Docket Numbe r EPA

- HQ-OPP

- 20 15

- 0061 www.regu lati ons.gov



# Tetraconazole Preliminary Work Plan Registration Review: Initial Docket Case Number 7043

Approved by:

Date: 

# September 2015

**Gbh~** 

# r

**v~~::n** Richard P. Kei gwin, J r. 

### D irector Pesticide R e - eva luation Divi sion

### T et racon az ol e Pre liminary Work P lan- Tabl e of Contents

OVERVIEW
............................................................... . ... . .. .. .. .. .. .. .. .. . ... . .. .. .. .. . .. ... . .. .. .. .. .. .. .. .. .. .. .. .. .. . 4 ANTICIPATED DATA NEEDS
. .. .. .. .. .. .. .. .. .. .. .. ... . ... .. .. . . .. . . .... . ... . ................................................... 5 STATUTORY AND RE G ULAT ORY AUTHORITY
...... . .............. . ................ . ... . .. .. .. . ... .. .. .. .. .. .. .. 6 CHEMICAL FACTS
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ... . .. .. ... .. .. . ... .. .. .. .. . ... . ... .. .. . .. .. .. .. .. . .. .. .. .. . ... .. .. . . . . . ... . ..... . . . .... 6 US E AND USA GE INFORMAT ION
................... . ........................................................................ 7 RECENT ACTIONS
.. .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. ... . ... . ... .. .. .. .. .. .. .. .. .. .. .. .. .. . .. .. .. .. . . . . . .. .. .. ... . .. . ... . ... . ....... . .. . ... . 8 ANTIC IPATED RISK ASSESSMENTS FOR R E G JSTRA TION REVIEW
................................ 8 TIMELINE
... . ... . ... .. .. . ... . .. . . . .... . .. . ........................... . ........... . ....... . ................ . .. . ... .. .. . .. .. . . .. .. .. .. .. ... .. .. 1 1 NEXT STEPS
.............................................................. . ... . ... . .. .. .. .. .. .. . ... . .. .. .. .. .. . .. .. .. .. .. .. .. .. .. .. .. .. ... . 11 Appendix

- Additional Areas Considered in the Tetraconazo le Regis tration Review

............. 12

Refe re nc es: This Preliminary Work P l an summarizes the Environmental Protection Agency's current pos i ti o n based on the following documents : 1. 

### R eg istration Rev iew : Preliminary Problem Formulation fo r Environmenlal Fate Ecologica l Risk , Endangered Species, and Drinking Water Exposure Assessments/or Tetraconazole. He Zhong , Ph

. D. , and C h r istopher M
. Koper , M
. S
. August 26,20 1 5. 

### 2. 

### Tetraconazole, Human Health Risk Assessment Scoping Document in Support of Reg is tration Rev ie w. Anwar Y. Dunbar , Ph

.. D., T homas B loem, and James Miller. August 26 , 2015. 3. 

### Tetraconazole: Tier I (Scoping) R ev iew of Human Incid ents. Elizabeth Evans and Shanna Recore
. May 21 , 2015.

4. 

### BE A D Chemical Profile ( BCP)for Registralion Review: Tetraconazo le (120603). Leonard You rman , Rafael A. P rieto , and Mic h e ll e Ranville

. May 6, 20 1 5
.


### 2

### 5
. 

### Tetraconazofe (120603). Screening Level Usage Analysis (SLUA). November 5 , 20 14. 6. 

### Environmen tal Fare and Effects Division Label Data Report Spreadsheet: PC Code: 120603

. November 5 , 2014. 7. 

### Health Effects Division Alaster Label Report Spreadsheet: PC Code 120603. November 5 , 20 14
. These and other supporting documents for th e tetraconazole registration review case may be found in the docket EPA -HQ-OPP- 2015-006 1 at http: //www . regu lati ons.gov.

3

### OVERVIEW The docket for t e traconazole is now op e n , initiating the first public comment period for this re g istration review (docket number EPA-HQ-OPP-2015-0061)
. Tetraconazole is a d e m e thylation inhibiting (DMI) fungicide registered for use on soyb e ans , sugar b ee ts, corn ( field , pop) , peanuts , and pecans , to contro l Cercospora blight , frogeye l eaf spot, powdery mildew , brown spot , and anthracnose. It is also registered for some crops in the crop subgroups 13-07F (small fruit vine climbing subgroup , except fuzzy kiwifmit) and 13-07G (low growing b e rry subgroup , excluding cranberry). Currently , there are no registere d non-agricultural uses for tetraconazole. This Preliminary Work Plan (PWP) document explains what EPA's Office of Pesticid e Programs knows about tetraconazole, highlighting anticipated data and assessment needs , identifying the types of information that would be especially useful to the Agency in conducting the review , and providing an anticipated tim e lin e for compl e ting th e registration review for tetraconazole

. The registration review process was designed to include a public participation component to solicit input from interested stakeholders. The Agency intends , by sharing this informat i on in the docket , to inforn1 the public of what it knows about te traconazol e and what types of new data or other information would be helpful for the Agency to receive as it moves toward a decision on tetraconazole

. The Agency encourages all interested stakeholders to rev iew the PWP and Appendix and to provide comments and additional information that will help the Agency ' s decision-making process for this chemical. In addition to gen e ral areas on which persons may wish to comment , there are some areas identified in the PWP and Appendix about which the Agency specifically seeks comments and information. Interested stakeholders could include: environmental non-profit or interest groups; pesticide manufacturers; agricultural labor or commodity groups ; commercial , institutional , residential, and other users of pesticides; or the public at large. Th e Pre liminary Work Plan begins by listing the anticipated data needs for tetraconazole. Next , it discusses the statutory and regulatory authority for Registration Review. Then the document provides chemical facts, use and usage information, recent actions , the anticipated risk assessments, and a projected registration review timeline for tetraconazole

. Fina ll y , the Appendix to this document includes identification and discussion of some areas that are consid e red generally in Registration Review along with some additiona l chemical cas e - specific information.

4ANTICIPATED DATA NEEDS Table I below summarizes anticipated data needs fo r tetraconazole

. For additional discussion of the an ticipated data needs , see the 

### Regis tration R ev i ew: Pr el iminary Problem Formulation for Environmental Fate Eco logical Risk , Endangered Species, and Drinking Water Exposure Assessments for Tetraconazole and Tetraconazole, Human Health Risk Assessment Scop ing Document in Support of R egis tration Revi ew. Table 1: Anticipated Data Needs for the Tetraconazole Registration Review Estimated Guideline Timefram e Number• Stud y Titl e Test Material (Months from receipt of DCI) Anticipated Data Needs for the Parent Tetraconazo le 835.4200 A nae robic so il metabo lism 2 TGAI 24 835.4400 A nae rob i c aq uat i c metabo li sm 3 T GA J 12 860.1380 Sto rage s tability in soil and wate r TGA I 12 850.6100 Env ironmenta l Che mistryMethods and TGAl 12 Assoc iated In depende nt Laborato r y Validation 850. 1350 Aquati c in vertebrate l ife cyc l e (sa l twate r) TGAI 12 850 .1 400 Fis h early- life stage (sa l twater) TGAJ 12 850.4100 Terrestrial p lant tox i c i

ty , seed lin g emergence TEP 1 2 850.4150 Terr estria l plant tox i city , vegetati ve vigor TEP 12 850.1500 Fi s h lif e cycle (f r eshwater) T GA I 24 850.4500 A l ga l toxic i ty (freshwater g r ee n a l ga , fres hwater TGA I 12 a nd mar ine diato m) 850.4550 Cyanobacteria 

### (Anabaenajlos-aquae) toxicity TGA l 12 850.2100 Av i a n ora l toxic ity (passer i ne) T GA I 1 2
875.2100 Di s l odgeable foliar residue and turf tra nsferab l e TGAI 12 r esidues Whole se dim ent
-c hro ni c (T wo freshwate r No n- a m p hip ods , 

### Hyalella azteca and 

### Chironomus TGA I 12 guide line 

### tentans, and one estuarin e/ marine a mphip o d, 

### L

ep to che irus plumulosus). Non- Honeybee ad ul t c hr onic ora l toxic i ty TGA I 12 g uid el i ne Non- Ho neybee larval ac ute a nd ch ronic oral toxicity TGAI 12 guide l i ne

1 On June 27 , 2012, EPA announced certain revision s in harmonized guide line series 850

- Ecologica l Effects Tests

- including renumbering a nd other designations or changes fo r so m e guidel ine s tudies. See " Final Test Gu idelin es ; OCSPP 850 S e ries ; Notice of Avai lab ility " 77 FR 38282 , Jun e 27 , 20 12. http: //www .regu lation s .gov /# ! documentDetai I; D= E P

A-HQ-O PPT

- 2009-0 I 54-0028 2 Four soil systems 3 One additional water / sed iment system 

### 5

### Tab le 1: Anticipated Data Needs for the Tetraconazole Registration Review Estimated Gu ideline Timeframe Number 1 

### Study Title Test Material (Months from receipt ofDCI)
·"- Non- Residues in pollen and nectar 4 

### TEP 24 guideline

No n- Semi-fie ld testing for pollinators 4 

### TEP 24 g uid el i ne 850
. 3040 Field testing for poll in ators 4 

### TEP 24 TGAI = technical grade active ingred1ent; TEP = typical end-use product ; 

### STATUTORY AND REGULATORY AUTHOIUTY The Food Quality Protection Act (FQPA) of 1996 mandated a registration re view program. All pesticides distributed or sold in the Un ited States (U.S.) generally must be registered by the Env ironmental Protection Agency (EPA or the Agency), based on scientific data showing that they will not cause unreasonable risks to hum an health or the environment when used as directed on product labeling. The registration review program i s intended to make sure that , as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable adverse effec ts to human health or the e nvironment. Changes in science , public policy , and pesticide use practices will occur over time . Through the registration review program, the Agency periodically reevaluates p e sti cides to make sure th at as change occurs, products in the marketplace can be used safely. Information on th is program is provided on EPA ' s website

. 5 Th e Agency i s implementing the registration review program pursuant to Section 3(g) of the Federal Insecticide , Fungicide , and Rodenticide Act (F IFRA ) , and will review each reg is tered pesticide e very 15 years to determine whether it continues to meet the FIFRA standard for registration

. The regulations governing registration review begin at 40 CFR 155.40. The Agency will consider benefits in fo rmation and data as required by FIFRA
. Th e pub li c phase qf registration review begins when the initial docket is opened for each case. The docket is the Agency's opportunity to state what i t knows about the pesticide and what additional ri sk analyses and data or inforn1ation it believes are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period , the Agency will develop a F in al Work Plan (FWP) and anticipated schedule for the registration review of tetraconazole

. 

### C H EMICAL FACTS Table 2 provides a summary of the chemical facts for tetraconazo l e.

4 Pending rei vi e w of lower Tier studies. 5 http: // www.epa.gov / oppsrrd 1 / registration_review/ 

### 6

### Table 2: Chemica l Facts for Tetraconazo le PC code 120603 Case Number 7043 CAS N umb er 112281-77-3 Year first registered 199 3 Pe sticide Type Fungicide Chemical class triazole Reregistration Eligibility Tetraconazole was registered after November 1984; therefore , it Decision (RED) was not subject to reregistration. Tolerance Reassess ment Tetraconazole was re g istered after November 1984 ; therefore, it Eligibility Deci sion (TRE D ) was not subject to tolerance reassessment. C umulati ve group No cumulative risk assessment is required at this time since the Agency has not made a determination regard ing a common mode of action. 40 CFR Citation Tolerances are estab lished in 40 CFR 180.557
. Du al -use Conventiona l pesticide uses only. Non-pesticidal uses No non - pesti c i dal uses . Pe st icide Re-evaluation Veronica Dutch , dutch.veronica @e p a .gov, (703-308-8585 Division , C hemical Review Manager Registration Di vision, Hope Johnson, J ohnson.Hope@e pa . gov , (703)-305-541 0 Product Manager 

### USE AND USAGE I NF O RMAT I ON Table 3 summarizes the use and usa ge inf ormation for te traconazo le. Please see the 

### BE A D Chemical Profile (BC P)for Registration Review : Tetraconazole (120603, in the regis tration review do cket for more details

. 

### Tab le 3 : Te t raco n azo le Use and Usage In forma ti on Summary of Use Tetraconazole is a broad spec trum syste mic fu ngic ide with protective, curati ve , and eradicative prop erties. Tetraconazo le is a conazole containing compound and a triazole systemic fungicide which acts primarily by interferi ng with cell growth, particularly the abil ity to build ce ll walls, through inhibition of ergosterol bio sy nthesis in cell membranes

. Use Sites Use sites for tetraconazo le are soybeans , sugar beets , corn ( fi e l d , pop), peanuts , pec ans , and berries. The predominant use si tes are soybean and sugar beets (98+% of total usage)
. Summary of Usage Average usage (2008-20 12) was approximately 77 , 000 pounds of act ive in gre dient applied annually on 1.1 million acres. Formulation Typ e(s) Tetraconazole is formulated as an emulsifiab le concentrate. Application Method(s) Product s can be applied broadcast by g round or a ir , by chemgation or sprinkler irri gation , or with a hi gh vo lume or low volume sprayer. 

### 7Table 3: Tctrac o na zo l c Usc and Usage Information Technical Registrant(s) Sipcam Agro USA , In c . , and Isagro (S
. P.A
. ) No. of Registrations 1 3 Section 3 products 6 Restr icted Use No Guidance for Com mcntcrs : Additional areas of 

### use and usage related information requested for th is reg i stration review , and of particular interes t to EPA , are described below.

• The label for EPA Registration # 60063-12 for peanuts , pecan, and sugar beets does not li s t maximum application rate per year or th e maximum number of applications per year. • Seasonal , rather than yea rl y application information , is prov ided fo r some uses on the labels of EPA Registration # s 80289 -1 8 and 80289 -8. The number of app li cat ions and the maximum application rate on an annual basis are needed for the risk assessment. • Soybean use : the label for EPA Registration # 7969-361 does not prohibit app li cat ion to soybean afte r the R5 crop stage
. Fo r a ll products except EPA Registration #s 7969-361 and I 0163-332
. The labels for so me products have no information on a minimum retreatment interva l for control of soybean rust ; available field trial data were d eve loped with a minimum retreatm ent interval of 10 days. Without this i nformation, EPA will need to re ly on conservative assumptions to conduct its risk assessments , and doing so may lead to overest imates of actua l risk. The Agency is will in g to work with re g istrant s to clarify infonnation on tetraconazo le product labels.

• In addition , u sage information for small vine fruits and pecans (i nclud in g lb s acti ve ingredient ap plied on an annual b as is , tota l area treate d , typ ical application rates, target pests , and state usage data ) will be useful for the Agency ' s assessments of tetraconazole

. RECENT ACTIONS There are no recent actions for tetraconazo le . ANTICIPATED RISK ASSESSMENTS FOR R EG ISTRATION REVIEW The most recent occupationa l assessment for tetraconazo le was comp leted in Apri l 20 1 1, and the most recent aggregate risk assessment f or tetraco na zo l e was completed in April 2015. The most recent ecological and environmental fate risk assessment was completed in 2014. Findings and concl u s ions from these risk assessments are summarized in 

### Tetraconazole. Human Health Risk Assessment Scoping Document in Support of Registration Review and 

### Reg istration Review: Preliminary Problem Formulation for Env ironm ental Fate Ecological Risk , Endangered Species, and Drinking Wa ter Exposure Assessme nt sfor Te traconazole. Durin g registration review , the Agency antic i pates the n ee d to conduct a comprehensive ecological risk assessment , i ncl ud ing an endangered species assessment, for a ll uses of

6 Section 3 product lab e ls can be obtai ned from the Pesticide Product Label Syst e m (PPLS) website (http: //oaspub.epa.gov/ p es tlabl/ ppls.home). 

### 8tetraconazole. For human health, EPA anticipates the need to re - evaluate to x i c i ty endpoints /dose selection , and to conduct revised dietary and occupational risk assessments. The need for sp ray drift and vo l at ili zation ri sk assessments for tetraconazole al so will be considered

. If toxicological endpo int s or po int s of departure are revised based o n the data th at are ant icipated to be required for reg i strati on rev iew, they w ill be cons idered in th e new assessments , as w ill any changes to the standard operating procedures or default exposure assumptions. Tab le 4 below summarizes the antic ip ated registration review risk assessme nt s based on the EFED Problem Formula t ion and HED Scoping Document.

9

### Tab le 4 : Anticipated Ri s k Assessments for the T etraconazole Regi s tr a tion Review Type of Risk As sess ment Conduct? Notes Eco log ical and Environmen t a l Fate 

### - Comp r e hen s iv e eco log i ca l 

### y The Agency w ill conduct a comprehensive eco logica l in cluding endangered species assessment , including an endange red species assessment. Incidents Wi ll For a discussion of reported ecologica l incidents for check for tetraconazole , see page 14 of the Problem F orrnulation.

updates T here are currently no ecologica l incidents reported fo r tetraconazo l e. 

### Human Health> D ietary Food 

### y As part of the registrat ion rev i ew , the dietary risk assessment may be re visited. D r inking water 

### y Concentrations in drinking water w ill be ree valuated as part of registration review. Occupational Handlers (m ixers , loaders , 

### y Occupational handler and post-application dermal and applicato rs) inh ala tion assessments wi ll be rev i sed to reflect all Post-ap plication 

### y poten tial exposure scenarios, updated policies , exposure data , a nd any updated toxico logica l PODs. R eside ntial H and lers 

### N Tetraconazo le is not u sed in residential settings , so a residential handler assessme nt is not needed. Po s t-application 

### N Tetraconazole is not used in residential settings. A co n ve n tional r esidential post-application assessment is not needed. The need for drift and vo latility assessments will be considered during r egistration rev i ew. Other Aggregate 

### y A revised aggregate assessment may be requ ired to reflect revised dietary exposure estimates and/or changes to the toxico log ical PODs. C umulative 

### N Tetraconazole is a member of of the triazole

- contai nin g class of pesticides. Structural similarities do not constitute a common mechanism of toxic i ty and there is curr e ntl y no ev idence to indicate that m e mbers of thi s class sha r e a comm o n mech a ni sm of tox icit y . To le r ances 

### y Th e Agency will revis it th e tolerances during registration review. Incidents Will For a discussion of reported human incidents for check for tetraconazole , see page 11 of the Seeping Do cument and

updates the 

### T e traconazole: Tier 1 ( Scoping) Review of Human Incid e nls.

10G uidan ce f o r Co mm cnt e rs: Additional 

### ecological information reque ste d for this registration r eview, and of particular interest to EPA , is desc r ibed below.

• Aggregated incidents not already repo rted to the Age ncy. • Water monitoring data. G uid a nce f o r Co mm cnt c rs: Additional 

### human health information requested for this r eg istrat ion review , and of particular interes t to EPA , is described below.

• Human health incidents not pre v iously reported to the Agency. 

### T IM EL I NE EPA has created the following estimated timeline for the completion of the tetraconazole registration review in Table 5 below. Ta b le 5 : P ro j ec te d T e t ra c onazo le R egis tra tion R ev iew Tim clin e Ac ti v iti es Es tim at e d D a te Opening the Docket Open Docket and 60-day Public Comment Per iod September-20 15 C lose P ublic Comment November-20 1 5 Case Development Final Work Plan February-20 16 I ssue DCI April-June -201 6 Data Submission Apri l- June -2018 60 -day Pub l ic Comment Period for Draft Risk October

- Dece mb e r-20 19 Assess ments7 Registration Revi ew Decision 60-day Pub li c Comment Period fo r Proposed Ju l y-Septembcr-2020 Registration Review Decision Reg istrat ion Review D ec is ion and Begin Po s t-Decision 2021 Fo l low-up Total (years) 6


### NEXT S T E PS After the 60-day pub li c comment period closes , the Agency will review and respond to any comments received in a t imely manner and then i ss ue a F inal Wo rk Plan for the registration review of tetraconazo lc.

7 The regulations governing R eg is tration Re view generally req uire th e Agency to provid e a public comment period of at l eas t 30 calendar da ys for draft risk assessment s; see 40 CFR Part 155.53(c). For co nv e ntional pesticides , th e Agency plans to provid e a 60 ca l e ndar day public comment period generally for draft ri s k assessments. I I

### Appendix- Additional Areas Considered in theTetraconazol e Regi s tration Review PUBLIC COMMENTS AND FEEDBACK: G uidanc e for Co mm e nte rs: The areas below highlight topics of special interest to the Agency where your comments , data sub missions , or reference to sources of additional information could be of particular u se. 

### Trade Irritants: Through the registration review process , the Agency intends to so li c it information on trad e irritants and , to the extent feasible, take steps toward facili tating irritant reso lution. The Agency will work to harmoni ze tolerances and internationa l maximum residue limit s (MRLs) and may modify toleranc e levels to do so, when possib le. Growers and other s tak e hold e rs are asked to co mment on any tr ade irritant issues resultin g from Jack of M RL s o r di s p arities between U.S. tole rances and MRLs in key export market s, providing as much specificity as possible regarding the nature of the concern. 

### Water Quality: Tetraconazole is not ident i fied as a cause of imp airme nt for any water bodies li sted as im paired under section 303(d) of th e Clean Water Act. 8 In addition, no Total Max imum Daily Loads (TMDL) have been d eve loped for tetraconazole. 9 More information on impaired water bodies and TMDLs can be found at the Agency ' s websitc. 1 0 The Agency in v ites s ubmi ss ion of w a ter quality data for thi s pesticide. To the extent possib le , data should conform to the quality s tandards in Appendix A of the 

### OP P Standard Operating Proc edure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP 's Regis tration Review Risk Assessment and Management Process'' in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments. 

### Env ironmental Justice: EPA seeks to achieve environme ntal justice, the fai r treatment and meaningful involvement of all p eop le , regardles s of race, color , national origin , or income, in the development , impleme nt ation, and enforcement of environmental laws , regulations , and policies. To help address potential e n v ironmental justice iss ues , the Agency seeks information on any groups or segments of the population who, as a re s ult of their loc ation, cultural practices , or other factors, may have atypical, unusua ll y high exposure to tetraconazolc compared to the general popu l ati on. Please co mm e nt if yo u a re aware of any sub-populations th a t may hav e atypical , unu s uall y hi g h ex po s ure compared to the ge n era l p op ul a tion .

8 http: //iaspub.epa.gov/tmdl waters I0/anains nation cv.causc detail 303d?p cause group id = 885 9http: //iaspub.epa.gov / tmdl waters I 0/artains nation.tmdl pollutant detail?p pollutant group id = 885&p pollutant gro up name = PESTI C ID ES I O !J..!.m :!/www.epa.gov/owow/tmdl/ 11 http: //www .epa.gov/oppsrrd I /registration review / water gual itv sop.h tm 1 2

### EN DANG E RED S P EC I ES : A risk assessment th at supports a complete endange r ed spec ies d e termi nat io n has not b ee n conducted for tetraconazo le . The ecological risk assessment planned du ring reg istratio n rev iew wi ll allow the Agency to determine whether use of tetraconazo l e has " no effect" or " may affect" federally listed threaten ed or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide's use " may affect" a listed spec i es o r its designated critical habitat , the Agency w ill consult with the U.S. Fish and Wildlife Service and / or National Marin e Fisheries Service (the Services), as appropriate. 

### EN DO C RIN E DI S R UPTOR SCREENING PRO G RAM : As req u ired by F IFRA and FFDCA, E PA reviews numerous studies to assess potential adverse outcomes from exposure to chemicals. Col lectively, these studies include acute, subchronic and chronic toxicity , including assessments of carcinogenicity, neurotoxicity , developmental , reproduct ive, and general or systemic toxicity. The se studies include e ndpoints which may be susceptible to e ndocrine influence , including effects on endocrine target organ histopatho logy , organ weights, estrus cycl icity, sexual maturati o n , fert il ity, pregnancy rate s, reproductive loss, and sex ratios in offspr ing. For ecological ha zard assessments, EPA evaluates acute tests and chronic studies that assess growth, deve lopme n tal and r eprodu ctive effects in differe n t taxo no mi c g roups. As part of its most recen t reg istratio n dec i s io n fo r t e tr aconazo le, E P A rev iewed these data and se lected the most se n s it ive e ndpo ints for re levant ri sk assessment scenarios from the existing hazard database. H owever, as required by FFDCA section 408(p) , tetraconazole is subject to the endocrine screening part of the Endocrine Disruptor Screening Pro g ram (EDSP ). E PA has developed the EDSP to determine whether certain substances (including pesticide active and other ingredients) may have an effect in humans or wild li fe sim il ar to an effect produced by a " naturally occu rri ng estrogen , or othe r s uch endocrin e effects as t h e Admi nistra t or may des ig nate. " T he EDS P emp loys a two-t iered approac h to m ak in g the stat uto ril y requi red determ inations

. T ier I consists of a battery of I I screening assays to identify the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal sys tems. Chemicals that go through Tier 1 screening and are found to have the potential to interact withE, A, or T hormona l systems w i ll proceed to the next stage of the EDS P where EPA will determine wh ich, if any, of the Tier 2 tests are necessary based on the availab le data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the substance, and establish a dose-response relationship between the dose and theE , A, or 

### T effect. Under FF D CA sec t ion 408(p) , the Agency must scree n all pest ic ide c hem icals. Betwee n October 2009 and February 20 

### I 0, EP A i ssued test orders/data call -i ns for the first group of 

### 67 chemicals, which contains 58 pesticide active in gred ients and 9 inert ingred ien ts . A second list of chemicals identified for E DSP screening was published on J une 14 , 2013 12 and includes some pe s ticides scheduled for registration review and chemicals found in water. Neither of these lists

12 See http: //www.regulations.gov/# !documentDetai i ;D = EPA-HO-OPPT -2009-04 77-0074 for the final second list of

chemicals. 1 3should be construed as a list of known or likely endocrine disruptors. Tetraconazole does not appear on either list. For furthe r information on the s tatus of the EDSP, the po li cies and procedures , the lists of chem ica ls , future lists , the test g uidelin es and the Tie r I sc reenin g battery , please v isit our webs ite. 13 HUMAN STUDIES: 

### Oc cupational Past tetraconazol e risk assessments rely in part on data from studies in which adult human s ubj ects were intenti o nall y exposed to a pesticide to determine their derma l and inhalation exposure. Many such stud ies, involving exposure to many different pestic ides , comp rise generic pesticide exposure databases suc h as the Pesticide Handlers Exposure Database (PHED ) and the Agricultural Reentry Task Force (ARTF) D atabase. EPA has reviewed all the studies supporting these multi

- pesticide g e neric exposure databases , and has found no clear and convincing evidence that the conduct of any of them was either fundamentally unethical or significantly deficient relative to the ethical standards prevai I ing at the time the research was conducted. All applicable requirements of EPA ' s Rule for the Protection of Human Subjects ofResearch (40 CF R Pa11 26) have been sat is fi ed, and there is no r egulatory barrier to continued reliance on these studies

.

13 hrrp: //www.epa.gov / endo/ 14