Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 2 of 63 Zinc Pyrithione Regi stration Review Team

Human Health & Environmental Effects David Bays Najm Shamim Siroos Mostaghimi William Erickson Tim McMahon Timothy Dole

Health Effects Division Donald Wilbur

Risk Management Sandra OPNeill Rose Kyprianou Zebora Johnson

Office of General Counsel Philip RossDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 3 of 63 TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD acute population adjusted dose ASRI activated sludge respiration inhibition
atm-m 3 /mole atmospheric pressure-cubic meter per mole BCF bioconcentration factor °C degrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese hamster ovary CMA Chemical Manufacturers Association CO 2 carbon dioxide COC concentration-of-concern cPAD chronic population adjusted dose DB database uncertainty factor DCI data call-in EC 50 median (or 50 percent) effect concentration EC 05 5 percent effect concentration ECOTOX ECOTOXicology EDI estimated daily intake EDSP Endocrine Disruptor Screening Program E-FAST Exposure and Fate Assessment Screening Tool EPI Suite Estimation Program Interface Suite EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Federal Food, Dr ug, and Cosmetic Act FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act FWP Final Work Plan g/mol grams per mole GLN guideline number HPV high production volume IDS Incident Data System Koc organic carbon normalized soil-water partition coefficient Kd soil-water partition coefficient Kow octanol-water partition coefficient LC 50 median (or 50 percent) lethal concentration LD 50 median (or 50 percent) lethal dose LOAEC lowest-observed-adverse-effect-concentration LOEC lowest-observed-effect-concentration LOAEL lowest-observed-adverse-effect-level Log K ow logarithm of the octanol-water partition coefficient μg microgram ml/g milliliter per gram mg/kg milligram per kilogram mg/kg/day milligram per kilogram per day mg/L milligram per liter mm Hg millimeter of mercury MOE margin of exposureDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 4 of 63 MRID Master Record Identification Number MRL maximum residue limit N/A not applicable
nm nanometers NOAEC no-observed-adverse-effect-concentration NOAEL no-observed-adverse-effect-level OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co-operation and Development OPP Office of Pesticide Programs PAD population adjusted dose PAI pure active ingredient PDM Probabilistic Dilution Model % percent PC Code Pesticide Chemical Code PCF pounds per cubic foot pH power of hydrogen or power of the concentration of the hydrogen ion PHED Pesticide HandlerPs Exposure Data PIS primary irritation score pKa power of the acid dissociation constant or negative base-10 logarithm of the acid dissociation constant of a solution ppb parts per billion ppm parts per million PWP Preliminary Work Plan QSAR quantitative structure-activity relationship RED Reregistration Eligibility Decision RfD Reference Dose SAR structure activity relationship SF safety factor SSTS Section Seven Tracking System SO 2 sulfur dioxide TEP typical end-use product TGAI technical grade active ingredient TMDL total maximum daily loads UF uncertainty factor UV/VIS ultraviolet/visible light absorption % w/w percent weight per weight. WP wettable powder WWTPs wastewater treatment plants ZnPT zinc pyrithioneDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 5 of 63 

### Table of Contents
1 Introduction .................................................................................................................. ........... 7 1.1 Statutory and Regulatory Authority ................................................................................. 7 1.2 Updates to the Workplan .................................................................................................. 7 1.3 Case Overview ............................................................................................................... 1 0 1.4 Chemical Identification and Properties .......................................................................... 10 1.5 Use/Usage Description ................................................................................................... 12 1.5.1 Registrations ........................................................................................................... 12 1.5.2 Summary of Regist ered Uses .................................................................................. 12 1.5.3 Usage Information .................................................................................................. 12 1.6 Regulatory History ......................................................................................................... 13 1.6.1 Tolerance Information ............................................................................................ 13 1.7 Incidents ..................................................................................................................... .... 13 1.7.1 Human Health ......................................................................................................... 13 1.7.2 Ecological ............................................................................................................... 14 2 Anticipated Data Needs ........................................................................................................ 14 3 Human Health Risk Assessment ........................................................................................... 16 3.1 Existing Toxicological Endpoints .................................................................................. 16 3.2 Dietary Exposure ............................................................................................................ 1 8 3.2.1 Food ........................................................................................................................ 1 8 3.2.2 Drinking Water ....................................................................................................... 18 3.3 Occupational and Residential Exposures ....................................................................... 18 3.3.1 Occupational Handler Exposure ............................................................................. 19 3.4 Residential Handler Exposures ...................................................................................... 19 3.4.1 Residential Post-Applic ation Exposures ................................................................. 20 3.5 Aggregate and Cumulative Exposure ............................................................................. 20 3.5.1 Aggregate Exposures .............................................................................................. 20 3.5.2 Cumulative Exposures ............................................................................................ 20 4 Environmental Risk Assessment........................................................................................... 21 4.1 Environmental Fate Assessment .................................................................................... 21 4.1.1 Adsorption/Desorption: Determination of Kds ....................................................... 22 4.1.2 Transmetallation of ZnPT ....................................................................................... 22 4.1.3 Leaching from Antifoulant Paint ............................................................................ 22 4.1.4 Persistence of ZnPT in Air ...................................................................................... 22 4.1.5 Degradation Products of ZnPT Identified from Various Studies ............................ 22 4.1.6 Water Quality .......................................................................................................... 23 4.2 Environmental Exposure Pathways ................................................................................ 23 4.3 Ecological Effects Assessment ....................................................................................... 24 4.3.1 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 24 4.4 Exposure Analysis Plan .................................................................................................. 26 4.4.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 26 4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 26 4.4.3 Endocrine Disruptor Screen ing Program (EDSP) ................................................... 26 5 Next Steps .................................................................................................................... ......... 27 6 References .................................................................................................................... ......... 28Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 6 of 63 Appendix A Toxicology Profile ............................................................................................... 29 Appendix B Residential Post-App lication Studies .................................................................. 40 Appendix C Environmental Fate ............................................................................................. 44 Appendix D Ecotoxicology Profile .......................................................................................... 46 Appendix E Screening Level Down-the-Drain Analysis ........................................................ 58 Appendix F Product Chemistry ............................................................................................... 59 Appendix G Comments Received Concerning th e Preliminary Work Plan ............................ 60

List of Tables Table 1 k Summary of Anticipated Risk Assessments and Data Needs: Zinc Pyrithione .............. 8 Table 2 k Chemical Identification of Zinc Pyrithione .................................................................. 10 Table 3 k Physical-Chemical and Environmenta l Fate Properties for Zinc Pyrithione ................ 11 Table 4 k ZnPT Registered Uses ................................................................................................ .. 12 Table 5 k Studies Anticipated as Needed for th e Registration Review of Zinc Pyrithione .......... 15 Table 6 k Existing Toxicologi cal Endpoints for ZnPT ................................................................. 16 Table 7 k Occupational Handler Ex posure Scenarios for ZnPT ................................................... 19 Table 8 k Residential Handler Exposure Scenarios for ZnPT ...................................................... 19 Table 9 k Residential Post-Applicati on Exposure Scenarios for ZnPT ........................................ 20 Table 10 k Summary of Results from E nvironmental Degradation of ZnPT ............................... 22 Table 11 k Available Ecological E ffects Endpoints for the TGAI ............................................... 25Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 7 of 63 

## 1 Introduction

This document is the United States Environmen tal Protection AgencyPs (USEPA, EPA or lthe agencym) Final Work Plan (FWP) for zinc pyrith ione (ZnPT). The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about ZnPT, highlighting anticipated data and assessment needs, identifying the types of inform ation that would be especially useful to the agency in conducting the review , and providing an anticipated timeline for completing ZnPTPs review.

The registration review process was designed to include a publi c participation component to solicit input from interested stak eholders. The agency intends, by sh aring this information in the docket, to inform the public of what it knows abou t ZnPT and what types of new data or other information would be helpful for the agency to receive as it moves toward a decision on ZnPT

.


## 1.1 Statutory and Regu latory Authority
The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion review program is 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 effects to human health or the environm ent. Changes in scien ce, public policy, and pesticide use practices will occur over time . Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Inform ation on this program is provided at http://www2.epa.gov/pesticide-reevaluation

. The agency is implementing the registration revi ew 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 determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agencyPs opportunity to state what it knows about the pesticide and what additional risk analyses and data or information it believes are needed to make a registration re view decision. The Zinc Pyrithione Preliminary Work Plan (PWP) wa s published on September 25, 2014 and the 60 day comment period ended on November 24, 2014.

Public comments received concerning the PWP and documents associated with the zinc pyrithione registration review case can be viewed at http://www.regulations.gov in docket EPAHQ-OPP-2014-0158.



## 1.2 Updates to the Workplan
Since the publication of the PWP, the agency has made the following updates:Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 8 of 63 x Corrected formatting and typographical errors.

x Provided more information on FDA ZnPT clearances in Section 1.6.1.

x Updated characterization of 2004 dietar y assessment in Sections 3 and 3.2.

x Added criterion information for chronic to xicity/carcinogenicity study in Appendix A

x Added Appendix G, Comments Received Concerning the Preliminary Work Plan.

The agency received comment submissions from three organizations du ring the public comment period on the initial docket. Comme nts were received from the Ce nter for Biological Diversity (Center), the Los Angeles Water Quality C ontrol Board (LA Water Board), and the San Francisco Bay Regional Water Quality Control Board (SF Bay Water Board). The CenterPs comments sought to confirm the agencyPs coordina tion with the U.S. Fish and Wildlife Service and the National Marine Fisheries under Secti on 7 of the Endangered Species Act (ESA) to ensure that ZnPt does not jeopard ize the continued existence of any listed species or result in adverse modification or destruc tion of critical habita t. LA Water Board comments focused on a request that the agency consider the potential aquatic impacts for form ation, persistence, and cumulative toxicity of zinc pyrit hione, including toxi city of copper pyrithione, in waters where copper antifouling paints are prevalent. Comm ents from the SF Bay Water Board expressed support for the comments submitted by the LA Water Board.

Please see Appendix G for the agencyPs responses to these comments.

Comments received did not result in a modification to the anticipate d data needs detailed in the Zinc Pyrithione PWP. This document makes fi nal the work plan for the zinc pyrithione registration review process.

Tables 1 and 2 below summarize th e issues relevant to this re gistration review case and the anticipated registration review schedule.

Table 1 – Summary of Anticipated Risk Asse ssments and Data Needs: Zinc Pyrithione

Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed

Dietary (food) Yes 2004 Updated Subchronic Neurotoxicity Immunotoxicity Chronic Toxicity/Carcinogenicity

Dietary (drinking water) Yes 2004 Updated Subchronic Neurotoxicity Immunotoxicity Chronic Toxicity/Carcinogenicity

Occupational Handler Yes 2004 Updated Indoor Dermal Exposure Indoor Inhalation Exposure

Residential Handler Yes 2004 Updated Indoor Dermal Exposure Indoor Inhalation ExposureDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 9 of 63 Risk Assessment Assessment Necessary to

Support Registration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed

Residential Post Application - Incidental Oral and Dermal Yes 2004 Updated None

Aggregate Yes 2004 Updated Subchronic Neurotoxicity Immunotoxicity Chronic Toxicity/Carcinogenicity

Cumulative No (see 3.5.2) 2004 None None

Ecological Yes 2009 Updated None

N/A = Not applicable

Table 2 – Anticipated Regi stration Review Schedule
Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2014-09 2014-09-25 Close Public Comment Period 2014-11 2014-11-24 Phase 2: Case Development

Issue Final Work Plan 2015-03 2015-03

Issue Data Call-In (DCI) 2016-03

Receive Data to be Considered in Risk Assessment 2019-03

Open 30-Day Public Comment Period for Preliminary Risk Assessment(s) 2020-09

Close Public Comment Period 2020-10
Phase 3: Registration Review Decision and Implementation
Open 60-Day Public Comment Period for Proposed Decision 2021-03

Close Public Comment Period 2021-05

Issue Final Decision 2021-09

Begin Post-Decision Follow-up 2021
Total (years) 7 *The anticipated schedule will be revised as necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 10 of 63 

## 1.3 Case Overview
The docket for the ZnPT case (case 2480) has been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2014-0158.



## 1.4 Chemical Identification and Properties

Table 2 presents the active ingredient to be assessed in case 2480: ZnPT (PC Code 088002).

Table 2 – Chemical Identifica tion of Zinc Pyrithione

Chemical Name Zinc pyrithione (ZnPT) Chemical Classification Organozinc; Omadine salt
PC Code 088002
CAS Number 13463-41-7
Molecular Formula C 10 H 8 N 2 O 2 S 2 Zn Molecular Weight (grams/mole) 317.68

Molecular Structure

The ZnPT product chemistry inform ation (MRID Nos. 42036701, 47330101, and 47330101) relevant to risk assessment is summarized in Ta ble 3, and the details of the environmental fate and product chemistry information are discussed in Appendix C and Appendix F , respectively.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 11 of 63 Table 3 – Physical-Chemical and Environmen tal Fate Properties for Zinc Pyrithione

Guideline No. Parameter Zinc pyrithione Physical/Chemical Properties 830.7000 pH 10% slurry in neutral distilled water 6.5-9.5 830.7200 Melting point ~240 °C. Decomposes before melting. 830.7220 Boiling point Not applicable. Decomposes 830.7550 Octanol-water partition coefficient (Log K ow ) 0.9 at 25 ஈ C
830.7840 Solubility in water 15 ppm 8 ppm at neutral pH 830.7950 Vapor pressure 4.9 x 10 -7 mm Hg Environmental Fate Properties Mobility
Organic Carbon Partitioning Coefficient (K oc ) 430454 L/Kg
Persistence in Water (half-life)

835.2120 Hydrolysis at 25 o C: pH 5, 7 & 9 Stable at the three pHs (5, 7, and 9) under abiotic, and buffered conditions.

Simulated sea water at pH 9 half-life is 96 days. (MRID 43864602). 835.2240 Aqueous photolysis at 25 o C ZnPT half -life is 13 minutes (MRID 44011501)

835.4300 Aerobic aquatic metabolism In both fresh and salt water, ZnPT degradation process is biphasic. Phase I half-life < 1 hour; Phase II half-lives range from 12-15 days. (MRIDs# 44850004 and 45876501)

835.4300 Aerobic aquatic metabolism (conducted in the presence of light) ZnPT degraded with a half- life of 35 minutes The study was conducted in salt water system (MRID# 45876501)

835.4400 Anaerobic aquatic metabolism half-life (days) Fresh and salt water, the half-life= 2 hours in phaseI; in phase II, in fresh water and salt water halflife= 25.5 hours;

Freshwater, and salt water half-life in sediment = 13 to 19 hours (MRIDs 44010403, 44850002).

835.1230 Adsorption/Desorption or batch equilibrium study Salt water sediment - K d 50-99 L/Kg, Fresh water sediment - K d 11-48 L/Kg (MRID# 45565201)

NA Leaching Rates from boat/ship bottoms antifoulant paints ZnPT as an antifoulant paint was applied from 2 to 7.4% and the leach rates varied between 1.2μg/cm 2 /day to 8.4 μg/cm 2 /day. (MRID#: 44833301, 45347201, 45349801, 44877103, 44877104, 44877105, and 44877106) Note: Almost all degradation pathways formed degradates of ZnPT and these are discussed in section 4.1.5Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 12 of 63 

## 1.5 Use/Usage Description

1.5.1 Registrations There are 60 products containing ZnPT as an act ive ingredient (a.i.). Thirty products are antifoulant paints that contai n 1.33 to 47.4 percent a.i., twen ty-five products are general preservatives that contain 0.054 to 99.6 percent a.i., and five products are technical or manufacturing use products that contain 48 to 99.6 percent a.i.



### 1.5.2 Summary of Registered Uses

Table 4 presents a listing of the registered uses of ZnPT. Thes e uses will be assessed in registration review. Application methods and application rates of ZnPT are also included.

Table 4 – ZnPT Registered Uses

Use Application Method Application Rate

Materials Preservative – Indirect Food Contact

Repeat use food contact polymers (utensils, food containers, countertops); food packaging adhesives Open pour Up to a maximum of 1000 ppm in the treated material (21 CFR 175.105)

Materials Preservative – Non Food Contact
Carpets fibers and backing Open pour 4000 ppm
Building materials (drywall, ceiling tiles, partitions) Open pour 4000 ppm
Textiles including clothing, mattress covers, tarps, tents, sails and boat covers. Open pour 3600 ppm

Non-Marine Paints and Coatings Open pour 5000 ppm
Plastics (Non-Food contact items) Open pour 4000 ppm
Antifouling Coatings

Antifoulant Boat Paint Brush/Roller/Airless Sprayer 1.3 to 4.8% (22 labels) 4.95% (#60061-118) 6.38% (#557-700) 7.3% (#2693-194)



### 1.5.3 Usage Information According to the Specialty Biocides North America Report 2004-2005 (Kline, 2005) ZnPT is used primarily as a materials preservative for plasti cs, resins, adhesives and sealants as well as in marine antifoulant coatings. The ma rket penetration is approximately 13 percent for plastics and resins, <1 percent for marine antifoulant coatings and <1 perc ent for adhesives and sealants.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 13 of 63 

## 1.6 Regulatory History
The first product containing ZnPT was registered by the EPA on June 19, 1975 for use as a microbiostat in dry vinyl wallpaper powder. In 2004, EPA completed a preliminary risk assessment to support the Reregistration Eligibility Decisi on (RED) (EPA, 2004). 1 Because the Reregistration Decision Document was not published in 2004, the agency entered into the registration review docket the do cument it intended to issue as a RED for this chemical.



### 1.6.1 Tolerance Information There are no tolerances or tolerance exemp tions established for ZnPT. The Food and Drug Administration (FDA) has established regulati on for ZnPT for use in the preservation of components of paper coatings (non-polymeric) us ed in the manufacture of paper and paperboard (Food Contact Notification 1169). Since the publi cation of the PWP, EPA confirmed that historical FDA clearances (from 1993 k 1995) exist for the following uses of Zn PT: adhesives, sponges and polyolefins (conveyor be lts, repeat-use applications). At that time, the FDA determined exposure to ZnPT was below their Threshold of Regulation (TOR) policy. The TORs from 1993-1995 are not identified in any publicly available documents or other information sources.



## 1.7 Incidents

1.7.1 Human Health

Individual Incident Reports

Incidents that are rated as mode rate (HC) or higher are report ed in individual reports which include information regarding the causes of the incident and symp toms experienced. In the case of ZnPT, there is one individual in cident report listed in the OPP Incident Data System (IDS) for the period 1/1/1999 to 5/05/14 (search conducted on 5/ 05/14). This incident is classified as human moderate (HC) and it involved dermal e xposure when workers were handling a pesticide product while not wearing gloves. This dermal exposure resulted in blis ters and rashes which resolved once the workers started wearing gloves.

Aggregate Incident Reports

Incidents that are rated as minor (HD) or that cannot be rated (HE) ar e reported in aggregate reports which are listings of the incidents for a manufacturer or distribu ter over a certain time period (often quarterly). Typical ly these reports only contain basi c information such as the date, location and product involved and more detailed in formation such the cause of the incident or symptoms experienced are not included. In the case of ZnPT, ther e are seven aggregate incidents listed in the IDS for the period 1/1/1999 to 5/05/14 (search cond ucted on 5/05/14). All

1 Zinc Pyrithione Preliminary Risk Assessment document s for the RED are available on regulations.gov, docket number EPA-HQ-OPP-2004-0147.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 14 of 63 of these incidents are classified as human minor (HD). In one incident, dermal irritation was experienced while using the product. There is no information regarding the other six incidents.



### 1.7.2 Ecological No ecological incidents are in the Incident Data System (IDS, v. 1.8) as of March 12, 2014.



## 2 Anticipated Data Needs

Table 5 presents a summary of the data anticipate d as being needed to su pport this registration review.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 15 of 63 Table 5 – Studies Anticipated as Needed for th e Registration Review of Zinc Pyrithione

GLN Study Name Test Substance Time Frame (Measured in months from DCI Receipt) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data

Requirement Applicable Exposure Scenario

Studies Anticipated to be Required th rough the Registration Review DCI

870.4300 Combined Chronic Toxicity/Carcinogenicity TGAI 36 Human Health Assessment All Use Sites Dietary and drinking water exposures

870.6200 1 90-Day Subchronic Neurotoxicity TGAI 12 Human Health Assessment All use sites All exposure scenarios

870.7800 1 Immunotoxicity TGAI 12 Human Health Assessment All use sites All exposure scenarios 875.1200 Indoor Dermal Exposure TGAI or surrogate 2 24 Occupational and Residential Material preservation including architectural paints See Footnote 3 875.1400 Indoor Inhalation Exposure

1 All 90-day subchronic studies in the rodent can be designed to simultaneously fulfill the anticipated requirements of the 90-d ay neurotoxicity and/or immunotoxicity studies by adding separate groups of animals fo r testing of neurotoxicity and/or immunotoxicity parameters.

2 It may be possible to use proprietary surrogate exposure data if data compensation issues are appropriately and adequately add ressed.

3 Exposure scenarios include Open Pour Addition of Liquids and Powders for Material Preservation, Airless Spray and Brush/Roller Application of Preserved Architectural Paints.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 16 of 63 

## 3 Human Health Risk Assessment

The agency anticipates the need to update the human health risk assessment for ZnPT. A human health risk assessment for ZnPT was conduc ted in 2004 and posted to regulations.gov under docket number EPA-HQ-OPP-2004-0147. In that 2004 as sessment, dietary risk was assessed for use of ZnPT as an antimicrobial pesticide in food packaging material s and in repeat use polymeric food contact materials. Drinking water risk was a ssessed from use of ZnPT in antifouling boat paint for recreationa l boats. Residential risk was a ssessed from use of ZnPT as a materials preservative.

Since the 2004 assessment, additional informati on on hazard and exposure has been submitted to the agency. To address hazard from dermal exposure to ZnPT, in vitro and in vivo data on the dermal absorption of ZnPT (MRIDs 48155702, 47986801) were submitted, as were data on the pharmacokinetics of ZnPT following oral and dermal exposures (MRID 47751201), and a physiologically-based pharmacokinetic (PBPK) m odel describing ZnPT kinetics after dermal exposure (MRID 48596001). Additional data on neurotoxicity, immunotoxicity, and carcinogenicity are also anticipated as being needed for registrati on review of ZnPT. These data will be reviewed and will be included in the revised risk assessment for ZnPT.



## 3.1 Existing Toxicological Endpoints
Table 6 presents the existing toxicological endpoi nts used in the agencyPs most recent risk assessment for ZnPT. The agency anticipates the need to revise these endpoints as part of registration review. All available informati on including existing toxicology studies, valid scientific literature, and studies available dur ing registration review will be considered in revising the existing toxicology endpoints for ZnPT . For a toxicological profile of ZnPT, see Appendix A.

Table 6

̽ Existing Toxicologica l Endpoints for ZnPTDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 17 of 63

Exposure Scenario Dose Used in Risk Assessment, Uncertainty Factor (UF) Target MOE, FQPA Safety Factor (SF) Study and Toxicological Effects Acute Dietary (Females 13 - 50) NOAEL = 0.5 mg/kg/day

UF = 100x

DB = 3x Acute RfD = 0.0016 mg/kg/day FQPA SF = 1x aPAD = acute RfD FQPA SF

aPAD a (females 13+) = 0.0016 mg/kg/day Developmental Toxicity Study in Rabbits

LOAEL = 1.5 mg/kg/day, based on increased post-implantation loss and decreased viable fetuses

Acute Dietary (General population, including infants/children) NOAEL = 0.75 mg/kg/day

UF = 100 DB = 3x Acute RfD = 0.0025 mg/kg/day FQPA SF = 1x aPAD = acute RfD FQPA SF

aPAD = 0.0025 mg/kg/day Developmental Toxicity Study in Rats

LOAEL = 3.0 mg/kg/day based on increased salivation in maternal rats.

Chronic Dietary (all populations) NOAEL = 0.5 mg/kg/day

UF = 100 DB = 3x Chronic RfD

= 0.0016 mg/kg/day FQPA SF = 1x cPAD = chronic RfD FQPA SF

cPAD = 0.0016 mg/kg/day Developmental Toxicity Study in Rabbits

LOAEL = 1.5 mg/kg/day, based on increased post-implantation loss and decreased viable fetuses

Incidental Oral, Short- and Intermediate-Term Maternal NOAEL= 0.75

mg/kg/day Target MOE 300 (residential) Developmental Toxicity Study in Rats LOAEL = 3.0 mg/kg/day, Based on increased salivation in maternal rats. Dermal, Short-, Intermediate-, and Long-Term Adults (including Females 13 - 50 years) NOAEL = 0.5 mg/kg/day

(3% DAF) Target MOE 300 (residential) 100 (occupational) Developmental Toxicity Study in Rabbits

LOAEL = 1.5 mg/kg/day, based on increased post-implantation loss and decreased viable fetuses.

Children (1-6 yrs) Dermal NOAEL = 100 mg/kg/day (DAF not required) Target MOE 300 (residential) 90-Day Subchronic Dermal Toxicity in Rats LOAEL = 1000 mg/kg/day, based on decreased body weight gain, food consumption, and food efficiency in female rats.

Inhalation, Short-, Intermediate-, and Long-Term Inhalation NOAEL = 0.0005 mg/L (0.13 mg/kg/day) Target MOE 300 (residential) 100 (occupational) Subchronic Inhalation Toxicity Study in Rats

LOAEL = 0.0025 mg/L Based on clinical signs of toxicity, decreased activity, and increased lung weights.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 18 of 63 

## 3.2 Dietary Exposure
The agency anticipates the need to revise the acute and chronic dietar y (food and drinking water) exposure assessment for registrati on review. Dietary exposure to ZnPT can occur from use in food packaging adhesives, food packaging material s, conveyor belts, and repeat use polymeric food contact materials. Information obtained by EPA on clearances established for ZnPT by FDA will also be used to revise the dietary e xposure assessment. In combination with the anticipated toxicology studies be ing requested (see Table 5), di etary risks may need to be reassessed if there is a change in the acute or chronic dietary endpoint and/or if aggregate risks exceed the agencyPs levels of concern.



### 3.2.1 Food In the 2004 ZnPT risk assessment, the agency eval uated exposure and risk from use of ZnPT in conveyor belts. The conveyor belt use was consid ered to represent the highest potential for dietary exposure of all the uses of ZnPT that could result in di etary exposure. This was based on repeatability of use, high freque ncy of use, and a short life at the use level for conveyor belts compared to other uses resulting in dietary e xposure. Assumptions regarding exposure were used in that assessment will be re-evaluated to be ce rtain that the latest information is used for the
assessment.


### 3.2.2 Drinking Water

In the 2004 risk assessment for ZnPT, a drinking water assessment was conducted based on the antifoulant paint use of ZnPT on recreational boats that were expected to impact surface water resources (lakes, rivers) that can serve as drin king water sources. The assumptions and models used in the 2004 risk assessment w ill be re-evaluated to be certai n that the latest information is used for the assessment.

Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA Safety Factor (SF). This calculation is perf ormed for each population subgroup for which an endpoint exists. A risk estimate th at is less than 100% of the ac ute or chronic PAD is not of concern. Acute and chronic dietary risk for ZnPT will be assessed by comparing dietary exposure estimates expressed in mg/kg/day to th e acute Population Adjusted Dose (aPAD) and chronic Population Adjusted Dose (cPAD).



## 3.3 Occupational and Re sidential Exposures
The agency anticipates the need to revise the occupational and resident ial assessments conducted in support of the 2004 risk assessment. This is needed to account for th e revised toxicological endpoints that are likely to be selected based on the toxicology studies that were submitted after 2004 and indoor exposure studies that are anticipated to be require d in registration review to account for dermal and inhalation routes of expos ure from the ZnPT mate rial preservation use siteDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 19 of 63 

### 3.3.1 Occupational Handler Exposure Occupational Handler Data Received Since the 2004 Risk Assessment

In response to the 2004 risk assessment, a Shipyard Painter Exposure Study (MRID 46707001) has been submitted. This study has been reviewed by EPA (D311326) and was used in the ORE assessment for the registration of a similar chemical, copper pyrithione, as a new active ingredient for use in antifoulant paints (D384689). This study will be used to assess shipyard painter ZnPT exposures dur ing registration review.

Occupational Handler Exposures to be Assessed during Registration Review

All of the occupational handler scenarios that were assessed in the 2004 risk assessment will need to be reassessed during re gistration review to account for th e new exposure data that have been submitted or that are anticipated to be required. The occupational handler scenarios to be assessed are presented in Table 7.
Table 7 – Occupational Handler Exposure Scenarios for ZnPT

Scenario Exposure Route(s) Duration Open Pour Addition of Liquids for Material Preservation Dermal, Inhalation Short and Intermediate Term Open Pour Addition of Powders for Material Preservation Dermal, Inhalation Short and Intermediate Term Airless Sprayer Application of Antifoulant Paints to Ships Dermal, Inhalation Short and Intermediate Term Brush/Roller and Airless Sprayer application of preserved paints to buildings Dermal, Inhalation Short and Intermediate Term



## 3.4 Residential Handler Exposures

Residential Handler Data Receive d Since the 2004 Risk Assessment

In response to the 2004 risk assessment, a recreational boat painte r study (MRID 46511801) has been submitted. This study has been reviewed by EPA and was used in the ORE assessment for a similar chemical, copper pyrithione (D384689). This study will be used to assess recreational boat painter ZnPT exposures during registration review.

Residential Handler Risk Exposures to be Assessed during Registration Review

All of the occupational handler scenarios that were assessed in the 2004 risk assessment will need to be reassessed during re gistration review to account for th e new exposure data that have been submitted or that are anticipated to be required. The residential handler scenarios to be assessed are presented in Table 8.
Table 8 – Residential Handler Exposure Scenarios for ZnPT

Scenario Exposure Route(s) Duration Brush/Roller Application of antifoulant paints to pleasure boats Dermal, Inhalation Short Term Brush/Roller and Airless Sprayer application of preserved paint to buildings Dermal, Inhalation Short TermDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 20 of 63 

### 3.4.1 Residential Post-Application Exposures Residential Post Application Data Received Since the 2004 Risk Assessment

Several post application studies have been re ceived since the 2004 risk assessment. These include four textiles leaching st udies, a carpet transferable resi due study and a plastics leaching study. Three of the textile leaching studies indi cated similar results, wi th leaching rates that ranged from 0.11% to 3.19%, depending on th e treatment type, while one study (MRID 48902609) indicated much higher leaching rate s of 7 to 51.3%. A repeat study (MRID 49149402) using the same product (Niccanon ZP-700) indicated leaching rates that were more consistent with the two studies with lower leaching rates. For detailed information on the agencyPs review of the post-applic ation studies, please see Appendix B

Residential Post Applicati on Exposures to be Assessed during Registration Review

All of the residential post appl ication scenarios that were asse ssed in the 2004 risk assessment will need to be reassessed during registration re view to account for the new residue data which have been submitted or that are anticipated to be required. The residential post application scenarios to be assessed are presented in Table 9.

Table 9 – Residential Post-Applicat ion Exposure Scenarios for ZnPT

Scenario Exposure Route(s) Duration Exposure to ZnPT preserved textiles Dermal, In cidental Oral Short and Intermediate Term Exposure to ZnPT preserved carpe ts Dermal, Incidental Oral Short and Intermediate Term
Plastics Dermal, Incidental Oral Short and Intermediate Term

Shoe Liners Dermal Short and Intermediate Term



## 3.5 Aggregate and Cumulative Exposure

3.5.1 Aggregate Exposures The agency anticipates the need to revise the aggregate assessment conduc ted in support of the 2004 ZnPT risk assessment. Upon a reevaluati on and selection of toxicology endpoints, combined with the human health exposure assess ments expected as a part of this registration review case, aggregate exposures an d risks will need to be assessed.

The risk assessment is anticipated to include an acute and chronic (non-ca ncer) aggregate dietary (food and water) assessment, a short-term a ggregate assessment (average food and water exposure plus short-term residential exposures ), an intermediate-ter m aggregate assessment (average food and water exposures plus interm ediate-term residential exposures, including exposures resulting from FDA regulated uses), and a cancer aggregate risk assessment (if positive results are observed in th e carcinogenicity studies).



### 3.5.2 Cumulative Exposures

With respect to cumulative exposure, unlike other pesticides for which EPA has followed a cumulative risk approach based on a common me chanism of toxicity, EPA has not made aDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 21 of 63 common mechanism of toxicity finding as to ZnPT and any other substances and ZnPT does not appear to produce a toxic metabolite produced by other substances. For the purposes of this registration review, ther efore, the agency has not assumed that ZnPT has a common mechanism of toxicity with other substances.

For information regarding EPAPs efforts to determine which chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

. 

## 4 Environmental Risk Assessment

No ecological risk assessment was conducted for the 2004 risk assessment. At that time, indoor uses, such as the materials preservatives uses, were not used to assess ecological risks. The antifoulant use also was not assessed due to lack of data needed to conduct an environmental risk assessment. In 2009, the agency completed an envi ronmental risk assessment for the use of zinc pyrithione in antifoulant boat pain ts to control growth of slim e, algae, and marine fouling organisms (e.g., barnacles, tubeworms, etc.) belo w the water line of recr eational and commercial boat hulls (EPA 2009). Results from the 2009 environmental risk assessment will be evaluated during registration review.

The ecological risk assessment planned during re gistration review will allow the agency to determine potential risks to aquatic organisms exposed to zinc pyrithione that may reach the aquatic environment. The risk assessment will allow the agency to determine whether each use of ZnPT has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticidePs use 'may affect' a listed species or its designated criti cal habitat, the agency will consult with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Services (i.e., Services), as appropriate.



## 4.1 Environmental Fate Assessment
Degradation Pathways :

Abiotic media : Although ZnPT is hydrolytically stable under abiotic conditions at pH 5, 7, and 9, in aqueous photolysis at pH 9, it degrades with a half-life of 13 minutes (MRID# 43864692, 44011501).

Biotic media : Under aerobic aquatic conditions in both fresh and salt water, ZnPT degraded biphasically with a phase I half -life of approximately an hour and a phase II half-life of 12-15 days. Biphasic degradation was also shown in bot h freshwater and salt water anaerobic aquatic metabolism studies. The phase I ha lf-life was approximately 2 hours, but the phase II half-life was 25 hours showing faster overall degradation in anaerobic syst ems than in aerobic systems (MRID# 44850004, 45876501).Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 22 of 63 

### 4.1.1 Adsorption/Desorption: Determination of Kds Two adsorption/desorption studies were conducted; one with salt water medium and the other with freshwater medium. Measured K d values were 50 to 99 L/kg for saltwater and, 11 to 48 L/kg for freshwater indicating that ZnPT binds to sediment more strongly in salt water than in fresh water. Overall, ZnPT can be considered to be mobile to moderately mobile (MRID# 45565201).



### 4.1.2 Transmetallation of ZnPT ZnPT is kinetically labile and can transmetallate in the presence of metal ions such as copper and iron. If ZnPT reaches the soil/ sediment of aque ous bodies, it is likely to form copper and or ferric pyrithiones which are more stable than ZnPT.



### 4.1.3 Leaching from Antifoulant Paint One of the major antimicrobial us es of ZnPT is as an antifoul ant paint for boat and small ship bottoms. ZnPT is used at various concentrations and with different colorants. Leaching rates for various ZnPT application concentrations have be en determined. The percent application of ZnPT as antifoulant ranges between 1% to 7%, and the rates of leaching from the treated boat or ship bottoms range between 1.2 μg/cm 2 /day to 8.4 μg/cm 2 / day. From these leaching rates, estimated environmental concentrations (EECs) can be de termined for ecological risk assessments of aquatic organisms.

Leaching rates from treated fabrics are discus sed in Appendix B of this document (MRID #s 45349801, 45347201, 44833310, 44877103, 44877106, 44877105, 44877104).



### 4.1.4 Persistence of ZnPT in Air The half-life of ZnPT estimated against the hydroxyl reaction is about 26.9 hours. ZnPT is moderately persistent in air (EPI Suite version 4.11, accessed on 05/23/14).



### 4.1.5 Degradation Products of ZnPT Identified from Various Studies
As seen in the structure shown in Table 2, ZnPT is an organo-metal complex of two pyrithione molecules joined by one zinc molecule. There were eight degradates iden tified in environmental fate studies, and all identified degradates retained the pyrimidin e ring structure. Table 10 lists the identified degradates and the studies wh ere individual degradates were identified.

Table 10 – Summary of Results from Environmental Degradation of ZnPT

Degradate Fate Studies* where Degradates ID 1. Pyrithione disulfide Hydrolysis Anaerobic Aquatic Metabolism 2. Pyrithione sulfinic acid Hydrolysis Anaerobic Aquatic Metabolism Aerobic Aquatic Metabolism 3. Pyrithione sulfonic acid Aerobic Aquatic Metabolism

4. Pyrithione thiosulfonic acid Aerobic Aquatic MetabolismDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 23 of 63 5. Pyridine disulfide Photolysis Anaerobic Aquatic Metabolism 6. Pyridine sulfinic acid Anaerobic Aquatic Metabolism

7. Pyridine sulfonic acid Photolysis Anaerobic Aquatic Metabolism Aerobic Aquatic Metabolism 8. 2-mercaptopyridine/2-mercaptopyrine-N-oxide (mixed disulfides) Photolysis Anaerobic Aquatic Metabolism * MRIDs of various fate studies: 43864602, 44011501, 44010403, 44850002, 44850004, 45876501

At this time the agency does not anticipate the ne ed to require additional environmental fate data for the ZnPT degradates because the degradates ar e not expected to have significant toxicity to non-target organisms.

Environmental Fate of Zinc

Zinc is a naturally occurring element which is most stable at an oxidation state of Zn 2+ . As a mineral, it exists as sphalerite [(Zn(Fe)S] in the earthPs crust. It is also an essential micronutrient and is found in many mammalian systems as zinc -enzymes which act as catalysts in many biochemical metabolic pathways. It forms many salts such as chloride, sulf ate, nitrate, carbonate and oxide.

Zinc from ZnPT in antifoulant paints is re leased into aqueous medium between 1.7 to 8.4 μg/cm 2 /day from treated ship bottoms. Once ZnPT dissociates in aqueous medium, bioavailability of zinc ions will depend on water chemistry. Zinc ions will be available as Zn 2+ and will form salts and complexes depending on pH and available anions.



### 4.1.6 Water Quality ZnPT is not identified as a cause of impairmen t for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at the agencyPs National Pesticides Cause of Impairment of Waters website (searched March 31, 2014) 2 . In addition, no Total Maximum Daily Loads (TMD L) have been developed for ZnPT, based on information provided at the agencyPs National Pesticide TMDL web site (searched March 31, 2014). ZnPT is likely to release zinc over a period of time as zinc ion in water. A search on the impaired water bodies show that a number of water bodies are f ound impaired because of the presence of zinc ions. More information on impaired wa ter bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/

.


## 4.2 Environmental Exposure Pathways
Aquatic organisms potentially at risk include those inhabiting water bodies adjacent to or downstream from ZnPT leaching from antifoulant pa int directly into freshwater or saltwater

2

. http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 24 of 63 environments. Water bodies might include im pounded bodies (e. g., harbors, lakes, reservoirs) or flowing waterways (e. g., streams, rivers). Fo r uses in coastal areas, aquatic habitat also includes estuaries and harbors. Aquatic organi sms likely to be acutely exposed include fish, invertebrates, aquatic stages of amphibians, and aquatic and semi-aquatic plants. Chronic exposure also is possible due to continuous or re peated exposures from antifoulant leachate.

For aquatic animals, the major route of exposure to ZnPT and its degradates is considered to be uptake via the respiratory surface (gills) or the integument from residues in surface waters or sediments. Based on the log K ow (0.97), bioaccumulation in aqua tic organisms is unlikely. For aquatic plants, the major route of exposure is considered to be uptake from surface water.

ZnPT as an antifoulant paint when leached from surface water (rivers, sea, lakes) reaches sediments and may adversely impact aquatic or ganisms like invertebrates and vertebrates; thereby reducing their survival, growth, and re production. ZnPT could be ingested by algae, resulting in reduction in algae production, reduction in prey. Vasc ular and non-vascular plants could be adversely impacted whic h could result in the reduction of habitat integrity in primary productivity and cover.

A screening-level risk assessment will be conducted as part of this registration review and will evaluate potential risks indicat ed above to ecological organisms from exposure to ZnPT.



## 4.3 Ecological Effects Assessment

4.3.1 Measures of Effect (Ecotoxicology Endpoints) Ecological effects data are used as measures of direct and indirect effects to aquatic and terrestrial organisms. Acute and chronic toxi city data from registrant-submitted studies conducted in accordance with the 850 OCSPP Harmoni zed Test Guidelines are used to evaluate the potential direct and indirect effects to plan ts and animals. Relevant data from the open literature also may be used if available.

4.3.1.1 Submitted data Acute and chronic toxicity data from registra nt-submitted studies conducted in accordance with the 850 OCSPP Harmonized Test Guidelines are used to evaluate the potentia l direct and indirect effects to plants and animals. All data requirements and avai lable ecotoxicity endpoints from studies submitted by registrants are tabulated in Appendix D . OPP uses the most sensitive of these endpoints for assessing risk to each terre strial and aquatic receptor group. The available endpoints selected for the risk assessment for technical-grade ZnPT are provided in Table 11. No additional data are expected to be needed. Ch ronic data are not available for estuarine/marine fish. However, those data are not anticipated to be needed, because estuarine/marine fish are much less acutely sensitive than freshwater fish, for which chronic data are available (Table 11). If a chronic endpoint is needed for the risk assessment, an NOAEC can be extrapolated by using the acute and chronic endpoints for freshwater fish and the acute endpoint for the estuarine/marine fish.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 25 of 63 The available toxicity endpoints for the zinc pyrithione degradates ( pyridine sulfonic acid and pyrithione sulfonic acid) are provided in the tables in Appendix D . Because these degradates have little if any toxicity to aquatic organisms, the risk assessment will be based on the data for technical-grade ZnPT. The agency also has some av ailable toxicity data fo r dissolved zinc in the water column, and those data also are presented in Appendix D .

Table 11 – Available Ecological Ef fects Endpoints for the TGAI

Receptor

Group Test Material Risk Scenario Toxicity Endpoint Reference (MRID#)

Freshwater fish TGAI Acute LC50 = 2.6 μg ai/L 43864606

Chronic NOAEC = 1.2 μg ai/L 45204102

Freshwater invertebrates TGAI Acute EC50 = 8.2 μg ai/L 43864604

Chronic NOAEC = 2.7 μg ai/L 44535401

Freshwater benthic invertebrates TGAI Subchronic Amphipod NOAEC = 0.95 mg ai/kg sediment 46250303

Estuarine/marine fish TGAI Acute LC50 = 400 μg ai/L 43864605

Chronic Not required --

Estuarine/marine

invertebrates TGAI Acute EC50 = 4.7 μg ai/L 43864607

Chronic NOAEC = 2.2 μg ai/L 44911101

Estuarine/marine benthic invertebrate TGAI Subchronic NOAEC <1.08 mg ai/kg sediment 46250304

Aquatic vascular plants TGAI EC50 NOAEC EC50 = 8.8 μg ai/L NOAEC = 4.0 μg ai/L 45204104

Algae and Cyanobacteria TGAI EC50 NOAEC EC50 = 0.65 μg ai/L NOAEC = 0.46 μg ai/L 46250305

Semi-aquatic plants TGAI EC50 NOAEC EC50 = 0.17 NOAEC = 0.10 46250301

Birds TGAI Acute oral LD50 = 60 mg ai/kg bw 43864611

4.3.1.2 Open literature Additional open literature studies will be identified through EPAPs ECOTOXicology (ECOTOX) database. The ECOTOX database will be search ed during the risk assessment phase of ZnPTDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 26 of 63 and the data reviewed following the agencyPs policy for reviewing public literature for use in assessing risks from pesticides. 3

Information on how the agency uses the open l iterature is presented on the agencyPs website http://www.epa.gov/pesticides/sci ence/literature -studies.html



## 4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

Available OPP models will be used to determ ine the estimated environmental concentration (EECs) in the aquatic environment. Resulting exposure estimates will be compared to the toxicity endpoints to determine if levels of concern are exceeded for each receptor group.



### 4.4.2 Screening Level Down-the-Drain Analysis The Down-the-Drain (DtD) module of E-FAST (E xposure and Fate Assessment Screening Tool) is not appropriate to assess ZnPT because there are no pesticidal uses which are expected to result in releases to domestic wastewater trea tment plants. Although there may be the potential for exposure to aquatic organisms from ZnPT ente ring industrial wastewater treatment plants as a result of industrial uses of Zn PT as a materials preservative, th is exposure is expected to be small relative to the exposure from leaching of antifoulant paints. During the risk assessment for ZnPT, non-target aquatic organism assessments w ill be based on leaching from antifoulant paint.



### 4.4.3 Endocrine Disruptor Screening Program (EDSP) As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of the 200 4 risk assessment for ZnPT, th e agency reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), ZnPT is subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).

The agency has developed the EDSP to determ ine whether certain substances (including pesticide active and other ingredie nts) may have an effect in hu mans or wildlife similar to an effect produced by a lnaturally occurring estr ogen, or other such endocrine effects as the Administrator may designate.m The EDSP empl oys a two-tiered approach to making the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a chemical substance to interact w ith the estrogen, androgen, or thyroid (E, A, or

3 http://www.epa.gov/pesticides/science/efed/policy_guidan ce/team_authors/endangered_s pecies_reregistration_wor kgroup/esa_evaluation_open_literature.htmDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 27 of 63 T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to th e next stage of the EDSP where EPA will determine which, if any, of the Ti er 2 tests are necessary based on the available data. Tier 2 testing is designe d to identify any adverse endocr ine-related effects caused by the substance, and establish a dose-re sponse relationship between the dos e and the E, A, or T effect.

Under FFDCA section 408(p), the agency must scr een all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 4 and includes some pesticides scheduled for registration review and chemicals found in water

. Neither of these lists should be construed as a list of known or lik ely endocrine disruptors. ZnPT was not on either of the EDSP screening lists.

For further information on the status of the ED SP, the policies and procedures, the lists of chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our website. 5



## 5 Next Steps

A DCI will be developed regarding the data needs listed under the lRisk Assessments and Anticipated Data Needsm section of this docum ent. The agency expects to issue the DCI by March of 2016.

4 See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the final second list of

chemicals.

5 http://www.epa.gov/endo/Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 28 of 63 

## 6 References

EPA. 2004. Zinc Pyrithione (ZnPT): AD Risk Assessment for the Reregistration Eligibility Decision (RED) Document. Chemical N o. 088002. Case No. 2480. DP Barcode: D308704, September 30, 2004

EPA. 2009. Ecological Hazards and Risk Assess ment Chapter for Antifoulant Use of Zinc Pyrithione. RASSB/AD, Ma rch 25. DP Barcode: D362199.

Kline and Company, 2005: Specialty Biocides 2004-2005 A Global Series of Regional Market Analyses Volume II: United States.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 29 of 63 

# Appendix A Toxicology Profile

Acute Toxicity Labeling

The acute toxicity database for ZnPT indicates th at by the oral route, ZnPT is moderately toxic (LD50 = 267 mg/kg; Toxicity Category II) but that acute toxicity by the dermal route is not as significant (LD50 > 2000 mg/kg; Toxicity Category III). Acute toxicity by the inhalation route is also relatively low (>0.61 mg/L; Toxicity Cate gory III). ZnPT is a severe eye irritant (Toxicity category I) but does not appear to dem onstrate significant derm al irritation (Toxicity category IV). ZnPT does not demonstrate dermal sensitization potential. The acute toxicity studies used for hazard classification of technical grade ZnPT are shown below:

Table A1 – Acute Toxicity Studies for ZnPT

Guideline No./ Study Type MRID No. Results Toxicity Category

870.1100/ Acute oral toxicity 42827901 LD50 = 267 mg/kg II

870.1200/ Acute dermal toxicity 42146701 LD50 > 2000 mg/kg III

870.1300/ Acute inhalation toxicity 42146703 LC50 >0.61 mg/L III

870.2400/ Acute eye irritation 42146702 severe irritant I

870.2500/ Acute dermal irritation 42146704 slight erythema and edema IV

870.2600/ Skin sensitization 43950201 no sensitization observed using Buehler method N/A N/A=Not available 

## Subchronic Toxicity

There is one 90-day dermal toxi city study for ZnPT and one 90-da y inhalation toxicity study for ZnPT. The summaries of these studies are included below.

MRID # 42827902 - In a subchronic dermal toxicity study, male and female CrlCD BR rats were treated with ZnPT (ZnPT®) FPS by derm al occlusion at doses of 0, 20, 100, and 1000 mg/kg/day for 6 hours/day, 5 days/week for 13 w eeks. Treatment-related effects included decreased food consumption (91.6% of control), decreased body wei ght gain (48.9% of control), and decreased food efficiency (53.8% of control) over the entire treatment period for females in the 1000 mg/kg/day dose group. Group mean body we ights for females (1000 mg/kg/day) were decreased 13% to 21% relative to contro ls for weeks 2-13. The systemic NOAEL = 100Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 30 of 63 mg/kg/day in females, and 1000 mg/kg/day in ma les. The systemic LOAEL = 1000 mg/kg/day in females (decreased body weight gain, food c onsumption, and food efficiency), and >1000 mg/kg/day in males.

This study is classified as accep table and satisfies the guidelin e requirement for a subchronic dermal toxicity study in rats.

MRID # 42827903 - In a subchronic inhalation toxicity study, groups of 15 male and 15 female Sprague-Dawley rats were dynamically exposed in whole-body exposure chambers to ZnPT (52.2% aqueous suspension) aerosols at con centrations of 0.0005, 0.0025, or 0.01 mg/L/day for 6 hours/day, 5 days/week for 13 weeks. One male and 1 female exposed to 0.0025 mg/L/day and 3 males and 4 females exposed to 0.01 mg/L/day di ed over the course of the study. Treatmentrelated clinical signs of toxicity included rales, labored br eathing, and gasping in animals that died on study. At 0.01 mg/L/day, body weights of females were depressed as much as 23%, compared to controls, total food consumpti on was decreased 10%, and food efficiency was decreased 53%. Hematologic, clinical chemistry, or urinalysis effects we re not considered biologically significant for any of the exposure gr oups, and ophthalmologic examinations and gross necropsy findings were negative. Biologically significant increases in absolute and (relative) lung weights of +20% (+34%) and +22% (+38 %) in males, and +13% (+18%) and +25% (+68%) in females were seen at concentrations of 0.0025 and 0.01 mg/L/day, respectively. The increased lung weights corresponded to histopat hologic findings of trace to mild subacute inflammation of the interstitial tissue of the lung and medial hype rtrophy of pulmonary arteries which were biologically signi ficant at 0.01 mg/L/day.

Based on the results of this study, the syst emic NOAEL = 0.0005 mg/L/day, and the systemic LOAEL= 0.0025 mg/L/day (labored breathing, rales, increased sali vation, decreased activity, dry red-brown material around the nose, increased abso lute and relative lung weights, and death of undetermined cause)

This study is classified acceptable and satisfi es the guideline requirement (OPPTS 870.3465) for a subchronic inhalation toxi city study in rats.



## Developmental Toxicity

This is an oral developmental t oxicity study in the rat, an oral developmental study in the rabbit, and a dermal developmental toxicity study in th e rat for ZnPT. The summ aries of these studies are shown below.

MRID # 42827904 - In a developmental study, thirty pr egnant Sprague-Dawley rats per group were administered ZnPT by oral gavage on days 6-15 of gestation at doses of 0, 0.75, 3, or 15 mg/kg/day. One dam in the 15 mg/kg/day dose gr oup died on gestation day 16 of unspecified causes. No maternal or developmental toxicity was observed at 0.75 mg/kg/day.

Maternal toxicity was observed at 3 and 15 mg/kg/day (increas ed salivation immediately after dosing; 27% and 97% of dams, respectively). Other dose-related signs seen at 15 mg/kg/day included biologically significant decr eases in body weight gains (67%; p d 0.01; absolutes of 4-Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 31 of 63 12%) and food consumption (24% during dosing, 16% throughout gestation; p d 0.01), and dilated pupils (57%). The maternal toxicity NOEL is 0.75 mg/kg/day, and the maternal toxicity LOAEL is 3.0 mg/kg/day, based upon exce ssive salivation during the dosing period.

Developmental toxicity was charac terized by a dose related increase in post-implantation loss at the mid and high doses with the 15 mg/kg/day gr oup being significantly diffe rent than controls (p < 0.01). This correlated with an increase in early resorptions (3.6%/d am) with whole litter resorption occurring in 3 high dose dams. There was also a significant reduction (p d 0.05) in the number of live fetuses per litter (12.5/litter compared to 14.5/litter in the c ontrols), mean fetal weights (16%), and gravid uterine weights (16%; p d 0.01) in the 15 mg/kg/day group as compared to controls.

A significantly greater number of litters in th e 15 mg/kg/day group contained fetuses with external, visceral, or skeletal malformations/var iations. The most common were digit anomalies (5 of 24 treated litters vs . 0 of 27 control litters; p d 0.05), dilated renal pelvis (7 of 24 treated litters vs. 1 of 27 control litters; p d 0.05) which is considered i ndicative of hydronephrosis, and a vertebral/rib anomaly (24 of 24 treate d litters vs. 0 of 27 control litters; p d 0.01). Others included sternal, rib, and limb (radius or ulna absent) malformations. Dose-related fused ribs were observed in the mid and high-dose groups (3 fetuses/2 litters, and 5 fetuses/4 litters, respectively). Although pairwise comparisons, on the basis of litters, were not statistically significant (p=0.226 and p=0.060 for the mid and hi gh-dose groups, respectivel y), a statistically significant linear trend was evident (Cochran-A rmitage test; p=0.009), an d historical control values were exceeded. The developmental toxicity NOEL is 0.75 mg/kg/day, and the developmental toxicity LOAEL is 3.0 mg/kg/day, based upon increa sed incidences of fused ribs.

This study is classified acceptable and satisfies the guideline requirement for a developmental study (OPPTS 870.3700) in rats.

MRID #42827905 - In a developmental toxicity study in rabbits, inseminated New Zealand White rabbits, randomly assigned to one control and three treatment groups of 20 animals each, were administered Zinc Pyrithione 48% Aqueous Dispersion by oral ga vage at doses of 0, 0.5, 1.5, or 3.0 mg/kg/day on gestation days (GD) 6 - 18. Cesarean section examinations were performed on all surviving does on GD 29, follo wed by an examination of all fetuses.

One mid-dose doe died on GD 16, pr obably due to a gavage error. A decrease in body weight gain (p d 0.01) during the dosing period for the mi d and high-dose groups (41% and 99%, respectively) cannot be considered biological ly significant since the absolute body weight changes were only -4% and -6%, respectively. There was no dose-related effect on food consumption. The does' body weights rebounded after the dosing interval. There were no compound-related gross lesions. One high-dose doe aborted on GD 27, and five others had total resorptions. One mid-dose doe ha d total litter resorption. Dose-re lated early resorptions were seen in the mid and high-dose does. These findings corresponded with a dos e-related increase in post-implantation loss (early resorpti on) and a decrease in viable fetu ses. It is not clear whether the resorptions were due to maternal or devel opmental toxicity. No st atistically significant differences were seen in the inci dence of external, visceral, or skeletal anomalies in the treatedDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 32 of 63 groups as compared to controls. Three fetu ses from two high-dose litters contained multiple cephalic and limb malformations.

The Maternal/Developmental NOAEL is 0.5 mg /kg/day. The LOAEL is 1.5 mg/kg/day, based on increased post-implantation loss and decreased number of viab le fetuses (it is not clear whether the resorptions were due to ma ternal or developmental toxicity).

This study is classified acceptable and satisfies the guideline requirement (OPPTS 870.3700) for a developmental toxicity study in rabbits.

MRID # 46534001- Dermal administration of zinc pyridinet hione to rats resulted in maternal toxicity at 30 and 60 mg/kg/day. Treatment-rela ted effects at 60 mg/kg/ day included clinical signs of toxicity (grade 1 erythema; grade 1 fl aking; limited or no use of hindlimbs; shuffling gait; dehydration; low carriage; chromodacyorrhea; emaciation; chromorhinorrhea; hunched posture; decreased body weight and body weight gain, decreased uterine weight, decreased corrected body weight and correct ed body weight gain, decreased absolute and relative feed consumption, and decreased muscle tone and mass. At 30 mg/kg/day, th ere was an increase in the number of dams with limited use of hindlim bs, shuffling gait, decreased body weight and body weight gain, decreased corrected body we ight and corrected body weight gain, and decreased absolute feed consumption. There were no treatment-related mate rnal effects at 10 or 15 mg/kg/day.

This study is classified acceptable and satisfies the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in the rat.



## Reproductive Toxicity

There is one reproductive toxicity study available for sodium pyrith ione that will satisfy the requirement for ZnPT. The summary of this study is shown below.

MRID # 41097201- In a two generation reproduction study conducted with 40% sodium pyrithione, Crl:CD(SD)BR rats recei ved the test chemical in dist illed water by gavage at dose levels of 0, 0.5, 1.5, or 3.5 mg/kg/day at a dos e volume of 10ml/kg. The high dose of 3.5 mg/kg/day was originally 4.5 mg/kg/day, but was scaled back to 3.5 mg/kg/day based on excessive toxicity at the 4.5 mg/ kg/day dose. At 3.5 mg/kg/day, one female parental rat in the F0 generation was sacrificed on day 87 after demo nstrating hunched posture, impaired hindlimb mobility, rapid breathing, and pe ri-orbital, peri-nasal, and ab dominal staining. In the F1 generation, two females at the 3.5 mg/kg/day dose were also sacrificed in days 225 and 235, based on similar clinical signs of toxicity as those observed in the F0 female. Excessive salivation was also observed in all male and fema le rats at the 1.5 and 3.5 mg/kg/day dose levels. Decreased body weight was observed in both pa rental generations of females and the F0 generation of males at the 3.5 mg/ kg/day dose. Decreases were in the range of 88-96% of control values. There was no reported effect on food consum ption of either sex or generation of parental rats. Wasting of hindlimb muscles was observed in those females at 3.5 mg/kg/day sacrificed during the study

. Skeletal muscle atrophy was observed histologically in both sexes and generations of parental rats at the 1.5 and 3.5 mg/kg/day dose levels. This was characterized asDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 33 of 63 reduction and variation in the diameter of musc le fibers, increase in number of sarcolemmal nuclei, and fatty replacem ent of muscle fibers.

Reproductive toxicity was observed at the 3.5 mg/kg/ day dose level in the F0 parents and the F1 offspring. Mating index in males was reduced signif icantly as was fertility index. The number of estrous cycles per mating was increased in F0 females at 3.5 mg/kg/day. There were no effects on total live pups, mean number of live pups per litter, live birt h index, viability index, or lactation index in F1 pups. Mean pup body weight was decreased slightly on post-natal day 1 but this decrease was not significant. Developmenta l landmarks (percentage of pups with ears open on lactation day 3 and percentage of pups with eyes open on lactation day 15) was decreased by 19% and 7% respectively, but was not statistica lly significant. Mean percentage of pups with startle response on lactation day 15 was decreased significantly by 10%. In the F1 parents and the F2 offspring, mating and fertility indices were reduced at all dose levels relative to control, but it is likely that atrophy of hindlimb mu scles in males could impact mating success and therefore would explain the decr ease in mating and fertility in dices. Mean percentage of pups with startle response on lactation day 15 and m ean percentage of pups with eyes open on lactation day 15 was decreased by 13% and 14% re spectively, but this was not statistically significant.

Based on the results of this study, the Systemic NOAEL is determined to be 0.5 mg/kg/day, and the Systemic LOAEL is determined to be 1.5 mg/kg/day, based on increased incidence of histological alterations of the hi ndlimb skeletal muscle in F0 ma les and F1 males and females.

The Reproductive toxicity NOAEL is determined to be 1.5 mg/kg/day, and the Reproductive toxicity LOAEL is determined to be 3.5 mg/kg/ day, based on slightly decreased number of pups per litter in both generations, delayed development in pups from both generations, and decreased pup body weight in both generations.

This study is classified as accep table and satisfies the data requirement for a reproductive toxicity study in rats. 

## Chronic Toxicity/Carcinogenicity

There were no submitted chronic toxicity or ca rcinogenicity studies on ZnPT. A dermal carcinogenicity study in mice and an oral carcin ogenicity study in rats exist for sodium pyrithione which have been reviewed by the Office of Pesticide Programs. There was no evidence for carcinogenicity in the rat study or the mouse study, but the mouse study was considered inadequate for risk assessment purpos es. Therefore, sodium pyrithione could not be classified as to carcinogeni c potential without an adequa te study in the mouse.

For ZnPT, the indirect food uses could potentiall y trigger the need for chronic toxicity and carcinogenicity data. The agency has establis hed toxicology testing requirements in 40 CFR 158.2230 for indirect food uses of antimicrobial pesticides. A 200 ppb residue level (based on total estimated daily dietary intake) is used as one criterion to determine whether higher tier studies (such as chronic and carci nogenicity studies) are needed to characterize hazard and risk from this use pattern. In addition, the indirect fo od use for ZnPT suggests there may be repeated exposure to ZnPT over a considerable portion of the human lifespan, which is also listed as aDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 34 of 63 criterion in determining the need for chroni c toxicity and carcinoge nicity data (40 CFR §158.2230). Based on preliminary calculations for Zn PT, the residue in the diet appears to exceed the 200ppb threshold and the indirect food use suggests repeated exposure. Therefore, the agency anticipates the need to require chronic t oxicity/carcinogenicity studies for ZnPT. 

## Mutagenicity

The database for mutagenicity is considered adequate for ZnPT. ZnPT was negative in a Salmonella typhimurium assay in the absence and presen ce of metabolic activation (MRID 41906502). In a mutagenicity study using Chin ese Hamster Ovary (CHO) cells (MRID # 41906503, zinc pyrithione failed to induce a mutageni c response in the absence of metabolic activation (doses of 0.25-2.0μg/ml) and in the pres ence of metabolic activa tion (2.5-30 μg/ml). In an in vivo micronucleus assay in mice (MRID # 41906501) , intraperitoneal injection of single doses of 11, 22, or 44 mg/kg zinc pyrithione ( 48% aqueous dispersion) to ICR mice did not cause a significant increase in the frequency of micronucleated polychr omatic erythrocytes (MPEs) in bone marrow cells harvested 24, 48, or 72 hours post-dose. High dose mice exhibited signs of toxicity (including mo rtality, lethargy, piloerection, and diarrhea) but there was no evidence of a cytotoxic effect on the target organ. Therefore, zinc pyrithione is concluded to be negative for mutagenicity in this test system. 

## Other Toxicological Effects

Several studies published in the open scientific litera ture have noted neurotoxic effects from exposure to ZnPT. Ross and Lawhorn (Neuro toxicol. Teratol 12(2): 153-159, 1990) observed reduction in forelimb and hindlimb grip streng th and electrophysiol ogical changes after administration of ZnPT in the diet at 50 ppm ( 2.5 mg/kg/day) indicative of neurotoxicity at the neuromuscular junction. Snyder et al. (Food Cosmet. Toxicol. 17(6), 651-660, 1979) observed progressive hind-limb weakness, motor inc oordination, and reduced sensory and mixed sensory/motor nerve-evoked potential amplitude (but no reduction in c onduction velocity) in male rats administered 250 ppm (12.5 mg/kg/day) zinc pyrithione in the diet for 9 or 14 days with a 4 week recovery period. Although clini cal signs abated duri ng the recovery period, decreases in nerve-evoked potential amplitude re mained decreased. Administration of ZnPT to dogs has produced blindness and retinal detach ment (Grant, W.M. Toxicology of the Eye. 3 rd ed. Springfield, IL. Charles C. Thomas, Pub.).

Data submitted to the agency for ZnPT also not e neurotoxic effects (see MRID review below). Hindlimb weakness was observed in the dermal developmental toxicity (MRID 46534001) and acute neurotoxicity (MRID 46534002). Based on the ev idence of neurotoxicity in other studies, and preliminary indications of dietary residue >200ppb, a subchronic ne urotoxicity study is anticipated to be needed for ZnPT.

MRID # 46534002 - In an acute neurotoxicity study, 9 w eek old Sprague-Dawley rats were given single oral doses of ZnPT at 0, 25, 75, and 150 mg/kg. Rats were observed for 15 days post-dosing. A neurobehavioral assessment [functional observati onal battery (FOB) and motor activity testing] were performed in 10 anim als/sex/group, pretest a nd Day 0 (one hour postdosing) in 10, 10, 10 and 9 males and 10, 10, 8 and 4 females from the control, low, mid andDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 35 of 63 high dose groups, respectively, at 7 and 14 days pos t dosing. At study termination, surviving rats were euthanized and perfused (in situ) for ne uropathological examination. Of the perfused animals, 5 animals/sex/group (when available) we re subjected to histop athological evaluation of brain and peripheral nervous system tissues.

The following findings were toxicologically signifi cant as compared to control values: increased mortality in high-dose females; an increase in certain clinical findings in high dose males and mid- and high-dose females (males: dehydration, so ft/liquid feces, urine-stained abdominal fur, and localized alcopecia on underside of body; female s: urine-stained abdomi nal fur, dehydration, soft/liquid feces, chromorhinorrh ea); statistically significant decreased body weights in highdose males on Days 0-9 and mid-dose males on Days 2 and 3; statistically significant decreased body weights in high-dose males on Days 0-1, 1- 2, 2-3 and 0-7 and in mid-dose males on Days 0-1 and 1-2; statistically si gnificant decreased body weight gain on Days 0-1 in high dose females; statistically significan t decreased relative food consump tion on Days 0-1 in low, mid , and high kdose males on Days 1-2 in mid and high kdose males on Days 2-3, 0-7 and 7-14 for highkdose males; and statistically significant decr eased relative food consumption for mid-and high females on Days 0-1 and high-dose females on Days 1-2, 2-3 and 0-7.

Toxicologically significant differences in the FOB results included: statistically significant decreased average body temperature in high dos e males and mid-and high-dose females on Day 0; a decrease (not statistically significant) in hindlimb grip strength in mid-and high dose males at one hours post dosing; and a statistically signi ficant decreased in hindlimb grip strength in high-dose males on Day 7. A toxicologically signif icant difference in motor activity in mid- and highkdose females was noted on Day 0 of the study. In addition, there was a significant decreases in total numbers of m ovements and total time spent in movements for females in these groups when measured one hour post-dosing, but not at later time points. The lack of adequate numbers (10/group) of females in the mid- and highkdose groups may have prevented an adequate assessment of persistent neurological effects at the latter tw o time points (Days 7 and 14). Unlike males, the females did not respond in a dose-related fashion to the grip strength test at any time point; further, at 7 days post-dos ing, the mid-dose females had a statistically significant increase in grip-strength as compared to controls. Therefore, it is possible that no change may have been observed had the full comple ment of female animals survived to the latter two time points.

There were no treatment related effects for th e animals on hindlimb evaluations (calf muscle mass and tone), gross and histol ogic pathology, or neuropathology.

Based on the effects seen in this study, the LOA EL was 75 mg/kg bw/day (based on decreases in body weight and food consumption, and reductions in body temperature, hindlimb grip test, and motor activity values noted one hour post-dos ing), with a NOAEL of 25 mg/kg bw/day.

This acute neurotoxicity study is classified as ACCEPTABLE k GUIDELINE and satisfies the guideline requirement for an acute neurot oxicity study in rats (870.6200; OECD 424).

An immunotoxicity study is a new 40 CFR Part 158-W data requirement for all use patterns of antimicrobial pesticide chemicals (78 FR 26936; May 8, 2013). The registrant can address this anticipated data requirement by either submitting a study according to the OCSPP 870.7800Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 36 of 63 guideline, by citing information from the scientif ic literature that addresses immunotoxicity of ZnPT, or by submitting a request for waiver of th is study using the agencyPs published guidance, available at: http://www.epa.gov/pesticides/r egulating/part158-tox- data-requirement.pdf.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 37 of 63 Appendix A References

1) Moreno O.M., Cerven D.R., Altenbach, E,J. (1986): Si ngle Dose Oral Toxicity in Rats/LD 50 in Rats. Study performed by M B Research La boratories, Inc, Spinnerstown, Pennsylvania for Olin Corporat ion. MRID # 42827901. Unpublished.

2) Cerven, D.R. (1991): Acute Dermal Toxicity in Rabbits/LD50 in Rabbits. Study performed by M B Research Laboratories, Inc, Spinnerstown, Pennsylvania for Olin Corporation. MRID # 42146701. Unpublished.

3) Ulrich, C.E. (1991): Acute I nhalation Toxicity Evaluation on ZnPT in Rats. Study performed by International Research and Development Corporation for Olin Corporation. MRID # 42146703. Unpublished.

4) Cerven, D.R. (1991): Primary Eye Irritation/Corro sion in Rabbits. Study performed by M B Research Laboratories, Inc, Spinnerstown, Penns ylvania for Olin Corporation. MRID # 42146702. Unpublished.

5) Cerven, D.R. (1991): Primary Dermal Irritation in Albino Rabbits. Study performed by M B Research Laboratories, Inc, Spinnerstown, Penns ylvania for Olin Corporation. MRID # 42146704. Unpublished.

6) Newcomb, T (1996): Delayed Contact Dermal Sensit ization Test (Buehler Method). Study performed by M B Research Laboratories, Inc, Sp innerstown, Pennsylvania for Olin Corporation. MRID # 43950201. Unpublished.

7) Ulrich, C.E. (1993): 90-Day Subchronic De rmal Toxicity Study on ZnPT in Rats. Study performed by International Research and Develo pment Corporation for Olin Corporation. MRID # 42827902. Unpublished.

8) Schardein, J.L. (1993): Developmental Toxic ity Study in Rats with ZnPT. Study performed by International Research and Development Corporation for Olin Corporation. MRID # 42827904. Unpublished.

9) Schardein, J.L. (1993): Developmental Toxi city Study in New Zealand White Rabbits with ZnPT. Study performed by International Resear ch and Development Corporation for Olin Corporation. MRID # 42827905 and 42827906. Unpublished.

10) Barnett, J. Jr. (2005). Pe rcutaneous developmental toxici ty study of zinc pyridinethione (ZPT) in rats. CR-DDS Argus Division (Horsh am, Pennsylvania). Argus AEN00006, April 7, 2005. MRID 46534001. Unpublished

11) Barnett, J. (2005) Oral (Gav age) Acute Neurotoxicity Study of Zinc Pyridinethione (ZPT) in Male and Female Rats: Final Report. Pr oject Number: AEN00002, AEN00001, AEN00002AA. Unpublished study prepared by Research Patholo gy Services, Charles River Laboratories and Pathology Associates, Inc. MRID 46534002.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 38 of 63 12) Ridgway, P. and Wood, C.M. (1989): Sodi um Omadine Rat Two-Generation Reproduction Toxicity Study. Study performed by Toxicol La boratories for Olin Corporation. MRID # 41097201. Unpublished.

13) Ulrich, C.E. (1993): Thirteen Week Subchronic Inhalation Toxicity Study on ZnPT in Rats. Study performed by International Research and De velopment Corporation for Olin Corporation. MRID # 42827903 and 42827907. Unpublished.

14) San, R.H.C. and Shelton, J.B. (1990): Salmonella/Mammalian - Microsome Plate Incorporation Mutagenicity Assay (Ames Test) with a Confirmatory Assay. Study performed by Microbiological Associates, Inc., Rockvill e, MD for Olin Corporation. MRID # 41906502. Unpublished.

15) Jacobson-Kram, D. and Sigler, C.I. (1990): CHO/HGPRT Mutation Assay with Confirmation. Study performed by Microbiological Associates, Inc., Rockville, MD for Olin Corporation. MRID # 41906503. Unpublished.

16) Putman, D.L. and Morris, M.J. (1990): Mi cronucleus Cytogenetic Assay in Mice. Study performed by Microbiological Associates, Inc., Rockville, MD for Olin Corporation. MRID # 41906501. Unpublished.

17) Preliminary Neurological Evaluation of Ge neralized Weakness in Zinc-Pyrithione treated rats. Study performed by Olin Corporation (no date given). Unpublished. HED document number 003933.

18) Klaassen, C (1976): Absorption, Distribution, and Excretion of Zinc Pyridinethione in Rabbits. Toxicol. Appl. Pharmacol. 35: 581-587.

19) Wedig, J.H., et al. (1978): Disposition of Zinc Pyrithione in the Rat. Fd. Cosmet. Toxicol. 16: 553-561.

20) Adams, M., Jordan, R., and Borzelleca, J. (no date): Acute Toxicity and Disposition of Sodium Omadine, ZnPT, and Omadine-MDS follo wing Intravenous Administration to Swine. Study performed by the Medical College of Virginia.

21) Husband, R.F., Newman, A.J., Lee, P.N. (1991): 104-Week Oral (Gavage) Combined Carcinogenicity and Toxicity Study in the Ra t. Study conducted by Toxicol Laboratories Ltd., Ledbury, England and submitted to the EPA under MRID 42100901. Unpublished.

22) Husband, R.F., Newman, A.J., Lee, P.N. ( 1991): 80-Week Dermal Carcinogenicity Study in the Mouse. Study conducted by Toxicol Laboratories Ltd., Ledbury, England and submitted to the EPA under MRID 42100801. Unpublished.

23) Johnson D.E. (1989): One Year Oral Toxi city Study in Cynomolgus Monkeys. Study conducted by International Research and Development Corporation, Mattawan, MI and submitted to the EPA under MRID 41178101. Unpublished.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 39 of 63 24) Ross, J.F. and Lawhorn, G.T. (1990): ZNPT -related Distal Axonopathy: behavioral and electrophysiologic correlates in rats. Neurotoxicol. Te ratol 12(2): 153-159, 1990

25) Snyder, D.R., deJesus, C.P.V., Towfighi, J., Jacoby, R.O., Wedig, J. H. (1979): Neurological, Microscopic, and Enzyme-Histochemical Assessme nt of Zinc Pyrithione Toxicity. Food Cosmet. Toxicol. 17(6), 651-660, 1979.

26) Grant, W.M. Toxicology of the Eye, 3 rd edition. Charles C. Thomas, pub. (1993)Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 40 of 63 

# Appendix B Residential Post-Application Studies

Table B1 – Summary of Zinc Pyri thione Textile Leaching Data

Treatment A Amount ZnPT Extracted (ug/g) Percent ZnPT in Fabric B Amount ZnPT Leached at Ambient Temp (ug/g) Percent Leach Rate B (Ambient Temp) Amount ZnPT Leached at 37 C (ug/g) Percent Leach Rate B (37 C) MRID# 47695602 Zinc Pyrithione Leached from Polyester Fabrics (Arch Chemicals) Blank Untreated Dipping Treatment Padding (Unwashed) Padding (Washed) <LOQ (1.45) 256.4 428.7 405.7 0.00007% 0.0256% 0.0428% 0.0406% <LOQ (1.45) <LOQ 13.7 <LOQ N/A 0.28% 3.19% 0.18% <LOQ (1.45) <LOQ 14.2 <LOQ N/A 0.28% 3.31% 0.18% MRID# 48902509 Zinc Pyrithione Leached fr om Marukacide Polyester Fabrics Untreated Blank Dipping (Unwashed) Padding (Unwashed) Padding (Washed) <LOD (19.8) 448.6 1549.7 1451.6 <0.002% 0.0449% 0.155% 0.145% <LOQ (3.23) <LOQ 4.85 <LOQ N/A 0.36% 0.31% 0.11% <LOQ (3.23) <LOQ 4.00 <LOQ N/A 0.36% 0.25% 0.06% MRID# 48902609 Zinc Pyrithione Leached fr om Niccanon ZP-700 Polyester Fabrics Untreated Blank Dipping (Unwashed) Padding (Unwashed) Padding (Washed) <LOD (19.8) 495.4 759.1 538.6 <0.002% 0.0495% 0.0759% 0.0539% <LOQ (77.8) 242.8 234.0 <LOQ N/A 49.0% 30.8% 7% <LOQ (77.8) 254 219 (n=4) <LOQ N/A 51.3% 28.8% 7% MRID# 49149402 Zinc Pyrithione Leached from Niccanon ZP-700 Polyester Fabrics (2 nd Study) Untreated Blank Dipping (Unwashed) Dipping (Washed) Padding (Unwashed) Padding (Washed) <LOD (2.7) 550 714 709 786 <0.003% 0.0550% 0.0714% 0.0709% 0.0786% <LOQ (2.2) <LOQ <LOQ <LOQ <LOQ N/A 0.20% 0.15% 0.16% 0.14% <LOQ (2.2) <LOQ <LOQ <LOQ <LOQ N/A 0.20% 0.15% 0.16% 0.14% Notes A. Except as noted there were n = 5 replicate samples per treatment type and temperature. B. One half the LOQ was used to calculate the leach ra tes when the ZnPT residue levels were below the LOQ.

MRID# 48168401 - Transferable residue study of carpets preserved with ZnPT

This study determined the total amount of ZnPT incorporated in the carpet, the transfer efficiency of ZnPT from the carpet to fabrics and the saliva extraction e fficiency of ZnPT from fabrics.

Total ZnPT in the carpet was determined by mi crowave-assisted dimethyl sulfoxide/acetone solvent extraction of fibers clipped from th e carpet, followed by liquid chromatography-mass spectrometry (LC/MS). The transfer efficiency of ZnPT to fabrics was measured using aDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 41 of 63 modified California roller samp ling technique, where 7.79 lb or 35 lb rollers were used to simulate the exposure condition for children and a dults, and a rolling frequency of 80 rolls was applied to the cotton or polyester fabric-covered carpet surface. The si ze of the fabric samples was 5mx 5m (161 cm 2 ) for the 7.79 lb roller and 16m x 16m (1650 cm 2 ) for the 35 lb roller. The 35 lb roller consisted of all th ree roller sections of a Robe rts Consolidated Model #10-935 Lightweight Roller, which has a diameter of 2.75 inches and a total width of 15 inches, while the 7.79 lb roller consisted of one section of the ro ller, which has a width of 5 inches. For the measurement of saliva extraction efficiency, the amount of ZnPT transfer red to the polyester fabric moistened with 0.9% saline solution was determined using the 7.79 lb roller. The amount of ZnPT leached from the moistened polyester into saline solution was then determined.

The analytical method was validated for linear ity, specificity, detection limit, accuracy, and precision. The limit of detection (LOD) was 0.005 ug/cm 2 and the limit of quantitation (LOQ) was 0.018 ug/cm 2 . The mean recovery of ZnPT ranged from 100.4% to 106.5% in the carpet samples spiked at 80 - 100% of the base ZnPT le vel in the treated carpet. The mean recovery of ZnPT in the transferable ZnPT and saliva effi ciency measurements ranged from 80.5% to 99.8% in the corresponding control samples spiked with ZnPT at 1XLOQ and 10XLOQ levels. Relative standard deviation (% RSD) of five repl icate sample analyses for the spiked samples ranged from 2.9% to 13.2%.

The ZnPT incorporation rate in the treated carpet fibers (excluding the backing) was determined to be 227.2 ug/cm 2 and the density of the carpet fibers was determined to be 155 gm/cm 2 . This corresponds to an application rate of 0.15 percent which is less than the maximum label application rate of 0.38 percent. The ZnPT incorporation rate in the untreated carpet was determined to be 0.32 ug/cm 2 which equates to an applicatio n rate of 0.00021 percent. The average transfer efficiency of ZnPT to dry cotton was 0.016% and 0.036%, respectively when the 7.79 lb or 35 lb roller was used. The average transfer efficiency of ZnPT to dry polyester was 0.020% and 0.044%, respectively when the 7.791b or 35 lb roller was used. The average transfer efficiency to moiste ned polyester was 0.026% when th e 7.79 lb roller was used. The saliva extraction efficiency of ZnPT ranged from 49% to 85%, with a mean of 64% of the transferred ZnPT being leached in to the saline solution. No ZnPT was detected on the control fabrics that were tested on untreated carpet.

MRID# 44108602 Plastics Leaching Study (Olin Corp., 1992)

This study was used in the 2004 risk assessment to ev aluate exposures to ZnPT in plastics. Disks of two types of plastics (polye thylene or polypropylene) trea ted with either 1000 ppm or 4000 ppm ZnPT were immersed in two t ypes of food simulants (corn oil or ethanol). The disks were 11 mm in diameter and 0.75 mm in thickness with a surface area of 2.16 cm 2 each. The polypropylene (PP) disks weighed ~50 mg and th e polyethylene (PE) disks weighed ~90 mg. The disks were placed into migration cells whic h consisted of 23 ml gl ass vials fitted with Mininert Teflon valves. Ten disk s and 22 ml of test so lvent were placed into each vial which yielded a volume to surface area of 1.07 mL/cm 2 . The vials were then covered with black electrical tape to prev ent photo-degradation of ZnPT and held in a 50 C (120 F) water bath with agitation at 50 cpm. Each migra tion study was done in triplicate and polymer blanks containing no ZnPT were also tested.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 42 of 63 Aliquots (250 uL) were collected at specified ti me intervals that ranged from 0 to 240 hours and were analyzed using HPLC according to a standa rd analytical method (CAM 5-90). Recovery and control aliquots were also analyzed to determine the chemi cal reaction of ZnPT in the food stimulant solvents. A 2000 ppm spike of ZnPT in to the solvent yielded a recovery of 71.5% to 96.4% for corn oil and 113.4% to 122.8% for etha nol. The results of th is study are summarized in Table 10. Because the LOD was not repor ted, it was estimated by dividing the lowest reported value of 40 ppb by a factor of 2. Th e leaching rates were highly variable and inconsistent. Although the samples treated with 4000 ppm generally leached at a higher rate than the samples treated with 1000 ppm, the differe nce was highly variable and was often much greater than the 4X difference th an would be expected. In a si milar manner, the results did not follow any coherent pattern with respect to time.

Table B2 – ZnPT Leach Rate Data from MRID 44108602

Polymer A Solvent ZnPT Content (ppm) ZnPT Content B (ug/sample) Maximum Leached (ppb) Maximum Leached C (ug/sample) Percent Leached D Time of Maximum Leaching (Hour) PP (500 mg per 10 disk sample) Corn Oil 1000 500 355 7.8 1.6 24 4000 2000 1735 38 1.9 144 Ethanol 1000 500 44 0.97 0.2 24 4000 2000 2320 51 2.6 216 PE (900 mg per 10 disk sample) Corn oil 1000 900 350 7.7 0.86 2 4000 3600 1475 32.4 0.90 144 Ethanol 1000 900 684 15.0 1.7 216 4000 3600 1067 23.4 0.65 120 A. PP = Polypropylene, PE = Polyethylene B. ZnPT Content (ug) = 10 disks * 50 or 90 mg/disk * 1000 or 4000 ppm * 1000 ug/mg C. Amount Leached (ug) = (Maximum Leached (ppb = ng/ml) * 22 ml solution volume * 0.001 ug/ng D. Percent Leached = Amount Leach ed (ug)/ZnPT Content (ug) * 100

MRID# 48172708 Plastics Leaching Study (Arch., 2010)

This study was submitted after the 2004 risk asse ssment. Disks of polypropylene treated with 600, 800 or 1000 ppm zinc pyrithione were immersed in two types of food simulant solvents (corn oil or ethanol). The disks were 11 mm in diameter and 3.175 mm in thickness and weighed ~0.29 mg. The disks were placed into migration cel ls which consisted of 22 ml amber glass vials with Teflon liner caps. Five disk s with a total surface area of 29.96 cm 2 and 20 ml of food simulant were placed into each vial which yielded a volume to surface area of 0.67 mL food simulant per cm 2 of plastic. The vials held at 50 C (120 F) in an incubator with agitation at 50 cpm. Each migration study was done in triplica te and polymer blanks containing no ZnPT were also tested.

Aliquotes (400 uL) were co llected at specified time interval s that ranged from 0 to 240 hours and were analyzed using LC/MS. Recovery and cont rol aliquots were also analyzed to determine the chemical reaction of ZnPT in the food stimulant solvents. A 2000 ppm spike of ZnPT into the solvent yielded a recovery of 71.5% to 96.4% for corn oil and 113.4% to 122.8% for ethanol.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 43 of 63 The LOQ was 5 ug/gram for the plastic sample s and 12.35 ng/gram for the leaching solutions. The leaching rates are listed in Table 11 and are sim ilar to those measured in the previous study.

Table B3 – ZnPT Leach Rate Data from MRID 44108602

Application Rate (Amount Measured) Solvent Leaching Rates in Percent Time of Maximum Leaching (hour) 0 hour 2 hour 24 hour 144 hour 240 hour 600 ppm (362 ppm) Corn Oil 0.08 0.42 1.07 1.60 1.50 144
Ethanol 0.20 0.59 1.73 1.77 0.94 144 800 ppm (478 ppm) Corn Oil 0.04 0.41 0.98 1.35 1.23 144
Ethanol 0.19 0.52 1.49 1.56 0.46 144 1000 ppm (590 ppm) Corn Oil 0.04 0.43 0.87 1.85 1.72 144
Ethanol 0.25 0.55 1.39 1.54 0.79 144Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 44 of 63 

# Appendix C Environmental Fate

Environmental Fate and Transport Properties of Zinc Pyrithione

The agency does not anticipate the need to re quire environmental fate studies for the ZnPT registration review case.

Water and Sediment

Hydrolysis

ZnPT appears hydrolytically stable in abiotic, buffered and simulated water systems with an extrapolated half-life between 99 and 123 days in buffered medium and 96 days (extrapolated) in simulated sea water (MRID 43864602). ZnPT degrades rapidly in both fresh and salt irradiated water with half-lives of 11-14 minutes (MRID 44011501). In a literature study, ZnPT hydrolyzed rapidly in seawater with a ha lf-life of 8.3 minutes (Maraldo a nd Dahllof , 2004). Nitrate and dissolved organic matter increase this degradation rate (Sakkas et al., 2007). These data indicate that in shallow, well-mixed, and clear irradiated waters ZnPT will degrade rapidly. However, suspended sediment and shading will i nhibit this route of degradation.

Aqueous Photolysis

Photolytic studies conducted in a buffered aque ous system and pH 9, ZnPT rapidly degraded with a half-life of 13 minutes and at the same pH and in a simulated sea water system, ZnPT degraded in 17 minutes. It does not appear to be stable on surface water (MRID# 44011501).

Octanol-Water Partition Coefficient

Log K ow is less than 3, and ZnPT is not likely to bioaccumulate in aquatic organisms.

Aerobic Aquatic Metabolism

In a study on aerobic aquatic system, ZnPT degr adation follows a biphasic process and in the first phase it degrades rapidly with a half- life of 0.065 hours in salt water and in 1.3 hours in fresh water samples. In the second phase, zinc pyrithione degradation half -life was 365 hours (15 days) in salt water samples and in fresh water samples it de graded in 298 hours (about 12.3 days) (44850004, 45876501).

A second aerobic aquatic degrada tion study was conducted on a salt water harbor used as a boat maintenance site. Degradation data were obtai ned on zinc and copper pyrithiones. Degradation half-lives were extracted by using a two-compartment model (water/sediment). Half-lives were determined for water and sediment samples separate ly. In water samples, and in the presence of pyrithione thiosulfate (OTS, whic h may be formed as a degradate or may be present in the sample), the half-life was 0.60 hour s. Degradation half- life in the sediment samples, in the presence of OTS, was 0.89 days, (OTS may be initially present or may be formed due toDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 45 of 63 degradation process. Kinetic pathway in the sedi ment samples was non-linear. In the absence of OTS, and through non-linear pathway, the degrad ation half-life decrea sed to 0.03 days. The sediment in this study was characterized as sand (% sand = 90, silt : 4% and clay: 6%).

Anaerobic Aquatic Metabolism

In anaerobic aquatic samples from fresh and salt water, ZnPT de graded through biphasic process. Anaerobically fresh water and salt water samples of zinc pyrithione degraded rapidly in the first phase with a half-life of about 2 hours. In the se cond phase, the degradation half-life in fresh and salt water samples increased to 25.5 hours. Fr esh water and salt sediment samples, zinc pyrithione degradation half was measured at 13.1 hours (45876501).

In a second study, water and sediment samples co llected from a salt marina (Little Harbor, MarbleHead, MA). Two compartment model was used to analyze the kinetic data ZnPT degraded in 0.50 hours in water sample and in 1 8.9 hours in the sediment sample. The sediment of this marina was characterized as sand (% sand = 86, silt: 6%, and clay: 8%). pH of the sediment was basic (7.9) and % organic C = 2.3.

Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

A soil column leaching study conducted on four soil samples: sand, sandy loam, loam and clay (unaged) and on sandy loam (aged) indicated th at zinc pyrithione is immobile in these systems.
An absorption/desorption study c onducted on Marblehead salt wate r soil, Marblehead salt water sediment, Portland freshwater soil and Portland freshwater sediment (all from MA), showed that ZnPT binds moderately strongly with Marble saltwater soil and sediment (K d = 50 and 99 respectively) and less strongly with Po rtland freshwater soil and sediment (K d =11 and 48). Marblehead salt water soil and sediment were characterized as sandy loam and Portland freshwater soil and sediment as loamy or silt loam (MRID# 45565201).

Aerobic Soil Metabolism

No study is anticipated to be required. Bri dging from aerobic aquatic study is adequate.

Anaerobic Soil Metabolism

No study is anticipated to be required. Bri dging from aerobic aquatic study is adequate.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 46 of 63 

# Appendix D Ecotoxicology Profile

The available toxicity endpoint s and ecotoxicity data require ments for ZnPT are presented below. Toxicity data for two degradates (pyr ithione sulfonic acid and pyridine sulfonic acid) also are available for some aquatic species. Acute and chronic toxicity data from studies submitted to OPP and reviewed public literature included in the Office of WaterPs Ambient Aquatic Life Quality Criteria for Zinc (USEPA 1987) also have been compiled by OPP to characterize the toxicity of dissolv ed zinc to aquatic receptors in the water column; those data are presented by receptor group (freshwater and sa ltwater) after the ZnPT profile. No additional ecotoxicity data are anticipated to be required.


### Toxicity of Zinc Pyrithione and Degradates

Terrestrial Organisms

Birds

One acceptable acute-oral (LD50) study categorizes technical-grade ZnPT as being moderately toxic to birds. The guideline (850.2100) is satisfied. Avian di etary studies (850.2200) are not required, but two studies were prev iously submitted and indicate th at zinc pyrithione is slightly to practically nontoxic when administ ered in the avian diet. No additional avian toxicity data are expected to be required.

Avian Acute-oral and Dietary Toxicity of Zinc Pyrithione

Test Species Test Material (% ai) Toxicity Toxicity Category EPA Study ID

Northern bobwhite ( Colinus virginianus ) ZnPT (96) LD50 = 60 mg ai/kg bw Moderately toxic 43864611 Acceptable

LC50 = 1063 ppm ai Slightly toxic 43864610 Acceptable

Mallard ( Anas platyrhynchos ) ZnPT (96) LC50 >5000 ppm ai Practically nontoxic 43864612 Acceptable

Nontarget Insects

Toxicity data for beneficial insects (850.3020, 850.3030) are not expe cted to be required to support the current use patterns, beca use zinc pyrithione is not regist ered as a wood preservative.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 47 of 63 Aquatic Organisms

Freshwater Fish, acute

The available acute toxicity stud ies categorize technical-grade ZnPT as being very highly toxic to freshwater fish. Some acute toxicity data also are available for two ZnPT degradates (pyridine sulfonic acid and pyrithione sulfonic acid). Those data categorize both de gradates as being only slightly toxic to practically nontoxic to freshwater fish. The guideline (850.1075) for acute toxicity testing is satisfied. No additi onal data are expected to be required.

Acute Toxicity of ZnPT and Degradates to Freshwater Fish

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Rainbow Trout ( Oncorhynchus mykiss) ZnPT (97.8) LC50 = 3.6 Very highly toxic 43864613 Acceptable Pyridine sulfonic acid (98) LC50 = 57,100 Slightly toxic 43864627 Acceptable
Pyrithione sulfonic acid (98.5) LC50 = 92,300 Slightly toxic 43864616 Acceptable
Pyridine sulfonic acid (98) LC50 = 68,500 Slightly toxic 43864621 Acceptable
Pyrithione sulfonic acid (98.5) LC50 = 58,800 Slightly toxic 43864618 Acceptable

Fathead minnow

( Pimephales promelas ) ZnPT (97.8) LC50 = 2.6 Very highly toxic 43864606 Acceptable

Freshwater Invertebrates, acute

The available acute toxicity study categorizes technical-grade ZnPT as being very highly toxic to freshwater invertebrates. Acut e toxicity data also are availa ble for the two ZnPT degradates (pyridine sulfonic acid a nd pyrithione sulfonic acid). Those data categorize both degradates as being practically nontoxic to freshwater inve rtebrates. The guideline (850.1010) for acute toxicity testing is satisfied. No additi onal data are expected to be required.

Acute Toxicity of ZnPT and Degradates to Freshwater Invertebrates

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Water flea ( Daphnia magna ) ZnPT (97.8) EC50 = 8.2 Very highly toxic 43864604 AcceptableDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 48 of 63 Pyridine sulfonic acid (98) EC50 >122,000 Practically nontoxic 43864622 Acceptable
Pyrithione sulfonic acid (98.5) EC50 >127,000 Practically nontoxic 43864619 Acceptable

Freshwater Fish and Invertebrates, chronic

Two studies are available for the TGAI and one for the degradate (pyridine-2-sulfonic acid). NOAECs have been determined for both fish and aquatic invertebrates. No add itional chronic data are needed for freshwater organisms (850.1300, 850.1400).

Chronic Toxicity of Zinc Pyrithione and De gradates to Freshwater Fish and Invertebrates

Species Test material (% ai) Toxicity (μg ai/L) Endpoint Status/ MRID

Fathead minnow ( Pimephales promelas ) ZnPT (98.2) NOAEC = 1.2 LOAEC = 2.8 Hatching, growth, and sublethal effects 45204102 Acceptable

Pyridine-2- sulfonic acid (98.2) NOAEC >10 LOAEC = nd No adverse effects at the highest concentration tested 45204102 Acceptable

Water flea ( Daphnis magna ) ZnPT (98.2) NOAEC = 2.7 LOAEC = 5.8 Reproduction and growth 44535401 Acceptable

Estuarine/Marine Fish and Invertebrates, acute

The available data categorize technical-grade ZnPT as being highly toxic to saltwater fish and very highly toxic to saltwater invertebrates. Ac ute toxicity data also are available for two ZnPT degradates (pyridine sulfonic acid and pyrithione sulfoni c acid). Those data are sufficient to categorize the degradates as being slightly to practically nontoxic. The guidelines for acute toxicity to estuarine/marine fish (850.1075) and invertebrates (850.1025, 850.1035) are satisfied. No additional data are expected to be required.

Acute Toxicity of Zinc Pyrithione and De gradates to Estuarine/Marine Fish and Invertebrates

Test Species Test Material (% ai) Toxicity Endpoint (μg ai/L) Toxicity Category EPA Study ID

Sheepshead minnow (Cyprinodon variegatus) ZnPT (97.8) LC50 = 400 Highly toxic 43864605 Acceptable Pyridine sulfonic acid (98) LC50 >127,000 Practically nontoxic 43864623 AcceptableDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 49 of 63 Pyrithione sulfonic acid (98.5) LC50 >137,000 Practically nontoxic 43864617 Acceptable

Mysid shrimp (Mysidopsis bahia) ZnPT (97.8) LC50 = 4.7 Very highly toxic 43864607 Acceptable Pyridine sulfonic acid (98) LC50 = 71,000 Slightly toxic 43864626 Acceptable
Pyrithione sulfonic acid (98.5) LC50 = 70,300 Slightly toxic 43864620 Acceptable

Eastern oyster ( Crassostrea virginica) ZnPT (97.8) EC50 = 22.0 Very highly toxic 43864608 Acceptable Pyridine sulfonic acid (98) EC50 = 85,600 Slightly toxic 43864624 Acceptable
Pyrithione sulfonic acid (98.5) EC50 = 96,200 Slightly toxic 43864615 Acceptable

Estuarine/Marine Fish and Invertebrates, chronic

One chronic study is available using technical-g rade ZnPT. Mysid NOAECs were determined for both growth and reproduction. The guideli ne (850.1350) for chronic testing with an estuarine/marine invertebrate is satisfied. Chronic data are not needed for fish. The sheepshead minnow is much less acutely sensitive than the freshwater fathead minnow, and chronic data are available for the fathead. No additional estuar ine/marine chronic data are expected to be required.

Chronic Toxicity of Zinc Pyrithione and De gradates to Estuarine/Marine Invertebrates

Species Test material (% ai) Toxicity (μg ai/L) Endpoint Status/ MRID

Mysid shrimp ( Mysidopsis bahia ) ZnPT (98.2) NOAEC = 2.2 LOAEC = 4.2 Growth 44911101 Acceptable NOAEC = 4.2 LOAEC = 9.1 Reproduction

Aquatic Plants

The available aquatic plant data indicate that the marine diatom is the most sensitive species tested. The guideline requirements for aquatic plant growth testing with a vascular species (850.5400), cyanobacteria (850.4550), and three algal species (850.4500) are satisfied. Additionally, green algae also were tested with pyridine sulfonic acid in two tests. This degradate is three orders of magnitude less toxic to green alga than is ZnPT.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 50 of 63 Toxicity of ZnPT and Degradates to Aquatic Plants

Species Test material (% ai) Toxicity (μg ai/L) Status/ MRID

Vascular:

Duckweed ( Lemna sp.) ZnPT (97.8) EC50 = 8.8 NOAEC = 4.0 45204104 Acceptable

Non-Vascular:

Green algae (Pseudokirchniriella subcapitata ) ZnPT (97.8) EC50 = 28 NOAEC = 7.8 43864609 Acceptable Pyridine sulfonic acid (98) EC50 = 28,900 NOAEC = 5460 43864625 Acceptable Pyrithione sulfonic acid (98.5) EC50 = 28,200 NOAEC = 11,800 43864614 Acceptable

Marine diatom ( Skeletonema costatum ) ZnPT (98.2) EC50 = 0.65 NOAEC = 0.46 46250305 Acceptable

Freshwater diatom ( Navicula pelliculosa ) ZnPT (98.3) EC50 = 2.6 NOAEC = 2.4 45565001 Acceptable Cyanobacteria ( Anabaena flos-aqua ) ZnPT (98.3) EC50 = 7.1 NOAEC = 3.8 45565001 Acceptable

Semi-aquatic Plants

One seedling emergence and one vegetative vigor study have been submitted for ZnPT. However, the vegetative vigor study (850.4250) is not required, because there are no spray applications that might lead to exposure of plan ts due to off-site drif t during application. The guideline requirement for a seedling emerge nce test (OPPTS 850.4225) is satisfied. No additional data are expected to be required.

Toxicity of ZnPT to Semi-aquatic Plants

Test Species Test material (% ai) Test type Toxicity Status/ MRID

Rice ( Oryza sativa ) ZnPT (98.3) Seedling
emergence EC25 = 0.172 mg/kg soil NOAEC = 0.100 mg/kg soil 46250301 Acceptable

ZnPT (48.8) Vegetative vigor EC25: 99,250 ppm NOEC: 49,000 ppm 46250302 Supplemental 1

1 The concentrations of the test substance in the test solutions were not verified analytically.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 51 of 63 Benthic Organisms

Two studies are available. An acceptable fres hwater amphipod test was previously submitted. Although testing with a fres hwater midge is not available, th e environmental fate properties of ZnPT in freshwater soil/sediment (Kds <50 L/ kg) indicate that ZnPT is not expected to accumulate in freshwater sediments. The study testing a marine amphipod did not establish an NOAEC. However, the agency has determined that risk to benthic organisms can be adequately assessed based on the existing data. Although Zn PT shows a stronger tendency to bind in saltwater soil/sediment (Kds 50-99), the agencyPs ecological risk assessment for antifoulant use of ZnPT in 2009 indicated minimal risks, ba sed on environmental modelling using MAM-PEC (USEPA 2009) that estimated sediment EECs of 0.00000013 and 0.00000006 μg/g dry wt in freshwater and saltwater marinas, respectively. Th erefore, additional sediment toxicity testing is not anticipated to be needed for these guidelines (850.1735, 850.1740).

Subchronic (10-day) Sediment Toxicity of ZnPT to Freshwater and Estuarine/Marine Invertebrates

Test Species Test material (% ai) Toxicity Status/ MRID

Freshwater amphipod ( Hyalella azteca ) ZnPT (98.2) NOAEC = 0.95 mg ai/kg dry sediment 46250303 Acceptable

Marine amphipod ( Leptocheirus plumulosus ) ZnPT (98.2) NOAEC <1.08 mg ai/kg dry sediment 46250304 Supplemental 1

1 a NOAEC was not determined



### Toxicity of Dissolved Zinc in the Water Column

Acute and chronic toxicity data from studies submitted to OPP and reviewed public literature included in the Office of WaterPs Ambient Aquatic Life Quality Criteria for Zinc (USEPA 1987) are presented below to characterize the toxicity of dissolved zinc to aquatic receptors in the water column. Because toxicity can be effected by wa ter hardness, toxicity values for freshwater organisms are presented for both soft wate r and hard water for each receptor group.

Toxicity of Zinc to Freshwater Organisms

Receptor Group Attribute Change Toxicity Endpoints (dissolved zinc, ppb) Softwater Hardwater

Freshwater fish Acute 34.7 422 Chronic 11.7 143 Freshwater Invertebrate Acute 12.3 150 Chronic 4.2 50.6 Aquatic Plants, Nonvascular Nonlisted 19 19 Listed No data No data Aquatic Plants, Vascular Nonlisted 10,000 10,000 Listed 654 654Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 52 of 63 Toxicity of Zinc to Saltwater Organisms

Receptor Group Risk Scenario Toxicity Endpoints (dissolved zinc, ppb)

Saltwater fish Acute 181
Chronic 43.5

Saltwater crustacean Acute 166
Chronic 39.8
Saltwater mollusk Acute 184

Aquatic Plants, Nonvascular Nonlisted 19
Listed No data

Aquatic Plants, Vascular Nonlisted 10,000
Listed 654Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 53 of 63 

### Appendix C References

USEPA 2009

USEPA 1987

43864611 Ecological Hazards and Risk Assessment Chapter for Antifoulant Use of Zinc Pyrithione. RASSB/AD, March 25, 2009.

Ambient Aquatic Life Water Quality Crite ria for Zinc - 1987. Office of Water, Regulations and Standards, Criteria a nd Standards Division, Washington, DC. EPA-440/5-87-003. 215 pp

Campbell, S.; Beavers, J.; Jaber, M. ( 1993) ZnPT: An Acute Oral Toxicity Study with the Northern Bobwhite: Lab Pr oject Number: 133-110. Unpublished study prepared by Wildlife International Ltd. 21 p.

43864610 Campbell, S.; Beavers, J. (1994) ZnPT: A Dietary LC50 Study with the Northern Bobwhite: Lab Project Number: 133-109. Unpublished study prepared by Wildlife International Ltd. 40 p.

43864612 Campbell, S.; Beavers, J.; Jaber, M. (1994) ZnPT: A Dietary LC50 Study with the Mallard: Lab Project Number: 133-111. Unpublished study prepared by Wildlife International Ltd. 40 p.

43864606 Boeri, R. ; Magazu, J.; Ward, T. (1994) Acute Toxicity of ZnPT (Zinc bis-1- Oxide-2(1H)-pyridinethionate) to the Fathead Minnow, Pimephales promelas : Lab Project Number: 19-OL. Unpublished study pr epared by T. R. Wilbury Labs, Inc. 29 p.

43864613 Boeri, R.; Magazu, J.; Ward, T. (1994) Acute Toxicity of ZnPT to the Rainbow Trout, Oncorhynchus mykiss : Lab Project Number: 20-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

43864616 Ward, T.; Kowalski, P.; Boeri, R. (1 994) Acute Toxicity of Omadine Sulfonic Acid (Pyridine-N-oxide-2-sulfoni c Acid) to the Rainbow Trout, Oncorhynchus mykiss : Amended Report: Lab Project Nu mber: 34-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

43864618 Ward, T.; Kowalski, P.; Boeri, R. (1 994) Acute Toxicity of Omadine Sulfonic Acid (Pyridine-N-oxide-2-sulfoni c Acid) to the Fathead minnow, Pimephales promelas : Lab Project Number: 33-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 54 of 63 43864621 Boeri, R.; Kowalski, P.; Ward, T. (1994) Acute Toxicity of Py ridine Sulfonic Acid to the Fathead Minnow, Pimephales promelas : Lab Project Number: 40-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

43864627 Ward, T.; Kowalski, P.; Boeri, R. (1993) Acute Toxicity of Py ridine Sulfonic Acid to the Rainbow Trout, Oncorhynchus mykiss : Lab Project Number: 41-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

44591204 Drake, J. (1998) Supporting Study: (Assessmen t of the Toxicity of Sponge Extracts to the Fathead Minnow, Pimephales promelas : Alpha 101. Unpublished study prepared by 3M Environmental Tec hnology and Services. 23 p. {OPPTS 870.1100}

43864604 Boeri, R.; Magazu, J.; Ward, T. (1994) Acute Toxicity of ZnPT (Zinc bis-1-Oxide2(1H)-pyridinethionate) to the Daphnid, Daphnia magna : Lab Project Number: 21- OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

43864619 Ward, T.; Kowalski, P.; Boeri, R. (1 994) Acute Toxicity of Omadine Sulfonic Acid (Pyridine-N-oxide-2-sul fonic Acid) to the Daphnid, Daphnia magna : Lab Project Number: 35-OL. Unpublished study pr epared by T. R. Wilbury Labs, Inc. 26 p.

43864622 Ward, T.; Kowalski, P.; Boeri, R. (1994) Acute Toxicity of Py ridine Sulfonic Acid to the Daphnid, Daphnia magna : Lab Project Number: 42-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 26 p.

44921801 Boeri, R.; Magazu, J.; Ward, T. (1999) Ac ute Toxicity of Zinc Pyrithione to the Amphipod, Hyalella azteca : Lab Project Number: 1681-OL. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 29 p.

43864605 Boeri, R.; Magazu, J.; Ward, T. (1994) Acute Toxicity of ZnPT (Zinc bis-1-Oxide2(1H)-pyridinethionate) to the Sheepshead Minnor, Cyprinodon variegatus : Lab Project Number: 22-OL. Unpublished study pr epared by T. R. Wilbury Labs, Inc. 30 p.

43864607 Boeri, R.; Magazu, J.; Ward, T. (1993) Acute Toxicity of ZnPT (Zinc bis-1-Oxide2(1H)-pyridinethionate ) to the Mysid, Mysidopsis bahia : Lab Project Number: 23- OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

43864608 Boeri, R.; Magazu, J.; Ward, T. (1994) Acute Flow-Through Mollusc Shell Deposition Test with ZnPT (Zinc bis- 1-Oxide-2(1H)-pyridinethionate): LabDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 55 of 63 Project Number: 24-OL. Unpublished study pr epared by T. R. Wilbury Labs, Inc. 27 p.

43864615 Boeri, R.; Kowalski, P.; Ward, T. (1994) Acute Flow-Through Mollusc Shell Deposition Test (Pyridine-N-oxide-2-sulf onic Acid) with Omadine Sulfonic Acid: (Eastern Oyster, Crassostrea virginica ): Lab Project Number: 38-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 27 p.

43864617 Boeri, R.; Kowalski, P.; Ward, T. ( 1994) Acute Toxicity of Omadine Sulfonic Acid (Pyridine-N-oxide-2-sulfoni c Acid) to the Sheepshead Minnow, Cyprinodon variegatus : Lab Project Number: 36-OL. Unpub lished study prepared by T. R. Wilbury Labs, Inc. 27 p.

43864620 Boeri, R.; Kowalski, P.; Ward, T. ( 1994) Acute Toxicity of Omadine Sulfonic Acid (Pyridine-N-oxide-2-sul fonic Acid) to the Mysid, Mysidopsis bahia : Lab Project Number: 37-OL. Unpublished study pr epared by T. R. Wilbury Labs, Inc. 28 p.

43864623 Boeri, R.; Kowalski, P.; Ward, T. (1994) Acute Toxicity of Py ridine Sulfonic Acid to the Sheepshead Minnow, Cyprinodon variegatus : Lab Project Number: 43-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 27 p.

43864624 Boeri, R.; Kowalski, P.; Ward, T. (1994) Acute Flow-Through Mollusc Shell Deposition Test with Pyridine Su lfonic Acid: (Eastern Oyster, Crassostrea virginica ): Lab Project Number: 45-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 27 p.

43864626 Boeri, R.; Kowalski, P.; Ward, T. (1994) Acute Toxicity of Py ridine Sulfonic Acid to the Mysid, Mysidopsis bahia : Lab Project Number: 44-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

44535401 Boeri, R.; Magazu, J.; Ward, T. (1998) Chronic Toxicity of ZnPT to the Daphnid, Daphnia magna : Lab Project Number: 1312-OL. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 39 p.

44535402 Skoulis, N. (1998) Discussion of Observed Differences in Toxicity of ZnPT in the Daphnid: Lab Project Number: OLIN 498. Unpublished study prepared by Olin Corp. 5 p.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 56 of 63 44735101 Goka, K. (1998) Embryotoxicity of Zinc Pyrithione, an Antidandruff Chemical, in Fish. Unpublished study prepared by Nationa l Institute for Environmental Studies. 7 p.

44911101 Boeri, R.; Magazu, J.; Ward, T. (1999) Ch ronic Toxicity of Zinc Pyrithione to the Mysid, Americamysis bahia : Lab Project Number: 1679-OL. Unpublished study prepared by T.R. Wilbury Labs., Inc. 48 p.

45204102 Ward, T.; Boeri, R.; Magazu, J. (1999) Early Life Stage Toxicity of Zinc Pyrithione and Pyridine-2-sulfonic Acid (Persistent Terminal Degradant) to the Fathead Minnow, Pimephales promelas . Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 69 p.

45204103 Hushagen, H. (1998) A 10 Day Sediment Bi oassay to Determine Acute Toxicity of ZnPT to the Sediment Reworker Corophium volutator (Pallas). Unpublished study prepared by Terra Environmental. 11 p. {OPPTS 850.1740}

45828501 Ward, T.; Wyskiel, D.; Boeri, R. (2002) Zinc Pyrithione: Terrest rial Plant Toxicity, Tier 1 (Seedling Emergence): Lab Project Number: 2360-AR. Unpublished study prepared by T.R. Wilbury Labor atories, Inc. 101 p. {OPPTS 850.4100}

43864609 Boeri, R.; Magazu, J.; Ward, T. (1994) Growth and Reproduction Test with ZnPT (Zinc bis-1-Oxide-2(1H)-pyridinethi onate) and the Freshwater Alga, Selenastrum capricornutum : Lab Project Number: 25-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 29 p.

43864614 Boeri, R.; Kowalski, P.; Ward, T. ( 1994) Growth and Reproduction Test with ZnPT Sulfonic Acid (Pyridine-N-oxide-2-s ulfonic Acid) and the Freshwater Alga, Selenastrum capricornutum : Lab Project Number: 39-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 28 p.

43864625 Boeri, R.; Kowalski, P.; Ward, T. ( 1994) Growth and Reproduction Test with Pyridine Sulfonic Acid and the Freshwater Alga, Selenastrum capricornutum : Lab Project Number: 46-OL. Unpublished study pr epared by T. R. Wilbury Labs, Inc. 28 p.

45204104 Ward, T.; Magazu, J.; Boeri, R. (1998) Toxicity of ZnPT to the Duckweed, Lemna gibba G3. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 26 p. {OPPTS 850.4400}Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 57 of 63 45564901 Ward, T.; Boeri, R. (2001) Zinc Pyrith ione: Influence on Growth and Growth Rate of the Alga, Anabaena flos-aquae : Lab Project Number: 2152-AR. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 27 p.

45565001 Boeri, R.; Ward, T. (2001) Zinc Pyrith ione: Influence on Growth and Growth Rate of the Alga, Navicula pelliculosa : Lab Project Number: 2151-AR. Unpublished study prepared by T. R. Wilbury Laboratories, Inc. 28 p.

46250305 Ward, T.; Boeri, R. (2004) Zinc Pyrith ione: Influence on Growth and Growth Rate of the Marine Diatom, Skeletonema costatum . Project Number: 2652/AR. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 26 p.

46250301 Ward, T.; Boeri, R. (2003) Zinc Pyrith ione: Terrestrial Plan t Toxicity, Tier II Seedling Emergence Using Rice, Oryzea oryza sative . Project Number: 2655/AR. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 40 p.

46170601 Ward, T.; Boeri, R. (2003) Zinc Pyrith ione: Influence on Growth and Growth Rate of the Marine Diatom: Skeletonema costatum : Preliminary Draft. Project Number: 2652/AR. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 27 p.

46170501 Boeri, R. (2003) Sediment Toxicity Test with Zinc Pyrithione and the Marine Amphipod, Leptocheirus plumulosus : Progress Report and Summary. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 9 p.

46170801 Boeri, R. (2003) Sediment Toxicity Test with Zinc Pyrithione and the Freshwater Amphipod, Hyalella azteca : Progress Report & Summary. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 10 p.

46250303 Ward, T.; Boeri, R. (2004) Sediment Toxi city Test with Zinc Pyrithione and the Freshwater Amphipod, Hyalella azteca . Project Number: 2653/AR. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 70 p.

46250304 Ward, T.; Boeri, R. (2004) Sediment Toxi city Test with Zinc Pyrithione and the Marine Amphipod, Leptocheirus plumulosus . Project Number: 2654/AR. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 64 p.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 58 of 63 

# Appendix E Screening Level Down-theDrain Analysis

The screening level Down-the-D rain (DtD) assessment was not conducted for ZnPT since there are no pesticidal uses expected to result in release to domestic WWTP.Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 59 of 63 

# Appendix F Product Chemistry

ZnPT product chemistry information is summar ized in Table E1 (source: MRID Nos. 42036701, 47330101, and 47330101).

Table E1 – Product Chemistry of Zinc Pyrithione
Guideline Numbers Physical and Chemical Properties Zinc pyrithione

830.1800 Enforcement analytical method Iodometric Titration 830.6302 Color Colorless
830.6303 Physical State Solid Powder 830.6304 Odor Slight amine odor

830.6313 Stability Stable under recommended storage conditions. Conditions to avoid: Light. Materials to avoid: Oxidizing agents, Heavy metals, Reducing agents 830.6314 Oxidation/Reduction Neither an oxidizing nor reducing agent 830.6315 Flammability No flash point 830.6316 Explodability Not explosive 830.6320 Corrosion Characteristic Not corrosive 830.7000 pH at25 °C 10% slurry in neutral distilled water 6.5-9.5 830.7050 UV/Visible Absorption Its decomposition by ultraviolet light is slow

830.7200 Melting point (°C) ~240 °C. Decomposes before melting.

830.7220 Boiling point (°C) Not applicable. Decomposes

830.7300 Density (g/cm 3 ) 1.76 g/cm3 Bulk Density: 0.3 g/cm 3

830.7370 Dissociation Constant pKa(s) 5.37 x 10 -9 at 20 ஈ C Low dissociation constant

830.7520 Particle size, fiber length, & diameter distribution (percent thru 20 mesh) 90

830.7550 Log Kow 0.9 at 25 ஈ C

830.7840 Solubility in water (mg/L) at 25 o C 15 ppm 8 ppm at neutral pH

830.7860 Solubility in organic solvents Ethanol 100 ppm Propylene glycol 200 ppm Chloroform 3000 ppm Mineral oil 1 ppm 830.7950 Vapor pressure (mm Hg) 0.30 ± 0.05 mmHg at 21CDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 60 of 63 

# Appendix G Comments Received Concerning the Preliminary Work Plan

On September 25, 2014 EPA opened a 60-day public comment period on the preliminary work plan (PWP) for the registration review of zinc pyrithione. The comment period ended on November 24, 2014. Comments received did not result in a modification to the anticipated data needs detailed in the Zinc Pyrithione PWP.

The agency received comment submissions from three organizations du ring the public comment period on the initial docket. Comme nts were received from the Ce nter for Biological Diversity (Center), the Los Angeles Water Quality C ontrol Board (LA Water Board), and the San Francisco Bay Regional Water Quality Control Board (SF Bay Water Board). The CenterPs comments sought to confirm the agencyPs coordina tion with the U.S. Fish and Wildlife Service and the National Marine Fisheries under Section 7 of the Endangere d Species Act to ensure that ZnPt does not jeopardize the con tinued existence of any listed species or result in adverse modification or destruction of critical habitat. LA Water Board comments focused on a request that the agency consider the potential aquatic impacts for formation, persistence, and cumulative toxicity of zinc pyrithione, including toxicity of copper pyrithione, in waters where copper antifouling paints are prevalent. Comments fr om the SF Bay Water Board expressed support for the comments submitted by the LA Water Board.

EPA generally used an outline format to address the comments (with name of submitter, comment and EPA response, in that order).Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 61 of 63 Comments Received on the Registration Review Preliminary Work Plan for Zinc Pyrithione

Submitter: The Center for Biol ogical Diversity (Center)

1. Comment: The CenterPs comments focus on EPAPs duty to consult with the U.S. Fish and Wildlife Service and the National Marine Fisheries Service (the Services) on the registration review of zinc pyrithione in acco rdance with the ESA. The Center mentions various aspects of the risk assessment process, including use of the be st available data to develop endangered species risk assessments, sources of data available to conduct an effects determination, and evaluation of effect s on endangered and threatened species and their designated critical habita t. The Center also expressed concern regarding the rigor of the agencyPs preliminary determinations re garding the effects of zinc pyrithione on endangered and threatened (listed) species a nd their designated critical habitat for the zinc pyrithione registration review.

EPA Response: EPA has reviewed the comments fr om the Center on the registration review docket opening for zinc pyrithione a nd plans to address many of the concerns raised by the Center as part of the impl ementation plan for assessing the risks of pesticides to listed species based on the recommendations of the April 2013 National Academy of Sciences (NAS) report (also c ited by the Center). EPA will address concerns specific to zinc pyrit hione in connection with the de velopment of its registration review decision for this pesticide.

In November 2013, EPA, along with the Serv ices and USDA, released a summary of their joint interim approaches for assessing ri sks to endangered and threatened (listed) species from pesticides. The interim approach es were developed jointly by the agencies in response to the NAS recommendations and reflect a common approach to risk assessment shared by the agencies as a way of addressing scientific differences between EPA and the Services. The NAS report [1] outlines recommendations on specific scientific and technical issues related to the development of pesticide risk assessments that EPA and the Services must conduct in connecti on with their obligati ons under the ESA and FIFRA.

The joint interim approaches were released prior to a stakeholder workshop held on November 15, 2013. In addition, EPA presente d the joint interim approaches at the December 2013 Pesticide Program Dialogue Co mmittee (PPDC) and State-FIFRA Issues Research and Evaluation Group (SFIREG) meetings. The agenci es also held stakeholder workshops in April and October 2014, allowi ng additional opportunitie s for stakeholders to comment on the interim approaches. Additional workshops are planned to enhance stakeholder involvement. As part of a phased, iterative process for developing the interim approaches, the agencies will al so consider public co mments on the interim approaches in connection with the deve lopment of upcoming registration review decisions. The details of the joint interim a pproaches are contained in the white paper,

[1] http://www.nap.edu/catalog.php?record_id=18344Docket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 62 of 63 Interim Approaches for National-Level Pes ticide Endangered Species Act Assessments Based on the Recommendations of the National Academy of Sciences April 2013 Report [2] , dated November 1, 2013.

Given that the agencies are continuing to de velop and work toward implementation of the interim approaches to assess the potential risk s of pesticides to listed species and their designated critical habitat, this FWP for zi nc pyrithione does not describe the specific ESA analysis, including effects determinations for specific listed species or designated critical habitat, to be conducted during regi stration review. Once the agencies have fully developed and implemented the scientific methods necessary to complete risk assessments for endangered and threatened (lis ted) species and their designated critical habitats, these methods will be applied to subsequent analyses for zinc pyrithione as part of completing this registration review.

Submitter: Los Angeles Water Qualit y Control Board (LA Water Board)

2. Comment: The Water Quality Control Plan for th e Los Angeles Region contains Total Maximum Daily Loads (TDML) for toxic pollu tants. The TDML is being revised to address an impairment by copper in the wa ter column which the LA Water Board attributes to antifouling hull paints. The LA Water Board requests that the agency consider the potential aquatic impacts for form ation, persistence, and cumulative toxicity of zinc pyrithione, including toxicity of copper pyrithione, in waters where copper antifouling paints are prevalent. The LA Water Board also pr ovides a list of preliminary documents to include in a potential review of peer-reviewed research regarding the potential presence and toxici ty of copper pyrithione.

EPA Response: The agency thanks the LA Water Board for its comments and continues to review ways to improve ecological risk assessments. EPA agr ees that exposure to mixtures of compounds may affect the overall toxicity of any chemical. A quantitative assessment of risks associated with mixtures requires extensive data. Currently EPA does not have adequate data and has not yet developed the methodology to quantitatively assess mixtures of chemicals in the environment.

EPA has a long term goal to develop a qua ntitative approach including guidance on weight-of-evidence analysis for assessing risks of pesticides mixtures. In the interim, EPA intends to qualitatively discuss the potenti al for differential exposure and toxicity from mixtures of compounds. EPA will incl ude review of the submitted documents as part of the search for relevant data from open literature.

The use of copper based antifoul ant paints will be addressed along with the other uses of copper under the registration review of copper. EPA will review the submitted research.

[2] http://www.epa.gov/espp/2013/nas.htmlDocket Number EPA-HQ-OPP-2014-0158 www.regulations.gov

Page 63 of 63 Submitter: San Francisco B ay Regional Water Quality Control Board (SF Bay Water Board)

3. Comment: The SF Bay Water Board urges the agency to carefully consider all potential aquatic impacts during the zinc pyrithione registration review, including the cumulative toxicity of zinc pyrithione in waters where copper antifoulin g paints are prevalent. The SF Bay Water Board also concurs with comments submitted by the LA Water Board.

EPA Response: AD appreciates submission of thes e comments. Please refer to the response provided to the LA Water BoardPs comments above.