United States
               Environmental Protection
               Agency
Office of
Pesticides and Toxic Substances
Washington DC 20460
January 1985
&EPA
               Pesticides
               TPTH  (Triphenyltin Hydroxide)
               Special Review Position
               Document 1

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          TRIPHENYLTIN HYDROXIDE
           POSITION DOCUMENT 1
   U.S. Environmental Protection Agency



Office of Pesticides and Toxic Substances



       Office of Pesticide Programs



            401 M Street, S.W.




             Washington, D.C.

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6560-50




               ENVIRONMENTAL PROTECTION AGENCY




                         [OPP-30000/42]




                    TRIPHENYLTIN HYDROXIDE




         SPECIAL REVIEW OF CERTAIN PESTICIDE PRODUCTS






AGENCY:  Environmental Protection Agency  (EPA).




ACTION:  Notice.




SUMMARY:  JT,his Notice announces that EPA  is initiating a




Special Review of all pesticide products  containing the




active  ingredient triphenyltin hydroxide  (TPTH^j.  EPA has




determined that TPTH which is registered  as a fungicide and




mite suppressant, produces teratogenic effects  in laboratory




rats and that sufficient exposure to applicators exists to




meet the risk criterion described in 40 CFR 162.11.  Accordingly,




a Special Review of products containing TPTH has been initiated




to determine whether additional regulatory actions, if any,




are required.  During the Special Review  process, EPA will




carefully examine the risks and benefits  of using TPTH products.




DATE:   Comments, evidence to rebut the presumptions in this




Notice, and other relevant information must be  received no  later




than 45 days from the date this notice is received or until




(insert date 45 days after date of publication  in the




FEDERAL REGISTER) (whichever is later).






84P-4070

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ADDRESS:  Written comments identified as "OPP-30000/42"




should be sent by mail to:




     Information Services Section,



     Program Management and Support Division (TS-757C),




     Office of Pesticide Programs,



     Environmental Protection Agency,



     401 M St., SW.,



     Washington, D.C. 20460.



     In person, bring comments to:



     Rm. 236, CM #2,



     1921 Jefferson Davis Highway,



     Arlington, VA.



     Information submitted in any comment concerning this



notice may be claimed confidential by marking any part or all



of  that  information as "Confidential Business Information"



(CBI).   Information so marked will not be disclosed except in




accordance with procedures set forth in 40 CFR Part 2.  An



edited copy of the comment containing material claimed to be



CBI must be submitted (with the CBI portions deleted) for



inclusion in  the public record.  Information not marked



confidential  may be disclosed publicly by EPA without prior



notice to the submitter.  All non-CBI written comments will




be  available  for public inspection in Rm. 236 at the Virginia




address given above, from 8 a.m. to 4 p.m., Monday through



Friday, excluding legal holidays.

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FOR FURTHER INFORMATION CONTACT:  By mail:




     Betty Shackleford,




     Registration Division (TS-767C),



     Office of Pesticide Programs,




     Environmental Protection Agency,




     401 M St., SW.,




     Washington, D.C. 20460.



     Office location and telephone number:



     Rm. 717, CM #2,




     1921 Jefferson Davis Highway,



     Arlington, VA,



     (703-557-7400).




SUPPLEMENTARY INFORMATION: The term "Special Review" is the



name now being used by EPA for the process previously called




the Rebuttable Presumption Against Registration (RPAR) process.



Modifications in the process will be proposed in regulations




in the near future.  Until other applicable final regulations



are adopted, the present Special Review will adhere to RPAR




procedures now in effect and set forth in 40 CFR 162.11.




     EPA has determined that a Special Review will be conducted




for all pesticide products containing TPTH as an active



ingredient.  EPA has also determined that data necessary to



conduct the Agency's risk assessment must be developed on an




accelerated basis, and that precautionary labeling is required



to reduce risk during the Special Review process.




     Issuance of this Notice means that potential hazards




associated with the use of TPTH have been identified.  These

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                            - 4 -




hazards will be examined further to determine the nature and




extent of the risk, and considering the benefits of TPTH,




whether such risks cause unreasonable adverse effects on the




environment.



     A document entitled "Guidance for the Interim Registration




of Pesticide Products Containing TPTH" (Guidance Document) has




been issued.  (The Guidance Document is also referred to as a



Registration Standard.)  The Guidance Document is available to



the public from the contact person named above.  This Guidance




Document explains the basis of EPA's decision to start a Special



Review and also contains references, background information,



data requirements, and other information pertinent to the con-




tinued registration of pesticides containing TPTH.



              I.  INITIATION OF A SPECIAL REVIEW



                          A. GENERAL



     A pesticide product may be sold or distributed in the



United States only if it is registered or exempt from registra-



tion under the Federal Insecticide, Fungicide, and Rodenticide



Act (FIFRA)  (7 U.S.C. 136 e_t seq. ) .  Before a product can be



registered,  it must be shown that it can be used without "un-



reasonable adverse effects on the environment" (FIFRA section



3(c)(5)), that is, without causing "any unreasonable risk to



man or the environment, taking into account the economic,




social, and environmental costs and benefits of the use of the



pesticide" (FIFRA section 2(bb)).  The burden of proving that




a pesticide meets this standard for registration is on the



proponent of initial or continued registration.  If at any

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                            - 5 -






time the Agency determines that a pesticide no longer meets



this standard for registration, the Administrator may cancel



the registration under section 6 of FIFRA.



     The Agency has created an administrative process for



fully evaluating whether a pesticide satisfies or continues to



satisfy the statutory standard for registration.   This Special



Review process provides an informal procedure through which



EPA may gather and evaluate information about the risks and



benefits of a pesticide's use.  It also provides  a means by



which interested members of the public may comment on and



participate in EPA's decision making process.  The regulations



governing this process are set forth at 40 CFR 162.11.



     A Special Review is begun when EPA determines that a



pesticide meets or exceeds one or more of the risk criteria



set out in the regulations (40 CFR 162.11(a)(3)).  The Agency



generally announces the beginning of the Special  Review by



issuing a Position Document 1 (PD 1) which is published in



the FEDERAL REGISTER.  In addition, registrants of affected



products will receive the PD 1 by certified mail.  Registrants



and other interested persons are invited to scrutinize the



basis for the Agency's decision to initiate the Special



Review and to submit data and information which rebuts or



supports the Agency's determination of risk.  Commenters may



also suggest methods to reduce risks of use of the pesticide.



In addition to addressing risk issues, commenters are encouraged



to submit evidence and discussions of the biological, economic,

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                            - 6 -




social, and environmental costs and benefits of use of the




pesticide.  The public participation stage is described in more




detail in Unit IV.  This Notice constitutes Position Document 1



for pesticide products containing TPTH.



     If risk issues are not satisfactorily resolved, EPA will




proceed to evaluate the risks and benefits of TPTH  in order  to




determine whether to propose regulatory actions to  reduce the



risks.  After providing an opportunity for comment  by the Scientific




Advisory Panel, the Secretary of Agriculture, registrants, and the



public on those actions and the reasons for them, EPA will issue




an appropriate final notice.  If EPA determines that the risks of



use exceed the benefits, EPA will issue a notice of intent to



cancel the registration of products intended for such use.   The



notice may state  athe  intention to cancel registrations outright



or may require certain changes in the composition,  packaging,



application methods and/or labeling of the product.  These changes



would  be  intended to reduce the risks to levels that when considered



against the benefits will not pose unreasonable adverse effects



to man or the environment.




     A notice initiating a Special Review is not a  notice of




intent to cancel the registration of a pesticide, and a Special




Review may or may not lead to cancellation.  This notice initiating



the Special Review for TPTH products is an announcement of EPA's



concern about the safety of the pesticide's use, and only after



carefully considering the risks and benefits of TPTH and determining



that it appears to cause unreasonable adverse effects on the



environment,  would EPA issue a notice of intent to  cancel.

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                            - 7 -
                       B.  PRESUMPTION




     EPA has determined that the use of pesticide products




containing TPTH has exceeded one of the risk criteria in




40 CFR 162.11(a)(3)(ii)(B) which provides that a Special



Review shall be conducted if the use of a pesticide "produces



any other chronic or delayed toxic effect in test animals at



any dosage up to a level, as determined by the Administrator.-




which is substantially higher than that to which humans can



reasonably be anticipated to be exposed, taking into account



ample margins of safety."  Studies submitted to the Agency in



support of the continued registration of TPTH have shown that



TPTH produces teratogenic effects in laboratory animals.



Based on these data and on an evaluation of potential exposure



of applicators to TPTH, the Agency concluded that TPTH has



exceeded the risk criterion for initiation of a Special



Review.



     1.  Toxicological concerns.  As part of the data require-



ments necessary to maintain the continued registration of the



pesticide, two independent laboratories conducted studies in



Sprague-Dawley rats to ascertain the teratogenic potential of



TPTH.  In the first study, conducted in 1976 by Cannon Labora-




tories, Inc., varying dosage levels of technical grade TPTH




were orally administered by gavage to pregnant rats on days 6



through 15 of gestation.  Increases in the incidences of




hydrocephalus (the abnormal accumulation of serous fluid with-




in the cranium accompanied by enlargement of the head, prominence




of the forehead, atrophy of the brain, mental weakness and.

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convulsions) and hydronephrosis (distention of the pelvis




and calyces of the kidney with urine, as a result of obstruction




of the ureter with accompanying atrophy of the parenchyma of



the organ) above the incidences in concurrent control animals




were observed in the fetuses at all dosage levels tested.



     A second teratogenicity study was performed by Battelle




Columbus Laboratories and submitted to the Agency in 1981.  In




this study, rats were mated and dosed with TPTH on days 5



through 19 of gestation.  Increased incidences of hydronephrosis



above the  incidence in the concurrent control fetuses were




again observed at all dosage levels tested.  Although hydro-



cephalus was seen in only one fetus, an increased incidence



of hydroureter  (abnormal distention of the ureter of the kidneys



with urine  or with a watery fluid) above the concurrent control




incidence  occurred at all dosage levels tested.  Based on



these studies, the Agency has determined that TPTH produces



teratogenic effects in laboratory animals.  A "no-observed-



effect-level" (NOEL) for these teratogenic effects has not



been determined because these lesions were observed at all



dosage levels.  The "lowest-observed-effect-level" (LOEL) was



1.0 mg/kg/day.




     To clarify whether some or all of the effects observed




in the teratogenicity studies are true developmental anomalies,




delayed maturation, or the like, the Agency has required a




"postnatal" teratology study.  The Agency believes this study




will elucidate the nature, severity, and/or reversibility of



the teratogenic effects manifested in the two studies referred



to above.

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                             - 9 -
     In the postnatal teratology study, twice the number of



dams typically observed in a teratology study are to be used.



One half of the dams are to be sacrificed near parturition



and the remaining half of the animals are permitted to deliver



normally with post-weaning sacrifice and examination of the



pups.  The specific test requirements are outlined in the



Guidance Document.  Results of the postnatal teratology study



must be submitted to the Agency by December 7, 1985.  In addition,



the Agency is conducting a teratogenicity "screening test" at



Research Triangle Park, N.C.  This testing is being performed



in two phases and is designed to provide insight into the



severity of the observed teratogenic effects.  Based on the



results of these data, which will be available in March 1985,



the Agency may initiate additional immediate regulatory actions.



     2.  Applicator risk assessment.  The Agency has estimated



potential applicator exposure to TPTH.  Because most applicator



exposure occurs by the dermal route, a risk assessment has been



performed based on dermal exposure to TPTH resulting from the



air blast application to pecan trees.  The risk assessment was



limited to this site and application method because 72 to 82



percent of the pesticidal use of TPTH is for controlling fungal



diseases in pecan culture.  TPTH is generally applied by air



blast application in pecan culture, although it may be applied



aerially.



     In calculating the dermal exposure risk calculation for



pecan tree applicators, the Agency made the following assumptions.

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                             - 10 -






     a.  Applicators have an average body weight of 70 kg.




     b.  Mixing/loading and pesticide application are done by




the same individual.



     c.  Potential inhalation exposure would be minimal when




compared to potential dermal exposure.



     d.  It was estimated that 3,000 cm2 of the skin surface




area would be exposed during the pesticide application.   This




is equivalent to wearing a short-sleeved, open-necked shirt,




long pants, and neither head covering nor gloves.



     e.  Exposure during mixing/loading assumes a worker  handles



a  50 percent wettable powder (WP) formulation packaged in



conventional bags.



     f.  In the absence of empirical dermal absorption data,



the Agency assumed dermal absorption would be 100 percent.



     Unit dermal exposure (mg/kg body weight/day) (mg/kg/ bw/day)



during  application was calculated from the linear regression




correlation derived from the Office of Pesticide Programs



Exposure Assessment Branch data base for air blast application



to orchards (p < 0.01).  Exposure during mixing and loading of



the wettable powder was calculated from the same data base.




Application rates typically range from 1.5 to 18.4 oz active



ingredient per acre (ai/A).




     The Agency estimated a typical exposure value for a




mixer/loader/applicator of 0.74 mg/kg/day, with a lowest  value



of 0.68 mg/kg/day and an upper value of 0.88 mg/kg/day.   This



range is derived from the range in application rates.

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                             - 11 -





     Because the teratogenic effects seen in the animal studies



occurred at all test dosage levels, the Agency has been unable to



determine "margins of safety" (MOS) (ratio of NOEL to exposure)



from the available test results.  Therefore, teratogenic "risk



quotients" (ratio of LOEL to exposure) were calculated based on



the LOEL.



     The risk quotient determination for teratogenicity indicates



that potential exposure of pesticide applicators in pecan



culture to TPTH occurs at a level that is known to produce



teratogenic effects in laboratory animals, thereby resulting in



a highly significant teratogenic risk for pregnant women.



     3.  Dietary exposure.  To assess potential teratogenic



hazards that might be associated with dietary exposure to TPTH,



the Agency has performed a risk assessment for the food commodities



listed in 40 CFR 180.236.  "Risk quotients" were again determined



because a NOEL was not observed in the teratogenicity studies.



The risk quotients are based on eating a single serving of the



respective food items by a 60 kg pregnant woman.  These data



are presented in Table I.

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          TABLE  I —  DIETARY  RISK QUOTIENT  DETERMINATION  FOR TERATOGENICITY
Commodity
Carrots
raw
cooked
Sugar
(beet)
Pecans
Peanuts
Potatoes
Kidney
Liver
Estimated
Serving Weight
Size (kg)l/

1 cup
1 cup
1/2 cupV
1/2 cup
1/2 cup
1 cup
3 oz .
3 oz .

0
0
0
0
0
0
0
0

.11
.15
.12
.06
.07
.20
.09
.09
TPTH
Tolerance
(ppm)

0
0
0
0
0
0
0
0

.10
.10
.10
.05
.05
.05
.05
.05
mq/serving

0
0
0
0
0
0
0
0

.011
.015
.012
.003
.0035
.010
.0045
.0045
11 R
mg/kg/body (
weight
b .w. =60kg

0
0
0
0
0
0
0
0

.00018
.00025
.00020
.00005
.00006
.00017
.00008
.00008
isk Quotient"
LOEL of 1.0
mg/kg/day divided
by mg/kg body weight)

5,
4,
5,
20
16
5,
12
12

600
000
000
,000
,700
900
,500
,500
                                                                                               ro
                                                                                               i
    From "Nutritive Value of American  Foods,"   Agriculture Handbook No. 456, USDA
    Washington, D.C.,  1975.
_£/ Estimated total daily  intake

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                             - 13 -








     The risk quotients presented in Table I indicate that



the existing tolerances provide a substantial or ample level of



protection from potential teratogenic effects that may be



associated with dietary exposure to the parent TPTH.  Because



the risk quotient determinations are based on a single serving



of the respective food commodities, individual dietary practices



may augment or lessen the risks accordingly.  However, adequate



protection exists even if multiple servings of the food commodities



listed in Table I are consumed.



     The Agency does not expect residues of the parent TPTH to



exceed the current existing tolerance levels.  However, there



is significant concern about the potential toxicological



activity of the mono- and diphenyltin metabolites of TPTH and



their contribution to the total food residue.  A reassessment



of the existing tolerances will be made once the analytical



methodology and residue data, including storage stability data,



for TPTH and its mono- and diphenyltin metabolites are submitted



for the plant commodities listed in 40 CFR 180.236.  Similar



residue data and storage stability studies for processed com-



modities derived from peanuts, potatoes, and sugarbeets are



also needed.  Studies on processed commodities must include



data for tetraphenyltin in addition to data for TPTH and the



mono- and diphenyltin metabolites.  Residue data and analytical



methodology for meat, milk, poultry, and eggs are also being



required.  The above information is being requested from the



registrants in the Guidance Document.

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     The Agency is also aware that TPTH and its acetate and




chloride analogues are used abroad.  The treated commodities




include dry beans (Bolivia), cocoa (Brazil), potatoes  (Brazil,




Cyprus, Ireland, Switzerland, and the United Kingdom), and rice




(Brazil).  The recommended international maximum residue limits




for the triphenyltin derivatives do not include contributions




that may be made by inorganic tin and di- and monophenyltin




moieties.  Subsequently, international commodities which do




not have an existing tolerance listed in 40 CFR 180.236 may be




subject to administrative action if found to contain TPTH residues




              C.  ADDITIONAL EFFECTS OF CONCERN




     Additional data submitted to the Agency in support of the




continued registration of TPTH have precipitated further




concerns about the safety of the pesticide.  At this time, the




available data on these effects are insufficient to determine




whether a Special Review risk trigger has been met or exceeded.




However, the Agency believes the effects described below merit




additional investigation and has required data to delineate




their exact nature and extent.




     TPTH has produced immunotoxic effects in mice and guinea




pigs.  A 90-day subchronic study using guinea pigs indicated




that the pesticide may inhibit lymphopoiesis and produce atrophy




of lymphoid tissues.  In this study, performed in 1960,




leukocyte counts were depressed at the lowest dosage level




tested (2.5 ppm or 0.1 mg/kg/day).  Although the Agency has




classified this study as minimally acceptable, the small number




of animals used in each test group as well as the absence of

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                            - 15 -



a NOEL for the observed effects have resulted in additional



data requirements.




     Exposure to TPTH also produced decreased testicular




weights in rat pups in a three-generation reproduction study



performed in 1967.  In this study, the F2b generation exhibited




decreased testicular weights when compared to the concurrent




controls at dosage levels of 1.0 ppm and above.  A NOEL for



the reproductive effects was estimated to be 0.025 mg/kg/day.



This study has been classified as provisionally invalid because




only summary data were submitted.  Registrants should submit



these supporting data, if available, to the Agency.  In the



event these data are not available, a new study as required




in the Guidance Document must be submitted.



     The oncogenic potential of TPTH cannot be determined



at this time.  In one study, female mice dosed with TPTH



developed endometrial hyperplasia at the lowest dosage level



tested, 1.05 mg/kg/day.  The development of a test chemical-



induced change in a reproductive organ is considered a serious




adverse effect by the Agency and because of the low dosage at



which the effect was observed it must be considered in the



overall assessment of TPTH toxicity.  Additional studies have




been required on an expedited basis in the Guidance Document




to clarify this concern.



     The Agency has also performed a preliminary risk




assessment, based on a 90-day inhalation study in rats and



calculated applicator inhalation exposure at 0.0016 mg/kg/day,




to determine potential risks to applicators by this exposure

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                              - 16 -




route.  A NOEL was not established for the effects observed




in the rat study (ie., alopecia, nasal discharge, red ears,



piloerection, etc.) and the resultant risk quotient (151) deter-




mination indicates it may be prudent to require respiratory




protection since any "margin of safety" assessment would result



in a lower safety factor.  TPTH is in EPA Toxicity Category I




(highest toxicity rating) by the inhalation exposure route.




     Additional studies which have been submitted to support the



continued registration of TPTH indicate the pesticide is highly




toxic to aquatic invertebrates, warmwater fish and estuarine/



marine organisms and is moderately to highly toxic to birds.



These studies suggest continued use of TPTH may have potentially




deleterious effects on wildlife and aquatic organisms.



      Data requirements are being mandated in the Guidance Document



on an expedited basis to clarify the environmental fate of TPTH.



These data include accumulation in rotational crops and fish,



leaching, adsorption, desorption, aerobic and anaerobic soil



metabolism, soil dissipation and photodegradation of the pesticide,



re-entry data, avian reproduction and dietary studies, and a



coldwater fish study.




     Based on the evaluation of the results of the studies required




above, the Agency will determine whether additional information




and/or restrictions are necessary.  Pivotal data requirements and



an expedited submission schedule are summarized in Table II.

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                              - 17 -
          TABLE II — DATA PIVOTAL TO THE SPECIAL REVIEW
Data Requirements
 Submission Date
Studies Pivotal to Teratogenicity

Teratogenicity

Postnatal Teratogenicity

Teratogenicityj/
(Dermal Exposure Route)

Analytical Methodology for
Plant and Animal Residues
Including Metabolites and
Tetraphenyltin Hydroxide

Residue Storage Stability
Data

Crop and Processed Commodities
Storage Stability Data
Including Metabolites and
Tetraphenyltin Hydroxide

Studies Pivotal to Additional Concerns

Soil and water photodegradation

Mobility Studies

Soil Dissipation Studies

Immunotoxicity Studies

Dermal Penetration

General Metabolism

Residue Determination for Food
Use Crops, Tobacco, Meat, Milk
Poultry and Eggs

Reproduction 2-generation

Chronic Toxicity

Oncogenicity
 December 7, 1985

       ii  11   n

        Reserved


     June 7, 1985
 December 7,  1985


     June 7,  1986
       n  n   n
       n   n    M
  January 1,  1986

       it  n   n


    March 7,  1986

     June 7,  1986




September 7,  1986

 December 7,  1988

       it  M   n
    Contingent on the results of the postnatal and standard
    teratogenicity and dermal penetration studies.

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                  D.  CURRENT REGULATORY ACTIONS




     Because the Agency has determined that TPTH produces terato-



genic effects in laboratory animals at concentrations to which




applicators may be exposed, the Guidance Document requires that a




warning be added to the pesticide label stating that TPTH causes




birth defects in laboratory animals and that exposure during



pregnancy should be avoided.  Additional label changes include




the  "Restricted Use" classification which limits the use of the




pesticide to certified applicators or to persons directly under



their supervision.  Protective clothing including a long-sleeved



shirt, long pants,  impermeable gloves, hat, boots, and an approved



pesticide respirator are also required.



     In addition to the protective clothing described above, a



face shield  is  required when the technical product is being



handled.  The Registration Standard also stipulates that no new



permits will be issued for the experimental use of TPTH as an



anti-fouling agent  in marine paints, nor will any FIFRA section 3




registration applications be considered during the Special Review.




     All currently registered TPTH products will remain registered




while the Special Review is in progress.  However, the Agency is



deferring final decisions on the reregistration of any products



containing TPTH as a sole active ingredient until the Special




Review is concluded.  No new uses for TPTH will be issued during




this period.  The Agency also will not approve pending requests



for  tolerances for TPTH on rice and soybeans or issue any new



tolerances during the Special Review.

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                            - 19 -






     The Agency is also currently considering the issuance



of a Data Call-in Notice pursuant to FIFRA section 3(c)2(B)  in




order to require registrants to submit specific information




on the use, exposure potential, and benefits of TPTH.



      E.  COMMENTS ON THE INITIATION OF THE SPECIAL REVIEW




     Prior to the initiation of a Special Review, technical



registrants receive private notification of the Agency's



determination that the criteria to initiate a Special Review




may have been met.  This notification includes information on



the toxicity findings, route of exposure and related general




information.  Registrants then have 30 days following receipt of



the notification to rebut the Agency's conclusions.



     In response to the Agency's notification that a Special



Review of TPTH was being considered, Uniroyal Corporation



proposed amending their product label in an effort to reduce



risks and obviate the Special Review of the pesticide.  Uniroyal



proposed classifying the pesticide as a restricted use chemical,



a 24-hour reentry label statement, a prohibition for female



applicators of childbearing age, and cancellation of all products



except those packaged in water soluble bags.



     The Agency believes the proposals submitted by Uniroyal




are generally in agreement with the requirements stipulated  in



the Guidance Document.  However, the Agency does not have the




information necessary to determine if these and other measures




will adequately reduce the risks from exposure to the pesticide




to an acceptable level.  This determination will be made through




the Special Review of TPTH.

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                             - 20 -






                     F.  REBUTTAL CRITERIA




     All registrants, applicants for registration, and other



interested members of the public are invited to submit evidence



either to support or to rebut the presumption that TPTH causes




teratogenic effects in rats and may cause such effects in humans.




Under 40 CFR 162.11(a)(4)(iii) the presumption initiating a




Special Review must be rebutted by proving, in the case of acute



and chronic toxicity criteria, "that the determination by the




Agency that the pesticide meets or exceeds any of the criteria




for risk was in error."



                   G.  BENEFITS INFORMATION



     The Agency will conduct a comprehensive benefits review



and analysis for TPTH during the Special Review process and will



consider that information in setting forth the Agency's proposed



regulatory decision in the Position Document 2/3 (PD 2/3).  A



preliminary analysis of the benefits of TPTH has been performed



and is presented here.



     The major use of TPTH is on pecans.  Over 72 percent of the



pesticide used annually is applied to this crop.  Georgia is the



primary pecan-producing State accounting for between one third




and one half of the total annual production of pecans in the



United States.  New Mexico, Texas, Alabama, and Louisiana make up




the remaining major pecan-producing States.  Any one of the




following States, Arkansas, Florida, Mississippi, North Carolina,




Oklahoma, and South Carolina generally account for less than




3  percent of the total national production.  Most of the

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                             - 21 -





TPTH applications occur in the Southeast because the environmental




conditions are conducive to disease development.



     Scab is the most important fungal disease in pecan culture



both in the Southeast and Southwest.  Preliminary data suggest



that although TPTH is the pesticide most commonly used in pecan



culture, registered alternatives are available for all pests with



the exception of sooty mold which is of minor concern.  It is



estimated that without the use of any fungicide, there would be a



substantial loss in the annual yield.  Use of the alternative



fungicide benomyl in pecan culture may reduce this loss signif-



icantly, although a major concern with the use of benomyl is



the development of benomyl resistant strains of fungi.  To



date, fungal strains that attack pecans have not demonstrated



a resistance to TPTH.  For this reason, TPTH and benomyl are



often used on an alternating schedule or applied in combination.



The chemical cost per acre difference between benomyl and TPTH



is minor.



     TPTH is also registered for use in controlling fungal



diseases in sugarbeets, peanuts, carrots, and potatoes.  On



peanuts, TPTH is used to control early leafspot and incidentally



contributes to mite suppression.  TPTH is also registered for use



on potatoes in controlling late and early blight.  Late blight  is



the more serious concern in potato culture, especially in the



Northeast.  Use of TPTH for control of diseases of carrots appears



to be minor but important for the control of Cercospora leafspot



of sugarbeets.  Benomyl is often applied for control for Cercospora,

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but TPTH is used where benomyl-resistant strains have developed.




The efficacy and potential unreasonable adverse effects  that may



be associated with alternatives for TPTH such as benomyl , metiram,




maneb, captafol, thiophanate-methyl, and others will be  fully




reviewed in Position Document 2/3.



     In addition to submitting evidence to rebut the presumptions




of risk in the Special Review, 40 CFR 162.11(a)(5)(iii)  provides



that a registrant or applicant "may submit evidence as to whether



the economic, social and environmental benefits of  the use of



the pesticide subject to the presumption outweigh  the risk of



use."  If  the presumption of risk is not rebutted,  the benefits



evidence submitted by registrants, applicants, and  other inter-



ested persons will be considered by the Agency when determining



the appropriate regulatory action.



     Registrants, applicants or other interested persons who



desire to  submit benefits information should consider submitting



information on the following subjects along  with any other



relevant information they desire:



     1.  Identification of the biological and economic importance




of TPTH uses.



     2.  Identification of alternative chemical and nonchemical



methods of control and any associated health effects and potential



for human  exposure.




     3. Determination of any change in costs to TPTH users for



obtaining  equivalent disease control with available substitute




products or management techniques.

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                            - 23 -



     4.  Assessment of the expected changes in the level of



efficacy, crop yield, crop quality, crop injury, and environmental




impacts associated with the use of alternative control measures.




     5.  Identification of increased or reduced risks associated




with the mixing, loading, and applying of alternative chemicals,




with their potential increase in use if TPTH were not available.




     6.  Identification of cultural and spray application




practices, that impact on farmworker exposure to TPTH.




     7.  Identification of cultural or integrated pest manage-



ment practices which are enhanced or limited by use of TPTH.



             II.  REBUTTAL SUBMISSION PROCEDURES



     All registrants and applicants for registration are



being notified by certified mail of the Special Review being



initiated on their products containing TPTH.




     The registrants and applicants for registration will



have 45 days from the date this notice is received or until



(insert date 45 days after date of publication in the FEDERAL



REGISTER) (whichever is later) to submit evidence in rebuttal



to the Agency's presumption.  Other interested parties may



submit comments during the same period.




     III.  DUTY TO SUBMIT INFORMATION ON ADVERSE EFFECTS




     Registrants are required by section 6(a)(2) of FIFRA to




submit any additional information regarding unreasonable adverse




effects on man or the environment which comes to their attention



at any time.  Registrants of TPTH products must immediately

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                            - 24 -




submit any published or unpublished information, studies,




reports, analyses, or reanalyses regarding any TPTH effects




in animal species or humans, and claimed or verified accidents




to humans, domestic animals, or wildlife which have not been




previously submitted to EPA.  These data should be submitted




with a cover letter specifically identifying the information




as being submitted under section 6(a)(2) of FIFRA.  Registrants




should notify EPA of any studies on TPTH currently in progress,




their purpose, the protocol, the approximate completion date,




a summary of all  results observed to date, the name and




address of the laboratory performing the studies, and a




statement as to whether these studies are being conducted  in




accordance with the Good Laboratory Practices specified in




40 CFR  Part 160,  published  in the FEDERAL REGISTER of




November  29, 1983  (48 FR 53946).




               IV.  PUBLIC  COMMENT OPPORTUNITY




      During the time allowed for submission of rebuttal




evidence, specific comments are solicited on the presumptions




set forth in this  Notice and in the Registration Standard.  In




particular, any documented  episodes of adverse effects on




humans or domestic animals  should be submitted to the Agency




as soon as possible.  Any information as to any laboratory




studies in progress or completed should be submitted to the




Agency as soon as possible  with a statement as to whether




those studies are  in compliance with the Good Laboratory




Practices specified in 40 CFR Part 160.  Specifically, infor-




mation on any adverse toxicological effects of TPTH, its

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                            - 25 -

impurities, metabolites, and degradation products is solicited.

Similarly, submission of any studies or comments on the

benefits from the use of TPTH is requested.  All comments and

information and analyses, which come to the attention of EPA,

may serve as a basis for final determination of regulatory

action following the Special Review.

     All comments and information should be sent to the

address given above, preferably in triplicate, to facilitate

the work of EPA and others interested in inspecting them.

The comments and information should bear the identifying

notation  [OPP-30000/42].

     During the comment period, interested members of the

public or registrants may request a meeting to discuss the

risk issues and methods of reducing risks.  Any records

pertaining to such meetings, including minutes, agendas, and

comments received will  be filed under docket number OPP-30000/42
Dated:  /"I/  /7 /
           /    /
                              Director,
                              Office of Pesticide Programs.

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