Docket Number EPA-HQ-OPP-20 14-0 I 08 

www.regulations.gov 

Polyoxin D Zinc Salt Amended Final Work Plan 

Registration Review Case Number 6076 

PC Code: 230000 

March 2016 

Approved by: ____ /Z __ {!l ___c ___ _ Robert McNally, Director 

Biopesticide and Pollution Prevention Division 

Date: _ 3---=--- {5__._ 0 ltk-=---
I NTRODUCTION 

This is the Environmental Protection Agency's (EPA or the Agency) Amended Final 

Work Plan (FWP) for the registration review of Polyoxin D Zinc Salt. Following the publication 

of the June 2015 Final Work Plan, the Agency identified two comments submitted in response to 

the Polyoxin D Zinc Salt PreliminCIIy Work Plan and SummCIIy Document (PWP). One 

submission was submitted on behalf of Kaken Pharmaceuti cal Co., Ltd. (Kaken), and included 

comments regarding technical corrections, use and usage inf01mation, corrections to registered 

Polyoxin D Zinc Salt pesticide product information, and corrections to MRJD citations. The 

second submission was submitted by the Center for Biological Diversity. These comments did 

not change the Agency's work plan as established in the PWP, and did not establish the need for 

a new risk assessment on Polyoxin D Zinc Salt. The specific comments submitted by Kaken and 

the Center for Biological Diversity are addressed below. This Amended Final Work Plan (FWP) 

document makes final the work plan for the Polyoxin D Zinc Salt registration review process. 

BACKGROUND 

The Agency is implementing the registration review program pursuant to Section 3(g) of 

the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), and will review each 

registered pesticide every 15 years to detennine whether it continues to meet the FlFRA standard 

for registration. Changes in science, public policy, and pesticide use practices will occur over 

time. The registration review program is intended to make sure that, as the ability to assess tisk 

evolves and as policies and practices change, all registered pesticides continue to meet the 

statutory standard. The public phase of registration review begins when the initial docket is 

opened for each case. Information on this program is provided on the Agency's website. 1 

Polyoxin D Zinc Salt is a biochemical derived from Streptomyces cacaoi var. asoensis, a 

soil-borne actinomycete originally isolated in Japan. This active ingredient is currently 

registered for use on food crops, turf, and ornamentals to control and/ or suppress fungal diseases 

of plants. The mode of action of polyoxin D zinc salt is to prevent the binding of uridine 

diphosphate-N-acetylglucosamine to fu ngal chitin synthetase and inhibit the normal biosynthesis 

of chitin in fungi. In susceptible fungi , polyoxin D competes with uridine disphosphate-Nacetylglucosamine for the chitin synthetase binding sites, resulting in insufficient chitin for 

normal cell wall growth and maki ng the fungus unable to express its pathogenicity against the 

plant. Polyoxin D Zinc Salt is not used as a drug in human or veterinary medicine. 

1 http://www.epa.gov/oppsrrd 1/registration_review/ 

2 
Agency's Response to Public Comments on the Preliminary Workplan and Summarv 

Document 

COMMENT#! 

Agency's response to comments submitted on behalf of Kaken Pharmaceutical Co., Ltd. 

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1. Kaken Pharmaceutical Co., Ltd. noted that page 5 of the Preliminary Work Plan and 

Summary Document correctly notes that uses of Polyoxin D Zinc Salt were expanded 

in 2008 to include the listed food uses. However, the Preliminary Work Plan and 

S ummary Document omits the September 12, 2012 significant label expansion to 

include additional {ood crop uses. 

Crop Group No. Crop Group Name Comments 

Root and tuber vegetables Carrots, ginseng, parsnips, potatoes 

and suf!ar beets 

Bulb ve~tetables All crop f!roup members. 

Leafy ve~tetab es All crop ~t oup members. 

Brassica (cole) leafy All crop group members. 

ve~tetables 

Le~tume vef!elables All crop f!roup members. 

Fruitin~t vef!etables All crop f!roup members. 

Cucurbit ve~t tahles All crop f!roup members. 

Citrus fruits All crop f!roup members. 

Po me fruits All crop ~troup members. 

Stone fruits All crop ~troup members. 

Berries and small fruits All crop ~troup members. 

Tree nuts Almonds and pistachios. 

Crops not assigned to a crop Artichokes and pomegranates. 

~troup 

EPA Response: EPA concurs with including the missing information from the September, 201 2, 

label expansion, which included additional food crop uses. 

Trade irritants: Canada is a significant trading partner for food crops grown in the United 

States. Currently, there are no Canadian MRLs for polyoxin D zinc salt. On September 18, 

2014, Kaken submitted an application for Canadian MRLs (PMRA Submission No. 2014-

3908). Expedited review has been requested based upon the inclusion of the U.S. EPA decision 

documents. 

EPA Response: EPA is aware ofKaken's submitted application for Canadian MRLs (PMRA 

Submission No. 2014-3908). EPA's scheduled date for completion of its registration review 

decision is December 2016. The Agency will explore opportunities to complete its decision 

sooner if possible. 

3 
Comments 011 Table 2 regarding use a11d usage information: 

Table 2. Polyoxin D Zinc Salt Use and Usage In formation 

Kaken Pharmaceutical Comme11ts EPA Response 

Summary of Use Polyoxin D Zinc Salt is registered for The Agency concurs with the 

use 65 afeliHF SfJHIJ' on food crops, turf, correction of use information. 

and ornamentals to control ami/or 

suppress {unxal diseases of plants. 

Use Sites Commercial agriculture1 go({ courses, The Agency concurs with the 

home lawns and gardens, parks, tmd additional site use 

commercial lmd industrial groumls1 information. 

nurseries, greenhouses and similar 

structures. 

Summary of Usage 1) Sod for sale and other commercial The Agency concurs with the 

use; 2) commercial seed production; 3) addition of usage 

researchj 4l commercial ag,ricullurej 5l information. home am/ earden. 

Application method(s) Pffld-ttefs CHJI be ttppf.ied by ltamllteld e~ The Agency concurs with the 

medumiea! SfJFfiJ'e~s. Hmul-held1 addition methods of 

ground1 and aerial (pliar sera'(.. Banded application information. 

(in-{wrowl se.raf.. Chemigation 

(sorink/er am/ drio). Soil drench. 

Technical Registrant lffH:e.H Kaken Pharmaceutical CO. LT». All typographica l errors has 

Co.1 Lid. been noted and addressed. 

No. of Registrations 8 (681 73-5. Registered on December 111 

2014.)_ 

Please note that footnote 2 to Table 2 of the Preliminary Work Plan and Summary Document 

states, "Refer to the Usage Report in Support of a Registration Review for Polyoxin D zinc 

salt (23000) in the registration review docket for more details. " However, the referenced 

Usage Report is not included in the docket. 

EPA Response: EPA notes the omission ofthe above mentioned reference; addition of the 

reference will be added to the docket. 

The following was omitted from EPA's bibliography and that are referenced in Tables, 4, 6, 7, 

8 and 9. 

U.S. EPA 2012, Memorandumfrom Manying Xue, Chemist, U.S. Environmental 

Protection Agency to Colin Walsh, Regulatory Action Leader: "Polyoxin D Zinc Salt 

(EPA Reg. NO. 68173-1) Science Review of Product Chemistry, Residue Chemistry, 

Non-target Organism and Toxicity Data in Support of a Label A mendment," May, 11, 

2012. 

U.S. EPA 2014, L etter from Linda A. Hollis, Chief, U.S. Environmental Protectio11 

Agency to Kaken Pharmaceutical Co., Ltd. regarding "Submission of data under 

Federal Insecticide, Fungicide, ami Rodenticide Act (FIFRA) section 6(a)(2) that 

4 
identify impurities not previously listed 011 the current applicable Confidential 

Statement of Formula (CSF) a11d impuritiesf otmd outside the previously approved 

certified limits," March 6, 2014. 

E PA Response: The Agency concurs with the correction to the omitted bibliography. The 

bibliography will be included in the Final Decision document. 

Table 3 on page 7 oftlt e Preliminary Work Plan ami Summary Docume11t includes many 

errors ami omissions. Please see the corrected table below. 

Ta ble 3. In formation About the CurrentlyR egister ed Polyoxin 0 Zinc Salt Pesticide Products 

EPA Reg. Product Date Application Application Use Sites EPA Res12onse 

No. Name Register ed " Ra tes Methods 

(%Active 

ingredient; 

Formulation 

Type) 

66330-41 ~tem9ef Turf: 0.275 lb Foliar ~ Turf(golf The Agency notes 

24. 2002 a. i./A drench courses, that the column 

Fcbru!!fY 27, Ginseng: 0.03 residential entitled Date 

2007 - 0.06 lb lawns, Registered has been 

a. i./ 100 gal/A parks, modified by adding 

Ornamentals: commercial the qualifier 

0.6-0.12 lb and superscript A which 

a.i./100 gal institutional refers to the date of 

grounds1 the most recently 

non-food accepted label. 

ginseng; The product (66330-

ornamentals 41) was federally 

ENDORS£TM registered on 

(2.5% a.i.: September 24, 2002. 

wettable The product label 

powder) was amended and 

stamped accepted on 

2/27/2007. The 

product label 

(storage & disposal) 

statement was 

updated via 

notification on 

8/31 /2009. 

The Agency concurs 

with the additional 

application rates, 

methods and use site 

information. 

66330-56 ENDORSETM ~eBFI:Ia~ ;; Up to ;; 6 Foliar S(;!rav, Outdoor The product was 

Water June 5, 2014 applications drench. agricultural registered (66330-

Dispersible July 23, 20 15 ~ 4.2 oz · £hcmigation crops, 56) October 27, 

Granules a.i./A) per (sprinklers greenhouse, 2005. June 5th, 

( 11.3% a.i.; season or drip nurseries, 2014 & July 23, 

granular) irrigation) turf, 20 15 constitute the 

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Table 3. Information About the Currently Registered Polyoxin D Zinc Salt Pesticide Products 

EPA Reg. Product Date Application Application Use Sites EPA Res12 onse 

No. Name Registered " Rates Methods 

(%Active 

ingredient; 

Formulation 

Type) 

ornamentals most recent stamped 

' accepted labels. 

The Agency concurs 

with the additional 

application rates, 

methods and use site 

information. 

68 173- 1 Polyoxin D August 29, Not Not All food and The Agency concurs 

Zinc Salt 20 12 applicable; applicable feed crO(!S with the additional 

Teclmical product is (Qre-harvest use site infonnation. 

(23.8% a.i.) for pesticide and 

manufacturing (!Ostharvcst). 

use only ornamentals, 

golf courses, 

residential 

lawns, parks 

and 

commercial 

and 

institutional 

grounds 

68 173-2 ENDORSE April 28, Turf: 0.03- Fol iar ~ Golf courses, The Agency concurs 

Wettable 2009 0.275 lb drench residential with the additional 

Powder a. i./A lawn, parks percentage of active 

Fungicide Ginseng: 0.03 and ingredient, 

(2.5% a.i.; - 0.06 lb commercial application rates. 

wettable a.i./100 gal/A and methods and use site 

QOwder) Ornamentals: institutional information. 

0.6-0. 12 lb grounds, 

a.i./100 gal non-food 

ginseng, 

ornamentals 

68 173-3 ENDORSE February 12, ~ Ol: a.i.!A ~ Foliar (!ra~ . Commercial The Agency concurs 

Water 2014 ,) drench. outdoor with the additional 

Dispersible lilflestseasen chemigation and indoor percentage of active 

Granules Food: Max (sprinklers food use, ingredient, 

(I 1.3% a.i.~ 4.2 oz or drip turf, application rates and, 

water a.i.A/season. irrigation) ornamentals methods and use site 

disQersible Ornamentals: information. 

granules) 0.03 -0.06 

lb a.i.LI 00 gal The Agency also 

Turf: 0.27 lb concurs with the 

a.i.! A correction to the 

application rates. 

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Table 3. Information About th e Currently Registered Polyoxin D Zinc Salt Pesticide Products 

EPA 

No. 

Reg. Product Date Application Application Use Sites EPA es ~on se 

Name Registered " Rates Methods 

(% Active 

ingredient; 

Formulation 

Type) 

68173-4 Veggieturbo April 26, Max. 4.2 oz Ground or Commercial The Agency concurs 

sse 201 3 a. i./A/season. aerial spray, emEioor with the additional 

Suspension 3.7S - 6.S fl soil drench, food use percentage of active 

Concentrate oz product! A or ingredient, 

Fungicide (protective); chemigation application rates and 

(S% a.i.: 6.S to 13.0 (sprinklers methods 

~en n fl oz/A (high or drip information. 

concentrate) disease irrigation), ill 

pressure or furrow The Agency also 

stand-alone concurs with the 

applications. correction to the use 

site information. 

700S I- Novel O.S% March S, Food and Foliar spray Gen=uf!ereial The Agency concurs 

11 6 SC Fungicide 2014 ornamentals: (hand outeeor with the additional 

(O.S% a.i.; Max. 2 pump ~ee lise percentage of active 

susQension teasQOOnS sprayer, Residential ingredient, 

concentrate) Qroduct I garden home and application rates, and 

guart water. sprayer, garden, use site infom1ation. 

Turf: I.S - 3.0 mister, or residential 

fl oz/gal other sprayer turf. The Agency also 

water; in a residential concurs with the 

minimum of2 indoor correction to the use 

gal mix/ 1,000 and outdoor site infonnation. 

ft 2 of ornamentals. 

treatment 

area. 

681 73 -L Polvoxin D Commercial The Agency's PWP 

Zinc Salt gost-harvest for Polyoxin D Zinc 

sse Salt addressed 

Post-Harvest current registered 

Fungicide products containing 

Polyoxin D Zinc Salt 

at the time when the 

registration review 

process began. The 

PWP does not 

address pending 

applications at the 

time of document 

production. 

A Date of most recently accepted label. 

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EPA Response: The Agency concurs with the corrected tables. The updated tables will be 

included in the Final Decision document. 

Table 4. Summa r y of Product Ana lysis Da ta for Polyoxin D Zinc Salt 

Ha rmonized Data Requir ement Has Da ta Requirement MRID No. or 

G uideline Been Addressed? How? Other Source 

Number 

880.1100 Product Identity and Composition Yes- Study 43261809 

442 14601 " 

880.1200 Description of Starting Materials, Yes- Study 43261809 

Production, and Fonnulation Process 4326 1810A 

44214601" 

49227701 8 

880.1400 Discussion of Fonnation of impurities Yes- Study 43261809 

442 14601 " 

44249801 " 

491 25501 ° 

49227701 ° 

830.1700 Preliminary Analysis Yes- Study 43261811 

44249701 '' 

44249801 \ 

49277301 8 

830.1750 Certified Limits Yes - Study 43291809 

442 14601 " 

49277301 ° 

830. 1800 Enforcement Analytical Method Yes- Study 43261811 

4326 1812 

43261813 

4326 1814 

43261815 

49125501 8 

4922770313 

A. U.S. EPA. 2008. 

B. U.S. EPA. 20 14. 

EPA Response: The Agency concurs with the corrected table. The updated tables will be 

included in the Final Decision document. 

~ a bl e 6 . ~ OXICO . I ogy D at a S u b mrtt . e d to EPA 

Ta ble 6. Summa ry of Human Health Assessment Da ta for Polyoxin D Zinc Salt 

Ha rmonized Data Requirement Has Data Req uirement MRID No. or 

G uideline Been Addressed'? How? Other Source 

Number 

870.3 100 90-dav Oral (I Soccies) Yes - Studv 4714 101 " 

870.3700 Prenat!JI Develogmental (2"d Yes - Studv 486533 15 II 

Soccies) 

870.3800 Rcgroduction and Fertility Yes - Study 471 20904 \ 

Effects 

870.5100 Bacterial Reverse Mutation Test Yes- Study 43323001 

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Table 6. Summa ry of Human Health Assessment Data for Polyoxin D Zinc Salt 

Ha rmonized Data Req uirement Has Data Requirement MRID No. or 

Guideline Been Addressed? How? Other Source 

Number 

48653313 I) 870.5300 In Vitro Mammalian Cell Assay Yes - Study 4326 1835 

870.5375 48653314 9 

870.5395 In Vivo Mammalian Yes- Study 47145102 " 

Cvtoe..enetics 

880.3550 lmmunotoxicitv Yes - Studv 47120901 \ 

A. U.S. EPA. 2008. 

B. U.S. EPA. 2012. 

EPA Response: The Agency concurs with the corrected table. The updated table will be 

included in the Final Decision document. 

Table 7: Non-Target Organism and Environmental Fate Data 

Table 7. Summary of Non-Target Organism and Environmental Fate Data for Pol oxin D Zinc Salt 

Ha rmonized Data Requirement Has Data Requirement MRID No. or 

Guideline Been Addressed? How? Other Source 

Number 

835.2120 Hvdrolvsis Yes - Studv 48653304A 

835.2240 Photodee.radation in Water Yes - Studv 48653305 ,, 

835.4100 Aerobic Soil Metabolism Yes - Studv 48653306 A 870.2100 Avian Acute Oral Toxicity Yes - Study 4326 1840 

1;261841 

870.2200 Avian Dietary Toxicity Yes - f>ata Wai .. •eF Study 43261841 B 

850.4100 Terrestrial Plant Tox icity, Seedling Yes - Data Waiver U.S. EPA, 2008 

Emergence 

850.4150 Terrestrial Plant Toxicity, Vegetative Vigor Yes - Data Waiver U.S. PA ~ 2008 

850.5400 Ah.tal Toxicitv Yes - Studv 48660403 A 880.4350 Nontarget Insect Testing Yes - Study 43261844 

48660404 A A. U.S. EPA. 2012. 

B. U.S. EPA. 1997. 

EPA Response: The Agency concurs with the corrected table. The updated table will be 

included in the Final Decision document. 

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Table 8: Residue Chemistry Data 

Table 8. Summarv of Residue ChemistrY Data for Polvoxin D Zinc Salt 

Harmonized Data Requirement Has Data Requirement MRID No. or 

Guideline Been Addressed? How? Other Source 

Number 

860.1100 Chemical denti~ Yes- Studv 48653307" 

860.1200 Directions for Use Yes - Study 48653307" 

48653308" 

860.1300 Nature of the Residue in Plants Yes - Study 48653309A 

48653310" 

48653311" 

860.1300 Nature of the Residue in Livestock Yes - data waiver 48653307" 

860.1 340 Residue Analvtical Method Yes- data waiver 48653307" 

860.1360 Multiresidue Method Yes- data waiver 48653307" 

860.1400 Magnitude of the Residue in Potable Water, Yes - data waiver 48653307" 

Fish and Irrigated 

Cro_g_s 

860.1460 Food Handling Yes - data waiver 48653307 ' 

860.1480 Magnitude of the Residue in Meat, Milk, Yes - data waiver 48653307'' 

PoultrY and E!!J?.S 

860.1500 Croo Field Trials Yes - data waiver 48653307" 

860.1520 Processed Food/feed Yes - data waiver 48653307" 

860.1540 Anticioated Residues Yes - data waiver 48653307" 

860.1550 Proposed Tolerances Yes - Study 48653307" 

860.1560 Reasonable Grounds in Sum~ort of the Yes - Studv 48653307" 

Petition 

A. U.S. EPA, 2012. 

EPA Response: The Agency concurs with the corrected table. The updated table will be 

included in the Final Decision document. 

Table 9. regarding efficacy am/ mode of action data is new and is provided below. Please note 

that: 

1. Efficacy (maximum inhibitory concentration) data were required by EPA to 

confirm that polyoxin D zinc salt is not an antibiotic; am/ 

2. Mode of action data were required by EPA to support the classification of 

polyoxin D zinc salt as a biochemical pesticide. 

Table 9. Summary of Efficacy and Mode of Action Data for Polyoxin D Zinc Salt 

Harmonized Data Requirement Has Data Requirement MRID No. or 

Guideline Been Addressed? How? Other Source 

Number 

810.0000 Efficacy (to confirm not an antibiotic) Yes - Study 43261802" 

48653308B 

810.0000 Mode of Action Yes- Study 43261803" 

43261804" 

43261805'' 

43261806" 

43261807" 

4326J808A 

10 
A. U.S. EPA. 1997. 

B. U.S. EPA. 2012. 

1 43372101 ,\ 

43372102:\ 

EPA Response: The Agency concurs with the corrected table. The updated table will be 

included in the Final Decision document. 

COMMENT #2 

Agency 's response to comments submitted by The CENTER for BIOLOGICAL DIVERSITY 

The Center for Biological Diversity's (CBD) comments focus on the EPA's duty to consult 

with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the 

Services) 0 11 the registration review of Polyoxin D Zinc Salt in accordance with the 

Endangered Species Act (ESA). The CBD comments mention various aspects of the risk 

assessment process, including use of the best available data to develop endangered species risk 

assessments, and evaluation of ef ects on endangered and threatened species and their 

designated critical habitat. CBD also expresses concern regarding the rigor of the Agency's 

preliminary determinations regarding the effects of Polyoxin D Zinc Salt 011 endangered and 

threatened (listed) species and their designated critical habitat for the Polyox in D Zinc Salt 

registration review. 

EPA Response: EPA has reviewed the comments from CBD on the Polyoxin D Zinc Sail 

Prelimina~y Work Plan and Summary Document and plans to address many of the concerns 

raised by CBD as part of the implementation plan for assessing the risks of pesticides to listed 

species based on the recommendations of the April 2013 National Academy of Sciences (NAS) 

report. EPA wi ll address concerns specific to Polyoxin D Zinc Salt in connection with the 

development of its final registration review decision for this pesticide. 

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AMENDED TIMELJNE 

Table 1: Registration Review for Polyoxin D Zinc Salt- Projected Registration Review Timeline 

Activities Estimated Date 

Opening the Docket 

Open Docket and 60-day Public Comment Period for PWP September 2014 - Completed 

Close Public Comment November 2014 - Completed 

Case Development 

Final Work Plan June 2015 - Completed 

Amended Final Work Plan February 2016 - Completed 

60-day Public Comment Period for Draft Risk Assessment NA 

Registration Review Decision 

Open 60-Day Public Comment Period for Proposed June 2016 

Registration Review Decision 

Close Public Comment Period August 2016 

Final Decision December 2016 

*Estimated Total (years) 2 years and 3 months .. • Th1s schedule IS subject to rev1s1on should unforeseen 1ssues anse dunng the reg1strat1on rev1ew process. In the 

event an issue arises, such as the fa ilure to acquire an EDSP exemption, another amended Final Work Plan will be 

issued at that time that will set forth a new timeline and, if applicable, any new data requirements wi ll be included 

in the amended document and a Data Call-In Notice will be issued. 

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