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Zinc Pyrithione Registration 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 Ross
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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-m3

/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 

CO2 carbon dioxide 

COC concentration-of-concern 

cPAD chronic population adjusted dose 

DB database uncertainty factor 

DCI data call-in 

EC50 median (or 50 percent) effect concentration

EC05 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, Drug, 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 

LC50 median (or 50 percent) lethal concentration 

LD50 median (or 50 percent) lethal dose 

LOAEC lowest-observed-adverse-effect-concentration 

LOEC lowest-observed-effect-concentration 

LOAEL lowest-observed-adverse-effect-level 

Log Kow 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 exposure 
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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 

SO2 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 pyrithione 

 
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Table of Contents 

1 Introduction ............................................................................................................................. 7

1.1 Statutory and Regulatory Authority ................................................................................. 7

1.2 Updates to the Workplan .................................................................................................. 7

1.3 Case Overview ............................................................................................................... 10

1.4 Chemical Identification and Properties .......................................................................... 10

1.5 Use/Usage Description ................................................................................................... 12

1.5.1 Registrations ........................................................................................................... 12

1.5.2 Summary of Registered 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 ............................................................................................................ 18

3.2.1 Food ........................................................................................................................ 18

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-Application 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 Wildlife Exposure Estimates ............................................ 26

4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 26

4.4.3 Endocrine Disruptor Screening Program (EDSP) ................................................... 26

5 Next Steps ............................................................................................................................. 27

6 References ............................................................................................................................. 28
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Appendix A Toxicology Profile ............................................................................................... 29

Appendix B Residential Post-Application 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 the 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 Environmental Fate Properties for Zinc Pyrithione ................ 11

Table 4 k ZnPT Registered Uses .................................................................................................. 12

Table 5 k Studies Anticipated as Needed for the Registration Review of Zinc Pyrithione .......... 15

Table 6 k Existing Toxicological Endpoints for ZnPT ................................................................. 16

Table 7 k Occupational Handler Exposure Scenarios for ZnPT ................................................... 19

Table 8 k Residential Handler Exposure Scenarios for ZnPT ...................................................... 19

Table 9 k Residential Post-Application Exposure Scenarios for ZnPT ........................................ 20

Table 10 k Summary of Results from Environmental Degradation of ZnPT ............................... 22

Table 11 k Available Ecological Effects Endpoints for the TGAI ............................................... 25
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1 Introduction 

This document is the United States Environmental Protection AgencyPs (USEPA, EPA or lthe 

agencym) Final Work Plan (FWP) for zinc pyrithione (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 information 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 public participation component to 

solicit input from interested stakeholders. The agency intends, by sharing this information in the 

docket, to inform the public of what it knows about 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 Regulatory Authority 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review program. All 

pesticides distributed or sold in the United States generally must be registered by the USEPA 

based on scientific data showing that they will not cause unreasonable risks to human health or 

the environment when used as directed on product labeling. The registration 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 environment. Changes in science, 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. Information on this program is provided at 

http://www2.epa.gov/pesticide-reevaluation. 

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

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

pesticide every 15 years to determine whether it continues to meet the FIFRA standard for 

registration. The regulations governing registration review begin at 40 CFR 155.40. The agency 

will consider benefits 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 review decision. The Zinc 

Pyrithione Preliminary Work Plan (PWP) was 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: 
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x Corrected formatting and typographical errors. 

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

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

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

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

The agency received comment submissions from three organizations during the public comment 

period on the initial docket. Comments were received from the Center for Biological Diversity 

(Center), the Los Angeles Water Quality Control 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 coordination with the U.S. Fish and Wildlife Service 

and the National Marine Fisheries under Section 7 of the Endangered Species Act (ESA) to 

ensure that ZnPt does not jeopardize the continued 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 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 anticipated data needs detailed in the 

Zinc Pyrithione PWP. This document makes final the work plan for the zinc pyrithione 

registration review process. 

Tables 1 and 2 below summarize the issues relevant to this registration review case and the 

anticipated registration review schedule. 

Table 1 – Summary of Anticipated Risk Assessments 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 Exposure 
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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 Registration Review Schedule 

Anticipated Activity Target Date* Completion Date

Phase 1: Opening 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).
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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 Identification of Zinc Pyrithione 

Chemical Name Zinc pyrithione (ZnPT) 

Chemical Classification Organozinc; Omadine salt 

PC Code 088002 

CAS Number 13463-41-7 

Molecular Formula C10H8N2O2S2Zn 

Molecular Weight (grams/mole) 317.68 

Molecular Structure 

The ZnPT product chemistry information (MRID Nos. 42036701, 47330101, and 47330101) 

relevant to risk assessment is summarized in Table 3, and the details of the environmental fate 

and product chemistry information are discussed in Appendix C and Appendix F , respectively. 
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Table 3 – Physical-Chemical and Environmental 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 Kow) 0.9 at 25ஈC 

830.7840 Solubility in water 15 ppm 

8 ppm at neutral pH

830.7950 Vapor pressure 4.9 x 10-7mm Hg 

Environmental Fate Properties

Mobility

Organic Carbon Partitioning Coefficient (Koc) 430454 L/Kg

Persistence in Water (half-life)

835.2120 Hydrolysis at 25 oC: 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 oC 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 phase 

I; 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 - Kd 50-99 L/Kg, 

Fresh water sediment - Kd 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/cm2

/day to 8.4 μg/cm2/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 4.1.5 
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1.5 Use/Usage Description 

1.5.1 Registrations 

There are 60 products containing ZnPT as an active ingredient (a.i.). Thirty products are 

antifoulant paints that contain 1.33 to 47.4 percent a.i., twenty-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. These 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 plastics, resins, adhesives and sealants as well as in 

marine antifoulant coatings. The market penetration is approximately 13 percent for plastics and 

resins, <1 percent for marine antifoulant coatings and <1 percent for adhesives and sealants. 
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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 Decision (RED) (EPA, 2004).1 Because the 

Reregistration Decision Document was not published in 2004, the agency entered into the 

registration review docket the document it intended to issue as a RED for this chemical. 

1.6.1 Tolerance Information 

There are no tolerances or tolerance exemptions established for ZnPT. The Food and Drug 

Administration (FDA) has established regulation for ZnPT for use in the preservation of 

components of paper coatings (non-polymeric) used in the manufacture of paper and paperboard 

(Food Contact Notification 1169). Since the publication 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 belts, 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 moderate (HC) or higher are reported in individual reports which 

include information regarding the causes of the incident and symptoms experienced. In the case 

of ZnPT, there is one individual incident 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 exposure when workers were handling a pesticide 

product while not wearing gloves. This dermal exposure resulted in blisters 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) are reported in aggregate 

reports which are listings of the incidents for a manufacturer or distributer over a certain time 

period (often quarterly). Typically these reports only contain basic information such as the date, 

location and product involved and more detailed information such the cause of the incident or 

symptoms experienced are not included. In the case of ZnPT, there are seven aggregate 

incidents listed in the IDS for the period 1/1/1999 to 5/05/14 (search conducted on 5/05/14). All 

 

1

 Zinc Pyrithione Preliminary Risk Assessment documents for the RED are available on regulations.gov, docket 

number EPA-HQ-OPP-2004-0147. 
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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 anticipated as being needed to support this registration 

review. 
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Table 5 – Studies Anticipated as Needed for the 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 through the Registration Review DCI 

870.4300 Combined Chronic 

Toxicity/Carcinogenicity TGAI 36 Human Health Assessment All Use Sites Dietary and drinking 

water exposures 

870.62001 90-Day Subchronic 

Neurotoxicity TGAI 12 Human Health Assessment All use sites All exposure scenarios

870.78001 Immunotoxicity TGAI 12 Human Health Assessment All use sites All exposure scenarios

875.1200 Indoor Dermal Exposure TGAI or 

surrogate2 24 Occupational and 

Residential 

Material preservation including 

architectural paints See Footnote3

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-day neurotoxicity and/or 

immunotoxicity studies by adding separate groups of animals for 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 addressed. 3 Exposure scenarios include Open Pour Addition of Liquids and Powders for Material Preservation, Airless Spray and Brush/Roller Application of Preserved 

Architectural Paints. 
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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 conducted in 2004 and posted to regulations.gov under 

docket number EPA-HQ-OPP-2004-0147. In that 2004 assessment, dietary risk was assessed for 

use of ZnPT as an antimicrobial pesticide in food packaging materials and in repeat use 

polymeric food contact materials. Drinking water risk was assessed from use of ZnPT in 

antifouling boat paint for recreational boats. Residential risk was assessed from use of ZnPT as a 

materials preservative. 

Since the 2004 assessment, additional information 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) model describing ZnPT kinetics after dermal 

exposure (MRID 48596001). Additional data on neurotoxicity, immunotoxicity, and 

carcinogenicity are also anticipated as being needed for registration 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 endpoints 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 information including existing toxicology studies, valid 

scientific literature, and studies available during 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 Toxicological Endpoints for ZnPT 
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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 

aPADa

 (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. 
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3.2 Dietary Exposure 

The agency anticipates the need to revise the acute and chronic dietary (food and drinking water) 

exposure assessment for registration review. Dietary exposure to ZnPT can occur from use in 

food packaging adhesives, food packaging materials, 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 exposure assessment. In combination with the 

anticipated toxicology studies being requested (see Table 5), dietary 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 evaluated exposure and risk from use of ZnPT in 

conveyor belts. The conveyor belt use was considered to represent the highest potential for 

dietary exposure of all the uses of ZnPT that could result in dietary exposure. This was based on

repeatability of use, high frequency of use, and a short life at the use level for conveyor belts 

compared to other uses resulting in dietary exposure. Assumptions regarding exposure were used 

in that assessment will be re-evaluated to be certain 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 drinking water sources. The assumptions and models 

used in the 2004 risk assessment will be re-evaluated to be certain 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 performed for each population subgroup for which an 

endpoint exists. A risk estimate that is less than 100% of the acute 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 the acute Population Adjusted Dose (aPAD) and 

chronic Population Adjusted Dose (cPAD). 

3.3 Occupational and Residential Exposures 

The agency anticipates the need to revise the occupational and residential assessments conducted 

in support of the 2004 risk assessment. This is needed to account for the 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 required in registration review to 

account for dermal and inhalation routes of exposure from the ZnPT material preservation use 

site 
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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 during 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 registration review to account for the 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 Received Since the 2004 Risk Assessment 

In response to the 2004 risk assessment, a recreational boat painter 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 registration review to account for the 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 Term
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3.4.1 Residential Post-Application Exposures 

Residential Post Application Data Received Since the 2004 Risk Assessment 

Several post application studies have been received since the 2004 risk assessment. These 

include four textiles leaching studies, a carpet transferable residue study and a plastics leaching 

study. Three of the textile leaching studies indicated similar results, with leaching rates that 

ranged from 0.11% to 3.19%, depending on the treatment type, while one study (MRID 

48902609) indicated much higher leaching rates 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-application studies, please see Appendix B 

Residential Post Application Exposures to be Assessed during Registration Review 

All of the residential post application scenarios that were assessed in the 2004 risk assessment 

will need to be reassessed during registration review 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-Application Exposure Scenarios for ZnPT 

Scenario Exposure Route(s) Duration 

Exposure to ZnPT preserved textiles Dermal, Incidental Oral Short and Intermediate Term 

Exposure to ZnPT preserved carpets 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 conducted in support of the 

2004 ZnPT risk assessment. Upon a reevaluation and selection of toxicology endpoints, 

combined with the human health exposure assessments expected as a part of this registration 

review case, aggregate exposures and risks will need to be assessed. 

The risk assessment is anticipated to include an acute and chronic (non-cancer) aggregate dietary 

(food and water) assessment, a short-term aggregate assessment (average food and water 

exposure plus short-term residential exposures), an intermediate-term aggregate assessment 

(average food and water exposures plus intermediate-term residential exposures, including 

exposures resulting from FDA regulated uses), and a cancer aggregate risk assessment (if 

positive results are observed in the 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 mechanism of toxicity, EPA has not made a 
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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, therefore, 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 environmental risk assessment for the use of zinc 

pyrithione in antifoulant boat paints to control growth of slime, algae, and marine fouling 

organisms (e.g., barnacles, tubeworms, etc.) below the water line of recreational 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 registration 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 critical 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 both freshwater and salt water anaerobic aquatic 

metabolism studies. The phase I half-life was approximately 2 hours, but the phase II half-life 

was 25 hours showing faster overall degradation in anaerobic systems than in aerobic systems 

(MRID# 44850004, 45876501). 
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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 Kd 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 aqueous 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 uses of ZnPT is as an antifoulant 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 been 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/cm2/day to 8.4 μg/cm2/ day. From these leaching rates, estimated 

environmental concentrations (EECs) can be determined for ecological risk assessments of 

aquatic organisms. 

Leaching rates from treated fabrics are discussed 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 identified in environmental 

fate studies, and all identified degradates retained the pyrimidine ring structure. Table 10 lists 

the identified degradates and the studies where 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 Metabolism 
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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 need to require additional environmental fate data 

for the ZnPT degradates because the degradates are 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 Zn2+. 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, sulfate, nitrate, carbonate 

and oxide. 

Zinc from ZnPT in antifoulant paints is released into aqueous medium between 1.7 to 8.4 

μg/cm2/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 Zn2+ 

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 impairment 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 (TMDL) 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 found impaired because of the presence of zinc 

ions. More information on impaired water 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 paint directly into freshwater or saltwater 

 

2

 . http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885
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environments. Water bodies might include impounded bodies (e. g., harbors, lakes, reservoirs) 

or flowing waterways (e. g., streams, rivers). For uses in coastal areas, aquatic habitat also 

includes estuaries and harbors. Aquatic organisms 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 repeated 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 Kow (0.97), bioaccumulation in aquatic 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 organisms like invertebrates and vertebrates; 

thereby reducing their survival, growth, and reproduction. ZnPT could be ingested by algae, 

resulting in reduction in algae production, reduction in prey. Vascular and non-vascular plants 

could be adversely impacted which 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 indicated 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 toxicity data from registrant-submitted studies 

conducted in accordance with the 850 OCSPP Harmonized Test Guidelines are used to evaluate 

the potential direct and indirect effects to plants 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 registrant-submitted studies conducted in accordance with 

the 850 OCSPP Harmonized Test Guidelines are used to evaluate the potential direct and indirect 

effects to plants and animals. All data requirements and available 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 terrestrial 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. Chronic 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. 
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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 available toxicity data for dissolved zinc in the 

water column, and those data also are presented in Appendix D . 

Table 11 – Available Ecological Effects 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 searched during the risk assessment phase of ZnPT 
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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 literature is presented on the agencyPs website 

http://www.epa.gov/pesticides/science/literature-studies.html

4.4 Exposure Analysis Plan 

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates 

Available OPP models will be used to determine 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 (Exposure 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 treatment plants. Although there may be the potential 

for exposure to aquatic organisms from ZnPT entering industrial wastewater treatment plants as 

a result of industrial uses of ZnPT as a materials preservative, this 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 will be based on leaching from antifoulant paint. 

4.4.3 Endocrine Disruptor Screening Program (EDSP) 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of the 2004 risk assessment for ZnPT, the 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 Screening Program (EDSP). 

The agency has developed the EDSP to determine whether certain substances (including 

pesticide active and other ingredients) may have an effect in humans or wildlife similar to an 

effect produced by a lnaturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate.m The EDSP employs 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 with the estrogen, androgen, or thyroid (E, A, or 

 

3

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_wor

kgroup/esa_evaluation_open_literature.htm 
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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 the next stage of the EDSP 

where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available 

data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the 

substance, and establish a dose-response relationship between the dose and the E, A, or T effect. 

Under FFDCA section 408(p), the agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 20134 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 likely endocrine disruptors. ZnPT was not on either of the EDSP 

screening lists. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, 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 document. 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/ 
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6 References 

EPA. 2004. Zinc Pyrithione (ZnPT): AD Risk Assessment for the Reregistration Eligibility 

Decision (RED) Document. Chemical No. 088002. Case No. 2480. DP Barcode: D308704, 

September 30, 2004 

EPA. 2009. Ecological Hazards and Risk Assessment Chapter for Antifoulant Use of Zinc 

Pyrithione. RASSB/AD, March 25. DP Barcode: D362199. 

Kline and Company, 2005: Specialty Biocides 2004-2005 A Global Series of Regional Market 

Analyses Volume II: United States. 
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Appendix A Toxicology Profile 

Acute Toxicity Labeling 

The acute toxicity database for ZnPT indicates that 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 Category III). ZnPT is a severe eye irritant 

(Toxicity category I) but does not appear to demonstrate significant dermal 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 toxicity study for ZnPT and one 90-day 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 dermal occlusion at doses of 0, 20, 100, and 1000 

mg/kg/day for 6 hours/day, 5 days/week for 13 weeks. Treatment-related effects included 

decreased food consumption (91.6% of control), decreased body weight 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 weights for females (1000 mg/kg/day) were 

decreased 13% to 21% relative to controls for weeks 2-13. The systemic NOAEL = 100 
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mg/kg/day in females, and 1000 mg/kg/day in males. The systemic LOAEL = 1000 mg/kg/day in 

females (decreased body weight gain, food consumption, and food efficiency), and >1000 

mg/kg/day in males. 

This study is classified as acceptable and satisfies the guideline 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 concentrations 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 died over the course of the study. Treatmentrelated clinical signs of toxicity included rales, labored breathing, 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 consumption was decreased 10%, and food efficiency was 

decreased 53%. Hematologic, clinical chemistry, or urinalysis effects were not considered biologically significant for any of the exposure groups, 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 histopathologic findings of trace to mild subacute 

inflammation of the interstitial tissue of the lung and medial hypertrophy of pulmonary arteries 

which were biologically significant at 0.01 mg/L/day. 

Based on the results of this study, the systemic NOAEL = 0.0005 mg/L/day, and the systemic 

LOAEL= 0.0025 mg/L/day (labored breathing, rales, increased salivation, decreased activity, dry 

red-brown material around the nose, increased absolute and relative lung weights, and death of 

undetermined cause) 

This study is classified acceptable and satisfies the guideline requirement (OPPTS 870.3465) for 

a subchronic inhalation toxicity study in rats. 

Developmental Toxicity 

This is an oral developmental toxicity study in the rat, an oral developmental study in the rabbit, 

and a dermal developmental toxicity study in the rat for ZnPT. The summaries of these studies 

are shown below. 

MRID # 42827904 - In a developmental study, thirty pregnant 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 group 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 (increased salivation immediately after 

dosing; 27% and 97% of dams, respectively). Other dose-related signs seen at 15 mg/kg/day 

included biologically significant decreases in body weight gains (67%; p d 0.01; absolutes of 4-
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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 excessive salivation during the dosing period.

Developmental toxicity was characterized by a dose related increase in post-implantation loss at 

the mid and high doses with the 15 mg/kg/day group being significantly different than controls 

(p < 0.01). This correlated with an increase in early resorptions (3.6%/dam) 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 controls), 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 the 15 mg/kg/day group contained fetuses with 

external, visceral, or skeletal malformations/variations. 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 indicative of hydronephrosis, and 

a vertebral/rib anomaly (24 of 24 treated 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 high-dose groups, respectively), a statistically 

significant linear trend was evident (Cochran-Armitage test; p=0.009), and 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 increased 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 gavage 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, followed by an examination of all fetuses. 

One mid-dose doe died on GD 16, probably due to a gavage error. A decrease in body weight 

gain (p d0.01) during the dosing period for the mid and high-dose groups (41% and 99%, 

respectively) cannot be considered biologically 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 had total litter resorption. Dose-related early resorptions were 

seen in the mid and high-dose does. These findings corresponded with a dose-related increase in 

post-implantation loss (early resorption) and a decrease in viable fetuses. It is not clear whether 

the resorptions were due to maternal or developmental toxicity. No statistically significant 

differences were seen in the incidence of external, visceral, or skeletal anomalies in the treated 
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groups as compared to controls. Three fetuses 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 viable fetuses (it is not clear 

whether the resorptions were due to maternal 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 pyridinethione to rats resulted in maternal 

toxicity at 30 and 60 mg/kg/day. Treatment-related effects at 60 mg/kg/day included clinical 

signs of toxicity (grade 1 erythema; grade 1 flaking; 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 corrected body weight gain, decreased absolute and relative feed 

consumption, and decreased muscle tone and mass. At 30 mg/kg/day, there was an increase in 

the number of dams with limited use of hindlimbs, shuffling gait, decreased body weight and 

body weight gain, decreased corrected body weight and corrected body weight gain, and 

decreased absolute feed consumption. There were no treatment-related maternal 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 pyrithione 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 received the test chemical in distilled water by gavage at dose 

levels of 0, 0.5, 1.5, or 3.5 mg/kg/day at a dose 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 demonstrating hunched posture, impaired hindlimb 

mobility, rapid breathing, and peri-orbital, peri-nasal, and abdominal 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 female rats at the 1.5 and 3.5 mg/kg/day dose levels. 

Decreased body weight was observed in both parental 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 consumption 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 as 
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reduction and variation in the diameter of muscle fibers, increase in number of sarcolemmal 

nuclei, and fatty replacement 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 significantly 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 birth 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. Developmental 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 statistically 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 muscles in males could impact mating success and 

therefore would explain the decrease in mating and fertility indices. Mean percentage of pups 

with startle response on lactation day 15 and mean percentage of pups with eyes open on 

lactation day 15 was decreased by 13% and 14% respectively, 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 hindlimb skeletal muscle in F0 males 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 acceptable and satisfies the data requirement for a reproductive 

toxicity study in rats. 

Chronic Toxicity/Carcinogenicity 

There were no submitted chronic toxicity or carcinogenicity studies on ZnPT. A dermal 

carcinogenicity study in mice and an oral carcinogenicity 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 purposes. Therefore, sodium pyrithione could not be 

classified as to carcinogenic potential without an adequate study in the mouse. 

For ZnPT, the indirect food uses could potentially trigger the need for chronic toxicity and 

carcinogenicity data. The agency has established 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 carcinogenicity studies) are needed to characterize hazard and risk 

from this use pattern. In addition, the indirect food use for ZnPT suggests there may be repeated 

exposure to ZnPT over a considerable portion of the human lifespan, which is also listed as a 
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criterion in determining the need for chronic toxicity and carcinogenicity data (40 CFR 

§158.2230). Based on preliminary calculations for ZnPT, 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 toxicity/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 presence of metabolic activation (MRID 

41906502). In a mutagenicity study using Chinese Hamster Ovary (CHO) cells (MRID # 

41906503, zinc pyrithione failed to induce a mutagenic response in the absence of metabolic 

activation (doses of 0.25-2.0μg/ml) and in the presence of metabolic activation (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 polychromatic erythrocytes 

(MPEs) in bone marrow cells harvested 24, 48, or 72 hours post-dose. High dose mice exhibited 

signs of toxicity (including mortality, 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 literature have noted neurotoxic effects from 

exposure to ZnPT. Ross and Lawhorn (Neurotoxicol. Teratol 12(2): 153-159, 1990) observed 

reduction in forelimb and hindlimb grip strength and electrophysiological 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 incoordination, and reduced sensory and mixed 

sensory/motor nerve-evoked potential amplitude (but no reduction in conduction 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 clinical signs abated during the recovery period, 

decreases in nerve-evoked potential amplitude remained decreased. Administration of ZnPT to 

dogs has produced blindness and retinal detachment (Grant, W.M. Toxicology of the Eye. 3rd ed. 

Springfield, IL. Charles C. Thomas, Pub.). 

Data submitted to the agency for ZnPT also note 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 evidence of neurotoxicity in other studies, 

and preliminary indications of dietary residue >200ppb, a subchronic neurotoxicity study is 

anticipated to be needed for ZnPT. 

MRID # 46534002 - In an acute neurotoxicity study, 9 week 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 observational battery (FOB) and motor 

activity testing] were performed in 10 animals/sex/group, pretest and Day 0 (one hour postdosing) in 10, 10, 10 and 9 males and 10, 10, 8 and 4 females from the control, low, mid and 
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high dose groups, respectively, at 7 and 14 days post dosing. At study termination, surviving rats 

were euthanized and perfused (in situ) for neuropathological examination. Of the perfused 

animals, 5 animals/sex/group (when available) were subjected to histopathological evaluation of 

brain and peripheral nervous system tissues. 

The following findings were toxicologically significant 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, soft/liquid feces, urine-stained abdominal fur, 

and localized alcopecia on underside of body; females: urine-stained abdominal fur, dehydration, 

soft/liquid feces, chromorhinorrhea); 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 significant decreased body weight gain on Days 0-1 in high dose 

females; statistically significant decreased relative food consumption 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 decreased 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 dose 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 significant decreased in hindlimb grip strength in 

high-dose males on Day 7. A toxicologically significant 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 movements 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 two 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-dosing, 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 complement of female animals survived to the latter 

two time points. 

There were no treatment related effects for the animals on hindlimb evaluations (calf muscle 

mass and tone), gross and histologic pathology, or neuropathology. 

Based on the effects seen in this study, the LOAEL 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-dosing), 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 neurotoxicity 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 870.7800 
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guideline, by citing information from the scientific literature that addresses immunotoxicity of 

ZnPT, or by submitting a request for waiver of this study using the agencyPs published guidance, 

available at: http://www.epa.gov/pesticides/regulating/part158-tox-data-requirement.pdf. 

 
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Appendix A References 

1) Moreno O.M., Cerven D.R., Altenbach, E,J. (1986): Single Dose Oral Toxicity in Rats/LD 

50 in Rats. Study performed by M B Research Laboratories, Inc, Spinnerstown, 

Pennsylvania for Olin Corporation. 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 Inhalation 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/Corrosion in Rabbits. Study performed by M B 

Research Laboratories, Inc, Spinnerstown, Pennsylvania 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, Pennsylvania for Olin Corporation. MRID # 

42146704. Unpublished. 

6) Newcomb, T (1996): Delayed Contact Dermal Sensitization Test (Buehler Method). Study 

performed by M B Research Laboratories, Inc, Spinnerstown, Pennsylvania for Olin 

Corporation. MRID # 43950201. Unpublished. 

7) Ulrich, C.E. (1993): 90-Day Subchronic Dermal Toxicity Study on ZnPT in Rats. Study 

performed by International Research and Development Corporation for Olin Corporation. MRID 

# 42827902. Unpublished. 

8) Schardein, J.L. (1993): Developmental Toxicity 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 Toxicity Study in New Zealand White Rabbits with 

ZnPT. Study performed by International Research and Development Corporation for Olin 

Corporation. MRID # 42827905 and 42827906. Unpublished. 

10) Barnett, J. Jr. (2005). Percutaneous developmental toxicity study of zinc pyridinethione 

(ZPT) in rats. CR-DDS Argus Division (Horsham, Pennsylvania). Argus AEN00006, April 7, 

2005. MRID 46534001. Unpublished 

11) Barnett, J. (2005) Oral (Gavage) Acute Neurotoxicity Study of Zinc Pyridinethione (ZPT) in 

Male and Female Rats: Final Report. Project Number: AEN00002, AEN00001, AEN00002AA. 

Unpublished study prepared by Research Pathology Services, Charles River Laboratories and 

Pathology Associates, Inc. MRID 46534002. 
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12) Ridgway, P. and Wood, C.M. (1989): Sodium Omadine Rat Two-Generation Reproduction 

Toxicity Study. Study performed by Toxicol Laboratories 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 Development 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., Rockville, 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): Micronucleus Cytogenetic Assay in Mice. Study 

performed by Microbiological Associates, Inc., Rockville, MD for Olin Corporation. MRID # 

41906501. Unpublished. 

17) Preliminary Neurological Evaluation of Generalized 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 following 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 Rat. 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 Toxicity Study in Cynomolgus Monkeys. Study 

conducted by International Research and Development Corporation, Mattawan, MI and 

submitted to the EPA under MRID 41178101. Unpublished. 
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24) Ross, J.F. and Lawhorn, G.T. (1990): ZNPT-related Distal Axonopathy: behavioral and 

electrophysiologic correlates in rats. Neurotoxicol. Teratol 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 Assessment of Zinc Pyrithione Toxicity. Food Cosmet. 

Toxicol. 17(6), 651-660, 1979. 

26) Grant, W.M. Toxicology of the Eye, 3rd edition. Charles C. Thomas, pub. (1993) 

 
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Appendix B Residential Post-Application 

Studies 

Table B1 – Summary of Zinc Pyrithione Textile Leaching Data 

TreatmentA Amount 

ZnPT 

Extracted 

(ug/g) 

Percent 

ZnPT in 

FabricB

Amount ZnPT 

Leached at 

Ambient Temp 

(ug/g) 

Percent 

Leach RateB

(Ambient 

Temp) 

Amount 

ZnPT 

Leached at 

37 C (ug/g) 

Percent 

Leach 

RateB

(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 from 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 from 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 (2nd 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 rates 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 efficiency of ZnPT from 

fabrics. 

Total ZnPT in the carpet was determined by microwave-assisted dimethyl sulfoxide/acetone 

solvent extraction of fibers clipped from the carpet, followed by liquid chromatography-mass 

spectrometry (LC/MS). The transfer efficiency of ZnPT to fabrics was measured using a 
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modified California roller sampling technique, where 7.79 lb or 35 lb rollers were used to 

simulate the exposure condition for children and adults, and a rolling frequency of 80 rolls was 

applied to the cotton or polyester fabric-covered carpet surface. The size of the fabric samples 

was 5mx 5m (161 cm2) for the 7.79 lb roller and 16m x 16m (1650 cm2) for the 35 lb roller. The 35 

lb roller consisted of all three roller sections of a Roberts 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 roller, which has a width of 5 inches. For the 

measurement of saliva extraction efficiency, the amount of ZnPT transferred 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 linearity, specificity, detection limit, accuracy, and 

precision. The limit of detection (LOD) was 0.005 ug/cm2 and the limit of quantitation (LOQ) 

was 0.018 ug/cm2. The mean recovery of ZnPT ranged from 100.4% to 106.5% in the carpet 

samples spiked at 80 - 100% of the base ZnPT level in the treated carpet. The mean recovery of 

ZnPT in the transferable ZnPT and saliva efficiency 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 replicate 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/cm2 and the density of the carpet fibers was determined to be 155 gm/cm2. 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/cm2 which equates to an application 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 moistened polyester was 0.026% when the 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 into 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 evaluate exposures to ZnPT in plastics. Disks 

of two types of plastics (polyethylene or polypropylene) treated with either 1000 ppm or 4000 

ppm ZnPT were immersed in two types 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 cm2

 each. The 

polypropylene (PP) disks weighed ~50 mg and the polyethylene (PE) disks weighed ~90 mg. 

The disks were placed into migration cells which consisted of 23 ml glass vials fitted with 

Mininert Teflon valves. Ten disks and 22 ml of test solvent were placed into each vial which 

yielded a volume to surface area of 1.07 mL/cm2

. The vials were then covered with black 

electrical tape to prevent photo-degradation of ZnPT and held in a 50 C (120 F) water bath with 

agitation at 50 cpm. Each migration study was done in triplicate and polymer blanks containing 

no ZnPT were also tested. 
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Aliquots (250 uL) were collected at specified time intervals that ranged from 0 to 240 hours and 

were analyzed using HPLC according to a standard analytical method (CAM 5-90). Recovery 

and control 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. The results of this study are summarized 

in Table 10. Because the LOD was not reported, it was estimated by dividing the lowest 

reported value of 40 ppb by a factor of 2. The 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 difference was highly variable and was often much 

greater than the 4X difference than would be expected. In a similar manner, the results did not 

follow any coherent pattern with respect to time. 

Table B2 – ZnPT Leach Rate Data from MRID 44108602 

PolymerA Solvent ZnPT 

Content 

(ppm) 

ZnPT 

ContentB

(ug/sample) 

Maximum 

Leached 

(ppb) 

Maximum 

LeachedC

(ug/sample) 

Percent 

LeachedD

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 Leached (ug)/ZnPT Content (ug) * 100 

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

This study was submitted after the 2004 risk assessment. 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 cells which consisted of 22 ml amber glass vials 

with Teflon liner caps. Five disks with a total surface area of 29.96 cm2 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 cm2 of plastic. The vials held at 50 C (120 F) in an incubator with agitation at 50 

cpm. Each migration study was done in triplicate and polymer blanks containing no ZnPT were 

also tested. 

Aliquotes (400 uL) were collected at specified time intervals that ranged from 0 to 240 hours and 

were analyzed using LC/MS. Recovery and control 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. 
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The LOQ was 5 ug/gram for the plastic samples and 12.35 ng/gram for the leaching solutions. 

The leaching rates are listed in Table 11 and are similar 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 

0 hour 2 hour 24 hour 144 hour 240 hour Leaching (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 0.79 144 

 
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Appendix C Environmental Fate 

Environmental Fate and Transport Properties of Zinc Pyrithione 

The agency does not anticipate the need to require 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 half-life of 8.3 minutes (Maraldo and 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 inhibit this route of degradation. 

Aqueous Photolysis 

Photolytic studies conducted in a buffered aqueous 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 Kow 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 degradation 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 degraded in 298 hours (about 12.3 

days) (44850004, 45876501). 

A second aerobic aquatic degradation study was conducted on a salt water harbor used as a boat 

maintenance site. Degradation data were obtained 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 separately. In water samples, and in the presence of 

pyrithione thiosulfate (OTS, which may be formed as a degradate or may be present in the 

sample), the half-life was 0.60 hours. 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 to
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degradation process. Kinetic pathway in the sediment samples was non-linear. In the absence of 

OTS, and through non-linear pathway, the degradation half-life decreased 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 degraded 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 second phase, the degradation half-life in fresh and 

salt water samples increased to 25.5 hours. Fresh water and salt sediment samples, zinc 

pyrithione degradation half was measured at 13.1 hours (45876501). 

In a second study, water and sediment samples collected 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 18.9 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 that zinc pyrithione is immobile in these systems. 

An absorption/desorption study conducted on Marblehead salt water 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 (Kd= 50 and 99 

respectively) and less strongly with Portland freshwater soil and sediment (Kd =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. Bridging from aerobic aquatic study is adequate. 

Anaerobic Soil Metabolism 

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

 
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Appendix D Ecotoxicology Profile 

The available toxicity endpoints and ecotoxicity data requirements for ZnPT are presented 

below. Toxicity data for two degradates (pyrithione 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 dissolved zinc to aquatic receptors in the water column; those data are 

presented by receptor group (freshwater and saltwater) 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 dietary studies (850.2200) are not 

required, but two studies were previously submitted and indicate that zinc pyrithione is slightly 

to practically nontoxic when administered 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 expected to be required to 

support the current use patterns, because zinc pyrithione is not registered as a wood preservative. 
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Aquatic Organisms 

Freshwater Fish, acute 

The available acute toxicity studies 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 degradates as being only 

slightly toxic to practically nontoxic to freshwater fish. The guideline (850.1075) for acute 

toxicity testing is satisfied. No additional 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. Acute toxicity data also are available for the two ZnPT degradates 

(pyridine sulfonic acid and pyrithione sulfonic acid). Those data categorize both degradates as 

being practically nontoxic to freshwater invertebrates. The guideline (850.1010) for acute 

toxicity testing is satisfied. No additional 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 Acceptable 
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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 additional chronic data are needed for 

freshwater organisms (850.1300, 850.1400). 

Chronic Toxicity of Zinc Pyrithione and Degradates 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. Acute toxicity data also are available for two ZnPT 

degradates (pyridine sulfonic acid and pyrithione sulfonic 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 Degradates 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 

Acceptable 
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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-grade ZnPT. Mysid NOAECs were determined 

for both growth and reproduction. The guideline (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 estuarine/marine chronic data are expected to be 

required. 

Chronic Toxicity of Zinc Pyrithione and Degradates 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 

NOAEC = 4.2 Acceptable 

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. 
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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 plants due to off-site drift during application. The 

guideline requirement for a seedling emergence 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 

Supplemental1 

1 The concentrations of the test substance in the test solutions were not verified analytically.
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Benthic Organisms 

Two studies are available. An acceptable freshwater amphipod test was previously submitted. 

Although testing with a freshwater midge is not available, the 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 ZnPT 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, based 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. Therefore, 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 

Supplemental1 

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 water hardness, toxicity values for freshwater 

organisms are presented for both soft water 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 654 654 
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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 654 

 
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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 Criteria for Zinc - 1987. Office of Water, 

Regulations and Standards, Criteria and 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 Project 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 prepared 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. (1994) Acute Toxicity of Omadine Sulfonic 

Acid (Pyridine-N-oxide-2-sulfonic Acid) to the Rainbow Trout, Oncorhynchus 

mykiss: Amended Report: Lab Project Number: 34-OL. Unpublished study 

prepared by T. R. Wilbury Labs, Inc. 28 p. 

43864618 Ward, T.; Kowalski, P.; Boeri, R. (1994) Acute Toxicity of Omadine Sulfonic 

Acid (Pyridine-N-oxide-2-sulfonic Acid) to the Fathead minnow, Pimephales 

promelas: Lab Project Number: 33-OL. Unpublished study prepared by T. R. 

Wilbury Labs, Inc. 28 p. 
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43864621 Boeri, R.; Kowalski, P.; Ward, T. (1994) Acute Toxicity of Pyridine 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 Pyridine 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: (Assessment of the Toxicity of Sponge Extracts 

to the Fathead Minnow, Pimephales promelas: Alpha 101. Unpublished study 

prepared by 3M Environmental Technology 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. (1994) Acute Toxicity of Omadine Sulfonic 

Acid (Pyridine-N-oxide-2-sulfonic Acid) to the Daphnid, Daphnia magna: Lab 

Project Number: 35-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 

26 p. 

43864622 Ward, T.; Kowalski, P.; Boeri, R. (1994) Acute Toxicity of Pyridine 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) Acute 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 prepared 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): Lab 
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Page 55 of 63

Project Number: 24-OL. Unpublished study prepared 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-sulfonic 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-sulfonic Acid) to the Sheepshead Minnow, Cyprinodon 

variegatus: Lab Project Number: 36-OL. Unpublished 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-sulfonic Acid) to the Mysid, Mysidopsis bahia: Lab 

Project Number: 37-OL. Unpublished study prepared by T. R. Wilbury Labs, Inc. 

28 p. 

43864623 Boeri, R.; Kowalski, P.; Ward, T. (1994) Acute Toxicity of Pyridine 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 Sulfonic 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 Pyridine 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. 
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44735101 Goka, K. (1998) Embryotoxicity of Zinc Pyrithione, an Antidandruff Chemical, in 

Fish. Unpublished study prepared by National Institute for Environmental Studies. 

7 p. 

44911101 Boeri, R.; Magazu, J.; Ward, T. (1999) Chronic 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 Bioassay 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: Terrestrial Plant Toxicity, 

Tier 1 (Seedling Emergence): Lab Project Number: 2360-AR. Unpublished study 

prepared by T.R. Wilbury Laboratories, 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)-pyridinethionate) 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-sulfonic 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 prepared 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} 
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45564901 Ward, T.; Boeri, R. (2001) Zinc Pyrithione: 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 Pyrithione: 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 Pyrithione: 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 Pyrithione: Terrestrial Plant 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 Pyrithione: 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 Toxicity 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 Toxicity 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. 

 
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Appendix E Screening Level Down-theDrain Analysis 

The screening level Down-the-Drain (DtD) assessment was not conducted for ZnPT since there 

are no pesticidal uses expected to result in release to domestic WWTP. 

 
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Appendix F Product Chemistry 

ZnPT product chemistry information is summarized 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/cm3) 1.76 g/cm3 

Bulk Density: 0.3 g/cm3

830.7370 Dissociation Constant pKa(s) 5.37 x 10-9 at 20ஈC 

Low dissociation constant 

830.7520 Particle size, fiber length, & diameter 

distribution (percent thru 20 mesh) 90 

830.7550 Log Kow 0.9 at 25ஈC 

830.7840 Solubility in water (mg/L) at 25 oC 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 21C 

 
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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 during the public comment 

period on the initial docket. Comments were received from the Center for Biological Diversity 

(Center), the Los Angeles Water Quality Control 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 coordination with the U.S. Fish and Wildlife Service 

and the National Marine Fisheries under Section 7 of the Endangered Species Act to ensure that 

ZnPt does not jeopardize the continued 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 from 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). 

 
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Comments Received on the Registration Review Preliminary Work Plan 

for Zinc Pyrithione 

Submitter: The Center for Biological 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 accordance with the ESA. The Center mentions 

various aspects of the risk assessment process, including use of the best available data to 

develop endangered species risk assessments, sources of data available to conduct an 

effects determination, and evaluation of effects on endangered and threatened species and 

their designated critical habitat. The Center also expressed concern regarding the rigor of 

the agencyPs preliminary determinations regarding the effects of zinc pyrithione on 

endangered and threatened (listed) species and their designated critical habitat for the 

zinc pyrithione registration review. 

EPA Response: EPA has reviewed the comments from the Center on the registration 

review docket opening for zinc pyrithione and plans to address many of the concerns 

raised by the Center as part of the implementation plan for assessing the risks of 

pesticides to listed species based on the recommendations of the April 2013 National 

Academy of Sciences (NAS) report (also cited by the Center). EPA will address 

concerns specific to zinc pyrithione in connection with the development of its registration 

review decision for this pesticide. 

In November 2013, EPA, along with the Services and USDA, released a summary of 

their joint interim approaches for assessing risks to endangered and threatened (listed) 

species from pesticides. The interim approaches 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 connection with their obligations under the ESA and 

FIFRA. 

The joint interim approaches were released prior to a stakeholder workshop held on 

November 15, 2013. In addition, EPA presented the joint interim approaches at the 

December 2013 Pesticide Program Dialogue Committee (PPDC) and State-FIFRA Issues 

Research and Evaluation Group (SFIREG) meetings. The agencies also held stakeholder 

workshops in April and October 2014, allowing additional opportunities 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 also consider public comments on the interim 

approaches in connection with the development of upcoming registration review 

decisions. The details of the joint interim approaches are contained in the white paper, 

 

[1] http://www.nap.edu/catalog.php?record_id=18344
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Interim Approaches for National-Level Pesticide 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 develop and work toward implementation of the 

interim approaches to assess the potential risks of pesticides to listed species and their 

designated critical habitat, this FWP for zinc pyrithione does not describe the specific 

ESA analysis, including effects determinations for specific listed species or designated 

critical habitat, to be conducted during registration review. Once the agencies have fully 

developed and implemented the scientific methods necessary to complete risk 

assessments for endangered and threatened (listed) 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 Quality Control Board (LA Water Board) 

2. Comment: The Water Quality Control Plan for the Los Angeles Region contains Total 

Maximum Daily Loads (TDML) for toxic pollutants. The TDML is being revised to 

address an impairment by copper in the water 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 formation, 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 provides a list of preliminary 

documents to include in a potential review of peer-reviewed research regarding the 

potential presence and toxicity 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 agrees 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 quantitative approach including guidance on 

weight-of-evidence analysis for assessing risks of pesticides mixtures. In the interim, 

EPA intends to qualitatively discuss the potential for differential exposure and toxicity 

from mixtures of compounds. EPA will include review of the submitted documents as 

part of the search for relevant data from open literature. 

The use of copper based antifoulant 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.html 
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Submitter: San Francisco Bay 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 antifouling paints are prevalent. The 

SF Bay Water Board also concurs with comments submitted by the LA Water Board. 

EPA Response: AD appreciates submission of these comments. Please refer to the 

response provided to the LA Water BoardPs comments above.