United States             Office of Pesticides and Toxic Substances
                           Environmental Protection      Office of Pesticide Programs  (TS-766C)
                           Agency                Washington, DC  20460

                                                            	54Q/FS-RR-120 / . ..
•    vvEPA       Pesticide
                           Fact Sheet
                           Name of Chemical:    TERBUFOS
                           Reason for Issuance:   Revised Registration Standard
                           Date issued:  September 9,  1988
                           Fact Sheet Number:   5.2
          1.  Description of Chemical

             Common Name:  Terbufos
             Chemical  Name:  S-[[(1,l-dimethylethyl)thio]methyl]0,0-diethyl
                            phosphorodithioate
             Other Chemical Nomenclature:  S-([tert-butylthio)methyl]0,0-diethyl
                            phosphorodithioate (IUPAC); S-(Jb-butylthio) methyl
                            0,O-diethyl-phosphorodithioate (CA, 8th Collective
                            Index); j3-tert-butylmercaptomethyl 0,O-diethyl
                            dithiophosphate
             Trade Names:  Contraven;  Counter; AC 92,100; CL 92,100r and ST-100
             Chemical  Abstracts Service  (CAS) Number:   13071-79-9
             EPA Shaughnessy Code:   105001
             Year of Initial Registration:  1974
             Pesticide Type:  Insecticide-Nematicide
             Chemical  Family:  Organophosphate
             U.S. Registrant:  American  Cyanamid Company

          2.  Use Patterns and Formulations

             Application Sites:  Terrestrial food crop  use on corn; grain
                sorghum; and sugar  beets.

             Formulations:  Granular

             Methods of Application:   Broadcast (nonsoil-incorporated) with air or
                ground equipment; and  soil-incorporated with ground equipment.

          3.  Science Findings

             Summary Science Statement:  Technical terbufos is highly acutely
                toxic  by the oral,  dermal, and inhalation routes of exposure
                (Toxicity Category  I for all three routes).  Terbufos does not
                demonstrate an acute neurotoxic,  oncogenic, mutagenic,
                reproductive, or teratogenic potential.  Animal studies have shown
                that the chemical is a cholinesterase inhibitor reducing plasma,
                brain, and red blood cell cholinesterase activity.   The use of

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   terbufos poses a potential risk to loaders and applicators and to
   persons reentering treated fields following nonsoil-incorporated
   broadcast application of the chemical.  This is due to the high
  'acute toxicity and the cholinesterase inhibiting properties of the
   chemical.

   Based on the plasma cholinesterase inhibition no-effect-level of
   0.00125 mg/kg/day as defined in a 4-week dog study and, using a
   safety factor of 10, the acceptable daily dietary intake for
   humans in 0.000125 mg/kg/day.  The theoretical maximum residue
   contribution from the established tolerances is estimated to be
   0.000052 mg/kg/day.  This is equivalent to 42 percent of the
   acceptable daily intake for the average U.S. population.  Due to
   the numerous gaps in residue chemistry data, the Agency is unable
   to complete a tolerance reassessment of terbufos.

   Terbufos is highly toxic to birds, fish, and aquatic invertebrates.
   The acceptable short-term field study shows significant acute
   mortalities of birds, mammals, reptiles, and fish resulting from
   broadcast application of terbufos to corn fields at •! pound active
   ingredient per acre (1 Ib ai/A).  In the same study, the application
   of terbufos as a soil-incorporated treatment to corn fields at 2
   Ib ai resulted in acute mortalities to birds and reptiles.

   The limited environmental fate data are not sufficient to assess
   the mobility and leaching properties of tebufos.  Terbufos residues
   were reported to occur in well water sampling in Iowa and Minnesota.
   These reports, however have not been confirmed in the laboratory
   and a resampling of the same Iowa wells a year later, in 1986,
   showed no detections for terbufos or its degradates.  Terbufos is
   one of the pesticides the Agency is sampling for in the National
   Well Water Survey.

Chemical/Physical Characteristics of the Technical Material:

   Color:  Clear, brownish
   Physical State:  Liquid
   Odor:  Mercaptan-like
   Boiling Point:  55 °C at 0.02 mmHg
   Stability:  Relatively stable in water under neutral or slightly
               acidic conditions but is subject to hydrolysis under
               alkaline conditions.

Toxicology Characteristics

o  Acute Oral:  Toxicity Category I (1.6 and 1.3 mg/kg for male and
      female rats, respectively).

o  Acute Dermal:  Toxicity Category I (0.81 and 0.93 mg/kg for male
      and female rabbits, respectively).

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o  Acute Inhalation:  Toxicity  Category  I  (<_ 0.2 mg/L).

o  Delayed Neurotoxicity:  No evidence of acute delayed neurotoxicity
      at the 40 mg/kg dosage level tested in hens.

o  Subchronic Feeding:  The NOEL for both systemic effects and
      cholinesterase inhibition in a rat subchronic  study is  0.25 ppm.

o  Subchronic Dermal:  The NOEL for systemic effects in a 30-day
      rabbit study is 0.020 mg/kg.

o  Mutagenicity:  Terbufos did  not exhibit mutagenic potential  in the
      Ames assay, the _in vivo cytogenetic assay, and the dominant lethal
      test.

o  Teratogenicity:  The NOEL for developmental toxicity in a  rat
      teratology study is 0.1 mg/kg/day.

o  Reproduction:  The NOEL for  reproductive  effects  in a three-
      generation rat reproduction study  is 0.25 ppm.

o  Oncogenicity:  No oncogenic  effects observed in an 18-month  mouse
      study and a 2-year rat study at doses  up to and including 12.0
      ppm (1.8 mg/kg/day) and 8.0 ppm (0.4 mg/kg/day), respectively.

o  Chronic Toxicity:  The NOEL  for plasma cholinesterase (ChE)
      inhibition from a 4-week  dog feeding study is  0.00125 mg/kg/day;
      the NOEL for brain/red blood cell ChE  from a 1-year dog study
      is 0.060 mg/kg/day.  The  NOEL for plasma and brain ChE  from a
      1-year rat feeding study  is 0.5 ppm.

o  Metabolism:  Terbufos was rapidly excreted as the diethyl
      phosphoric acid and other polar metabolites (83%) in urine
      within 168 hours of administration to  male rats.  Terbufos
      and its metabolites were  not noted to  accumulate in tissues.

Ecological Characteristics:

Based on acceptable laboratory  data, technical terbufos is highly
   toxic to birds, fish, and aquatic invertebrates.

Acute Avian Toxicity:  28.6 mg/kg (bobwhite).
Dietary Avian Toxicity:  143 and 157 ppm (from two bobwhite studies).
Avian Reproduction:  Terbufos was not considered to  produce avian
   reproductive effects based on results of  a bobwhite quail  study
   and a mallard duck study.
Freshwater Fish Acute Toxicity:  Ranges from 0.77 to 20.00 ppb.
Freshwater Invertebrate Acute Toxicity:  0.31 ppb for Daphnia magna.
Marine/Estuarine Fish Acute Toxicity:  Data  gap.
Marine/Estuarine Invertebrate Toxicity:  Data gap.
Marine/Estuarine Mollusk Toxicity:  Data gap.

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Terrestrial Field Study (Level 1):  Both soil-incorporated (2 Ib
  >ai/A) and nonsoil-incorporated (1 Ib ai/A) resulted in nontarget
   mortalities, with the latter application much more severe in its
   effects.

Based on the adverse effects observed in the level 1  field study
   described above, level 2 terrestrial field studies are required to
   assess the potential effects on populations of birds, mammals, and
   reptiles.  Based on the high acute toxicity to aquatic organisms
   and results of initial modeling1  conducted by the Agency for the
   1983 Terbufos Registration Standard, the estimated environmental
   concentration (EEC) of terbufos residues likely to occur in the
   aquatic environment may pose an acute hazard for freshwater and
   marine/estuarine species.  This modeling was conducted for the
   soil-incorporated application of terbufos.

Potentially greater hazards are likely for aerial applications of
   terbufos granules since soil-incorporated applications typically
   provide less exposure than aerial broadpast applications.

Although these theoretical calculations and modeling indicate that
   the use of terbufos may result in significant adverse effects to
   aquatic species, actual field monitoring data are not available
   to support this finding.  Moreover, the environmental fate charac-
   teristics of terbufos are not accurately defined by available
   data.  Thus, the models can be used only on a limited basis.

Aquatic residues monitoring studies are required to determine actual
   residues in aquatic systems exposed to runoff and spray drift.
   Although these studies were previously requested in the 1983
   Terbufos Registration Standard, their initiation was delayed
   pending the Agency's recalculation of the EECs.  Prior to the
   completion of this task, reports of fish kill incidents demonstrating
   the potential exposure to aquatic organisms under actual field use
   conditions became available.  These fish kills reportedly resulted
   from aerial applications of terbufos to corn fields during conduct
   of the level 1 terrestrial field study.  In addition, several
   environmental fate studies previously found acceptable do not meet
   current guideline requirements and need to be repeated.

Terbufos has been identified by the Office of Endangered Species
   (OES), U.S. Fish and Wildlife Service (USFWS), as being likely to
   jeopardize the continued existence of certain endangered species
     Agency used computer models (SWRRB) and EXAMS) to simulate
 runoff from granular application of terbufos and to predict aquatic
 concentrations of the chemical.  SWRRB is a hydrology model combined
 with a pesticide runoff model.  EXAMS is a hydrologic model to pre-
 dict "steady-state" and "pulseload" behavior of organic toxicants in
 aquatic ecosystems.

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   when used on corn and sorghum.  Based on this determination, OES
   specified reasonable and prudent alternatives to avoid jeopardizing
   the continued existence of the identified species.  EPA is working
   with USFWS and other Federal and State agencies to implement the
   alternatives in a technically sound manner.

Formal consultation will be initiated with OES under Section 7 of the
   Endangered Species Act regarding the potential exposure to
   endangered species resulting from the registered use of terbufos
   on sugar beets.

Environmental Characteristics;

Results of an acceptable hydrolysis study indicate that terbufos
   hydrolyzes at pH 5, 7, and 9 with a half-life of 2.2 weeks.
   Formaldehyde was the major degradate detected in this study.
   Results of an acceptable aerobic soil metabolism study indicate
   that terbufos degrades in silt loam soil with a half-life of
   26.7 days.  The major .degradates detected in this study included
   carbon dioxide, terbufos sulfoxide, and terbufos sulfone.

Results of a field dissipation study, classified as supplementary,
   indicate that terbufos residues have a half-life of less than
   40 days in field plots of loam soil located near Arcola, Illinois,
   and sandy loam soil located near Greeley, Colorado treated with
   a 15 percent granular formulation at an application rate of 1 Ib
   ai/A.  The sampling protocol was inadequate to accurately assess
   the dissipation of terbufos residues in field soil and a new study
   is required.

The available data reviewed by the Agency are not sufficient to
   fulfill data requirements nor to assess the environmental fate of
   terbufos.  Four studies previously reviewed and found acceptable
   under the 1983 Terbufos Registration Standard do not meet the
   requirements of the Agency's current guidelines and new studies
   are required.  These are:  anaerobic soil metabolism, leaching,
   fish accumulation, and field dissipation.

In addition, several new studies are now required due to the
   additional method of nonsoil-incorporated, broadcast (air or
   ground equipment) application which was not registered at the
   time of the 1983 Terbufos Registration Standard.

Tolerance Assessment;

Tolerances for combined residues of terbufos and its ChE-inhibiting
   metabolites in or on food commodities are published under Section
   180.352 of Title 40 of the Code of Federal Regulations (40 CFR
   180.352).  These tolerances range from 0.05 to 0.5 ppm.

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Residue Data;

In the Terbufos Registration Standard dated June 1983, no outstanding
   data gaps were identified for residue chemistry.  However, subse-
   quent amendments to registered uses for terbufos and addenda to
   the Pesticide Assessment Guidelines (Subdivision 0) for Residue
   Chemistry have made it necessary to reevaluate portions of the
   data base previously reviewed under the June 1983 Standard.  As a
   result, some of the original conclusions regarding adequacy of the
   data and support for tolerances have been modified in this revised
   Registration Standard.

Based on the available plant metabolism studies, the nature of
   residues in plants is adequately understood.  Of the phosphorylated
   metabolites, terbufoxon sulfoxide and terbufos sulfoxide comprised
   <_ 30 percent of the residues, and terbufos sulf one and terbuf oxon
   sulfone comprised _<_ 7 percent.  The major nonphosphorylated metabo-
   lite which comprised _<_ 30 percent of the organosoluble residues was
   nonphosphorylated terbufoxon sulfone.  The available poultry and
   ruminant feeding studies do not meet current Guideline requirements
   for data depicting the metabolism of terbufos in livestock and new
   studies are required. The basic GLC analytical procedure published
   as Method I in PAM Vol. II is adequate for collection of data per-
   taining to the combined residues of terbufos and its ChE-inhibiting
   metabolites on commodities with established tolerances.  Method
   validation data pertaining to recovery of individual metabolites
   from representative plant commodities are being required.  The ade-
   quacy of the available methods for detection of terbufos residues
   of concern in animal products will be evaluated upon receipt of the
   required animal metabolism data.  Field trial studies are required
   for all crops for which there are terbufos tolerances.  Processing
   studies are also required in addition to storage stability residue
   data.

The available poultry and ruminant feeding studies show that no
   detectable residues occur in eggs, chicken tissues, milk, or
   cattle tissues from animals fed exaggerated dietary levels of
   terbufos and its ChE-inhibiting metabolites.  However, additional
   animal metabolism data are required and a determination regarding
   the need for and nature of tolerances for residues in meat, milk,
   poultry, and eggs will be made upon receipt and evaluation of
   these data.

The established tolerances for terbufos are presently expressed in
   terms of terbufos and its ChE-inhibiting metabolites without
   specifying the latter as phosphorylated metabolites.  The Agency

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   will propose revising 40 CFR 180.352 by changing the wording to
   read:

   "... terbufos . . . and its phosphorylated  (cholinesterase-
   inhibiting) metabolites:

   o  Phosphorothioic acid, S-(t-butyl-thio) methyl 0,0-diethyl ester.

   o  Phosphorothioic acid, S-( t-butyl-sulf inyl) methyl C),_0-diethyl
      ester.

   o  Phosphorothioic acid, S-(_t-butyl-sulfonyl) methyl _0,^D-diethyl
      ester.

   o  Phosphorodithioic acid, S-(t-butyl-sulfinyl) methyl 0^,0-diethyl
      ester.

   o  Phosphorodithioic acid, S-( jt-butyl-sulfonyl) methyl £,0-diethyl
      ester."

Acceptable Daily Intake;

Based on the plasma ChE inhibition NOEL as defined in a 4-week dog
   study (0.00125 mg/kg/day) and using a safety factor of 10, the
   acceptable daily intake or reference dose (RfD) for humans is
   0.000125 mg/kg/day.

Summary of Regulatory Positions and Rationales

Terbufos is not being placed in special review at this time.  Field
   studies are needed to completely assess the potential risk to
   wildlife, including endangered species.  The Agency is conducting
   a comparative avian risk assessment of various granular pesticides,
   including terbufos.  When this assessment is completed, further
   regulatory action may be taken.

The restricted use classification of the 15 percent granular end-use
   product based on the high acute oral and dermal toxicity to humans
   is being retained.

A level II terrestrial field study; monitoring studies in soil,
   water, sediment, and fish; and aquatic organism field studies are
   being required for the completion of the Agency's assessment of
   the potential risk to both avian and aquatic species.

A special 21-day dermal study in rats and a dislodgeable residue
   study are being required for the completion of the Agency's
   assessment of the potential risk to workers reentering corn fields
   following a nonsoil-incorporated application of terbufos.

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    Due to the lack of pertinent environmental fate data, no conclusions
       regarding the potential for terbufos to contaminate ground water
       can be made.

    EPA is developing a program to reduce or eliminate exposure to endangered
       species to a point where use does not result in jeopardy, and will
       issue notice of any necessary labeling revisions when the program
       is developed.  No additional labeling is required at this time.
       Labeling requirements issued in PR Notices 87-4 and 87-5 have been
       withdrawn pending reissuance.

5.  Summary of Required Label Modifications

    An updated Environmental Hazard statement is required.

    Updated worker safety rules and protective clothing statements are
       required.

    A 7-day reentry interval statement is required for use of terbufos as
       a broadcast application to corn.

    A label statement prohibiting use of terbufos as a broadcast
       application to seed corn prior to detasseling activities is
       required.

6.  Summary of Outstanding Data Requirements

               Data                        Due Date1/

    Toxicology

    Special 21-day rat dermal              12 Months
    Rabbit teratology                      15 Months

    Fish s Wildlife

    Acute toxicity to estuarine
      and marine organisms                 12 Months
    Fish early life stage                  15 Months
    Aquatic organism accumulation          12 Months
    _VDue date is measured from the date of receipt of the Standard by
      the registrant unless otherwise specified.

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           Data

Fish & Wildlife  (cont'd)

Terrestrial field study
Aquatic organism field study

Reentry

Dislodgeable residue study

Environmental Fate

Photodegradation in water
Photodegradation on soil
Photodegradation in air
Anaerobic soil metabolism
Leaching and absorption/desorption
Lab volatility
Soil field dissipation
Rotational crop  (field)
Fish accumulation
Monitoring study (soil, water,
  sediment, fish)

Residue Chemistry

Crop field trials
Processing studies
Storage stability
Ruminant and poultry metabolism
Residue analytical methodology data

Product Chemistry

Majority of data
Due Date^/
 6 Months for protocol
27 Months
 9 Months
 9 Months
 9 Months
27 Months
12 Months
12 Months
27 Months
50 Months
12 Months
 6 Months (protocol!
18 Months
24 Months
15 Months
18 Months
15 Months
 6-15 Months
_1_/Due date is measured from the date of receipt of the Standard by
  the registrant unless otherwise specified.
2/1 st Annual Report	  December 31 , 1989
  2nd Annual Report*  	  December 31, 1990
  3rd Annual Report*  	  December 31, 1991
  Final Report**	December 31, 1992

 *A determination may be made at this time to conclude the study, in
  which case a final report will be due 3 months after notification.
**The due date applies if the study has not been determined to be
  concluded by earlier reviews.

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7.  Contact person at EPA

    William H. Miller
    Product Manager (16)•
    Insecticide-Rodenticide Branch
    Registration Division (TS-767C)
    Environmental Protection Agency
    VJashington, DC 20460

    Phone:  (703) 557-2600.

DISCLAIMER:  The information presented in this Chemical Information Fact
Sheet is for informational purposes only and may not be used to fulfill
data requirements for pesticide registration and reregistration.

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