints

    The dose at which no adverse effects are observed (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 intraspecies differences. Based on 
the weight of evidence presented, the Agency concluded that a 
developmental neurotoxicity (DNT) study with comparative cholinestrase 
(ChE) measurements in adults and pups is required for fosthiazate. The 
available data base confirms that fosthiazate is a ChE inhibitor and 
the increased sensitivity for this effect cannot be confirmed until the 
results of DNT study are known. Based on the lack of a DNT study, the 
Agency also concluded that a Database Uncertainty Factor (UFdb) is 
necessary. The available data suggest that results of a DNT study, as 
well as additional ChE data, could potentially impact the doses 
selected for risk assessment. Therefore, a 10X UFdb is required for 
acute dietary risk assessment and a 3X UFdb is required for chronic 
dietary risk assessment. Refer to Unit III.D.3 of this document for a 
detailed discussion of these uncertainty factors.
    For dietary risk assessment (other than cancer) the Agency uses 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 (SF) is retained 
due to concerns unique to the FQPA, this additional factor is applied 
to the RfD by dividing the RfD by such additional factor. The acute or

[[Page 18269]]

chronic Population Adjusted Dose (aPAD or cPAD) is a modification of 
the RfD to accommodate this type of FQPA SF.
    For non-dietary risk assessments (other than cancer) the UF is used 
to determine the LOC. For example, when 100 is the appropriate UF (10X 
to account for interspecies differences and 10X for intraspecies 
differences) the LOC is 100. To estimate risk, a ratio of the NOAEL to 
exposures (margin of exposure (MOE) = NOAEL/exposure) is calculated and 
compared to the LOC.
    The linear default risk methodology (Q*) is the primary method 
currently used by the Agency to quantify carcinogenic risk. The Q* 
approach assumes that any amount of exposure will lead to some degree 
of cancer risk. A Q* is calculated and used to estimate risk which 
represents a probability of occurrence of additional cancer cases 
(e.g., risk is expressed as 1 x 10-6 or one in a million). 
Under certain specific circumstances, MOE calculations will be used for 
the carcinogenic risk assessment. In this non-linear approach, a 
``point of departure'' is identified below which carcinogenic effects 
are not expected. The point of departure is typically a NOAEL based on 
an endpoint related to cancer effects though it may be a different 
value derived from the dose response curve. To estimate risk, a ratio 
of the point of departure to exposure (MOEcancer = point of 
departure/exposures) is calculated. A summary of the toxicological 
endpoints for fosthiazate used for human risk assessment is shown in 
Table 2 of this unit:

     Table 2.--Summary of Toxicological Dose and Endpoints for Fosthiazate for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
                                                                  Hazard and Exposure
          Exposure Scenario            Dose (mg/kg/day) UF/MOE     Based Special FQPA    Study and Toxicological
                                                                     Safety Factor               Effects
----------------------------------------------------------------------------------------------------------------
                                                   Dietary risk assessments
-----------------------------------------------------------------------------------------
Acute dietary (general population      NOAEL = 0.4                         1X            Acute oral
 including infants and children)       UF = 100...............                            neurotoxicity/rat
                                       UFdb* = 10.............                           LOAEL = 10 mg/kg/day
                                                                                          based on inhibition of
                                                                                          RBC ChE in males
                                                                                          within 3 hrs post
                                                                                          dosing
                                      ---------------------------------------------------
                                          Acute RfD and Acute PAD = 0.0004 mg/kg/day
-----------------------------------------------------------------------------------------
Chronic dietary                        NOAEL = 0.05                        1X            Chronic oral toxicity/
                                       UF = 100...............                            rat
                                       UFdb* = 3..............                           LOAEL= 0.38 mg/kg/day
                                                                                          based on inhibition of
                                                                                          plasma and RBC ChE in
                                                                                          males
                                      ---------------------------------------------------
                                        Chronic RfD and Chronic PAD = 0.00017 mg/kg/day
----------------------------------------------------------------------------------------------------------------
 * UFdb = database uncertainty factors of 10X and 3X are applied for lack of a DNT study and ChE data

C. Exposure Assessment

    1. Dietary exposure from food and feed uses. Currently there are no 
tolerances established for fosthiazate on any commodity. Risk 
assessments were conducted by EPA to assess dietary exposures from 
fosthiazate in food as follows:
    i. Acute exposure. Acute dietary risk assessments are performed for 
a food-use pesticide if a toxicological study has indicated the 
possibility of an effect of concern occurring as a result of a one day 
or single exposure. The Dietary Exposure Evaluation Model 
(DEEMTM) analysis evaluated the individual food consumption 
as reported by respondents in the USDA 1994-1996 and 1998 nationwide 
Continuing Surveys of Food Intake by Individuals (CSFII) and 
accumulated exposure to the chemical for each commodity. The following 
assumptions were made for the acute exposure assessments: The acute 
dietary risk assessment was based on field trial residues in tomato 
(1/89/21/13/23/85/83/8 limit of quantitation (LOQ) parent + 
1/89/21/13/23/85/83/8 LOQ ASC-67131) and 100% crop treated 
(CT). Risks of concern were considered at the 95th percentile because 
field trial data with 1.3X application rate, minimum preharvest 
interval (PHI) and 100% CT were used, which are considered conservative 
inputs. No detectable residues of either the parent or its metabolite 
of concern were found in the edible portion during these field trials 
at a limit of detection (LOD) of 0.01 ppm using gas chromatograph/flame 
photometric detector (GC/FPD) (phosphorus) as an analytical method.
    The Agency believes that the default assumption of 
1/89/21/13/23/85/83/8 LOD of the GC/FPD (phosphorus) 
analytical method for each of the parent and metabolite significantly 
exaggerates actual exposures. Radiolabeled tomato metabolism studies 
were done at a 1.3X rate and using an analytical method GC/FPD 
(phosphorus) with a much lower LOD of 0.001 ppm (an order of magnitude 
lower). No residues were found in the edible fruit following the 
radiolabel studies. This means that residues, if present, would be 
present at <0.001 ppm at this application rate. Thus, the use of 
1/89/21/13/23/85/83/8 LOD of the GC/FPD (phosphorus) 
analytical method for both parent and metabolite is a conservative 
estimate of exposure (compounded by a 100% CT assumption): Radiolabel 
metabolism studies suggest that residues are at least five times lower 
than the 1/89/21/13/23/85/83/8 LOD of the GC/FPD (phosphorus) 
analytical method assumed in the assessment, and even more if one were 
to take into account the 1.3X application rate.
    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 1994-1996 and 
1998 nationwide CSFII and accumulated exposure to the chemical for each 
commodity. The following assumptions were made for the chronic exposure 
assessments: The chronic dietary risk assessment was based on field 
trial residues in tomatoes, 100% CT, and average daily consumption 
estimates for each food/food form.
    iii. Cancer. In accordance with the EPA Draft Guidelines for 
Carcinogen Risk Assessment (July 1999), the Agency has classified 
fosthiazate as ``not likely to be carcinogenic to humans.'' This 
classification is based on the lack of evidence for carcinogenicity in 
studies with mice and rats; therefore, a quantitative cancer dietary 
assessment has not been conducted.

[[Page 18270]]

    2. Dietary exposure from drinking water. The Agency lacks 
sufficient monitoring exposure data to complete a comprehensive dietary 
exposure analysis and risk assessment for fosthiazate 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 fosthiazate.
    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 Groundwater (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 residential uses. Since 
DWLOCs address total aggregate exposure to fosthiazate, they are 
further discussed in the aggregate risk sections in Unit E.
    Based on the PRZM/EXAMS and SCI-GROW models, the EECs of 
fosthiazate for acute exposures are estimated to be 2.1 parts per 
billion (ppb) for surface water and 2.4 ppb for ground water. The EECs 
for chronic exposures are estimated to be 0.6 ppb for surface water and 
2.4 ppb for ground water. These estimates are based on the assumption 
that application will be made by drip irrigation in bands with plastic 
mulch. Runoff as a result of this use may be unlikely from the day of 
application until the day of harvest (approximately 90 days) when the 
field is covered by the plastic mulch, unless an extremely heavy amount 
of rain falls immediately after application and causes runoff from 
under the mulch into the uncovered area. For this reason, application 
is prohibited when heavy rainfall is predicted. Runoff after the 
removal of the plastic cover may be possible, however the amount of 
fosthiazate remaining in soil and available for runoff would be much 
less than the amount applied, due to chemical degradation and 
dissipation in soil and to chemical uptake into plants. Assuming that 
half of the amount applied is absorbed by plants and the remaining half 
dissipates in soil at a rate of 45 days (based on laboratory and field 
studies), it is expected that only about one eighth of what was 
originally applied would be available for runoff after the cover is 
removed (90 days postapplication). Maximum application rate is 1.5 lbs 
a.i. per acre with only one application per season. Therefore, the 
Agency predicts that the peak estimated drinking water concentrations 
(EDWC) would be roughly 2.1 [mu]g/L and the chronic EDWC would be 0.6 
[mu]g/L for the maximum application rate. These concentrations were 
modeled under the most conservative scenarios and likely exceed the 
actual level of contamination in the environment. In actual practice, 
the same plastic mulch is left in the field for rotated crops, thus 
making the EEC calculations based on the mulch being removed after 90 
days even more conservative.
    SCI-GROW assumes the pesticide is applied above ground without 
cover and the subsequent and heavy amount of water (140% of yearly 
average amount of rainfall) leaches some of the pesticide down to 
ground water. The plastic mulch cover would minimize volatilization and 
runoff, therefore increasing the amount of the chemical available for 
leaching. However, with the drip irrigation method, a small amount of 
water is slowly dripped into soils precisely where it is needed, thus 
lessening the amount of water flowing down through the soil past the 
root zone where it cannot be used by the crop. This should greatly 
reduce the potential for the chemical to reach ground water systems. 
For this reason, the Agency does not expect ground water contamination 
from the drip irrigation method under plastic mulch to exceed the 
levels calculated by the SCI-GROW model. Terrestrial field dissipation 
studies indicate no leaching of fosthiazate residues below the top (0-
15 cm) soil layer.
    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).
    Fosthiazate is not registered for use on any sites that would 
result in residential exposure.
    4. Cumulative exposure to substances with a common mechanism of 
toxicity. Section 408(b)(2)(D)(v) of the FFDCA requires that, when 
considering whether to establish, modify, or revoke a tolerance, the 
Agency consider ``available information'' concerning the cumulative 
effects of a particular pesticide's residues and ``other substances 
that have a common mechanism of toxicity.''
    Fosthiazate is an OP pesticide, and has a common mechanism of 
toxicity with other OPs. The Agency has completed a Revised Cumulative 
Risk Assessment (CRA) for OPs, which can be found on the Agency's web 
site www.epa.gov/pesticides/cumulative. This assessment examined the 
cumulative effects of exposure to the OP pesticides considering 
monitoring values for OPs in food and water, and potential residential 
exposures. The relative potency factor (RPF) for fosthiazate was 
determined using the estimated benchmark dose (BMD)10 for female brain 
ChE data from feeding toxicity studies in the rat. The BMD10 is the 
estimated dose at which ChE is inhibited 10% compared to background 
inhibition. Although fosthiazate was considered in the cumulative 
hazard and dose-response assessment, it was not included in the OP 
cumulative exposure assessment since this OP pesticide (i) is not 
monitored by the USDA's Pesticide Data Program (PDP) or other 
monitoring data sets used in the cumulative OP assessment and is not 
expected to be present in food as a result of its use on tomatoes at 
levels that would be detectable by monitoring; (ii) is not expected to 
be present in surface water or ground water to a degree that would have 
any impact on the data on drinking water residues of

[[Page 18271]]

OPs used in the cumulative risk assessment; and (iii) has no 
residential uses. Residue data are available for fosthiazate from crop 
field trials conducted with tomatoes in which maximum (label) 
application rates and minimum (label) preharvest intervals were used. 
No residues were detected in these field trials (<0.01 ppm). Thus, EPA 
concludes that there is reasonable expectation that fosthiazate 
residues would not be detected in monitoring data from use on tomato. 
Further, fosthiazate would not contribute to the total estimated 
cumulative dietary risk in the OP cumulative risk assessment since non-
detectable residues in monitoring data were considered to have a 
residue value of ``zero.'' None of the OPs in the CRA made a 
significant contribution to overall exposure via the drinking water 
pathway, and fosthiazate does not look as though it makes a significant 
exposure by the water pathway from the use on tomato because of the low 
application rate, only one application per season, application method 
of drip irrigation under plastic mulch, and no leaching of the compound 
below the top soil layer. Accordingly, after considering the cumulative 
effects of the OPs, EPA concludes that the overall cumulative risk has 
a limited bearing on this tolerance action because fosthiazate exposure 
will have no impact on the estimate of cumulative risk for OPs.

D. Safety Factor for Infants and Children

    1.In general. Section 408 of the FFDCA provides that EPA shall 
apply an additional tenfold margin of safety for infants and children 
in the case of threshold effects to account for prenatal and postnatal 
toxicity and the completeness of the data base on toxicity and exposure 
unless EPA determines that a different margin of safety will be safe 
for infants and children. Margins of safety are incorporated into EPA 
risk assessments either directly through use of a MOE analysis or 
through using uncertainty (safety) factors in calculating a dose level 
that poses no appreciable risk to humans.
    2. Prenatal and postnatal sensitivity. In a 2-generation 
reproduction study, there is qualitative and quantitative evidence of 
increased susceptibility in offspring following prenatal and postnatal 
exposure to fosthiazate since the effects on pups are considered to be 
severe and occurred at a lower dose than those on parental animals.
    Since there is evidence of increased susceptibility of the young 
following prenatal and postnatal exposure to fosthiazate in the rat 
reproduction study, the Agency performed a Degree of Concern Analysis 
to: (i) Determine the level of concern for the effects observed when 
considered in the context of all available toxicity data; and (ii) 
identify any residual uncertainties after establishing toxicity 
endpoints and traditional uncertainty factors to be used in the risk 
assessment of this chemical.
    In determining the degree of concern for these findings in the 
reproduction study, the Agency considered the overall quality of the 
study; the dose levels at which the pup effects were observed; the dose 
response of the pup effects; and the comparative severity of the 
effects seen. It was determined that there is a low degree of concern 
and no residual uncertainties for the susceptibility since: (i) The 
study was well conducted; (ii) the dose-response in the offspring is 
well characterized; (iii) clear NOAEL and LOAEL were established for 
the effects on the offspring; (iv) although the decrease in pup 
survival seen at the LOAEL is severe, this could be attributed to 
exposure to higher levels of the chemical since the mortalities 
occurred during early lactation; and (v) although cholinesterase 
activity was not measured in this study, cholinergic signs and 
cholinesterase inhibition were seen at comparable doses in other 
studies and thus could have been a cause for the pup mortality.
    3. Conclusion. The toxicological data base for fosthiazate is not 
complete and therefore, EPA has retained the FQPA safety factor, in the 
form of a UFdb, at the level of 10X for acute risk and 3X for chronic 
risk. A 28-day inhalation study in rats is required, in order to better 
characterize exposure via the inhalation route. A DNT study in rats 
with comparative ChE measurements in adults and pups is also required, 
and is currently being conducted by the registrant. The available data 
base confirms that fosthiazate is a ChE inhibitor and the increased 
sensitivity for this effect cannot be confirmed until the results of a 
DNT study are known.
    A FQPA safety factor, in the form of a Ufdb, was retained because 
the available data suggest that results of a DNT study could 
potentially impact the doses selected for risk assessment. ChEI has 
been shown to be the most sensitive endpoint for fosthiazate in adults; 
it can also be assumed that ChEI may potentially be the most sensitive 
endpoint for pups. The regulatory dose level for acute dietary risk 
assessment is the NOAEL of 0.4 mg/kg/day selected from the acute 
neurotoxicity study in adult rats. The regulatory dose level for 
chronic dietary risk assessment is the NOAEL of 0.05 mg/kg/day from the 
2-year chronic/carcinogenicity toxicity study in rats. The dose levels 
in the reproductive toxicity study are estimated to be 0, 0.21, 0.69, 
2.09, and 7.21 mg/kg/day. The offspring NOAEL and LOAEL are 0.69 mg/kg/
day and 2.09 mg/kg/day, respectively, based on decreased pup weight, 
viability index, and litter size in the F1 pups.
    It can be assumed that doses used in a DNT study may be similar to 
those used in the reproductive toxicity study. Although it is not 
likely given the effects seen to date in the fosthiazate data base, the 
results from the DNT may show severe effects at the lowest dose tested 
(estimated at 0.21 mg/kg/day). In such circumstances, EPA may impose up 
to a 10X safety factor to project a NOAEL for the DNT which would mean 
a projected NOAEL of 0.02 mg/kg/day. Thus, the DNT may result in an 
acute ChE NOAEL for pups that is greater than 10X lower than the 
established offspring NOAEL of 0.69 mg/kg/day and the NOAEL of 0.4 mg/
kg/day currently used for establishing the acute RfD. Given that the 
DNT could impact the level chosen for estimating the acute RfD by 10X 
or greater, EPA concludes that reliable data do not support removing 
the 10X children's safety factor and thus have retained that factor in 
the form of a 10X UFdb for acute dietary risk assessment.
    As to the chronic RfD, the projected multi-dosing ChE NOAEL for 
pups from the DNT may be lower than the established chronic ChE NOAEL 
of 0.05 mg/kg/day from the 2-year chronic/carcinogenicity study and 
could be as low as 0.02 mg/kg/day (i.e., 10X lower than the lowest dose 
in the reproductive toxicity study). Although the DNT may possibly 
impact the level chosen for estimating the chronic RfD, there is 
reliable data supporting use of a 3X additional factor for chronic 
dietary risk assessment, because, the 0.05 mg/kg/day NOAEL currently 
used for risk assessment is approximately 3X higher than the potential 
lower NOAEL (0.02 mg/kg/day) that could be attained in the DNT. 
Therefore, EPA has chosen a 3X safety factor for the protection of 
infants and children, in the form of a 3X UFdb for chronic dietary risk 
assessment.
    In absence of the 28-day inhalation study, the Agency is assuming 
100% absorption for the route to route extrapolation. As the Acute 
Toxicity Category for the oral route is II and the Acute Toxicity 
Category for the inhalation route is III, it is unlikely that an 
inhalation NOAEL would be lower than the oral NOAEL being used 
currently. However, in order to better characterize exposure via the 
inhalation

[[Page 18272]]

route specifically, this study would provide information on portal of 
entry effects specific to the nasal passages and pulmonary tract.
    The dietary food exposure assessment is conservative, using field 
trial level residues and assuming 100% CT. Dietary drinking water 
exposure is based on conservative modeling estimates and there are no 
residential uses. These assessments will not underestimate the exposure 
and risks posed by fosthiazate.

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 USEPA Office of Water are used to calculate 
DWLOCs: 2 liter (L)/70 kg (adult male), 2L/60 kg (adult female), and 
1L/10 kg (child). Default body weights and drinking water consumption 
values vary on an individual basis. This variation will be taken into 
account in more refined screening-level and quantitative drinking water 
exposure assessments. Different populations will have different DWLOCs. 
Generally, a DWLOC is calculated for each type of risk assessment used: 
Acute, short-term, intermediate-term, chronic, and cancer.
    When EECs for surface water and 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. Using the exposure assumptions discussed in this 
unit for acute exposure, the acute dietary exposure from food to 
fosthiazate will occupy 12% of the aPAD for the U.S. population, 10% of 
the aPAD for females 13-49 years of age, 11% of the aPAD for all 
infants <1 year of age and 29% of the aPAD for children 1-2 years of 
age. In addition, there is potential for acute dietary exposure to 
fosthiazate in drinking water. After calculating DWLOCs and comparing 
them to the EECs for surface water and ground water, EPA does not 
expect the aggregate exposure to exceed 100% of the aPAD, as shown in 
Table 3 of this unit:

                      Table 3.--Aggregate Risk Assessment for Acute Exposure to Fosthiazate
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                 aPAD (mg/      % aPAD     Water EEC    Water EEC   Acute DWLOC
                                                     kg)         (Food)       (ppb)        (ppb)        (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                       0.0004           12          2.1          2.4           12
----------------------------------------------------------------------------------------
Infants (<1 year)                                     0.0004           11          2.1          2.4            4
----------------------------------------------------------------------------------------
Children (1-2 years)                                  0.0004           29          2.1          2.4            3
----------------------------------------------------------------------------------------
Females (13-49 years)                                 0.0004           10          2.1          2.4           11
----------------------------------------------------------------------------------------------------------------

    2. Chronic risk. Using the exposure assumptions described in this 
unit for chronic exposure, EPA has concluded that exposure to 
fosthiazate from food will utilize 7% of the cPAD for the U.S. 
population; 4% of the cPAD for all infants <1 year; 15% of the cPAD for 
children 1-2 years; and 6% of the cPAD for females 13-49 years. There 
are no residential uses for fosthiazate that result in chronic 
residential exposure to fosthiazate. In addition, there is potential 
for chronic dietary exposure to fosthiazate in drinking water. After 
calculating DWLOCs and comparing them to the EECs for surface water and 
ground water, it is noted that the DWLOCs are slightly exceeded by the 
estimated ground water EECs for two population subgroups. However, 
these concentrations were modeled under the most conservative scenarios 
and likely exceed the actual level of contamination in the environment. 
SCI-GROW, used to model ground water exposures, is a Tier 1 unrefined 
assessment and therefore, highly conservative. Importantly, pesticide-
specific aspects to this use of fosthiazate are likely to significantly 
exaggerate the conservativeness of the SCI-GROW estimates. SCI-GROW 
assumes the pesticide is applied above ground without cover and a 
subsequent and heavy amount of water (140% of yearly average amount of 
rainfall) leaches some of the pesticide down to ground water. However, 
with the proposed registration using the drip irrigation method, a 
small amount of water is slowly dripped into soils precisely where it 
is needed, thus lessening the amount of water containing pesticide 
residues flowing down through the soil past the root zone where it 
cannot be used by the crop. This is expected to reduce the potential 
for the chemical to reach into ground water systems, and the actual 
ground water EECs would be less than what SCI-GROW predicted. Further, 
fosthiazate is required to be applied in fields using plastic mulch 
which significantly decreases the effect of rainfall on pesticide 
leaching. Finally, terrestrial field dissipation studies submitted to 
the Agency indicate no leaching of fosthiazate residues below the top 
(0-15 cm) soil layer. Therefore, EPA does not expect the aggregate 
exposure to exceed 100% of the cPAD, as shown in Table 4 of this unit:

[[Page 18273]]



               Table 4.--Aggregate Risk Assessment for Chronic (Non-Cancer) Exposure to Fosthiazate
----------------------------------------------------------------------------------------------------------------
                                                                             Surface       Ground
              Population Subgroup                cPAD (mg/kg/    % cPAD     Water EEC    Water EEC     Chronic
                                                     day)        (Food)       (ppb)        (ppb)     DWLOC (ppb)
----------------------------------------------------------------------------------------------------------------
U.S. population                                      0.00017            7          0.6          2.4            6
----------------------------------------------------------------------------------------
Infants (< 1 year)                                   0.00017            4          0.6          2.4            2
----------------------------------------------------------------------------------------
Children (1-2 years)                                 0.00017           15          0.6          2.4            2
----------------------------------------------------------------------------------------
Females (13-49 years)                                0.00017            6          0.6          2.4            5
----------------------------------------------------------------------------------------------------------------

    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).
    Fosthiazate is not registered for use on any sites that would 
result in residential exposure. Therefore, the aggregate risk is the 
sum of the risk from food and water, which do not exceed the Agency's 
level of concern.
    4. Intermediate-term risk. Intermediate-term aggregate exposure 
takes into account residential exposure plus chronic exposure to food 
and water (considered to be a background exposure level).
    Fosthiazate is not registered for use on any sites that would 
result in residential exposure. Therefore, the aggregate risk is the 
sum of the risk from food and water, which do not exceed the Agency's 
level of concern.
    5. Aggregate cancer risk for U.S. population. Fosthiazate has been 
classified into the category ``Not likely to be carcinogenic to 
humans.'' This classification is based on the lack of evidence for 
carcinogenicity in mice and rats. Therefore, fosthiazate is not 
expected to pose a cancer risk.
    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 fosthiazate residues.

IV. Other Considerations

A. Analytical Enforcement Methodology

    Adequate enforcement methodology is available to enforce the 
tolerance expression. The method may be requested from: Chief, 
Analytical Chemistry Branch, Environmental Science Center, 701 Mapes 
Rd., Ft. Meade, MD 20755-5350; telephone number: (410) 305-2905; e-mail 
address: [email protected].

B. International Residue Limits

    There are currently no established Codex, Canadian, or Mexican 
maximum residue limits (MRLs) for residues of fosthiazate in/on plant 
or livestock commodities.

V. Conclusion

    Therefore, the tolerance is established for combined residues of 
fosthiazate, (O-ethyl S-(1-methylpropyl)(2-oxo-3-
thiazolidinyl)phosphonothioate) and its metabolite ASC-67131 ((RS)-S-
sec-Butyl O-ethyl N-[2-(methylsulfonyl)ethyl] phosphoramidothioate), in 
or on tomato at 0.02 ppm.

VI. Objections and Hearing Requests

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

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

    You must file your objection or request a hearing on this 
regulation in accordance with the instructions provided in this unit 
and in 40 CFR part 178. To ensure proper receipt by EPA, you must 
identify docket ID number OPP-2003-0296 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 June 7, 
2004.
    1. Filing the request. Your objection must specify the specific 
provisions in the regulation that you object to, and the grounds for 
the objections (40 CFR 178.25). If a hearing is requested, the 
objections must include a statement of the factual issues(s) on which a 
hearing is requested, the requestor's contentions on such issues, and a 
summary of any evidence relied upon by the objector (40 CFR 178.27). 
Information submitted in connection with an objection or hearing 
request may be claimed confidential by marking any part or all of that 
information as CBI. Information so marked will not be disclosed except 
in accordance with procedures set forth in 40 CFR part 2. A copy of the 
information that does not contain CBI must be submitted for inclusion 
in the public record. Information not marked confidential may be 
disclosed publicly by EPA without prior notice.
    Mail your written request to: Office of the Hearing Clerk (1900C), 
Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001. You may also deliver your request to the 
Office of the Hearing Clerk in Rm. 104, Crystal Mall 2, 1921 
Jefferson Davis Hwy., Arlington, VA. The Office of the Hearing Clerk is 
open from 8 a.m. to 4 p.m., Monday through Friday, excluding legal 
holidays. The telephone number for the Office of the Hearing Clerk is 
(703) 603-0061.
    2. Tolerance fee payment. If you file an objection or request a 
hearing, you must also pay the fee prescribed by 40 CFR 180.33(i) or 
request a waiver of that fee pursuant to 40 CFR 180.33(m). You must 
mail the fee to: EPA Headquarters Accounting Operations Branch, Office 
of Pesticide Programs, P.O. Box 360277M, Pittsburgh, PA 15251. Please 
identify the fee submission by labeling it ``Tolerance Petition Fees.''
    EPA is authorized to waive any fee requirement ``when in the 
judgement of the Administrator such a waiver or refund is equitable and 
not contrary to the purpose of this subsection.'' For additional 
information regarding the waiver of these fees, you may contact

[[Page 18274]]

James Tompkins by phone at (703) 305-5697, by e-mail at 
[email protected], or by mailing a request for information to Mr. 
Tompkins at Registration Division (7505C), Office of Pesticide 
Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., 
Washington, DC 20460-0001.
    If you would like to request a waiver of the tolerance objection 
fees, you must mail your request for such a waiver to: James Hollins, 
Information Resources and Services Division (7502C), Office of 
Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania 
Ave., NW., Washington, DC 20460-0001.
    3. Copies for the Docket. In addition to filing an objection or 
hearing request with the Hearing Clerk as described in Unit VI.A., you 
should also send a copy of your request to the PIRIB for its inclusion 
in the official record that is described in Unit I.B.1. Mail your 
copies, identified by docket ID number OPP-2003-0296, to: Public 
Information and Records Integrity Branch, Information Resources and 
Services Division (7502C), Office of Pesticide Programs, Environmental 
Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460-
0001. In person or by courier, bring a copy to the location of the 
PIRIB described in Unit I.B.1. You may also send an electronic copy of 
your request via e-mail to: [email protected]. Please use an ASCII 
file format and avoid the use of special characters and any form of 
encryption. Copies of electronic objections and hearing requests will 
also be accepted on disks in WordPerfect 6.1/8.0 or ASCII file format. 
Do not include any CBI in your electronic copy. You may also submit an 
electronic copy of your request at many Federal Depository Libraries.

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

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

VII. Statutory and Executive Order Reviews

    This final rule establishes a tolerance under section 408(d) of the 
FFDCA in response to a petition submitted to the Agency. The Office of 
Management and Budget (OMB) has exempted these types of actions from 
review under Executive Order 12866, entitled Regulatory Planning and 
Review (58 FR 51735, October 4, 1993). Because this rule has been 
exempted from review under Executive Order 12866 due to its lack of 
significance, this rule is not subject to Executive Order 13211, 
Actions Concerning Regulations That Significantly Affect Energy Supply, 
Distribution, or Use (66 FR 28355, May 22, 2001). This final rule does 
not contain any information collections subject to OMB approval under 
the Paperwork Reduction Act (PRA), 44 U.S.C. 3501 et seq., or impose 
any enforceable duty or contain any unfunded mandate as described under 
Title II of the Unfunded Mandates Reform Act of 1995 (UMRA) (Public Law 
104-4). Nor does it require any special considerations under Executive 
Order 12898, entitled Federal Actions to Address Environmental Justice 
in Minority Populations and Low-Income Populations (59 FR 7629, 
February 16, 1994); or OMB review or any Agency action under Executive 
Order 13045, entitled Protection of Children from Environmental Health 
Risks and Safety Risks (62 FR 19885, April 23, 1997). This action does 
not involve any technical standards that would require Agency 
consideration of voluntary consensus standards pursuant to section 
12(d) of the National Technology Transfer and Advancement Act of 1995 
(NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272 note). Since 
tolerances and exemptions that are established on the basis of a 
petition under section 408(d) of the FFDCA, such as the tolerance in 
this final rule, do not require the issuance of a proposed rule, the 
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et 
seq.) do not apply. In addition, the Agency has determined that this 
action will not have a substantial direct effect on States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government, as specified in Executive Order 13132, entitled Federalism 
(64 FR 43255, August 10, 1999). Executive Order 13132 requires EPA to 
develop an accountable process to ensure ``meaningful and timely input 
by State and local officials in the development of regulatory policies 
that have federalism implications.'' ``Policies that have federalism 
implications'' is defined in the Executive Order to include regulations 
that have ``substantial direct effects on the States, on the 
relationship between the national government and the States, or on the 
distribution of power and responsibilities among the various levels of 
government.'' This final rule directly regulates growers, food 
processors, food handlers and food retailers, not States. This action 
does not alter the relationships or distribution of power and 
responsibilities established by Congress in the preemption provisions 
of section 408(n)(4) of the FFDCA. For these same reasons, the Agency 
has determined that this rule does not have any ``tribal implications'' 
as described in Executive Order 13175, entitled Consultation and 
Coordination with Indian Tribal Governments (65 FR 67249, November 6, 
2000). Executive Order 13175, requires EPA to develop an accountable 
process to ensure ``meaningful and timely input by tribal officials in 
the development of regulatory policies that have tribal implications.'' 
``Policies that have tribal implications'' is defined in the Executive 
Order to include regulations that have ``substantial direct effects on 
one or more Indian tribes, on the relationship between the Federal 
Government and the Indian tribes, or on the distribution of power and 
responsibilities between the Federal Government and Indian tribes.'' 
This rule will not have substantial direct effects on tribal 
governments, on the relationship between the Federal Government and 
Indian tribes, or on the distribution of power and responsibilities 
between the Federal Government and Indian tribes, as specified in 
Executive Order 13175. Thus, Executive Order 13175 does not apply to 
this rule.

VIII. Congressional Review Act

    The Congressional Review Act, 5 U.S.C. 801 et seq., as added by the 
Small Business Regulatory Enforcement Fairness Act of 1996, generally 
provides that before a rule may take effect, the agency promulgating 
the rule must submit a rule report, which includes a copy of the rule, 
to each House of the Congress and to the Comptroller General of the 
United States. EPA will submit a report containing this rule and other 
required information to the U.S. Senate, the U.S. House of 
Representatives, and the Comptroller General of the United States prior 
to publication of this final rule in the Federal Register. This final

[[Page 18275]]

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: March 26, 2004.
James Jones,
Director, Office of Pesticide Programs.

0
Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

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

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

0
2. Section 180.596 is added to subpart C to read as follows:


Sec.  180.596  Fosthiazate; tolerances for residues.

    (a) General. Tolerances are established for the combined residues 
of Fosthiazate (O-ethyl S-(1-methylpropyl)(2-oxo-3-
thiazolidinyl)phosphonothioate and its metabolite O-ethyl S-(1-
methylpropyl)[2-(methylsulfonyl)ethyl] phosphoramidothioate) (ASC-
67131).

------------------------------------------------------------------------
                                                              Parts per
                         Commodity                             million
------------------------------------------------------------------------
Tomato.....................................................         0.02
------------------------------------------------------------------------

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

[FR Doc. 04-7864 Filed 4-6-04; 8:45 am]
BILLING CODE 6560-50-S