Page 2 of 77DCOIT Registration Review Team

Human Health & Environmental Effects Siroos Mostaghimi James Breithaupt David Bays Jonathan Chen Nathan Mottl Don Wilbur

Risk Management San Y vette Williams Rose Kyprianou Seiichi Murasaki

Office of General Counsel Philip Ross

TERMS, ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD a cute p opulation a djusted d ose ASRI a ctivated sludge r espiration i nhibition
atm

- m 3 /mole a tmospheric pressure

- cubic meter per mole BCF b ioconcentration f a ctor °C d egrees Celsius CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese h amster o vary CMA Chemical Manufacturers Association CO 2 c arbon dioxide COC c oncentration

- of

- c oncern cPAD c hronic p opulation a djusted d ose DCI data call

- in EC 50 m edian (or 50 percent) e ffect c oncentration EC 05 5 p ercent e ffect c oncentration ECOTOX ECOTOXicology EDI e stimated daily i ntake EDSP E ndocrine 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 Feder al Food, Drug, and Cosmetic Act

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act

Page 3 of 77FWP F inal Work Plan g/mol g rams per mole GLN guideline number HPV h igh production v olume IDS Incident Data System Koc o rganic carbon normalized soil

- water partition coefficient Kd s oil

- water partition coefficient Kow o ctanol

- water partition coefficient LC 50 m edian (or 50 percent) l ethal c oncentration LD 50 m edian (or 50 percent) l ethal d ose LOAEC l owest

- o bserved

- a dverse

- e ffect

- c oncentration LOEC l owest

- o bserved

- e ffect

- c oncentration LOAEL lowest

- observed

- adverse

- e ffect

- l evel Log K ow l ogarithm of the oc tanol

- water partition coefficient μg m icrogram ml/g m illiliter p er g ram mg/kg m illigram p er k ilogram mg/kg/day m illigram p er k ilogram p er d ay mg/L m illigram p er l iter mm Hg m illimeter of mercury MOE m argin of e xposure MRID Master Record Identificat ion Number MRL m aximum r esidue l imit N/A n ot a pplicable

nm n anometers NOAEC no

- observed

- adverse

- effect

- c oncentration NOAEL n o

- o bserved

- a dverse

- e ffect

- l evel OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co

- op eration and Development OPP Office of Pesticide Programs PAD p opulation a djusted d ose PAI p ure active i ngredient PDM Probabilistic Dilution Model % p ercent PC Code Pesticide Chemical Code PCF p ounds p er c ubic foot pH power of h ydrogen or power of th e con centration of the hydrogen ion PHED Pesticide Handler’s Exposure Data PIS primary i rritation s core pKa p ower of the acid dissociation constant or negative base

- 10 logarithm of the acid dissociation constant of a solution ppb p arts p er b illion ppm p arts p er m illion PWP Preliminary Work Plan QSAR q uantitative s tructure

- a ctivity r elationship RED Rere gistration Eligibility Decision SAR s tructure a ctivity r elationship SF s afety f actor SSTS Section Seven Tracking System TEP t ypical e nd

- u se p ro duct TGAI t echnical grade active i ngredient
Page 4 of 77TMDL total maximum daily l oads UF uncertainty factor UV/VIS ultraviolet/v isible light a bsorption % w / w p ercent weight per weight. WP w ettable powder WWTPs w astewater treatment plants

Page 5 of 77

### Table of Contents
1 Introduction

................................ ................................ ................................ ............................. 8 1.1 Statutory and Regulatory Authority

................................ ................................ ................. 8 1.2 Updates to t he Work Plan

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

................................ ................................ ................................ ................ 11 1.4 Chemical Identification and Properties

................................ ................................ .......... 11 1.5 Use/Usage Description

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

................................ ................................ ................................ ............ 12 1.5.2 Summary of Registered Uses

................................ ................................ .................. 12 1.5.3 Usage Information

................................ ................................ ................................ ... 13 1.6 Regulatory History

................................ ................................ ................................ ......... 13 1.6.1 Tolerance Information (Antimicrobia l Uses)

................................ .......................... 13 1.7 Incidents

................................ ................................ ................................ .......................... 14 1.7.1 Human Health

................................ ................................ ................................ ......... 14 1.7.2 Ecological

................................ ................................ ................................ ................ 14 2 Anticipated Data Needs

................................ ................................ ................................ ......... 15 3 Human Health Risk Assessment

................................ ................................ ........................... 16 3. 1 Existing Toxicological Endpoints

................................ ................................ .................. 17 3.2 Dietary Exposure

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

................................ ................................ ................................ ......................... 18 3.2.2 Drinking Water

................................ ................................ ................................ ........ 19 3.3 Occupational and Residential Exposures

................................ ................................ ....... 19 3.3.1 Occupational Handler Exposure

................................ ................................ .............. 19 3.3.2 Residential Handler Exposures

................................ ................................ ............... 20 3.3.3 Residential Post

- Application Exposures

................................ ................................ . 20 3.4 Aggregate and Cumulative Exposure

................................ ................................ ............. 20 3.4.1 Aggregate Exposures

................................ ................................ ............................... 20 3.4.2 Cumulative Exposures

................................ ................................ ............................. 21 4 Environmental Risk Assessment

................................ ................................ ........................... 21 4.1 Environmental Fate Assessment

................................ ................................ ..................... 21 4.1.1 Leaching (W ood/Antifoulant)

................................ ................................ ................. 22 4.1.2 Water and Sediment

................................ ................................ ................................ 22 4.1.3 WWTP

................................ ................................ ................................ ..................... 23 4.1.4 Water Quality

................................ ................................ ................................ .......... 24 4.2 Ecological Effects Assessment

................................ ................................ ....................... 24 4.2.1 Mechanism of Action

................................ ................................ .............................. 24 4.2.2 Measures of Effect (Ecotoxicology Endpoints)

................................ ...................... 24 4.3 Exposure Analysis Plan

................................ ................................ ................................ .. 25 4.3.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............. 25 4.3.2 Screening Level Down

- the

- Drain Analysis

................................ ............................ 26 4.4 Effects Analysis Plan

................................ ................................ ................................ ...... 27 5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 27 6 Optional Label Changes

................................ ................................ ................................ ........ 28 7 Next St eps

................................ ................................ ................................ ............................. 29 8 References

................................ ................................ ................................ ............................. 30

Page 6 of 77Appendix A Toxicology Profile

................................ ................................ ............................... 31 Appendix B Environmental Fate

................................ ................................ .............................. 41 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 58 Appendix D Screening Level Down

- the

- Dra in Analysis

................................ ......................... 73 Appendix E Product Chemistry

................................ ................................ ............................... 74 Appendix F Public Comments Received on the Preliminary Work Plan

................................ 76

List of Tables Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review: DCOIT

................................ ................................ ................................ ................................ ............... 9 Table 2

– Anticipated Registration Review Schedule

................................ ................................ ..... 10 Table 3

– Chemical Identification of 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

- (DCOIT)

.......... 11 Table 4

– Physical

- Chemical and Environmental Fate Properties for 3(2H)

- isothiazolone, 4, 5

- dichloro

- 2

- octyl

- (DCOIT)

................................ ................................ ................................ ............... 11 Table 5

– Summary of DCOIT Registered End Uses

................................ ................................ ..... 12 Table 6

– Studies Anticipated as Needed for the Registration Review of DCOIT

......................... 15 Table 7

– Existing Toxicological Endpoints for DCOIT

................................ ................................ 17 Table 8

– Occupational Handler Exposure Scenarios for DCOIT

................................ .................. 20 Table 9

– Residential Handler Exposure Scenarios for DCOIT

................................ ..................... 20 Table 10

- Summary of Environmental Fate Data for DCOIT in Water and Sediment

.................. 23 Table 11

– Ecological Effects Endpoints Selected for Assessing R isks from DCOIT Use

............. 24 Table 12

- Results of a Screening Level Down

- the

- Drain Analysis for DCOIT

............................ 26

Page 7 of 77

## 1 Introduction

This document is the United States Environmen tal Protection Agency ’s ( USEPA, EPA or “the agency ”) Final Work Plan ( F WP ) for 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl ( DCOIT )

. The F WP document explains what EPA's Office of Pesticide Programs (OPP) knows about DCOIT
, highlighting anticipated data and a ssessment 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 DCOIT’s review. This work plan also addresses the public comments received c oncerning the Preliminary Work Plan (PWP) which was posted in the DCOIT registration review docket (EPA

- HQ

- OPP

- 2014

- 0403). Further, this document makes final the work plan for the DCOIT registration review process.



## 1.1 Statutory and Regulatory Authority

The F ood 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 reevalu ates 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 t o 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 CF R 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 agency ’s opportunity to state wha t 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 public comment period for the preliminary work plan (PWP), published September 24, 2014, closed Nove mber 24, 2014. As stated in Appendix F, comments were submitted by the FIFRA Endangered Species Task Force (FESTF) and by Dow Chemical Company. After reviewing and responding to the comments received in the docket , the agency has develop ed a F inal W ork P lan (FWP) which include s an anticipated schedule for the DCOIT case

. Documents associated with this registration review can be viewed at http://www.regulations.gov in docket EPA

- HQ

- OPP

- OPP

- 2014

- 0 40 3

. Tables 1 and 2 b elow summar ize s the issues relevant to this registration review case and the anticipated registration review schedule

.

Page 8 of 77Table 1

– Summary of Anticipated Risk Assessments and Data Needs for Registration Review : DCOIT

Risk Assessment Assessment Necessary to

Support Regist ration Review Date of Most Recent Assessment Type of Assessment

Required (New/Updated) Data Anticipated as Needed

Dietary (food) Yes None New None Dietary (drinking water) Yes 9 /20 13 New None

Occupational Handler Yes 1/ 2008 Updated 875.1200 Dermal Exposure

– Indoor 875.1400 Inhalation Exposure

– Indoor 875.1700 Product Use 870. 3700 Rabbit Developmental Toxicity 870. 7 800 Immunotox icity

Residential Handler Yes 1/2008 Updated 875.1200 Dermal Exposure

– Indoor 875.1400 Inhalation Exposure

– Indoor 87 5.1700 Product Use 870. 3 700 Rabbit Developmental Toxicity 870. 7 800 Immunotoxicity

Residental Post Application

- Incidental Oral and Dermal No 9/2013 None None

Residental Post Application

- Inhalation No None None None

Aggregate Yes None New None

Cumu lative No None None None

Ecological Yes N/A New Activated sludge respiration inhibition (850. 3300 ) Honeybee acute contact (850.3020) N/A = Not applicable * Table 1 is a summary of the anticipated risk assessments and data needs for Registration Review.

Page 9 of 77Table 2

– Anticipated Registration Review Schedule
Anticipated Activity Target Date * Completion Date Phase 1: Opening the Docket

Open Docket and 60

- Day Comment Period for Preli minary Work Plan 2014

- 0 9 2014

- 24

- 09

Clos e Public Comment Period 2014

- 1 1 2014

- 24

- 11 Phase 2: Case Development

Issue Final Work Plan 2015

- 0 3 2015

- 03

Issue Data Call

- In (DCI) 2016

- 0 3

Receive Data to be Considered in Risk Assessment 201 8

- 0 3

Open 30

- Day Public Comment Period for Prelim inary Risk Assessment(s) 201 9

- 0 9

Close Public Comment Period 201 9

- 1 0 Phase 3: Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Pro posed Decision 20 20

- 0 3

Close Public Comment Period 20 20

- 0 5

Issue Final Decisio n 20 20

- 0 9

Begin Post

- Decision Follow up 20 20 Total (years) 6

* 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).


## 1.2 Updates to the Work Plan
Since publication of the DCOIT PWP, the agency has made the following updates:

• Updated Table 2

– Anticipated Registration Review Schedule to reflect comment period completion date.

• Added information to Section 1.6.1 on the e xi s ting of Food C ontact Notification (FCN) allowing uses as a slimicide, mold

- proof agent and preservative.

• Revised 3.2 Dietary Exposure and 3.2.1 Food section s to reflect the need for assessments. This includes an interim, screening

- level assessment on DCOIT migration fr om treated paper products into food.

• Updated Table 5

- Corrected maximum use rate values.

• Table 6

– corrected guideline number for Rabbit Developmental Toxicity study and updated test substances for 875.1200 and 875.1400.

• Updated Table 9

– Added “latex” for the do

- it

- yourself scenario assessment.

• Added to Section 6 Optional Label Changes

– that the Acticide PDP 20

- F should not be used for adhesives that may come in contact with food.

Page 10 of 77• Deleted “ Guidance for Commenters ” s ection

.
• Updated Next Steps section

.
• A dded Appendix F Public Comments Received on the Preliminary Work Plan

.
• Corrected formatting and typographical errors and made other editorial changes.



## 1.3 Case Overview

The docket for 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

- (DCOIT) ( c ase 5023 ) has been estab lished at http://www.regulations.gov in docket number EPA

- HQ

- OPP

- 2014

- 0 403

. 

## 1.4 Chemical Identification and Properties

Table 3 presents the active ingredient to be assessed in case 5023 : DCO IT (PC Code 128101 )

.
Table 3

– Chemical Identification of 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

- (DCOIT)

Chemical Name 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

- (DCOIT) Chemical Classification Isothiazolone
PC Code 128101
C AS N umber 64359

- 81

- 5 Molecular Formula C 11 H 17 Cl 2 NOS Molecular Weight (grams/mole) 281.040802

Molecular Structure

The 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

- DCOIT product chemistry information (MRID 40808501 and 41351601 ) relevant to risk assessme nt is summarized in Table 4 and the details of the product chemistry are discussed in Appendix E

.
Table 4

– Physical

- Chemical and Environmental Fate Properties for 3(2H)

- isothiazolone, 4 , 5

- dichloro

- 2

- octyl

- (DCOIT)

Guideline No. P a rameter 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

Physical/Chemical Properties 830.7000 pH Not required 830.7050 UV/Visible Absorption Not reported 830.7200 Melting point ( o C) 40

- 41 o C 830.7220 Boiling point ( o C) Decomposes before boiling 830.7300 D ensity 1.28 g/ml at 25oC (melted and solidified) 830.7370 Dissociation c onstant (pKa) Not required

830.7550 Octanol

- water partition coefficient at 25 o C (Log K ow ) 2.8

830.7840 Solubility in water (mg/L) 14 ppm at 25oC 830.7950 Vapor pressure (mmHg) 4.5 x 10

- 6 mm Hg

Page 11 of 77Guideline No. P a rameter 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

None (calculated) 1 Henry's l aw c onstant at 25 o C (atm

- m 3 /mol) 1.2 x 10

- 7

atm

- m 3 /mol = atmosphere cubic meter per mole; o C = degrees Celsius; mg/L = milligrams per liter; mmHg = millimeters of mercury.



## 1.5 Use/Usage Description

1.5.1 Registrations

The re are 27 products (three are manufacture use products or MUPs) registered for uses for incorporation into products such as adhesives, coatings, fuels, metal working fluids (MUP only)
, resin emulsions, paints and various other specialty industrial products (as a preservative); and, as a microbiocide in pulp/paper mills, cooling water systems, oil field operations (MUP only)
, industrial process waters and air washers systems. The compound is also registered for use to treat wood products (seasoned/unseasone d forest products and various finished wood products).
The manufacturing use product (EPA Reg # 707

- 224) specifies several uses (sap stain , in

- can preservatives for laundry detergents and household cleaners, oil injection waters and metal working fluid pre servatives) that have no registered end

- use product labels, application rates or directions for use

. 

### 1.5.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses of DCOIT that will be assessed in this registration review. DCOIT can be applied by the following application methods: liquid open pour, wood pressure treatment, airless spray, dip or brush. The product is sold as ready

- to

- use solutions. Since there are certain uses on MUPs for products EPA Reg #s 707

- 224 and 67071

- 58 but not on EUPs that include directions for use and application rate, these uses will not be assessed

as part of registratio n review because the y can not be used on any EUP until added to a EUP label. T he EPA encourages the registrant to amend these uses. If they are amended to add th e uses to the EUP in the future , t he agency would assess this amendment as a new use under PRIA.

Table 5

– Summary of DCOIT Registered End Uses

Use Application Method Application Rate (ppm a.i.) Industrial Process and Water Systems Recirculating Cooling Tower + Air Washer Water+ Ornamenta l Fountains+ Brewery Pasteurizer Open Pour, Meter ed Pump 6 ppm 6 ppm 6 ppm 6 ppm

Material Preservative

A dhesives, industrial Caulks Open Pour and Metered Pump 2
, 0 00 ppm 2
, 0 00 ppm

Page 12 of 77Use Application Method Application Rate (ppm a.i.)
C oatings, industrial E mulsions, resin/latex/polymer P aints (in

- can) P aints, latex/oil/varnish and applied film Paints, l atex/oil/varnish Pulp+ Plastics/ Rubber products ++ 2
, 0 00 ppm 2
, 0 00 ppm 2
, 0 00 ppm 2
, 0 00 ppm Brush, Roller and Airless Spray 2
, 0 00 ppm Open Pour and Metered Pump 100 ppm 0.2 lb ai/ton 2
, 0 00 ppm

Wood Prese rvative

W ood pressure treatment to forest products Pressure Treatment 50 0

- 1
, 600 ppm

Antifoulant Paints and Coatings

P aints, latex/oil/varnish (applied film) Bush, Airless Spray, and Roller 192 sq ft/gallon 3.6% + EPA Reg 707

- 259

++ P lastic use s do no t include toys or pacifiers and plastics are not to contact food

. 

### 1.5.3 Usage Information According to the Kline Biocides Report for 2004/2005 (Kline, 2005),

~ 56,000 lb of DCOIT was estimated to be produced in 2004.



## 1.6 Regulatory Histor y
DCOIT w as first registe red in the United States January 24, 1983

. 

### 1.6.1 Tolerance Information (A ntimicrobial Uses)

F or the active ingredient DCOIT, EPA has not established tolerances or exemptions from tolerances in r aw agricultural commodities or processed food and feed products under FFDCA Section 408. The US Food and Drug Administration (US FDA) has established a Food Contact Notification (FCN No. 11) for the Rohm and Haas Company. This FCN was established April 1
, 2000 and allows for the following uses: 1. As a slimicide, in compliance with 21 CFR 176.300, at a maximum level of 0.034 pound per ton of dry weight fiber. 2. As a mold

- proofing agent applied to the surface of uncoated paper and paperboard and in coat ings for paper and paperboard, in compliance with 21 CFR 176.170(b), at a level not to exceed 100 parts per million (ppm) based on dry fiber weight. 3. As a preservative in wet lap and sheet pulp, in compliance with 21 CFR 176.170(a) prior to repulping to produce paper and paperboard, at a level not to exceed 100 parts per million (ppm) based on dry fiber weight. 4. As a preservative in pigment dispersions, in compliance with 21 CFR 176.170(b), at a level not to exceed 50 parts per million (ppm).

Page 13 of 77

## 1.7 Inciden ts
1.7.1 Human Health

There are no human health incidents listed in the OPP Incident Data System (IDS) for the period 9/2001 to the present (search conducted on 5/25/2014).



### 1.7.2 Ecological There are no aquatic or terrestrial wildlife incidents listed in the OPP In cident Data System (IDS) for the period 9/2001 to the present (search conducted on 5/7/2014).

Page 14 of 77Docket Number EPA

- HQ

- OPP

- 2014

- 0403 www.regulations.gov 

## 2 A nticipated Data Needs

Table 6

– Studies Anticipated as Needed for the Registration Review of DCOIT

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

850. 33 00 (Modified) Activated

s ludge respiration inhibition (ASRI) TGAI 12 months Ecological Assessment Down

- the

- drain uses Cooling towers

850.3020 Honeybee acute contact TGAI 12 months Ecological Assessment Wood preservative uses Wood treatment

870. 3700 Rabbit Developmental Toxic TG AI 24 months Occupational and Residential Assessment All All

870.7800 Immunotoxicology TGAI 24 months Occupational and Residential Assessment All All

875.1200 Indoor Dermal Exposure T EP 24 months Occupational and Residential Assessment All Pour liqui ds

Brush/Roller Airless Sprayer Pressure treatment

875.1400 Indoor Inhalation Exposure TEP 24 months Occupational and Residential Assessment All Pour liquids

Brush/Roller Airless Sprayer Pressure treatment

875.1700 Product Use TGAI 12 mon ths All All All

Page 15 of 77Docket Number EPA

- HQ

- OPP

- 2014

- 0403 www.regulations.gov



## 3 Human Health Risk Assessment

The a gency anticipates the need to conduct a human health risk assessment for DCOIT. The

a gency anticipates issuing a generic data call

- in (GDCI) which will require additional data for use in conducting the re gistration review risk assessment

. On November 16, 1999, the Health Effects Division's Hazard Identification Assessment Review Committee (HIARC) evaluated the toxicology database of DCOIT
, and selected the toxicological endpoints for acute and chronic diet ary as well as occupational and residential exposure risk assessments. The HIARC also addressed the potential sensitivity of infants and children from exposure to DCOIT as required by the Food Quality Protection Act (FQPA) of 1996. A FQPA Safety Factor o f 1 x was selected for dietary risk assessments.

On May 10, 2007, the Antimicrobials Division Toxicity Endpoint Selection Committee (ADTC) revised the original endpoint selection in 1999, based on additional data submitted, including a reproductive toxicity study, open literature information on neurotoxicity, and a 21

- day dermal toxicity. Incidental oral endpoints were selected and added to the endpoint report. The conclusions presented in the 2007 ADTC report superseded the conclusions of the original 199 9 HIARC report.

On December 6, 2007, the Health Effects Division's Hazard Science Policy Council (HASPOC) met to discuss whether the need for a chronic/cancer rodent bioassay study on DCOIT was justified based on the available chemistry, metabolism, and t oxicity information for DCOIT and other isothiazolone biocides. Based on the available evidence for DCOIT and other members of isothiazolone biocides, the HASPOC concluded that “the absence of a chronic bioassay would not likely impact the risk assessment on DCOIT”.

On July 9, 2013, the ADTC met to revise the chronic Reference Dose (RfD) for DCOIT. The existing toxicological end

- points selected are summarized in Table 7

. Endpoints will be revised as appropriate based on the data to be required through the DCI for th i s registration review. A detailed description of the toxicity studies is provided in Appendix A.

Page 16 of 77

## 3.1 Existing Toxicolo gical Endpoints

Table 7

– Existing Toxicological Endpoints for DCOIT

Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicologica l Effects

Dietary Risk Assessments

Acute Dietary (females 13

- 49) NOAEL (developmental) = 30 mg/kg/day FQPA SF = 1 x UF = 100 (10x inter

species extrapolation, 10x intra

- species variation) Acute RfD (aPAD) = 0.3 mg/kg/day Developmental toxicity study

– Rat (MRID 43471604) LOAEL = 100 mg/kg/day based on increased incidence of wavy ribs.

Acute Dietary (general population) NOAEL (maternal) = 30 mg/kg/day FQPA SF = 1 x UF = 100 x (10x inter

species extrapolation, 10x intra

- species variation) Acute RfD (aP AD) = 0.3 mg/kg/day Developmental toxicity study

– Rat (MRID 43471604) LOAEL = 100 mg/kg/day based on increased incidence of wavy ribs.

Chronic Dietary (all populations) NOAEL (offspring)

= 16 mg/kg/day FQPA SF = 1 x UF = 100 (10x inter

species extrapo lation, 10x intra

- species variation) Chronic RfD (cPAD) = 0.16 mg/kg/day Reproduction toxicity study

– Rat (MRID 45756501) Offspring LOAEL = 30 (M) and 33(F) mg/kg/day, based on decreased spleen and thymus weights.

Non

- Dietary Risk Assessments Incidenta l Oral Short

- Term (1

- 30 days) Intermediate

term(30

- days

– 6months) NOAEL (offspring) = 16 mg/kg/day Target MOE = 100 (10x inter

- species extrapolation, 10x intra

species variation) Reproduction toxicity study

– Rat (MRID 45756501) Offspring LOAEL = 30 (M) and 33(F) mg/kg/day, based on decreased spleen and thymus weights.

Dermal Short

- Term (1 to 30 days) and Intermediate

term (30 days

- 6 months) LOAEL = 32 μg/cm 2 Target MOE = 100 (10x inter

- species extrapolation, 3x intra

species variation, 3x for l ack of derived 10% response level) Dermal sensitization study

– guinea pigs (MRID 47004002) LOAEL = 32 μg/cm 2 based on positive dermal sensitization response.

Dermal Long

- Term (>6 months) a NOAEL = 10 mg/kg/day Target MOE = 300 (10x inter

- species
extr apolation, 10x intra

species variation; 3x for lack of chronic study) 90

- day oral toxicity study

– Dog (MRID 45747201) LOAEL (systemic) = 46 mg/kg/day, based on decreased body weight and food consumption and alterations in hematology and clinical chemis try

.

Page 17 of 77Exposure Scenario Dose Used in Risk Assessment (mg/kg/day) Target Margin of Exposure (MOE), Uncertainty Factor (UF), FQPA Safety Factor (SF) Study and Toxicologica l Effects

Inhalation (all durations) NOAEL = 0.02 mg/m 3 Target MOE = 100 (10x inter

- species extrapolation, 10x intra

species variation) 90

- day Inhalation toxicity study

– rat (MRID 43487501) LOAEL = 0.63 mg/m 3 , based on histopathological alterations of the nose, lung, and larynx. Cancer The Health Effects Division’s HASPOC committee determined that a cancer study would not likely impact the risk assessment for DCOIT, and is not required for DCOIT at this time.

a Based on the results of a dermal absorpt ion study (MRID # 43471610), a dermal absorption value of 50% will be used in dermal risk
assessments. * FQPA SF = FQPA safety factor

. 

## 3.2 Dietary Exposure

The agency anticipates the need to conduct a dietary exposure (food only) assessment to support registr ation review since no previous dietary assessments have been conducted for DCOIT. The re are several approved uses of DCOIT that may result in dietary (food) exposure , includ ing: in

- container materials preservatives in household cleaners, dishwashing deter gents, and sponges and use in pulp and papermills to control fungal, bacterial, and algal growth on paper and paperboard machines, for preparation of mold

- resistant food

- contact paper or paperboard, and the preservation of wet

- lap or sheet pulp

. With respect to drinking water exposure, several approved uses may result in DCOIT being discharged into waste water and subseque ntly running off into surface water , which will need to be assessed to support registration review

. 

### 3.2.1 Food

The a gency anticipates the need to conduct dietary exposure assessments as part of the registration review process since none have been previously cond ucted. Current uses as in

- can materials preservatives and in/on food contact paper and paperboard may result in dietary (food)
exposure

. Residue chemistry data are not anticipated to be required at this time. The dietary exposure contribution will be considered in the aggregate assessments conducted during registration review. If the toxicological point of departure for either the acute or chronic scenario changes during the registration review process, additional residue chemistry data may be necessary

. In the interim, a screening

- level assessment was completed to estimate t he amount of DCOIT that may migrate from treated paper products into food using updated assumptions (20% of food consumed in the human diet may contact paper; 100 pounds of slurry contains 1 pound of pulp by weight) and NHANES/WWEIA 2003

- 2008 consumption d ata. Exposure estimates for the treated paper products utilized <1% of the aPAD and <1.5% of the cPAD for the general U.S. population, and utilized ≤3% of the aPAD and ≤6% of the cPAD for children 1

- 2 years old, the most highly

- exposed population subgroup (aPAD= 0. 3 mg/kg/day ; cPAD = 0. 16 mg/kg/day ).

Page 18 of 77Screenin g

- level assessments were not completed for the in

- can materials preservative uses since there do not appear to be end

- use products associated with the technical label

.
3.2.2 Drinking Water A quantitative drinking water assessment was conducted based on pressure

- treated wood for fresh water use in 2013

. Acute dietary risks to adults and children from consuming DCOIT

contaminated drinking water were less than 1% of the aPAD and chronic dietary risks to adults and children were also less than 1% of the cPAD. These conservative estimates were well below the a gency's levels of concern (100% of the respective PAD). The a gency anticipates the need to refine these estimates to consider exposure to down

- the

- drain, antifoulant paint and pressure treated wood scenarios

. 

## 3.3 Oc cupational and Residential Exposures

The a gency anticipates the need to develop a new occupational and residential (ORE)
assessment. EPA identified existing agency risk assessments of the wood pressure treatment and antifoulant uses. However, EPA anticipat es that an ORE assessment will be need ed for uses that have not been assessed (e.g., latex paint, and industrial process and water system uses)

. Also, EPA may need to update the ORE for uses that already have been assessed (anti foulant paint and wood treatment) as a result of new data and new approaches

. EPA anticipate s the need for exposure data to assess these use scenarios in registration review.



### 3.3.1 Occupational Handler Exposure Occupational handler exposures were assessed for registration in 2008 for pressure treatment of wood preservative uses (D330114 and D340329) and for the antifoulant paint uses (D252378) in 1999

. For the wood preservative uses, the inhalation exposures were assessed using the Human Equivalent Concentratio n (HEC) of 0.0024 mg/m 3 from a 90 day inhalation rat toxicity study in the ORE (D330114 and D340329) . The resulting MOEs ranged from 21 to 120, most scenarios were greater than the target inhalation MOE of 30. The scenarios which resulted in MOEs of poten tial concern included treatment operators, treatment assistants, and packagers. The dermal exposures for short and intermediate

- term exposures were not assessed for the occupational handler because the endpoint is based on dermal sensitization. Instead, d ermal sensitization exposures need to be mitigated using personal protective equipment requirements. Chronic dermal exposures were above the target MOE of 300 and were not of concern. EPA will reassess the pressure treatment wood uses in registration rev iew upon receipt of the anticipated exposure data.

The agency assessed antifouling paint uses in 199 9 . The a gency also assessed occupational handler exposure to airless sprayer for antifoulant paint s in 1999 . The results indicated potential dermal MOEs of concern for applicators were less than the target MOE of 100. The agency plans to reassess this exposure scenario with updated exposure data for antifoulant paints during registration review
The occupational handler scenarios as listed in Table 8 will need to be assessed during registration review.

Page 19 of 77Table 8

– Occupational Handler Exposure Scenarios for DCOIT

Scenario Exposure Route(s) Duration Open Pour Addition for Industrial Process/Water Systems Treatment and Material Preservati on Dermal
, Inhalation Short and Intermediate Term Brush/Roller Application of preserved p aints
, antifouling paints, and stains Dermal
, Inhalation Short and Intermediate Term Airless sprayer application of preserved paints, antifouling paints
, and sta ins Dermal
, Inhalation Short and Intermediate Term

Wood Pressure Treatment Dermal
, Inhalation Short and Intermediate Term



### 3.3.2 Residential Handler Exposures Residential handler dermal and inhalation exposures to DCOIT were not assessed for the application o f treated latex paints and stains, but would need to be assessed during registration review. The residential handler scenario as listed in Table 9 will need to be reassessed during registration review to utilize the exposure data that are anticipated to be needed for registration review.

Table 9

– Residential Handler Exposure Scenarios for DCOIT

Scenario Exposure Route(s) Duration Brush/Roller and Airless Spray a pplication of latex paints and stains Dermal
, Inhalation Short a nd Intermediate Term



### 3.3.3 Residential Post

- Application Exposures Residential post application exposures were assessed for dermal irritation and incidental ingestion exposure to pressure treated wood. Potential dermal and incidental oral exposure of children c an result while playing on DCOIT

- treated structures such as decks and/or play sets. Both the ST

- dermal and the ST

- incidental oral MOEs were above the t arget MOE of 100. The

a gency does not anticipate that a new residential post

- application assessment is ne eded unless toxicological endpoints, exposure algorithms or application rates change. The residential post

application exposure MOEs for the wood preservative uses were initially determined in the ORE 2008 (D330114 and D340329) and then reassessed in 2013 in the human health risk assessment (D405995) . The recalculated MOEs were above the target MOE of 100.
Residential post

- application inhalation exposures from treated paint (e.g., treated hard surfaces/walls) are not expected since the vapor pressure is lo w (4.5 x 10

- 6 mm Hg ) and exposure is expected to be minimal.



## 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures EPA anticipates the need to conduct an aggregate assessment as part of this registration review. An aggregate risk assessment considers food, drinking water, residential, and any other non

Page 20 of 77occupational sources of exposure for which there are reliable dat a. For DCOIT , aggregate exposure may result from wood treatment and antifoulant paint use s and there are currently FDA dietary uses for pulp and paper

. 

### 3.4.2 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 common mechanism of toxicity finding as to DCOIT and any other substances and DCOIT does not appear to produce a toxic metabolite produced by other substan ces. For the purposes of this registration review, therefore, EPA has not assumed that DCOIT has a common mechanism of toxicity with other substances. For information regarding EPA’s 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

The agency has not previously conducted a risk assessment that supports a complete endangered species determination for DCOIT

. An endangered species effect determination w as not made in the previous risk assessment for treated wood.

Based on numerous uses of DCOIT, potential pathways of exposure to aqua tic organisms include transport from in

- service use to surface water by way of wastewater treatment plants (WWTPs), leaching from treated wood in terrestrial structures and subsequent runoff to surface water, and leaching from pressure

- treated wood in aqua tic environments. The risk assessment will also allow the agency to determine whether each use of DCOIT has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an asses sment concludes that a pesticide’s 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 (the Services), as appropriate.

Based on the antimicrobial uses of DCOIT with active products in Table 5, t he agency has created c onceptual m odels for potential routes of environmental exposure which are included in “Conceptual Models for Environmental Exposure Pathways of Antimicrobial Pesticides
, ” found in the docket at www.regulations.gov EPA

- HQ

- OPP

- 2014

- 0638

- 001 . For the uses with active products, the relevant page numbers are 13

- 14 ( cooling towers )
, 17 (adhesives and caulks), 15 (plastics and rubber), 24

- 25 ( non

- antifoulant paints and varnish ) , 11 (antifoulant paint), and 29 (wood preservation) . All relevant routes of environmental exposure will be considered in the risk assessment.



## 4.1 Environmental Fate Assessment
Even though there are potential pathw ays by which DCOIT can reach the aquatic environment, DCOIT degrades very rapidly in aquatic environment s via various processes with half

- lives of < 1 hour to 2.9 days . DCOIT is not readily biodegradable in a wastewater treatment plant (WWTP), as defined by the criteria of 70 % degradation in 28

- days and 60 % in a 10

- day period, but 80 % of DCOIT degraded in 28 days and 52 % of DCOIT did degrade in a 10

- day period.
Page 21 of 77However, the d egradates N

- (n

- octyl) malonamic acid and N

- (n

- octyl) acetamide were readily b iodegradable in a WWTP

. DCOIT that is used in paper mills and cooling towers can also reach aquatic environment s since WWTP transit times are <1day

. DCOIT that leach es out of products can be subsequently transported to surface water via runoff but woul d not be expected to persist in the terrestrial and aquatic environments based on its rapid potential to degrade by biotic processes.

DCOIT (parent compound, 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

- ) degrades by biodegradation and dechlorination to f orm the primary metabolites N

- (n

- octyl) malonamic acid, N

- (n

- octyl) oxamic acid, and N

- (n

- octyl) acetamide which are low

- molecular weight nitrogenous carboxylic acid compound s. These degradates undergo demethylation and loss of CO 2 (decarboxylation) to ev entually form the terminal degradates, formic acid and CO 2 . The degradation rate of DCOIT is generally faster in biotic than abiotic conditions.



### 4.1.1 Leaching ( Wood/ Antifoulant ) The agency has reviewed 19 antifoulant leaching studies (including 29 paints) in simulated seawater which demonstrated an average leach rate of 20.4 ug/cm 2 /day . In the antifoulant leaching studies, the leaching rates were highly variable and unrelated to DCOIT content. The agency has also received five wood leaching studies that de monstrate the potential for terrestrial exposure and aquatic exposure
, of which two have been reviewed ( multiple studies, see Appendix B for further details). The reviewed studies indicate an average leach rate of 1.9 ug/cm 2 /day. The extent of exposure f rom DCOIT used to preserve wood will be addressed in registration review

. 

### 4.1.2 Water and Sediment DCOIT is soluble in water (14 ppm, Table 4) but is expected to preferentially partition to the sediment phase of the aqueous environment rather than to water an d air. DCOIT has a H enry’s Law constant of 1.2 x 10

- 7 atm m 3 mol

- 1 which indicates that partitioning to air from aqueous media is not a significant route of dissipation (Table 4 ). 2 Sorption to soil and sediment increases as the soil and sediment organic carbon (OC) content increases, and will move from soil into
water in low OC environments. Parent DCOIT did not b ioconcentrate in fish to a significant degree , but the straight

- chain polar metabolites were the primary residue in bluegill sunfish

.
DCOI T biotic degradation studies demonstrated the formation and decline of degradates to form straight chain, nitrogenous carboxylic acid degradates, formic acid, and CO 2

. The half

- lives in aquatic studies (representing surface water) were <1 hour to 2.9 days in fresh

- and saltwater systems, and these aquatic metabolism half

- lives are relatively consistent with the hydrolysis half

- lives of 3.5 days at pH 9. Most of the aquatic metabolism study systems (water only or
water: sediment) had a pH range of 7 to 8, and sorption accounts for a large percentage of the rapid dissipation when sediment was used. Table 10 below contains additional information on the water and sediment dissipation of DCOIT and its degradates.

2 Henry’s Law values are calculated using the equation [VP (mm Hg) * molecular weight (gr ams/mol)]/[760 * water solubility (mg/l )]. Page 22 of 77Table 10

- Summary of Environmental Fate Data for DCOIT in Water and Sediment

Test Guideline (parent compound unless stated) Study Result (half

lives ) 3 Significant Degradation Products 4 Reference (MRID)

Hydrolysis pH 4 (260 days ) pH 7 (71 days ) pH 9 (3.5 days ) DCOIT s ulfinic acid P ropiolic acid amine 46780744

Photodegradation in
water 17.2 days N

- (n

- octyl) oxamic acid N

- (n

- octyl malonamic acid) 41845001

Anaerobic Aquatic Metabolism <1 hour N

- (n

- octyl) malonamic acid N

- (n

- octyl) oxamic acid 4 1845002 42341101
0.33 day ( 8 hours ) No significant degradates 4 6816306

Aerobic Aquatic metabolism 0.04 days ( <1 hour ) N

- (n

- octyl) malonamic acid and N

- (n

- octyl) oxamic acid 41845003 42341102 42772802

2.9 days (67 hours) 2

- (n

- octyl) carbamoyl

- 2

- chlo roethylene sulfonic acid N

- (n

- octyl) oxamic acid 46816307

0.86 day (21 hour) None 46816306

Adsorption/Desorption Kd values of 14

- 76 L/kg ( 0.2

- 4.4 % OC) and 625

- 905 L/kg (4.1

- 5 % OC)

Koc values of 1,691

- 7,865 L/kg (0. 2

- 4.4 % OC) and 15,441

- 18,100 L/kg (4.1

- 5 % OC) Not applicable 41845004 164668 M obile to hardly mobile in soil based on Koc values and FAO classification. 5

Bioaccumulation study in fish (BCFs, % depuration)

Edible (660X, 77) Non

- edible ( 200X , 78)
, Whole fish ( 660X , 60) Polar metabolites ( straight

chain degradates) were highest residues in fish 164507 164508 41845006



### 4.1.3 WWTP

Studies on degradation , sorption, and toxicity to wastewater organisms for DCOIT have been submitted. As a result of these studies, the agency expects sorption of DCOI T to sludge with a Kd of 2,566 L/kg resulting in limited outflow of DCOIT and its N

- (n

- octyl) malonamic and N

- (n

- octyl) acetamide degradates to surface water from a WWTP (MRID 46780735) . The extent of toxicity to WWTP organisms is uncertain. DCOIT is not readily biodegrad able but the

3 Adsorption/desorption and bioaccumulation in fish studies represent partitioning and not half

- lives

. 4 Significant degradates formed at > 10 % of applied parent compound

. 5 http://www.fao.org/docrep/003/x2570e/x2570e06.htm

. Page 23 of 77degradates N

- (n

- octyl) malonamic acid and N

- (n

- octyl) acetatamide were readily biodegradable ( MRID s 46780741 and 46780742) . The submitted ASRI study (MRID 46816305) was not tested at an adequate concentration and must be rep eated because the registrant did not establish an IC 50

. This is an anticipated data need.



### 4.1.4 Water Quality

DCOIT and its degradates are not identified as a cause of impairment for any water bodies listed as impaired under section 303(d) of the Clean Wa ter Act

. 6 In addition, no Total Maximum Daily Loads (TMDL) have been developed for DCOIT

. 7 More information on impaired water bodies and TMDLs can be found at EPA’s website

. 8



## 4.2 Ecological Effects Assessment

The agency has a complete data set for DCOIT and wi ll be able to conduct a risk assessment on the current uses of this chemical. However, since DCOIT is used as a wood preservative , risk to honeybees from wood treated with DCOIT will need to be assessed. A honeybee stud y is included as an anticipated da ta need for use in a risk assessment on the wood preservative uses of this chemical (850.3020: honeybee, acute contact ).



### 4.2.1 Mechanism of Action The specific mechanisms by which DCOIT inactivates or kills wood rotting organisms in not known. It most likely disrupts the internal mechanisms of the target organism.



### 4.2.2 Measures of Effect (Ecotoxicology Endpoints) Ecotoxicity endpoint data are used as measures of effects to aquatic and terrestrial organisms. All available ecotoxicity endpoints in the agency ’ s files from DCOIT s tudies submitted by registrants or other interested parties, federal laboratory data, or from the public literature are tabulated in Appendix C along with the data requirements and data gaps. The most sensitive values for each receptor group are used for the risk assessment . Table 1 1 contains the ecological endpoints for use in risk assessment. These selected endpoints will be updated during the risk assessment phase based on any additional submitted data or data found in the public literature.

Table 11

– Ecological Effects Endpoints Selected for Assessing Risks from DCOIT Use

Receptor

Group Surrogate Species Risk Scenario Toxicity Endpoint Reference

Freshwater fish Bluegill Sunfish Acute 96

- h LC 50 = 1.4 ug/L MRID# 41465801

Rainbow Trout Chronic NOAEC = 0.56 ug/L MRID# 45865201 Freshwater invertebrates Daphnia magna Acute 48

- h EC 50 = 9,7 ug/L MRID# 47802222

6 http://iaspub.epa.gov/tmdl_wa ters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

. 7 http://iaspub.epa.gov/tmdl_waters10/attain s_nation.tmdl_pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

. 8 http://www.epa.gov/owow/tmdl/

. Page 24 of 77Receptor Group Surrogate Species Risk Scenario Toxicity Endpoint Reference

Chronic NOAEC = 0.627 ug/L MRID# 45153101 Freshwater benthic invertebrates Freshwater midge Subchronic/ Chronic 10

- day LC 50 = 13 mg/kg NOAEC = 4.9 mg/kg MRID# 468516304

Estuarine/marine fish Sheepshead minnow Acute 96

- h LC 50 = 20.5 ug/L MRID# 41741502 Chronic Not required A

--

Es tuarine/marine

invertebrates Mollusk Acute 48

- hr EC 50 = 24 ug/L MRID# 41756801

Shrimp Acute 96

- hr LC 50 = 4.7 ug/L MRID# 41741503 Chronic Not required A

-- Estuarine/marine benthic invertebrates Marine amphipod Subchronic/ Chronic 10

- day LC 50 = 95.4 mg /kg NOAEC = 64.8 mg/kg MRID# 46780740

Algae Green alga Nonlisted 96

- hr EC 50 = 47 ug/L MRID# 45862503

Listed NOAEC = 7.8 ug/L MRID# 45862503

Aquatic vascular plants Duckweed Nonlisted EC 50 = 166 ug/L MRID# 45865204

Listed NOAEC = 11.8 ug/L MRID# 458 65204

Seedling Emergence Red clover Nonlisted E C 25 = 8.4 mg/kg MRID# 45870601

Listed NOAEC = 5 mg/kg MRID# 45870601

Vegetative vigor Canola Nonlisted EC 25 = 0.94 mg/kg MRID# 45905001

Listed NOAEC = 0.12 mg/kg MRID# 45905001

Birds Northern bo bwhite quail Acute LD 50 = 2002 mg/kg MRID# 47802224

Mallard duck Subacute dietary LC 50 >4639 mg/kg MRID# 42214902 Chronic Not required A

--

Mammals Acute NOAEL = 30 mg/kg/day MRID# 43471604

Chronic NOAEL = 16 mg/kg/day MRID# 45756501 Nontarget insects Honey bee Acute R equired B

--

A Not required for this use pattern.

B Required for this chemical because it is used as a wood preservative.



## 4.3 Exposure Analysis Plan

4.3.1 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.
Page 25 of 77

### 4.3.2 Screeni ng Level Down

- the

- Drain Analysis

The Down

- the

- Drain (DtD) module of E

- FAST (Exposure and Fate Assessment Screening Tool) was used to determine the potential for aquatic organisms downstream of domestic wastewater treatment plants that receive discharges fr om end

- use of DCOIT to be exposed to DCOIT and its degradates. The results of the DtD module runs are expressed as number of days of exceedance of concentrations of concern (COC) for aquatic organisms. A detailed description of derivation of data for inp ut parameters selected to run the DtD module and of the theoretical basis for this model is presented in Appendix E. A 77% removal was assumed for model runs based on an Activated Sludge Sorption Isotherm study (MRID 46780743) . The model accounts for deg r adation and removal within the treatment facility, but since transit times through th e facility are <1day, some DCOIT is expected to be release to the surface water.
The DtD analysis for DCOIT is intended to serve two purposes: (1) to demonstrate the

max imum WWTP influent volume of DCOIT that would trigger potential concerns for aquatic organisms exposed to DCOIT downstream of domestic wastewater treatment plants and (2) to evaluate potential exposures based on the assumptions that the total production vo lume of DCOIT enters domestic wastewater treatment plants. A key purpose of the DtD analysis for DCOIT is to determine the lowest maximum annual WWTP influent volumes of DCOIT that would trigger potential concerns for aquatic organisms downstream of domes tic WWTPs.

Table 12 presents results of a screening

- level DtD analysis for DCOIT which, based on laboratory toxicity data for freshwater organisms, is highly toxic. Based on these aquatic toxicity data and the total annual produc tion volume reported in the EPA Section Seven Tracking System (SSTS) of approximately 470
, 000 kilograms of DCOIT , t he DtD model predicted e xceedences of concentrations of concern for acute, chronic and endangered aquatic organisms. Both high end and a vera ge scenarios were run and the results are presented in the following table.

Table 12

- Results of a Screening Level Down

- the

- Drain Analysis for DCOIT

High End Scenario

WWTP Influent Volume Freshwater Fish Acute (COC = 0.7 ug/L) Endangered Freshwater Fish Acute (COC = 0.07 ug/L) Freshwater Fish Chronic (COC = 0.56 ug/L) 470000 k ilograms/year Exceeded 154 day s per year Exceeded 327 day s per year Exceeded 175 day s per year
WWTP Influent Volume Freshwater Invertebrates Acute (COC = 4.85 ug/L) Endangered Freshwater Invertebrates Acute (COC = 0.485 ug/L) Freshwater Invertebrates Chro nic (COC = 0.624 ug/L) 470000 kilograms/year Exceeded 19 day s per year Exceeded 189 day s per year Exceeded 166 days per year
Average

– Case Scenario

Page 26 of 77WWTP Influent Volume Freshwater Fish Acute (COC = 0.7 ug/L) Endangered Freshwater Fish Acute (COC = 0.07 ug/L) Freshwater Fish Chronic (COC = 0.56 ug/L) 470000 kilograms/year Exceeded 19 day s per year Exce eded 77 day s per year Exceeded 23 day s per year

WWTP Influent Volume Freshwater Invertebrates Acute (COC = 4.85 ug/L) Endangered Freshwater Invertebrates Acute (COC = 0.485 ug/L) Freshwater Invertebrates Chronic (COC = 0.624 ug/L) 470000 kilograms/year E xceeded 2 day s per year Exceeded 25 day s per year Exceeded 21 day s per year

This screening level analysis assumes that all DCOIT used in a year may be released to domestic
wastewater treatment p lants. Based on registered uses of DCOIT presented in Table 5 of this F WP , there are some use s , such as commercial and industrial cooling water systems and paper mill water systems, for which discharges may enter industrial WWTPs rather than domestic WWTPs prior to entering surface water. Different methods and tool s for assessing potential exposures and associated ecological risks will be applied for these other types of uses.
Information on the various uses of DCOIT will reduce the uncertainty regarding the amount of DCOIT that would be expected to enter domestic v ersus industrial WWTP and will allow the agency to refine the risk assessment. T he a gency does not have high quality data on the toxicity of DCOIT to activated sludge microorganisms in wastewater treatment plants

. Consequently, the Agency anticipates th e need to require data on Activated Sludge Respiration Inhibition (OECD 209) or Modified Activated Sludge Respiration Inhibition (OCSPP 850.6800)

. 

## 4.4 Effects Analysis Plan
Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOT OX) database. The ECOTOX database will be searched during the risk assessment phase of DCOIT and the data reviewed following the agency ’s policy for reviewing public literature for use in assessing risks from pesticide s

. 9 Those ecotoxicity values found i n the public literature to be more sensitive than those currently in the database of submitted guideline studies or which satisfy existing data gap(s) will be used during the risk assessment phase of DCOIT. ECOTOX was created and is maintained by the USE PA, Office of Research and Development, and the National Health and Environmental Effects Research Laboratory's Mid

- Continent Ecology Division

. 

## 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews numerous studies to ass ess 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. T hese 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

10 http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/endangered_species_reregistration_wor kgroup/esa_evaluation_open_literature.htm

. Page 27 of 77chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of its reregistration decision for DCOIT, EPA 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), DCOIT is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP).
EPA 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 “naturally occurring estrogen, or other such endocri ne effects as the Administrator may designate.” 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 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 determi ne 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, 2013 10 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.
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. 11


## 6 Optional Labe l Changes

The agency invites any label amendments that could be considered to eliminate the anticipated need for EPA to require certain data, reduce the possibility that EPA’s planned risk assessments overestimate risk due to reliance on conservative assum ptions, and/or improve label clarity. For DCOIT, i t is recommended that all labels and uses be clarified as to whether or not they are intended for food or nonfood contact. Additionally as noted in Sections 1.5.1 and 3.2 , there are uses on technical label s that may result in potential dietary exposure (materials preservatives in cleaning solutions and in

- container preservatives), but there are not corresponding uses on end

use products. R egistrants of products EPA Reg Nos 707

- 224 and 6701

- 58 are encouraged to

remove the uses f r o m the technical label or provide the appropriate application rate and directions for us e on the EUP labels through an amendment

.

10 See http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0477

- 0074 for the final second list of

chemicals.
11 http://www.epa.gov/endo/ Page 28 of 77

## 7 Next Steps

After the F WP for the DCOIT case is posted to th e docket at EPA

- HQ

- OPP

- 2014

- 0403 , a Data Call In (DCI) is anticipated to be issued a year later

.

Page 29 of 77

## 8 References

Product Chemistry Citations

MRID 40808501. Chang, S. (1987) Product Chemistry RH

- 25,287 Technical: Project ID NAL

88

- 002. Unpublished study prep ared by Rohm and Haas Co. 106 p.

MRID 41361601. Chang, S. (1987) Product Chemistry: RH

- 25,287 Technical: Lab Project Number: NAL

- 88

- 002. Unpublished study prepared by Rohm & Haas Co. 98 p.

Agency Citations

U.S. Environmental Protection Agency (EPA). 20 02. ECOTOX User Guide: ECOTOXicology Database System. Version 3.0. Available: http://www.epa.gov/ecotox/

. Mostaghimi, Siroos. August 13, 2007. Estimated Environmental Concentrations Reported by Registrant for Kathon 287 WT Wood Preservative. D330125.
U.S. Environmental Protection Agency. High Production Volume Information System (HPVIS). http://www.epa.gov/hpvis/

.

Page 30 of 77

# Appendix A T oxicology Profile

Acute Toxicity for Product Lab eling

As summarized in Table A1, acute toxicity data show that 1,2

- benzisothiazolin

- 3

- one (DCOIT) is moderately toxic by the oral route (Toxicity Category III ); however, because the irritation and corrosivity of the chemical, the acute dermal, acute inha lation, primary eye irritation and primary skin irritation studies for the technical material are waived (Toxicity category I). DCOIT is a dermal sensitizer.

Table A1

– Acute Toxicity Studies for DCOIT

Guideline Number Study Type MRID Numbers Results Toxi city Category

870.11 00 Acute Oral 42977701 LD 50 =1636 mg/kg III

870.1200 Acute Dermal N/A waiver for technical material I

870.1300 Acute Inhalation 43471602 LC 50 not determined (Corrosive) I

870.2400 Primary Eye Irritation N/A waiver for technical material I

870.2500 Primary Skin Irritation N/A waiver for technical material I

870.2600 Dermal Sensitization 47004002; 48748511 Sensitizer N/A

Page 31 of 77Subchronic Toxicity

There are three subchronic stud ies: one 90

- day rat oral study (MRID 43471603), one 90

- day dog oral study (MRID 45747201), and one 90

- day rat inhalation study (MRID 43487501).

90

- day rat oral toxicity study (MRID 43471603)
In the subchronic rat oral study, oral administration of DCOIT Technical via the diet to Crl:CDBR rats[10/sex/group for 13 weeks at dose levels of 0, 100 ppm [6.2 males/7.2 females mg/kg/day], 500 ppm [32.5 males/36.7 females mg/kg/day], 1000 ppm [60.7 males/74.7 females mg/kg/day], and 4000 ppm [248.2 males/278.4 fem ales mg/kg/day ] resulted in decreased body weight throughout the study at the high dose level in both sexes [males 86%/ females 80% of control at 13 weeks], decreased overall body

- weight gain [males 79%/ females 77% (4000 ppm) females 85% (1000 ppm) of co ntrol], decreased food consumption at 4000 ppm for both sexes and at 1000 ppm in females initially, decreased water consumption 4000 ppm, changes in several hematology/blood chemistry parameters consistent with chronic, low level blood loss, and microscopi c, treatment related, changes in the forestomach [increase in mucosal erosion/ulceration, submucosal edema, acute inflammation, hyperplasia of the mucosal epithelium, and/or hyperkeratosis). The NOAEL is at 500 ppm [32.5 males/36.7 females rug/kg/day], the LOAEL at 1000 ppm [60.7 males / 74.7females mg/kg/day], based on microscopic lesions in the forestomach in males and decreased body weight/gain and food consumption, decreased serum triglyceride levels, and microscopic lesions in the forestomach in female s. This 90

- day oral toxicity study in the rat is Acceptable/Guideline and satisfies the guideline requirement for a 90

- day oral toxicity study (OPPTS 870.3100; OECD 408) in rats.

90

- day dog oral toxicity study (MRID 45747201)
In the subchronic dog oral to xicity study 45747201), DCOIT [98.42 a.i.] was administered to beagles (4/sex/dose) in the diet at dose levels of approximately 0, 100, 300 and 1500 ppm for 13 weeks. No treatment

- related effects were observed on survival, clinical or neurobehavioral findi ngs, ophthalmology, physical examinations, organ weights or macroscopic pathology in either sex at ≤ 1500 ppm. Some microscopic effects were considered to be secondary and caused by decreased body weight and food consumption (thymic atrophy).
One 1500 ppm female beagle exhibited severe morbidity due to complications with the feeding regimen, morbidity was not associated with treatment with the test material. There were no changes in mean body weight gain and mean food consumption for Groups 1

- 3 for both sex es. Administration of 1500 ppm resulted in decreased mean body weight gain for both males and females over the length of treatment, compared to controls. The decrease in body weight was correlated with reductions in mean food consumption for these animals.
Several changes were observed in hematology parameters including substantial decreases in erythrocyte count (20 decrease at week 7; 14% decrease at week 13), hemoglobin (21% decrease at week 7; 15% decrease at week 13), reticulocyte count (61% decrease a t week 7; 39% decrease at week 13), and hematocrit values (20% decrease at week 7; 11% decrease at week 13) in 1500 ppm males. Statistical significance was only reached at Week 7 for erythrocyte count, hemoglobin and hematocrit. Platelet counts were elevat ed in both males and females at Week 7

Page 32 of 77(22 and 26%, respectively) and Week 13 (47 and 43%, respectively), but only reached statistical significance in males at Week 7. Several changes in clinical chemistry parameters also were noted in 1500 ppm animals. To tal protein, albumin, and hemoglobin were reduced in 1500 ppm males (Week 7 and 13), and total protein and globulin were reduced in 1500 ppm females (Weeks 7 and 13). Statistical significance was reached in males at Week 7 for total protein and albumin at Week 13 in females. It is likely that these changes were a result of the decreased body weights observed in these animals. A decreased was seen in the absolute thymus weight in both 1500 ppm males and females. The decrease in thymus organ weight was suppo rted by both macroscopic and microscopic findings. At the 1500 ppm dose level, the thymus gland was reported as small in %males and 2/4 females, ranging from mild to severe. Consistent with necropsy findings, a marked diffuse atrophy of the cortical and me dullary lymphoid areas of the thymus were observed in the 1500 ppm females was secondary to the decreased body weight and food consumption observed. A NOAEL of 300 ppm (10.2 mg/kg/day in males, 10.1 mg/kg/day in females) is indicated. The LOAEL is based on decreased body weight and food consumption, hematologic and clinical chemistry parameter changes observed at 1500 ppm (47.5 mg/kg/day in males and 25.9 mg/kg/day in females). This 90

- day oral toxicity study in the dog is Acceptable/Guideline and satisfies the guideline requirement for a 90

- day oral toxicity study (OPPTS 870.3150; OECD 409) in non

- rodent species.

90

- day rat inhalation study (MRID 43487501)
In this subchronic rat inhalation study, groups of 32 male and 32 female Crl;CD BR rats received

nose

- only inhalation exposure for 6 hours per day, 5 days per week, for thirteen weeks to air, an aerosol of o

- xylene (the vehicle) at 238.5 mg/m 3 , or DCOIT at concentrations of 0.02, 0.63, and 6.72 mg/m 3 . At the end of the thirteen week exposure period, half of the animals in each group were necropsied, 5 from each group were necropsied at six months, and the remaining animals were necropsied at the end of a one

- year recovery period. Mean mass median aerodynamic diameter of DCOIT was 1.4 μm, and the mean geom etric standard deviation was 4.6, with 72% respirable fraction. Increased mortality was observed in the vehicle control group of female rats during the exposure period, but was attributed to over

- restraint in the nose

- only tubes. There was no other treat ment

- related increase in mortality either during the treatment period or during the recovery period. The incidence of rales was increased in high dose males and females beginning at weeks 2

- 3 of exposure. Significant differences were observed in body weig ht gain between the air control and vehicle control group during treatment, indicating an effect of vehicle on body weight gain. When compared with the vehicle control, the test material resulted in decreased body weight gain of approximately 20% at the h igh dose level beginning at week 2 and persisting throughout the thirteen week exposure period for male and female rats. During recovery, there were no significant effects on body weight gain in treated male or female rats. No statistically significant d ifferences were observed in treated rats vs. vehicle or control rats in clinical chemistry or hematology parameters at any dose tested. Treatment

- related microscopic lesions in the nose, larynx, and lungs were observed in mid

- and high

- dose treated rats. M inimal or mild subacute inflammation of the nose was observed in increased incidence, as was transitional respiratory epithelial hyperplasia and goblet cell hyperplasia. In the epiglottis, hyperplasia of the squamous and cuboidal epithelium was observed in mid

- and high dose rats, as was chronic

- active inflammation of the epiglottis. Goblet cell hyperplasia and acute inflammation was observed in increased incidence in the lungs of high dose rats. Based upon the histopathological alterations observed in the nose, larynx, and lungs, the systemic

Page 33 of 77LOAEL is determined to be 0.63 mg/m 3 , and the systemic NOAEL is determined to be 0.02 mg/m 3

. This 90

- day subchronic inhalation study in the rat is Acceptable/Guideline and satisfies the guideline requirement for a subchronic inhalation toxicity study (OPPTS 870.3465) in the rat.
Developmental Toxicity
There are two developmental toxicity studies available in assessing the developmental effects of DCOIT: one rabbit developmental study which was consider ed unaccepta ble to be used in risk assessment and one acceptable rat developmental study.
1) Rabbit Developmental Toxicity Study (MRID 47802217)
In the developmental toxicity study (MRID 47802217), DCOIT (97.1% a.i.; Batch # 156732) was administered in the diet to 24 tim e

- mated New Zealand White (CRL:KBL[NZW]) rabbits/group at dose levels of 0, 125, 500, or 2000 ppm (equivalent to 0, 5, 20, or 59 mg/kg/day) from gestation day (GD) 6 through 28. All surviving does were killed on GD 28; their fetuses were removed by cesarea n section and examined.
There were no effects of treatment on mortality, clinical signs, gravid uterus weight, or gross pathology. One 2000 ppm doe (#88) was found dead on GD 28, and was found to have dark red discoloration of the forestomach and a rupture of the peritoneum at necropsy. This death was considered incidental. At 2000 ppm, a body weight loss (

- 76 g) was observed during GD 6

- 9, and cumulative body weight gains (expressed as% relative to GO 6) were decreased from GD 9 through GD 28. These findin gs were associated with decreased mean absolute (g/animal/day) and relative (g/kg BW/day) food consumption (deer. 17

- 58%) during GO 6

- 19, resulting in an overall (GD 0

- 28) decrease of 19%. However, the magnitude of the decreases diminished with time. There fore, the decreased food consumption is considered to be a result of decreased palatability of the diet, and not a manifestation of systemic toxicity. The maternal LOAEL was not observed. The maternal NOAEL is 2000 ppm (equivalent to 59 mg/kg/day).

There were no treatment

- related abortions, premature deliveries, or complete litter resorptions. No effects of treatment were observed on corpora luteal doe, implantations/doe, live fetuses/doe, resorptions/doe (early, late, or complete litter), sex ratio, post

- implantation loss, or fetal or placental weight. There were no treatment

- related external, visceral, or skeletal malformations or variations. The developmental LOAEL was not observed. The developmental NOAEL is 2000 ppm (equivalent to 59 mg/kg/day).

This study is classified Unacceptable

- Guideline and does not satisfy the guideline requirements (OPPTS 870.3700b; OECD 414) for a developmental toxicity study in the rabbit because, the test compound was administered via the diet as opposed to the normal meth od of administration (oral gavage). As palatability affected maternal health at 2000 ppm due to reduced food consumption, higher dietary concentrations would not have been appropriate. The r abbit developmental toxicity study is a n anticipated data need

. 2) Ra t Developmental Toxicity Study (MRID 43471604)
In a developmental toxicity study in rats (MRID # 43471604), groups of pregnant female CD rats (25/dose) were administered DCOIT (98.8% purity) by gavage at dose levels of 0, 10, 30, and

Page 34 of 77100 mg/kg/day on ges tation days 6 through 15. At 100 mg/kg/day, clinical signs of toxicity were observed in maternal animals, consisting of scant feces, soft feces, and/or diarrhea. One dam died at the 100 mg/kg/day dose level. Decreased body weight gain was observed at 100 m g/kg/day (73% of control in pregnant dams). There were no significant differences in the number of corpora lutea/dam, implantations/dam, live fetuses/dam, resorptions/dam, or in pre

- or post

implantation losses, litter weight, or fetal body weight. There w ere no fetal external variations or developmental retardations, and there were no fetal soft tissue developmental retardations. Fetuses at the high dose showed an increase in the number of fetuses with wavy ribs, along with an increase in number of litters with this effect as well as the severity of the effect. The Maternal NOAEL is determined to be 10 mg/kg/day, based on decreased food consumption during dosing and clinical signs at 30 mg/kg/day. The Developmental NOAEL is determined to be 30 mg/kg/day, based on increased litters with wavy ribs at 100 mg/kg/day.

The s tudy is classified Acceptable/Guideline and satisfies the guideline requirement for a prenatal developmental toxicity study (OPPTS 870.3700) in the rat.
Reproductive Toxicity

There is one t wo

- generation reproduction study (MRID 457565

- 01). In the study, DCOIT (100.3% a.i.) was administered via diet to male and female Crl:CD ® BR rats at dose levels of 0, 200, 800, or 3200 ppm (equivalent to 0, 16

- 20, 62

- 88, and 235 mg/kg/day in males during p remating and 0, 18

- 21, 67

- 93, and 259 mg/kg/day in females during premating). Significant offspring mortality at 3200 ppm caused an insufficient number of pups available to produce a second generation; consequently, all surviving 3200

- ppm offspring were eu thanized prior to sexual maturation. An additional treatment group of 400 ppm (equivalent to 30

- 39 mg/kg/day in males during premating and 33

- 41 mg/kg/day in females during premating) and a concurrent control group were initiated. P1 and P2 males and fema les were 6 or 3 weeks of age, respectively, when dosing was initiated and were exposed to the test article for at least 10 weeks prior to mating. Treatment continued until termination and included gestation and lactation periods.

There was clear evidenc e of parental effects in 800

- and 3200

- ppm animals including clinical signs of toxicity (paleness), significantly decreased body weights (3200

- ppm P1 and 800

- ppm P2 animals), significantly decreased body weight gain (3200

- ppm P1 and 800

- ppm P2 animals), si gnificantly decreased body weight and body weight gain in 3200

- ppm P1 females during gestation, significantly decreased body weight in 3200

- ppm P1 females during lactation, and significantly decreased mean food consumption (3200

- ppm P1 and 800

- ppm P2 anima ls).
Other findings included treatment

- related hyperplasia and hyperkeratosis of the nonglandular stomach in 3200

- ppm P1 males and females. Additionally, at 3200 ppm, an increased incidence of hypertrophy/vacuolation of the zona glomerulosa of the adrena l cortex was observed in both P1 males and females. Therefore, the NOAEL for parental toxicity is 400 ppm for males (30

- 39 mg/kg/day) and females (33

- 41 mg/kg/day), while the LOAEL for parental toxicity is 800 ppm (male: 62

- 88, femal: 67

- 93 mg/kg/ day) and is based on decreased body weight and body weight gain (and food consumption in the females).
There was clear evidence of offspring effects in 800

- and 3200

- ppm animals including clinical signs of toxicity (paleness and distended abdomens in 3200

- ppm F1 pups), significant decrease

Page 35 of 77in pup weight (800

- ppm F1 and F2 animals and 3200

- ppm F1 animals), significant gross necropsy findings (3200

- and 800

- ppm F1 pups), significant decreases in absolute and relative mean thymus (800 and 3200 ppm) and spleen (400, 8 00, and 3200 ppm) weights in F1 males, significant decreases in mean thymus weights (800 and 3200 ppm) in F1 females, and significant decreases in absolute and relative mean thymus weights (400 and 800 ppm) in F2 animals (both sexes). The mean age at prep utial separation was delayed at 800 ppm and the mean age at vaginal opening delayed at 400 and 800 ppm. There was no treatment related effect on anogenital distance in the F2 offspring.
Additionally, at 3200 ppm, the lactation index for P1 females was sig nificantly decreased due to the significant increase in the number of litters with liveborn pups that did not survive to postnatal day (PND) 21. Concurrently, the number of pups dying, missing and/or cannibalized significantly increased on PND 5

- 21 and 0

- 21, contributing to the decreased lactation index.
Therefore, the offspring toxicity NOAEL is 200 ppm (male: 16

- 20, female: 18

- 21 mg/kg/day) and the offspring toxicity LOAEL is 400 ppm (male: 30

- 39, female: 33

- 41 mg/kg/day) based on decreased absolute and relative spleen and thymus weight.
This reproductive and fertility toxicity study in the rat is classified Acceptable/ Guideline and satisfies the guideline requirement [ OPPTS 870.3800] for a Reproduction and Fertility Effects/Rat.

Immun o toxicity

There is currently no existing immunotoxicity study for DCOIT . This is a required study and has been identified as a data gap and an anticipated data need . The agency anticipates requiring this study.
Chronic toxicity/ Carcinogenicity
On December 6, 2007, the Hea lth Effects Division's Hazard Science Policy Council (HASPOC) considered a request made by the registrant for waiver of a carcinogenicity study for DCOIT. This waiver request was made by the registrant on the basis of the available chemistry, metabolism an d toxicology data for DCOIT. The HASPOC concluded that there was a significant toxicology database of acceptable studies for DCOIT, including subchronic, metabolism, developmental, reproductive, and genotoxicity studies. The similarity in structure, funct ion, and biocidal mode of action supports bridging of data across the isothiazolone biocide chemicals. The available toxicology data on DCOIT shows that it is not mutagenic and does not produce any significant systemic toxicity. Toxicity found from the av ailable data in experimental animals shows the primary effects to be associated with the irritant properties of the chemical, that is, irritation at the site of contact depending on the route of exposure. There were also no biological indicators from the a vailable toxicology data that show systemic lesion(s) indicative of precursor effects that may lead to tumor formation. Thus, a risk assessment based on the irritant effects of DCOIT (the most sensitive effect of the chemical) is likely to afford protecti on against other potential systemic effects including carcinogenicity. Therefore, the lack of a chronic bioassay for DCOIT would not likely impact the risk assessment for the chemical, and will not be needed for DCOIT.

Page 36 of 77Mutagenicity

DCOIT was tested for gene mutations in bacteria ( S. typhimurium and Escherichia coli WP2 uvrA ) and mammalian cells (Chinese hamster ovary, CHO cells at the HGPRT locus) and found to be negative up to cytotoxic concentrations. It was also negative for chromosome aberrations in CHO cells and micronucleus induction in mouse bone marrow up to a lethal dose. Based on these findings, there is not mutagenicity concern for DCOIT. The associated studies are listed below.

In Vitro Studies
Salmonella Gene Mutation Assay; MRID 47107006

In a reverse gene mutation assay in bacteria (MRID 47107006), strain WP2 uvr A of E. Coli was exposed to O c thilinone, (46.2% a.i.; Lot #6110D015), SkaneTM M8 at concentrations of 1.5, 5, 15, 50, 150, 500, or 1500 μg/plate in the presence and absence of mammali an metabolic activation in the plate incorporation procedure . Mammalian metabolic activation was derived from the livers of Aroclor 1254

- induced Sprague

- Dawley rats. These doses were selected based on a range

- finding assay in which SkaneTM M8 was tested u p to toxic concentrations (0.15

- 5000 μg/plate, ±S9).

SkaneTM M8 was tested up to toxic concentrations. In the range

- finding assay, SkaneTM M8 (2

- n

- octyl

- 4

- isothiazolin

- 3

- one) was found to be toxic at ≥150 or 500 μg /plate. In the mutagenicity assays, the t est article induced a reduction in the growth of the bacterial background lawn at ≥150 μg/plate, ±S9. There were no significant increases in the frequency of revertant colonies as compared to the corresponding solvent control at any dose level in any cond ition. Toxicity was observed at the high doses (1500 μg/plate) in both the assays; hence the test material was tested up to the toxic limit. The positive controls induced the appropriate responses. There was no evidence of induced mutant colonies over b ackground under the conditions of the assays.
This study is classified as A cceptable

- N on - G uideline and does not satisfy the guideline requirement for Test Guideline OPPTS 870.5100; OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data . Five or more strains were not used as required in the guidelines. The data for this one strain, however, is still valid.
Salmonella Gene Mutation Assay; MRID 43471605
In two independent microbial gene mutation assays, Salmonella strains TA1535, TA1537, TA98, TA100 were exposed to non

- activated doses of 0.3, 1, 3, 10, 30 ug/plate (initial trial) or 0.1, 0.3, 1, 3 or 7.5 ug/plate (confirmatory trial) or S9

– activated doses of 3,10, 30, 100 or 300 ug/plate (initial trail) or 1, 3, 7.5, 30, or 75 ug/plate (confirmatory trial) of RH

- 287 technical. Cytotoxicity was achieved at levels of > 3 ug/plate

– S9 and > 75 ug/plate +S9. There was no evidence of a mutagenic response at any dose either in the absence or presence of S9 in either trial. All strains responded in the expected manner to the corresponding nonactivated and S9

- activated positive controls. The study is classified as Acceptable

- Guideline and satisfies the requirement for a microbial gene mutation assay.

Page 37 of 77Gene Mutation in Cultured Mammalian Cells (Chi nese Hamster Ovary CHO Cells); MRID 43471606
In two independent Chinese hamster ovary (CHO) in vitro gene mutation assays (MRID No. 43471606), cell cultures were exposed to non

- activated concentrations of 0.005, 0.025, 0.05, 0.1, or 0.5 ug/ml (initial tr ail) or 0.025, 0.05, 0.1, 0.2, 0.4, 0.5 or 0.75 ug/ml (confirmatory trail) or S9

- activated doses of 0.5, 1.0, 2.5, 5.0, 10 or 25 ug/ml (initial trail) or 2.5, 5.0, 6.0, 8.0 9.0, 10 or 15 ug/ml (confirmatory trail). The S9 fraction was derived from Aroclor 1254

- induced rat liver and the test material was delivered to the test system in acetone.
In both trails, cytotoxicity was achieved at levels > 0.5 ug/ml

- S9 and >1 0 ug/ml +S9. There was, however, no evidence of a mutagenic response at any dose either wit h or without S9 or without S9 activation in either trail. CHO cells responded in the expected manner to the non

- activated and S9

- activated positive controls.
The study is classified as Acceptable

– Guideline and satisfies the requirements for Gene Mutatio n in Cultured Mammalian Cells (Chinese Hamster Ovary CHO Cells)

. In Vitro Mammalian Cytogenetics Chromosome Aberration in Chinese Hamster Ovary Cells ; MRID 43471607

In two independent Chinese hamster ovary in vitro cytogenetic assays (MRID 43471607) cel l cultures were exposed to non

- activated doses of 0.3, 0.6, or 0.7 ug/ml (initial trail) or 0.5, 0.6 or 0.7 ug/ml (confirmatory trail) or S9

– activated concentrations of 6.0, 7.0, or 8.0 ug/ml (both trails). Cell harvest times were 23 hours (initial non

- a ctivated trail), 23 and 47 hours (confirmatory non

- activated trial), 20 hours (initial S9 activated trail), or 20 and 44 hours (confirmatory S9

- activated trail). The S9 fraction was derived from Aroclor 1254

- indsuced rat livers and the test material was de livered to the test system in acetone.
Cytotoxicity, as indicated by reduced mitotic indices (app. 50%), was seen at > 0.7 ug/ml

– S9 and 8.0 ug/ml +S9; interference with cell

- cycle kinetics was also observed at non

- activated doses as low as 0.05 ug/ml and at S9

- activated levels of > 4.0 ug/ml. Slight increases in the frequency of cells bearing structural aberrations, particularly complex aberrations, were noted in cultures harvested after prolonged recovery from exposure to the highest non

- activated or S

- 9 a ctivated dose. Complex structural aberrations were also never exceeded 3% of the examined population and never approached a level of statistical significance. The evidence is, therefore, not sufficient to conclude that RH

- 287, tested up to cytotoxic level s, induced clastogenic response in the presence or absence of S9 activation. This study is classified Acceptable/Guideline

. In Vivo Studies

In Vivo Mammalian Cytogenetics

- Erythrocyte Micronucleus Assay in Mice; MRID 46790759

In a bone marrow micronucleu s assay (MRID 46780759), fasted (3 hours prior to dosing), young adult CD

- 1 mice (5

- 9/sex/dose/harvest time) were treated once by gavage (10 mL/kg) with Kathon RH

- 287 (100.3% a.i., Lot # 0159F005) in corn oil at doses of 0, 60, 300, or 600 mg/kg. Bone marrow cells were harvested at 24 or 48 post

- dosing.

Page 38 of 77Mortality was observed in one 600 mg/kg female. Clinical signs of toxicity including diarrhea, anogenital staining, soft or scant feces, passiveness, and ataxia were observed in both sexes at 600 mg/kg. A significant (p<0.05) decrease in PCE/NCE ratio was observed in both sexes at 600 mg/kg at 48 hours post

- dosing, indicating that Kathon RH

- 287 was toxic to the bone

marrow.

No treatment

- related increases in the MPCE frequency were observed in any treatment group at any sacrifice time when compared to controls. The positive control induced the appropriate response. This study is classified as A cceptable

- N on - G uideline and satisfies the guideline requirement for Test Guideline (OPPTS 870.5395; OECD 474) for i n vivo cytogenetic mutagenicity data.

In Vivo Micronucleus Assay in CD1 mice; MRID 43471608

In an in vivo micronucleus assay, groups of CD

- 1 mice (5,5 or 7/dose/sex/sacrifice time) received single oral gavage administrations of 32.5, 162.5, or 325 mg/kg R H

- 287 technical in corn oil. Bone marrow cells were examined 24 and 48 hours post

- treatment for the frequency of polychromatic erythrocytes (MPEs). The observation of mild and transient clinical signs (passive behavior and scant feces in high dose males an d females) suggests that the maximum tolerated dose (MTD) was not achieved.
There was also no evidence of target cell cytotoxicity at any dose or harvest time. A slight but dose

- related increase in MPEs was observed in male mice of the mid

- and high dose g roups at the 24 hour sacrifice. The increase was significant at 325 mg/kg (p<0.05). However, the findings do not provide sufficient evidence to classify RH

- 287 as clastogenic/aneugenic in this test system.
Additional information submitted by the registrant to resolve the issue of the MTD led to the following conclusion by HED: “TBII has reached the decision that testing at higher dose levels would likely cause mortality. In light of this decision, we also agree that the significance increase in micronuclei seen in the high dose males was probably an anomalous finding since increases were not seen at 48 hours and were not observed in females at any dose or harvest time. We conclude that nothing further would be gained by repeating the micronucleus assay, RH

- 2 87 technical is, therefore, considered to be negative in this in vivo system. The study is considered acceptable and satisfies the guideline requirement for a micronucleus assay.”
Other Toxicological Effects
Dermal Absorption Factor Study:

Dermal absor ption of RH

- 287 was examined in male Crl:CD:BR rats (MRID # 43471610). There were six experimental groups of 4 rats each. Two concentrations of RH

- 287 were employed, 3% and 0.045%. Dermal application was made to a shaved 2 x 2 cm area on the interscapular region of the back, which was fitted with a contoured glass ring secured with cyanoacrylate glue and a porous top secured with rubber bands after application of the test substance in a dose aliquot of 60 μl. Two groups (A and B) received either 3% of 0.0 45% RH

287 and urine and feces samples obtained at 10 hours post

- dose, at which time the animals were killed and analysis for radioactivity performed in whole blood, plasma, and remaining carcass. Two additional (groups 9C and D) received either 3% or 0.04 5% RH

- 287 and were subjected to

Page 39 of 77the same procedures as groups A and B, except exposure duration was 24 hours. The last two groups (E and F) received either 3% or 0.045 % RH

- 287, and urine and feces samples taken at 0, 10, 24, 48, and 72 hours post

- dose. A nimals in this group were sacrificed at 72 hours post

- dose and analysis for radioactivity performed as for the other groups. Results of this study showed that at a dose of 0.045% RH

- 287, 44

- 50% of the dose was absorbed after a 10 hour exposure, and 70% af ter a 24 hour exposure. Administration of 3% RH

- 287 resulted in 31

- 34% absorption after 10 hours of exposure, and 52% absorption after 24 hours exposure. This study is Acceptable/Guideline and satisfies the guideline requirements (OPPTS 870.7600; OECD 42 7) for a dermal penetration study in rats.

Page 40 of 77

# Appendix B Environmental Fate

Environmental Fate and Transport Properties of DCOIT and its Straight

- Chain Degradates

T his environmental fate assessment addresses the persistence and mobility of the parent compound 4,5 dich loro

- 2

- n

- octyl

- 4

- isothiazolin

- 3

- one (DCOIT) and the significant ( > 10 % of applied parent) straight

- chain degradates which include N

- (n

- octyl) malonamic acid, N

- (n

octyl) oxamic acid, N

- (n

- octyl) acetamide, DCOIT sulfinic acid, propiolic acid amine, and 2

- (N

octyl) carbamoyl

- 2

- chloroethylene sulfonic acid. These straight chain degradates eventually degrade by biodegradation to acetic acid, formic acid and CO 2

. Based on the chemical and physical properties (Table 4 ) and environmental fate propert ies (Table B1 ) of DCOIT, DCOIT has limited water solub ility
, degrades more quickly at higher environmental pH values, and essentially stable to photodegradation in water by natural sunlight, and degrades with half

- lives of up to 2 days in aerobic soil and <21 hours under aquatic conditions. Based on its vapor pressure of 4.5 x 10

- 6 mm Hg
, its Henry’s Law constant of 1.2 x 10

- 7

, and its rapid degradation with half

- lives of <2 days, DCOIT is not expected to volatilize from water or soil

. DCOIT is not expect ed to be mobile in soil and most residues were associated with sediment in the aquatic metabolism studies. Bioconcentration and subsequent depuration in fish can occur and the primary residues were polar straight

- chain metabolites. In a wastewater
treat ment plant (WWTP), DCOIT was not readily biodegradable but the N

- (n

- octyl) malonamic and N

- (n

- octyl) oxamic acid degradates were readily biodegradable. Sorption to activated sludge is a significant route of dissipation.

There is no record of review for the AWPA E11

- 06 accelerated leaching of wood preservatives i n water (MRIDs 48414312 and 48424701) and AWPA E20

- 08 leachability of wood preservatives in soil contact (MRID 48236002) studies. These data will be reviewed during registration review.

Water and Sediment

Hydrolysis

The rate of hydrolytic degradation of DCOIT increases as the pH increases. At 25 o C, DCOIT degraded with calculated half

- lives of 260, 71, and 3.5 days at pH 4, 7, and 9, respectively. The degradates included the straight

- chain compo unds DCOIT sulfinic acid and propiolic acid amine (MRID 46780744, OECD 111).

Aqueous Photolysis

The registrant submitted two photodegradation in water studies for DCOIT. Using natural light at 25 o C, DCOIT photodegraded with a dark

- control half

- life of 17.2 days at 25 o C. The major degradates included N

- (n

- octyl) oxamic acid and N

- (n

- octyl) malonamic acid (combined 67 % of

Page 41 of 77parent) and minor degradate N

- (n

- octyl) acetamide reached 7.7 % of parent (MRID 41845001, OCSPP 835.2210). In a supplemental photod egradation in water study using natural sunlight, the registrant measured photodegradation degradates at 25 o C. In this study, the major degradate was N

- (n

- octyl) oxamic acid at 31 % of applied parent and the minor degradates were N

- (n

octyl) carbamic aci d (5 %) and 4,6

- dichloro thiazole (1.9 %) [MRID 42772801, OCSPP 835.2210 ].

Octanol

- Water Partition Coefficient

The octanol

- water partition coefficient (log P or log Kow) is 2.8 ( < 3) [MRID 47802208], which indicates sorption to soil and sediment and potent ial bioconcentration in aquatic organisms can

occur

. This intermediate log P value is consistent with the extent of sorption and bioconcentration observed in the submitted and accepted studies. 12

Aerobic Aquatic Metabolism

DCOIT degraded in a under a ero bic aquatic conditions with a half

- life of <1 hour in a silt loam:seawater system at 25 o C

. The only significant degradates were N

- (n

- octyl) malonamic acid, N

- (n

- octyl) oxamic acid, and N

- (n

- octyl) acetamide. Virtually all the residues were associated wi th sediment throughout the study (MRID 4184500 3, 4241102, 42772802, OCSPP 835.4 3 00). In an aerobic aquatic metabolism study conducted according to the OECD 308 test guideline, the half

- life of DCOIT in a clay loam:pond water system was 0.86 days (21 hours ) at 9

o C. No significant degradates were formed in the study, and sediment residues accounted for virtually all radioactivity by 7

- 13 days (MRID 46816306). In an aquatic metabolisms study using only surface water with no sediment (OECD 309), the half

- li fe was 2.9 days (67 hours) at 18 o C. The significant degradates in the surface water study were 2

- (N

- octyl) carbamoyl

- 2

- chloro

- ethylene sulfonic acid and N

- (n

- octyl) oxamic acid (MRID 46816307).

A na erobic Aquatic Metabolism

DCOIT degraded in a silt loa m:seawater system under anaerobic aquatic conditions with a half

life of <1 hour

. The degradates N

- (n

- octyl) malonamic acid and N

- (n

- octyl) oxamic acid were formed at significant concentrations in the study and declined to non

- significant concentrations i n the study. Sediment accounted for virtually all residues throughout the study (MRID 41845002, OCSPP 835.4400). In another anaerobic aquatic metabolism study (OECD 308), the half

- life in a clay loam:pond water system was 0.33 days (8 hours) at a tempera ture of 9 o C. No significant degradates were found in the study and sediment residues accounted for virtually all radioactivity by 7

- 14 days (MRID 46816306).

Bioconcentration in Fish
DCOIT bioconcentrated in bluegill sunfish with bioconcentration factors (BCF) values of 6 60X, 200X, and 660X for edible, non

- edible, and whole fish . A BCF is the ratio of the fish concentrations to the water concentrations. Depuration of 77, 78, and 60 % in edible, non

- edible,

12 MRIDs 41845004 and 2659908 fo r sorption and MRID 41845006 for bioconcentration in fish. Page 42 of 77and whole fish occurred by 21 days

. Polar meta bolites (straight

- chain degradates) were highest residues in fish (MRID 41845006 , OCSPP 850.1730 ).

Leaching from Treated Boat Paints and Wood

DCOIT will leach from treated boat paints and wood into soil and water and create environmental exposure. For boa t paints, the agency has received and reviewed 19 ASTM D5108

- 90 studies containing leaching rates from 30 paints that contain DCOIT (See Table B3 for further details). The maximum, minimum, and average leaching rates in simulated seawater ranged from 5.2

- 100.6, 0

- 27.3, and 1.8

- 50.8 ug/cm 2 /day, respectively. The cumulative leaching rates ranged from 92

- 2,250 ug/cm 2 . The agency has also received five wood leaching studies that demonstrate the potential for terrestrial exposure and aquatic exposure, and onl y two have been reviewed (see Table B2 for more details). The extent of exposure from DCOIT used to preserve wood will be addressed in Registration Review.

Soil

Soil Leaching/Adsorption/Desorption Batch Equilibrium

DCOIT is mobile to mobile to hardly mo bile in soil and sediment, based on the Koc values from the submitted batch equilibrium studies (MRIDs 41845002 and 00 164668 ). 13 The Kd values

were 31

- 76 L/kg in 4 soils with 0.4

- 1.35 % organic carbon (OC) and a Kd of 625 L/kg in a sediment with 4.1 % OC. The Koc values were 5,662

- 7,865 L/kg in 4 soils with 0.4

- 1.35 % OC and 15,441 L/kg in sediment with 4.1 % OC. Sorption was related to organic carbon content (r 2 =0.94) and pH (r 2 =0.71) [ MRID 41845004 ] . In another study, the Kd values were 14

- 74 L/kg in 4 soils with 0.2

- 4.4 % organic carbon (OC) and a Kd of 905 L/kg in a sediment with 5 % OC. The Koc values were 1,691

- 6,850 L/kg in 4 soils with 0.2

- 4.4 % OC and 18,100 L/kg in a sediment with 5 % OC. Sorption was related to organic carbon content (r 2 =0.46 ) [ MRID 00 164668 ]

.
Aerobic Soil Metabolism

DCOIT degraded in aerobic silt loam and sandy soils with non

- linear half

- lives of 3

. 2 and 49 hours, respectively. Significant ( > 10 % of applied) degradates were not formed in the study (MRID 44791101).

A na erobi c Soil Metabolism

Data on anaerobic soil metabolism (OCSPP 835.4200) were not submitted for DCOIT and were waived (MRID 46780763). However, the 835.4200 data requirement is satisfied with the results of the anaerobic aquatic metabolism stud ies with a DCOIT half

- life of < 8 hours (MRID 41845002, OCSPP 835.4400 ; MRID 46816306, OECD 308 ).

13 http://www.fao.org/docrep/003/x2570e/x2570e06.htm

. Page 43 of 77Carbon and Nitrogen Trans formation Test (for soil microorganisms)

The IC50 of DCOIT was 393 mg/kg for carbon transformation (OECD 217) and the IC50 for nitrogen transformatio n was 155 mg/kg (OECD 216) [MRID 46780727]. Based on these results and the results of the metabolism studies (MRIDs 44791101, 41845002, 42341101, 41845003, 42341102, 42778202, 46816306, 46316307) that demonstrate rapid degradation in soil and sediment, it is unlikely that DCOIT poses any risk to microorganisms in soil and sediment.

Fate and Transport in WWTP
Activated Sludge Sorption Isotherm
DCOIT was sorbed tightly to activated sludge with a Kd of 2,466 L/kg (MRID 46780735, OCSPP 835.1110).
Ready Biode gradability
The registrant conducted three ready biodegradability studies (OECD 301B), one for parent DCOIT and two for the major degradates N

- (n

- octyl) malonamic acid and N

- (n

- octyl) acetamide. For a compound to be readily biodegradable, 70 % must degrad e in the 28

- day study and >60 % must degrade in a 10

- day period. 14 For DCOIT, 80 % degraded in the 28

- day study and 52 % degraded in a 10

- day period at 20

- 23 o C (MRID 467800743). As a result, DCOIT is not considered to be readily biodegradable. However, the degradates N

- (n

- octyl) malonamic acid and N

- (n

- octyl) acetamide were readily biodegradable. For N

- (n

- octyl) malonamic acid, 88 % degraded in the 28

- day study and 65 % degraded in a 10

- day period at 20

- 23 o C (MRID 467800741). For N

- (n

- octyl) malonamic acid, 88 % degraded in the 28

- day study and 65 % degraded in a 10

- day period at 20

- 23 o C (MRID 467800741). ). For N

- (n

- octyl) acetamide, 89 % degraded in the 28

- day study and 65 % degraded in a 10

- day period at 20

- 23 o C (MRID 467800742).
Activated Sludg e Respiration Inhibition (ASRI)
The IC50 for DCOIT was >5.7 mg/l (ppm), which is less than the level of concern of 20 mg/l. At the reported water solubility of water in the ASRI study (5.7 ppm) , 25 % inhibition of respiration occurred. However, the water solubility reported in MRID 40808501 was 14 ppm, and the submitted ASRI study (MRID 46780735) that was considered to be acceptable is now unacceptable and requires repeating. It is identified as an anticipated data need in Table 6.

14 http://www.oecd

ilibrary.org/docserver/download/9730101e.pdf?expires=1398444902&id=id&accname=guest&checksum=83B700B 0ADDF5B296DA80F317FA501FF

. Page 44 of 77Table B1. Status o f Environmental Fate Data Requirements and Study Results

Test Guideline (parent compound unless stated) OCSPP Guideline No. (unless specified) Study Result (half

- lives unless specified) Significant Degradation

Products 15 Study status Reference (MRID) and Co mments

Hydrolysis OECD 111 pH 4 (260 days) pH 7 (71 days) pH 9 (3.5 days) DCOIT s ulfinic acid P ropiolic acid amine Acceptable 46780744 25 o C

Photodegradation in water 835.2240 15 and 116 days in irradiated and dark controls

Adjusted half

- life of 17.2 days N

- (n

- octyl) oxamic acid and N

- (n

octyl malonamic acid) Acceptable 41845001 Natural sunlight

None reported (degradate identification study only) N

- (n

- octyl) oxamic acid Acceptable 42772801 Natural sunlight 25 o C

Aerobic Soil Metabolism 835.410 0 3.2 and 49 hours in silt loam and loamy sand No significant degradates Acceptable 44791101

Anaerobic Soil Metabolism 835.4200 Waived Not applicable Waived 46780763

Anaerobic Aquatic Metabolism 835.4400 <1 hour N

- (n

- octyl) malonamic acid and N

- (n

- octy l) oxamic acid Acceptable 41845002 42341101 Salt water:sediment system pH 6.6 for sediment and pH 7.4 for seawater Sediment residues accounted for virtually all radioactivity in the study

15 Significant degradates form ed at > 10 % of applied parent compound

. Page 45 of 77OECD 308 8 hours No significant degradates Acceptable 4 6816306 C lay loam:water pond system pH 8.1 for system Sediment residues accounted for virtually all radioactivity by 7

- 14 days Aerobic Aquatic metabolism 835.4300 <1 hour N

- (n

- octyl) malonamic acid and N

- (n

- octyl) oxamic acid Acceptable 41845003 42341102 42772802 Saltwater system pH 6.6 for sediment and pH 7.4 for seawater 25 o C Sediment residues accounted for virtually all residues throughout the study

OECD 309 2.9 days (67 hours) 2

- (n

- octyl) carbamoyl

- 2

- chloroethylene sulfonic acid and N

- (n

- octyl) oxamic acid Acceptable 46816307 Surface water only pH 7.2 18 o C

OECD 308 0.86 day (21 hour) None Acceptable 46816306 Clay loam:water pond system pH 8.1 for system 9 o C Sediment residues accounted for virtually all radioactivity by 7

- 13 days

Page 46 of 77Adsorption/Desorption 835.1230 Kd values of 31

- 76 L/kg (0.4

- 1.35 % OC) and 625 L/kg (4.1 % OC)

Koc values of 5,662

- 7,865 L/kg (0.4

- 1.35 % OC) and 15,441 L/kg (4.1 % OC) Not applicable Acceptable 41845004

Sorption related to organic carbon (OC) content (r 2 =0.94) and pH (r 2 =0.71)

Classified as mobile to hardly mobile in soil based on Koc values and FAO classification. 16

835.1230 Kd values of 14

- 74 L/kg in soils (OC of 0.2

- 4.4 %) and 905 L/kg (5 % OC)

Koc values of 1,691

- 6,850 L/kg (0.2

- 4.4 % OC) and 18,100 L/kg (5 % OC) Not appli cable Supplemental 164668

Sorption related to organic carbon (OC) content (r 2 =0.46)

Soil Column Leaching 835.1240 DCOIT was 31

- 47 % of applied compound by 21 days. 80

- 100 % of total residues sorbed in top 6 inches of column <1 % in leachates Numerous de gradates formed but not identified Acceptable 41845005

16 http://www.fao.org/docrep/003/x2570e/x2570e06.htm

. Page 47 of 77Bioaccumulation in fish 850.1730 BCFs of 660X, 200X, and 660X for edible, non

edible, and whole fish

77, 78, and 60 % depuration in edible, non

- edible, and whole fish by 21 days Polar metabolites (st raight

- chain degradates) were highest residues in fish Supplemental 164507 164508 41845006

Activated Sludge, Respiration Inhibition Test OECD 209 EC 50 of >5.7 mg/l (water solubility of parent compound)

25 % respiration inhibition at 5.7 mg/L Not applicab le Study does not

measure degradates Unacceptable 46816305

Study was previously considered to be acceptable but the water solubility from 40808501 is 14 ppm, which is >5.7 ppm. Therefore, the study is now unacceptable and requires repeating.

Ready Biode gradability OECD 301B Not readily biodegradable 80 % degradation in 28

- day study and 52% degradation by 10

- day period Not applicable Study does not

measure degradates other than CO 2 Satisfied (all studies were

acceptable) 46780743 DCOIT 20

- 23 o C

Read ily biodegradable

88.4 % degradation in 28

- day study and 65.1 % degradation in 10

- day period. 46780741 N

- (n

- octyl) malonamic acid 20

- 23 o C

Readily biodegradable 46780742 N

- (n

- octyl) acetamide
Page 48 of 7789.1 % degradation in 28

- day study and 65.3 % degradation in 10

- day period 20

- 23 o C

Soil Microorganisms: Nitrogen Transformation Test OECD 216 EC 50 of 155 mg/kg Not applicable Degradates not tracked in study Acceptable 46780727 19.5

- 21 o C

Soil Microorganisms: Carbon Transformation Test OECD 217 EC 50 of 393 mg /kg Not applicable

Degradates not tracked in study Acceptable 46780727

19.5

- 21 o C

Activated Sludge Adsorption Isotherm Test 835.1110 Kd of 2,466 L/kg Degradates not analyzed. Acceptable 46780735

Page 49 of 77Table B2 Results of Wood Leaching Studies 17 , 18 , 19

St udy Description Test Guideline Leaching rate Status MRID and
comments

Wood leaching study in

water (block study) AWPA EN

- 84 2.2 (max) 0.9 (min) 1.7 (average) 19.8 (cumulative) Acceptable 46780750

Wood leaching study in

water (block study) AWPA E11

- 97 1 .6 (max) 0.05 (min) 0.36 (average) 3.5 (cumulative) Acceptable 48168201

Wood leaching study in

water (block study) AWPA E11

- 06 Data to be reviewed No record of review 48414312 Ecolife One

- Pack

Wood leaching study in

water (block study) AWPA E11

- 06 Da ta to be reviewed No record of review 4 8424701 Ecolife One

- Pack

Leachability of Wood Preservatives in Soil Contact (stake study) AWPA E20

- 08 Data to be reviewed No record of review 48236002

Table B3 Leaching from Tre ated Boat Paints (ASTM D5108

- 90)

St udy Identification (MRID) Study Result 20 Study Status Comments

43468402 44239501 37.8 (max) 18.6 (min) 27.6 (average) 1,196 (cumulative) Acceptable 45

- day study Red Paint 3 % DCOIT

43768605 36.5 (max) 1.2 (min) 14.5 (average) 868 (cumulative) Acceptabl e 73

- day study Sea

- Nine 211 Hempel Formulation 7199E

- 19990 2.02 % DCOIT

43.4 (max) 6.6 (min) 23.7 (average) 1,510 (cumulative) Acceptable 73

- day study Sea

- Nine 211 Hempel Formulation 7199E

- 51110 Red Paint 1.97 % DCOIT 46439601 57.3 (max) 9.0 (min) 25.9 (average) 1,057 (cumulative) Acceptable 45

- day study Sea

- Nine 211 Hempel Antifouling Globic 81920 Red Paint 1.9 % DCOIT 44066802 34.8 (max) 7.6 (min) Acceptable Sea

- Nine 211 45

- day study

17 Max, min, and average leaching rates in ug/cm 2 /day

. 18 Cumulative leaching in ug/cm 2

. 19 Degrada tes not measured in study

. 20 Maximum, minimum, and average leaching rates in ug/cm 2 /day and cumulative leaching in ug/cm 2

. Page 50 of 7716 (average) 665 (cumulative) Courtaulds Coatings Lot CPBB002 Blue Paint 3.49 % DCOIT 49.8 (max) 17.3 (min) 28.5 (average) 1,157 (cumulative) Acceptable Sea

- Nine 211 45

- day study Courtaulds Coatings Lot CPBB004 Blue Paint 3.75 % DCOIT 10.9 (max) 6.8 (min) 8.6 (average) 376 (cumulative) Acceptable Sea

- Nine 211 45

- day study Courtaulds Coatings Lot CPBB006 Blue Paint 2.7 % DCOIT 44317710 5.2 (max) 0 (min) 1.8 (average) 92 (cumulative) Acceptable Sea

- Nine 211 45

- day study No

- Foul SN

- 1 White Paint 2 % DCOIT 44110102 46.8 (max) 13.5 (min) 23.4 (average) 949 (cumul ative) Acceptable Sea

- Nine 211 45

- day study Courtaulds Lot No. CPBB038 Blue Paint 2.98 % DCOIT 100.6 (max) 22.6 (min) 50.8 (average) 2,174 (cumulative) Acceptable Sea

- Nine 211 45

- day study Courtaulds Lot No. CPBB043 Blue Paint 1.96 % DCOIT 93.6 (max) 27.1 (min) 48(average) 1,977 (cumulative) Acceptable Sea

- Nine 211 45

- day study Courtaulds Lot No. CPBB031 Blue Paint for Fiberglass 2.82 % DCOIT 63.0 (max) 27.3 (min) 42.3 (average) 1,849 (cumulative) Acceptable Sea

- Nine 211 45

- day study Courtaulds Lot No. CPBB046

- 09 Clear Paint 3.69 % DCOIT 44627102 48.7 (max) 13.3 (min) 20.9 (average) 869 (cumulative) Acceptable Sea

- Nine 211 45

- day study Jotun Valspar 60A5000 Sea Victor 50 Red Paint 2.44 % DCOIT 45673201 20.8 (max) 6.0 (min) 10.4 (average) 449 (cum ulative) Acceptable Sea

- Nine 211 45

- day study Sigma Nexxium 20 Paint Reddish

- Brown Paint 3.43 % DCOIT 45578401 70.3 (max) 19.9 (min) 44.5 (average) 1,989 (cumulative) Acceptable Sea

- Nine 211 45

- day study No Foul SN

- 1 Black Antifouling Paint 3 % DCOIT 455 78402 75.6 (max) 20.6 (min) 49.2 (average) Acceptable Sea

- Nine 211 45

- day study No Foul SN

- 1 Blue Antifouling Paint

Page 51 of 772,250 (cumulative) 3 % DCOIT 45578201 15.7 (max) 6.8 (min) 10.4 (average) 455 (cumulative) Acceptable Sea

- Nine 211 45

- day study Hempel’s An tifouling Globic SP

- ECOI 81952

- 50300 Antifouling Paint Light Red 2 % DCOIT 45578204 21.6 (max) 8.7 (min) 13.7 (average) 566 (cumulative) Acceptable Sea

- Nine 211 45

- day study Hempel’s Antifouling Globic SP

- ECOI 81952

- 51110 Antifouling Paint Red 2 % DCOIT 45752201 19 (max) 3.5 (min) 9.0 (average) 347 (cumulative) Acceptable Sea

- Nine 211 45

- day study Sigmaplane Ecol HA 5294 Brown Antifouling Paint 2.4 % DCOIT 45752202 19.2 (max) 2.9 (min) 8.1 (average) 286 (cumulative) Acceptable Sea

- Nine 211 45

- day stud y Sigmaplane Ecol HA 5294 Green Antifouling Paint 2.4 % DCOIT 45752203 17.5 (max) 1.7 (min) 6.6 (average) 218 (cumulative) Acceptable Sea

- Nine 211 45

- day study Sigmaplane Ecol HA 5294 Blue Antifouling Paint 2.4 % DCOIT 45752204 24.8 (max) 4.7 (min) 1 0.6 (average) 378 (cumulative) Acceptable Sea

- Nine 211 45

- day study Sigmaplane Ecol HA 5294 Black Antifouling Paint 2.4 % DCOIT 44879701 14 (max) 1.7 (min) 5.3 (average) 207 (cumulative) Acceptable Sea

- Nine 211 45

- day study Reddish

- brown paint 2.5 % DCO IT 46088608 12.7 (max) 3.6 (min) 6.0 (average) 278 (cumulative) Acceptable Sea

- Nine TM21 45

- day study Sea Grand Prix CF

- 10 paint 3.66 % DCOIT 44753401 34.7 (max) 8.1 (min) 21.2 (average) 891 (cumulative) Acceptable Sea

- Nine 45

- day study Marine Antifou lant and Yacht Paint Formulation No. BOA 341 3.186 % DCOIT 36.5 (max) 15.2 (min) 21.2 (average) 915 (cumulative) Acceptable Sea

- Nine 45

- day study Marine Antifoulant and Yacht Paint Formulation No. BOA 344 3.108 % DCOIT 34.4 (max) 18.0 (min) 22.6 (ave rage) 979 (cumulative) Acceptable Sea

- Nine 45

- day study Marine Antifoulant and Yacht Paint Formulation No. BOA 347

Page 52 of 773.175 % DCOIT 20.8 (max) 11.8 (min) 14.7 (average) 640 (cumulative) Acceptable Sea

- Nine 45

- day study Marine Antifoulant and Yacht Paint Formulation No. XUU 781 2.147 % DCOIT 9.0 (max) 5.3 (min) 6.9 (average) 298 (cumulative) Acceptable Sea

- Nine 45

- day study Marine Antifoulant and Yacht Paint Formulation No. XUU 843 3.104 % DCOIT

Works Cited
MRID 00164507. Forbis, A.; Georgie, L.; B unch, B. (1985) Uptake, Depuration and Bioconcentration of [Carbon 14]

- RH

- 5287 by Bluegill Sunfish (Lepomis macrochirus): ABC Final Report #32970. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 256 p.

MRID 00164508. Leak, T. (19 86) Metabolite Characterization of RH

- 5287 in Bluegill Sunfish (Lepomis macrochirus): ABC Final Report #32971. Unpublished study prepared by Analytical Bio

- Chemistry Laboratories, Inc. 167 p.
MRID 00164668. Warren, J. (1986) Determination of Adsorption/De sorption Constants of C

9211/[Carbon 14]

- RH

- 5287: Report No. 32116: Amended Final Report. Unpublished Rohm and Haas's No. 310

- 86

- 31 prepared by Analytical Bio

- Chemistry Laboratories, Inc. 375 p

. MRID 41845001. Kesterson, A.; Lawrence, B.; Lawrence, L. (19 90) "Aqueous Photolysis of [Carbon 13/14] RH

- 5287 in Natural Sunlight": Photodegradation in Water: Lab Project Number: 292: 1303: 34

- 90

- 73. Unpublished study prepared by PTRL East, Inc. 110 p.

MRID 41845002. Kesterson, A.; Lawrence, B.; Lawrence, L. (1991 ) Anaerobic Aquatic Metabolism of [Carbon 13/14] RH

- 5287: Anaerobic Aquatic Metabol i sm Studies: Lab Project Number: 1313: 295: 34

- 91

- 06. Unpublished study prepared by PTRL East, Inc. 87 p.

MRID 41845003. Lawrence, L.; Lawrence, B.; Jackson, S.; et al. (19 91) Aerobic Aquatic Metabolism of [carbon 13/14] RH

- 5287: Final Report Re

- Issue: Lab Project Number: 1291: 294: 34

- 91

- 01. Unpublished Study prepared by PTRL East, Inc. 79 p.
MRID 41845004. Olson, G.; Lawrence, L. (1991) Soil Adsorption/Desorption of [Car b

- on 13/14] RH

- 5287 by the Batch Equilibrium Method: Mobility Studies Leaching and Adsorption/ Desorption Studies: Lab Project Number: 1246: 296: 34

- 90

- 28. Unpublished study prepared by PTRL East, Inc. 67 p.

MRID 41845005. Olson, G.; Lawrence, L. (1991) "Leaching of [Carbon 13/14] RH

- 5287 in Four Soil Types Following 30 Days or One Half

- life of Aerobic Aging in Sandy Loam Soil: Lab Project Number: 1296: 297: 34

- 90

- 6 7. Unpublished study prepared by PTRL East, Inc. 71 p.

Page 53 of 77MRID 41845006. Santangelo, M.; Ja cobson, A.; Derbyshire, R.; et al. (1991) Metabolism of RH

- 5287 in Bluegill Sunfish: Lab Project Number: 34

- 90

- 7 1. Unpublished study prepared by Rohm and Haas Co. 86 p.
MRID 42341101. Kesterson, A.; Atkins, R. (1992) Supplemental Study on the Anaerobic A quatic Metabolism of carbon 13/14| RH

- 5287: Lab Project Number: 295: 1313: 34

- 92

- 46. Unpublished study prepared by PTRL

- East, Inc. 27 p.
MRID 42341102. Kesterson, A.; Atkins, R. (1992) Supplemental Study on the Aerobic Aquatic Metabolism of carbon 13/14| R H

- 5287: Lab Project Number: 294: 1291: 34

- 92

- 13. Unpublished study prepared by PTRL

- East, Inc. 29 p.
MRID 42772801. Mazza, L. (1993) Supplemental Study on the Aqueous Photolysis of (carbon 14) RH

- 5287 in Natural Sunlight: Lab Project Number: 34

- 92

- 98. Unp ublished study prepared by Rohm and Haas Co. 116 p.
MRID 42772802. Mazza, L. (1993) Supplemental Study on the Aerobic Aquatic Metabolism of RH

- 5287: Lab Project Number: 34

- 93

- 31. Unpublished study prepared by Rohm and Haas Co. 85 p.

MRID 43468402. Anthon y, C. (1991) Leach Rate Determinations of Antifoulant Paint Containing RH

- 287: Data Acquired Using Draft Interim ASTM Test Method For Organotin Release Rates of Antifoulant Coating Systems in Sea Water: Lab Project Number: B

- 92

- 43. Unpublished study prepar ed by Case Consulting Labs, Inc. 56 p.
MRID 43768605. Marbo, M. (1995) Dynamic Leach Rate of RH

- 287 from Marine Anti f oulant (MAF) Paint (Hempel's Antifouling Combic Tin Free 7199E): Lab Project Number: BER000: TR

- 94

- 51: 29P

- 94

- 016. Unpublished study prepa red by Rohm and Haas Co. 154 p.
MRID 44066802. Marbo, M. (1995) Dynamic Leach Rate of RH

- 287 from Marine Anti f oulant (MAF) Paint: Lab Project Number: 24P

- 95

- 010: BNAR0R: TR

- 95

- 27. Unpublished study prepared by Rohm and Haas Co. 179 p.

MRID 44110102. Hitc hen, D. (1996) Dynamic Leach Rate of RH

- 287 from Marine Antifoulant (MAF) Paint: Lab Project Number: BNAR0M: TR

- 96

- 02: 24P

- 95

- 014. Unpublished study prepared by Rohm and Haas Co. 130 p.
MRID 44239501. Anthony, C. (1997) Leach Rate Determinations of Antifo ulant Paint Containing RH

- 287: Lab Project Number: 03779: B

- 92

- 43. Unpublished study prepared by Case Consulting Labs., Inc. 56 p.

MRID 44317710. Willis, C. (1997) Leach Rate Determination of No Foul SN

- 1 Antifoulant Paint Containing RH

- 287: Final Report: Lab Project Number: 1460

- 01: D 5108

- 90. Unpublished study prepared by Case Consulting Labs., Inc. 34 p.
MRID 44627102. Willis, C. (1997) Leach Rate Determination of Jotun Valspar 60A5000 Sea Victor 50 Anti f ouling Paint Containing RH

- 287: Lab Project Numb er: 920

- 04. Unpublished study prepared by Case Consulting Laboratories, Inc. 33 p.

Page 54 of 77MRI D 44753401. Patel, A. (1998) Release Rate Determination of Sea

- Nine 211 Active Ingredient (RH

- 287) from Marine Anti f oulant and Yacht Paints: Lab Project Number: BNAR0R: TR

- 98

- 082. Unpublished study prepared by Courtaulds Coatings Inc. 218 p.
MRID 44879701. Willis, C. (1997) Leach Rate Determination of an Antifouling Paint Containing RH

- 287: Lab Project Number: 920

- 03: 5108

- 90. Unpublished study prepared by Case Consultin g Labs., Inc. 40 p.
MRID 44791101. Reynolds, J. (1999) Aerobic Soil Metabolism of (carbon 14) RH

- 5287: Lab Project Number: XBL95001: RPT00433: 34P

- 94

- 70. Unpublished study prepared by XenoBiotics Laboratories, Inc. 289 p.
MRID 45578201. Sinning, D. 2001 . Leach Rate Determination of Hempel’s Antifouling Globic SP

- ECO 81952

- 50300 Paint Containing Sea Nine 211 TM Antifouling Agent. Unpublished study prepared by Case Consulting Laboratories, Inc. 11p.
MRID 45578204. Sinning, D. 2001. Leach Rate Determin ation of Hempel’s Antifouling Globic SP

- ECO 81952

- 51110 Paint Containing Sea Nine 211 TM Antifouling Agent. Unpublished study prepared by Case Consulting Laboratories, Inc. 23p.
MRID 45578401. Sinning, D. (2001) Leach Rate Determination of No Foul SN

- 1 B lack Antifouling Paint Containing Sea Nine 211 (RH

- 287) Antifouling Agent: Lab Project Number: 2140

- 05. Unpublished study prepared by Case Consulting Laboratories, Inc. 20 p.
MRID 45578402. Sinning, D. (2001) Leach Rate Determination of No Foul SN

- 1 Blue A ntifouling Paint Containing Sea Nine 211 (RH

- 287) Antifouling Agent: Lab Project Number: 2140

- 04. Unpublished study prepared by Case Consulting Laboratories, Inc. 20 p.
MRID 45673201. Sinning, D. (2002) Leach Rate Determination of Sigma Nexxium 20 Paint C ontaining Sea Nine 211 and AFO28 Antifoulings: Lab Project Number: 630

- 16. Unpublished study prepared by Case Consulting Laboratories, Inc. 34 p.
MRID 45752201. Sinning, D. 2002. Leach Rate Determination of Sigmaplane Ecol HA 5294 Brown Antifouling Pain t Containing Sea Nine TM (RH

- 287) Antifouling Agent. Unpublished study prepared by Case Consulting Laboratories, Inc. 22p.
MRID 45752202. Sinning, D. 2002. Leach Rate Determination of Sigmaplane Ecol HA 5294 Green Antifouling Paint Containing Sea Nine T M (RH

- 287) Antifouling Agent. Unpublished study prepared by Case Consulting Laboratories, Inc. 22p.
MRID 45752203. Sinning, D. 2002. Leach Rate Determination of Sigmaplane Ecol HA 5294 Blue Antifouling Paint Containing Sea Nine TM (RH

- 287) Antifouling Agent. Unpublished study prepared by Case Consulting Laboratories, Inc. 22p.

Page 55 of 77MRID 46088608. Sinning, D. (2003) Leach Rate Determination of Sea Nine TM21 1 Antifouling Agent and Zinc Omadine from Sea Grand Prix CF

- 10: Final Report. Project Number: 2750/0 3. Unpublished study prepared by Case Consulting Laboratories, Inc. 34 p.
MRID 46439601. Sinning, D. (2004) Leach Rate Study for Sea

- Nine 211. Project Number: 320/52. Unpublished study prepared by Case Consulting Laboratories, Inc. 22 p.

MRID 46780727. v an der Kolk, J. (2002) RH

- 287 Technical: Determination of the Effects on Soil Microflora Activity: Final Report. Project Number: 01RC/142, 1007/079/747. Unpublished study prepared by Springborn Laboratories (Europe) Ag. 74 p.

MRID 46780735. Swales, S. (20 02) (Carbon 14)

- RH

- 287 Technical: Activated Sludge Adsorption Isotherm: Final Report. Project Number: 616/30, 616/30/D2149, 02RC/0029. Unpublished study prepared by Covance Laboratories, Ltd. 88 p.
MRID 46780741. Seyfried, B. (2003) Ready Biodegradability of N

- (N

- Octyl) Malonamic Acid in a CO2 Evolution (Modified Sturm) Test. Project Number: 843969, 24P/2002/026, GLP/2003/033. Unpublished study prepared by RCC Umweltchemie Ag. 44 p.
MRID 46780742. Seyfried, B. (2003) Ready Biodegradability of N

- (N

- Octyl ) Acetamide in a CO2 Evolution (Modified Sturm) Test. Project Number: 843970, 24P/2002/027, GLP/2003/034. Unpublished study prepared by RCC Umweltchemie Ag. 44 p.
MRID 46780743. Seyfried, B. (2003) Ready Biodegradability of RH

- 25,287 in a CO2 Evolution (M odified Sturm) Test. Project Number: 847085, 24P/2003/009. Unpublished study prepared by RCC Umweltchemie Ag. 38 p.
MRID 46780744. Marbo, M. (2001) Hydrolysis of (Carbon 14)

- RH

- 5287 at pH 4,7, and 9, at 25 and 40(Degrees) C. Project Number: TR/01/012, 24P /99/011, TD2001/090. Unpublished study prepared by Rohm and Haas Co. 108 p.
MRID 46780750. Broughton, H. (2005) Leachates from RH

- 287 Treated Wood. Project Number: 24P/2005/043, GLP/2005/070, 226/519. Unpublished study prepared by BRE. 228 p.

MRID 46816 305. Ward, T.; Kowalski, P.; Boeri, R. (1997) Activated Sludge Respiration Inhibition Test w ith RH

- 287. Project Number: 96RC/0129, 1034/RH. Unpublished study prepared by T.R. Wilbury Laboratories, Inc. 47 p.

MRID 46816306. Millais, A. (2005) (Carbon 14)

- RH

- 5287: Degradability and Fate in the Water Sediment System. Project Number: 24P/2002/002, TR/05/93, RAS/262. Unpublished study prepared by Rohm and Haas Co. and Huntingdon Life Sciences, Ltd. 214 p.

MRID 46816307. Guo, I.; Jacobson, A.; Eisenschmied, M. (2004) Aerobic Transformation of RH

- 5287 in Surface Water. Project Number: 24P/2001/033, GLP/2004/26, 3969/08. Unpublished study prepared by Rohm and Haas Co. 192 p.

Page 56 of 77MRID 48168201. Ashmore, J. (2010) Determination of RH

- 287 Leached from Southern Pine Tre ated with Kathon 287WT According to AWPA E11

- 97 Test Protocol. Project Number: GLP/2010/020, AWPA/E11/97. Unpublished study prepared by Rohm and Haas Co. 20 p.

MRID 48236002. Jin, L. (2009) Kathon 287

- WT

- Soil Depletion Study in Accordance with American Wood Protection Association Standard E20. Project Number: ELP001. Unpublished study prepared by Viance, LLC. 20 p.

MRID 48414312. Doshi, D. (2011) Determination of DCOIT in Water Leached from Southern Pine Treated with Ecolife One

- Pack. Project Number: GL P/2011/011, 24P/2011/004. Unpublished study prepared by Dow Chemical Company. 12 p.
MRID 48424701. Laganella, D. (2011) Determination of Ecolife One

- Pack Leaching Using AWPA E11 for Active Ingredient 4,5

- Dichloro

- 2

- n

- Octyl

- 4

- Isothiazolin

- 3

- One (DCOIT, RH

287). Project Number: 24P/2011/004, 24P/2011/005, GLP/2011/018. Unpublished study prepared by Dow Chemical Company. 19 p.

Page 57 of 77

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Receptors

Birds, Acute and Subacute
For wood product uses, an acute oral toxicity study using the technical grade of the active ingredient (TGAI) is required to establish the toxicity of these chemicals to birds. The preferred test species is either mallard duck (a waterfowl) or northern bobwhite quail (an upland game bird). Several a vian acute toxicity studies were found in the a gency’s files for this chemical. Avian acute oral toxicity testing (850.2100/71

- 1), preferably using the bobwhite quail, is required to support the registration of this chemical.
Avian dietary toxicity st udies using the TGAI of these chemicals are not required for these uses. The results from the avian acute toxicity and dietary studies obtained from the a gency’s files are summarized in the table below (Table C 1 ).

Table C 1

Test and Organism Results LC 5 0 (mg/L) or LD 50 (mg/kg) Toxicity Category Comments Reference

Avian dietary LC 50 Bobwhite Quail ( Colinus virginianus ) >4,639

NOEC = 11,112 Practically non

toxic Core study Pedersen & Helsten. 1992

MRID#

- 42214901

Avian dietary LC 50 Mallard Duck ( A nas platyrhynchos ) >4.369

NOEC = 529 Practically non

toxic Core study Pedersen & Helsten. 1992

MRID#

- 42214902

Eight

– day avian dietary LC 50 Mallard Duck ( Anas pl

atyrhyncho s ) >10,000 Practically non

toxic Core Study Fink, R. 1976

ACC.#

- 249935

Acute oral LD 50 Mallard Duck ( Anas platyrhynchos ) >2,784 Practically non

toxic Core Study Fink, R. 1976

ACC#

- 249935

Page 58 of 77The results of the dietary avian studies indicate that Kathon is practically non

- toxic to both mallard duck and bobwhite quail. In the a cute oral study, the chemical was found to be practically non

- toxic to mallard duck. All of these studies were considered to be core and met guideline requirements at the time they were submitted to the a gency.

Mammals
A wild mammal test is not required by the a gency. Mammalian toxicity values obtained from studies conducted to support data requirements for human health risk assessments substitute fo r wild mammal testing. In subchronic toxicity testing RH

- 287 was administered to beagles in the diet for 13 weeks. No treatment

– related effects were observed on survival, clinical or neurobehavioral findings, ophthalmology , physical examinations, organ w eights or macroscopic pathology in either sex at < 1500 ppm (Serota, D.G. 2002: MRID# 45747201)
A summary of mammalian toxicity of Kathon is presented in the “Evaluation of Toxicity Database for Registration Eligibility Decision Document Disciplinary Chapter”. 

## Toxicity to Aquatic Receptors

Freshwater Fish, Acute
Freshwater fish toxicity studies using the TGAI are required to establish the toxicity of chemicals to fish. Data are generally required for only one species. Testing in two fish spec ies is required for stable chemicals with high volume effluents (e.g., including, but not limited to, egg washing, fruit and vegetable rinses, swimming pools or materials preservatives) and if the LC 50 in the first species is greater than (>) 1 ppm. The p referred test species are rainbow trout (a coldwater fish) and bluegill sunfish (a warmwater fish), although other test species identified in the OPPTS Guideline (i.e., OPPTS 850.1075 (e)(4)(i)(A)) may also be used. Several freshwater fish acute toxicity studies were identified from peer

- reviewed literature (Table C 2 ). Several freshwater fish acute toxicity studies were found in the Agency’s files (Table C 3 ). Freshwater fish acute toxicity testing (850.1075/72

- 1) on both species, the rainbow trout and bl uegill sunfish, are required to support the registration of this chemical.
The results from freshwater fish acute toxicity studies obtained from the Agency’s files are summarized in the table below (Table C 2 ).

Page 59 of 77Table C 2

Test and Organism Results LC 50 (ug a.i./L) Toxicity Category Comments Reference

Acute 96

- hr toxicity to Rainbow Trout determined under static conditions ( Oncorhynchus mykiss) 25 mg ai/L Slightly toxic Supplemental Study

(Test chemical is Acetamide) Rhodes, J.E., 2002

MRID#

- 467807

- 32

Acute 96

- hour Freshwater Fish Toxicity Bluegill Sunfish ( Lepomis macrochirus ) 1.4 Very Highly toxic Core Study 1991

MRID#

- 41465801

Acute 96

- hour Freshwater Fish Toxicity Rainbow Trout ( Oncorhynchus mykiss ) 2.7 Ver y Highly toxic Core Study 1991

MIRD#

- 41465802

Acute Toxicity LC 50 Bluegill Sunfish ( Lepomis macrochirus ) 22 Very Highly toxic Supplemental Study Buccafusco, R.J. 1977

ACC.#

- 249935

Acute Toxicity LC 50 Bluegill Sunfish ( Lepomis macrochirus ) 29 Very Hi ghly toxic Supplemental Study Buccafusco, R.J. 1976

ACC.#

- 249935

Acute Toxicity LC 50 Sheepshead minnow 22 Very Highly toxic Core Study Heitmuller, T. 1983

Page 60 of 77( Cyprindon variegates ) ACC.#

- 249935

Acute Toxicity LC 50 Rainbow Trout ( Salmo gairdneri ) 10 Ve ry Highly toxic Supplemental Study Buccafusco, R.J. 1977

ACC.#

- 249935

Acute Toxicity 96

- hr LC 50 Rainbow Trout ( Oncorhynchus mykiss) 9.7 Very Highly toxic Supplemental Study Buccafusco, R.J. 1976

ACC.#

- 249935

As shown in Table C 2 , the toxicity ranged from 1.4 to 29 ppb, which indicated that this chemical was very highly toxic to fish.

Freshwater or Estuarine/Marine Fish, Chronic
Fish early life stage toxicity test using the TGAI is required to establish the chronic toxicity o f a pesticide to fish. The preferred test species is the most sensitive species

– freshwater or estuarine/marine. A fish early

- life stage study testing the TGAI and using the most sensitive species, either freshwater or estuarine/marine is required for t he registration of this chemical (850.1300/850.1400/72

- 4). Two studies were found in the a gency’s files (See Table C 3 )

.
Table C 3

Test and Organism Results Toxicity Category Comments Reference

Marine Fish Early Life Stage Toxicity Test Sheepshead Minno w ( Cyprinodon variegates ) NOEC = 2.9 ug a.i./L
LOEC = 6.0 ug a.i./L for percent hatch Supplemental Study Ward, T.J. & Boeri, R.L. 1990 MRID#

- 41741504

Freshwater Fish Early Life Stage Toxicity Test Rainbow Trout 61 days post

hatc h (growth)

NOEC = 0.56 ug a.i./L Core Study Rhodes, J.E. 2003

MRID#

- 45865201

Page 61 of 77( Oncorhynchus mykiss ) LOEC = 1.2 ug a.i./L

MATC = 0.82 ug a.i./L

As shown in table 3, the NOEC for marine fish was 2.9 ug a.i./L and for freshwater fish the NOEC was 0.56 ug a.i./L. The Agency re

- examined the sheepshead minnow study and determined that the study would remain classified as supplemental, but would not need to be repeated by the registrant. The NOEC was revised to a lower number (2.9 instead of 6.0 ug a.i./L) and can be used in a risk assessment of this chemical. The rainbow trout study was core and the results can be used in a risk assessment.

Freshwater Invertebrates, Acute
A freshwater aquatic invertebrate toxicity test using the TGAI is required to establish the toxic ity of a pesticide to aquatic invertebrates. The preferred test species is Daphnia magna or Daphnia pulex. Several studies testing these organisms were found in the a genc y’ s files (Table C 4 ). Freshwater invertebrate acute toxicity testing (850.1010/72

- 2) is required for the registration of this chemical

.
Table C 4

Test and Organism Results Toxicity Category Comments Reference

Acute toxicity to the water flea determined under static conditions, Daphni a magna 48

- hr EC50 = 28 mg ai/L

48

- hr NOEC = 9.5 mg ai/L Slightly toxic Core Study (Test chemical is Acetamide) Rhodes, J.E. 2002

MRID#

- 467807

- 33

Acute toxicity to the water flea under static conditions, Daphnia
magna 24

- hr EC50 = >282 mg ai/L

48

- hr EC50 = 157 mg ai/L

48

- hr NOEC = 69 mg ai/L Practically nontoxic Supplemental Study

(Test chemical is Malonamic Acid) Hahne, R. 2002

MRID#

- 467807

- 31

Page 62 of 77Freshwater invertebrate flow

- thru toxicity Daphnia
magna 48

- hr. EC 50 = 5.2 ug a.i./l Very highly toxic Core Study 1992

MRID#

- 41741501

Freshwater Invertebrate Static Acute Toxicity Daphnia
magna 48

- hr. LC 50 = 8 ug a.i./l Very highly toxic Core Study Buccafusco, R.J. 1977

ACC.#

- 249935

Freshwater Invertebrate Static Acute Toxicity Daphnia
magna 48

- hr. LC 50 = 9.2 ug a.i./L Very highly toxic Core Study Buccafusco, R.L. 1976

ACC.#

- 249935

As shown in Table C 4 , this chemical is very highly toxic to aquatic invertebrates.

F reshwater and Marine Invertebrates, Chronic
Chronic aquatic invertebrate testin g (OPPTS 850.1350) is conditionally required for the currently registered wood preservative use of this chemical. Two studies were found in the a gency’s files (Table C 5 ).

Table C 5

Test and Organism Results Toxicity Category Comments Reference

Chronic Tox icity in Whole Sediment to the Freshwater Midge ( Chironomus riparius) 10

- day survival LC50 or EC50 = 13 mg/kg dry sediment, NOEC = 4.9 mg/kg dry sediment

10

- day dry weight LC50 or EC50 = >14 mg/kg dry sediment, NOEC = 14 Slightly toxic Core Study Aufderheide, J 2003

MRID#

- 468163

- 04

Page 63 of 77mg/kg dry sediment

% adult emergen ce LC50 or EC50 = 22 mg/kg dry sediment, NOEC = 9.7 mg/kg dry sediment

Whole Sediment Chronic Toxicity Test Marine Invertebrate ( Ampelisca abdita ) LC 50 = 320 (mg ai/kg dry sediment)

NOEL 6. 9 mg/kg Practically non

toxic Supplemental Study Putt, A.E. 1994

MRID#

- 44755903

Flow

- Thru Chronic Toxicity
Mysid ( Americamysis bahia ) 28

- day LC 50 = >2.5 ug/L

LOEC = 1.24 ug/L

NOEC = 0.627 ug/L

MATC = 0.882 ug/L None given Core study Ward, T.J. & Boeri, R.L. 2000

MRID#

- 45153101

Chronic Toxicity in Whole Sediment to the Marine Amphipod ( Leptocheirus plumulosus) 28

- day LC 50 = >78 ug/kg dry sediment LOEC = 19 mg/kg

NOEC = 10 mg/kg

MATC = 14 mg/kg Slightly toxic Supplemental study Jones, A. and Auf derheide, J. 2003

MRID#

- 467807

- 36

Page 64 of 77Chronic Toxicity in Whole Sediment to the Marine Polychaete ( Neanthes arenaceodentata ) 28 day LC 50 = >69 mg/kg dry sediment

LOEL = >69 mg/kg

NOEC = 69 mg/kg Slightly toxic Invalid study Hughes, C. and Aufderheide, J. 2003

MRID#

- 467807

- 38

The results of the above study indicate that Kathon is practically non

- toxic to a marine invertebrate in a whole sediment chronic toxicity test. The test was considered s upplemental. This chemical was chronically toxic in ppb to t he mysid.

E stuarine and Marine Organisms
Acute toxicity testing with estuarine and marine organisms using the TGAI (850.1026/850.1035/850.1045/850.1075/72.3) is conditionally required for the registration of
this chemical. Acute LC 50 testing with an es tuarine/marine fish, mollusk and shrimp species is required for the registration of this chemical. Several studies on marine/estuarine invertebrates were found i n the a gency’s files (Table C 6 ).

Table C 6

Test and Organism Results Toxicity Category Comments Reference

Acute toxicity in whole sediment to the marine amphipod ( Leptocherirus plumulosus) 10

- day LC50 = 95.4 mg/kg dry sediment

NOEC (survival) = 64.8 mg/kg dry sediment

LOEC (survival) = 133 mg/kg dry sediment Slightly toxic Supplemental Study Au fderheide, J.A. 2002

MRID#

- 467807

- 40

Acute Static Estuarine/Marine Invertebrate Toxicity, Mysid Shrimp 96

- hr. LC 50 = 4.7 ug a.i./L Very highly toxic Core Study 1992

MRID#

- 41741503

Page 65 of 77( Mysidopsis bahia )

Acute Static Estuarine/Marine Mollusk Toxicity, Eastern Oyster ( Crassostrea virginica ) 48

- hour EC 50 = 24 ug a.i./L

(in natural seawater) Very highly toxic Supplemental study 1992

MRID#

- 41756801

Acute Flow

- thru Estuarine/Marine Fish Toxicity, Sheepshead Minnow ( Cyprinodon variegates ) 96

- hr. LC 50 = 20.5 ug a.i./L Very highly toxic Core Study 1992

MRID#

- 41741502

Acute Toxicity Embryos

- larvae of Bay Mussels ( Mytilus edulis ) 48

- hr. EC 50 = 1.9 ug a.i./L Very highly toxic Supplemental Study Hollister, T. 1979

ACC.#

- 249935

Acute Toxicity to Bay M ussels ( Mytilus edulis ) 96

- hr. LC 50 = 850 ug a.i./L Very highly toxic Supplemental Study Heitmuller, T. 1979 ACC.#

- 249935

Acute Toxicity Fiddler Crabs ( Uca pugilator ) 96

- hour EC 50 = 1.7 mg a.i./L Moderately toxic Supplemental Study Heitmuller, T. 197 7 ACC.#

- 249935

Acute Toxicity Brown Shrimp ( Penaeus aztecus ) 96

- hour LC 50 = 16 ug a.i./L Very highly toxic Core Study Heitmuller, T. 1977 ACC.#

- 249935

Acute Toxicity Embryos of Eastern Oysters ( Crassostrea virginica ) 48

- hour EC 50 = 9 ug a.i./L Very h ighly toxic Core Study Hollister, T. 1977 ACC.#

- 249935

Bivalve Acute Toxicity Test (Embryo

- Larval) with the Bay 48

- hr EC 50 = 0.411 mg ai/L Very highly toxic Invalid study Boeri, R.L., Wyskiel, D.C. and Ward, T.J.

Page 66 of 77Mussel ( Mytilus edulis) 2001 MRID 467 807

- 29

As shown in Table C 6 , this chemical is very highly toxic to mysid shrimp, eastern oyster, sheepshead minnow, bay mussel, fiddler crab and brown shrimp.

Toxicity to Plants
Terrestrial and aquatic plant testing is required for the registration of th is chemical. Several terrestrial and aquatic plant toxicity studies on this chemical were found in the a gency’s files (Table C 7 ).

Table C 7

Test and Organism Results Toxicity Category Comments Reference

Toxicity to the Saltwater Diatom ( Skeletonema
costat um) 96

- hr EC50 = 0.19 mg ai/L

NOEC = 0.13 mg ai/L Not used for plant studies Supplemental Study

(Test chemical is Malonamic Acid) Hahne, R. 2002

MRID#

- 468163

- 10

96

- hr. Toxicity Test with the Unicellular Green alga (Selenastrum capricornutum) 96

- hr EC5 0 = 9.7 mg ai/L

NOEC = 5.9 mg ai/L Not used for plant studies Core Study Rhodes, J.E. 2002

MRID#

- 467807

- 34

96

- hr. Toxicity Test Blue

Green Alga ( Anabaena flos

- aquae ) EC 50 = 0.0058 mg a.i./kg

NOEC = 0.0028 ug a.i./kg Not used for plant studies Core St udy Hughes, C. 2002

MRID#

- 45865202

Toxicity to the unicellular green alga ( Selenastrum capricornum) 96

- hr EC50 = 6.64 mg ai/L 96

- hr NOEC = 1.82 mg ai/L Not used for plant studies Core Study

(Test chemical is Malonamic Acid) Hahne, R. 2001 MRID#

- 46 7807

- 30

Page 67 of 7796

- hr Toxicity Test with Unicellular Green Alga ( Selenastrum capricornutum ) 96

- hour EC 50 = 0.047 mg a.i./kg

NOEC = 0.0078 mg a.i./kg Not used for plant studies Core Study Hughes, C. 2002

MRID#

- 45862503

Effects of Seedling Emergence and Growth , canola ( Brassica napus ), red clover ( Trifolium pretense ), rice ( Oryza sativa ) Red clover
EC 25 = 8.4 mg a.i./l = kg

NOEC = 5.0 mg a.i./kg

Canola

EC 25 = 13.0 mg a.i./kg

NOEC = 5.0 mg a.i./kg

Rice

EC 25 = 11.0 mg a.i./kg
NOEC = 10 mg a.i./kg Not used for pla nt studies Core Study Teixeira, D. 2002

MRID#

- 45870601

Effects of Vegetative Vigor, canola ( Brassica nupus ), red clover ( Trifolium prantense ), rice ( Oryza sativa ) Red clover

EC 25 = 0.94 mg a.i./kg

NOEC = 0.12 mg a.i./kg

Rice

EC 25 = 4.7 mg a.i./kg

NOEC = 0.64 mg a.i./kg None given Core study Teixeira, D. 2002

MRID#

- 45905001

Page 68 of 77Canola

EC 25 = 3.7 mg a.i./kg

NOEC = 2.6 mg a.i./kg

Toxicity to Duckweed ( Lemna gibba ) static conditions Frond # EC 50 = 0.166 mg a.i./kg

NOEC = 0.0118 mg a.i./kg Not used for plant studies Core study Rhodes, J.E. 2002

MRID#

- 45865204

Toxicity to marine alga ( Skeletonema
costatum ) 96

- hour EC 50 (decrease in chlorophyll) = 26 ppb

96

- hour EC 50 (decrease in cell numbers) = 18 ppb Not used for plant studies Supplemental study Hollister , T.A. 1977

ACC.#

- 249935

As shown in Table C 7 , Kathon was toxic to freshwater alga at microgram concentrations.

REFERENCES
ACC # 249935: Buccafusco, R.J. (1976) Acute toxicity of RH

- 287 to bluegill, rainbow trout, and the water flea. Fish 96

- ho ur LC50 (Bluegill). EG&G, Bionomics

. ACC # 249935: Buccafusco, R.J. (1976) Acute toxicity of RH

- 287 to bluegill, rainbow trout, and the water flea. Aquatic invertebrate 48

- hour LC50. EG&G, Bionomics

. ACC # 249935: Buccafusco, R.J. (1976) Acute toxicit y of RH

- 287 to bluegill, rainbow trout and the water flea. Fish 96

- hour LC50 (Rainbow Trout). EG&G, Bionomics

. ACC# 249935: Buccafusco, R.J. (1977) Acute toxicity of C

- 9211 Technical to bluegill, rainbow trout and the water flea. Aquatic invertebrate 4 8

- hour LC50. EG&G, Bionomics

. ACC# 229935: Buccafusco, R.J. (1977) Acute toxicity of C

- 9211 to bluegill, rainbow trout, and the water flea. Fish 96

- hour LC50 (Rainbow Trout). EG&G, Bionomics

.

Page 69 of 77ACC # 249935: Buccafusco, R.J. (1977) Acute toxicity of C

- 9211 Technical to bluegill, rainbow trout and the water flea. Fish 96

- hour LC50 (bluegill). EG&G, Bionomics

. ACC# 249935: Fink, R. (1976) Acute oral LD50

– Mallard Duck. Project No. 129

- 112. Wildlife International, Ltd.

ACC# 249935: Fink, R. (1976) E ight

- day dietary LC 50

– Mallard Duck. Project No. 192

- 110. Wildlife International, Ltd.
ACC# 249935: Heitmuller, T. (1977) Acute toxicity of C

- 9211 to brown shrimp ( Penaeus aztecus ). EG&G, Bionomics

. ACC# 249935: Heimuller, T. (1977) Acute toxicity of C

- 9211 to fiddler crabs ( Uca pugilator )

. EG&G, Bionomics

. ACC# 249935: Heimuller, T. (1977) Acute toxicity of C

- 9211 to sheepshead minnows ( Cyprinodon variegates ). EG&G, Bionomics

. ACC#s 249935: Heimuller, T. (1979) Acute Toxicity of Biocide C

- 9211 to bay mussels ( Mytilus edulis) . EG&G, Bionomics

. ACC# 249935: Hollister, T (1977) Acute toxicity of C

- 9211 to embryos of eastern oysters ( Crassostrea virginica ). EG&G, Bionomics

. ACC# 249935: Hollister, T. (1979) Acute toxicity of biocide C

- 9 211 to embryos

- larvae of bay mussels ( Mytilus edulis ). EG&G, Bionomics

. ACC# 249935: Hollister, T.A. (1977) Toxicity of C

- 9211 to the marine alga Skeletonema
costatum. EG&G, Bionomics

.
MRID# 414658

- 01: (1991) Acute 96

- hour freshwater fish toxicity, blue gill sunfish ( Lepomis macrochirus )

.
MRID# 414658

- 02: (1991) Acute 96

- hour freshwater fish toxicity, rainbow trout ( Oncorhynchus myiss )

.
MRID# 417415

- 01: (1992) Freshwater invertebrate flow

- thru toxicity to Daphnia magna. EnviroSystems Division, Resou rce Analysts, Inc.

MRID# 417415

- 02: (1992) Acute flow

- thru estuarine/marine fish toxicity, sheepshead minnow ( Cyprinodon variegates ). EnviroSystems D ivision , Resource Analysts, Inc.

MRID# 417415

- 03: (1992) Acute Static estuarine/marine invertebrate tox icity, mysid shrimp ( Mysidopsis bahia). EnviroSystems Division, Resource Analysts, Inc.

MRID# 417415

- 04: Ward, T.J. and Boeri, R.L. (1990). Early life stage toxicity of RH

- 287 to the sheepshead minnow, Cyprinodon variegates . EviroSystems Division, Reso urce Analysts, Inc.

Page 70 of 77MRID# 417568

- 01: (1992). Acute Static estuarine/marine mollusk toxicity, eastern oyster ( Crassostrea virginica ).

MRID# 422149

- 1: Pedersen, C.A. and Helsten, B.R. (1992). RH

- 287 Technical: 8

- day acute dietary LC50 study in bobwhit e quail. Laboratory study ID. BLAL No. 111

- 001

- 01. Bio

- Life Associates, Ltd.

MRID# 422149

- 02: Pedersen, C.A. and Helsten, B.R. (1992). RH

- 287 Technical: 8

- day acute dietary LC50 study in mallard ducklings. Laboratory study ID. BLAL No. 111

- 002

- 02. Bi o

- Life Associates, Ltd.

MRID# 447559

- 03: Putt, A.E. (1994). RH

- 287 Technical

– acute toxicity to amphipods ( Ampelisca abdita ) during a 10

- day sediment exposure under static conditions. Springborn laboratories, Inc.

MRID# 451531

- 01: Ward, T.J., and Bo eri, R.L. (2000). RH

- 287: Flow

- through chronic toxicity to the mysid, Americamysis bahia. T.R. Wilbury Laboratories, Inc.

MRID# 458652

- 01: Rhodes, J.E. (2003). Early life

- stage Toxicity of RH

- 287 Technical to the rainbow trout ( Oncorhynchus mykiss ) . Stu dy No. 46578. ABC Laboratories, Inc.

MRID# 458652

- 02: Hughes, C. (2002). Toxicity of RH

- 287 Technical to the blue

- green alga Anabaena flos

- aquae . ABC Laboratories, Inc.

MRID# 458652

- 03: Hughes, C. (2002). Toxicity of RH

- 287 Technical to the unicell ular green alga, Selenastrum capricornutum. ABC Laboratories, Inc.

MRID# 458652

- 04: Rhodes, J.E. (2002). Toxicity of RH

- 287 Technical to Duckweed ( Lemna gibba ) G3, determined under static test conditions. ABC Laboratories, Inc.

MRID# 458706

- 01: Teix eira, D. (2002). RH

- 287 Technical

– Determination of effects on vegetative vigor of three plant species. Springborn Smithers Laboratories.

MRID# 458706

- 02: Teixeira, D. (2002). TH

- 287 Technical

– Determination of effects on seedling emergence and seedlin g growth of three plant species. Springborn Smithers Laboratories.

MRID# 467807

- 29: Boeri, R.L., Wyskiel, D.C. and Ward, T.J. (2001). RRH

- 287 Technical: Bivalve Acute Toxicity Test (Embryo

- Larval) with the Bay Mussel, Mytilus edulis . T.R. Wilbury La boratories, Inc.

MRID# 467807

- 30: Hahne, R. (2001). Toxicity of N

- (n

- ocyl) Malonamic Acid, PMN to the Unicellular Green Alga, Selenastrum capricornutum . ABC Laboratories, Inc.

MRID# 467807

- 31: Hahne, R. (2002). Acute toxicity of N

- (n

- ocyl) Ma lonamic Acid, Technical, PMN, to the water flea, Daphnia magna, under static conditions. ABC Laboratories, Inc.

Page 71 of 77MRID# 467807

- 32: Rhodes, J.E. (2002). Acute toxicity of N

- (n

- ocyl) Acetamide t the Rainbow Trout, Oncorhynchus mykiss , determined under sta tic conditions. ABC Laboratories, Inc.

MRID# 467807

- 33: Rhodes, J.E. (2002). Acute toxicity of N

- (n

- ocyl) Acetamide to the water flea, Daphnia magna , determined under static test conditions. ABC Laboratories, Inc.

MRID# 467807

- 34: Rhodes, J.E. (20 02). Toxicity of N

- (n

- ocyl) Acetamide to the Unicellular green alga, Selenastrum capricornutum
, ABC Laboratories, Inc.

MRID# 467807

- 36: Jones, A. and Aufderheide, J. (2003). RH

- 287 Technical: Chronic Toxicity in Whole Sediment to the Marine Amphipod, L eptocherirus plumulosus . ABC Laboratories, Inc.

MRID# 467807

- 38: Hughes, C. and Aufderheide, J. (2003). RH

- 287 Technical: Chronic Toxicity I Whole Sediment to the Marine Polychaete, Neanthes arenaceodentata . ABC Laboratories, Inc.

MRID# 467807

- 40 : Aufderheide, J.A. (2002). Acute toxicity of RH

- 287 Technical in whole sediment to the marine amphipod ( Leptocheirus plumulosus) . ABC Laboratories, Inc.

MRID# 468163

- 04: Aufderheide, J. (2003). RH

- 287 Technical: Chronic toxicity in whole sediment t o the freshwater midge, Chironomus riparius . ABC Laboratories, Inc.

MRID# 468163

- 10: Hahne, R. (2002). Toxicity of N

- (n

- ocyl) Malonamic Acid, Technical, PMN to the saltwater diatom, Skeletonema costatum . ABC Laboratories, Inc.

Page 72 of 77

# Appendix D Screening Level Down

- the

- Drain Analysis

The Down

- the

- Drain (DtD) module of E

- FAST (Exposure and Fate Assessment Screening Tool), [version 2] was used to screen for the potential for aquatic organisms downstream of domestic wastewater treatment plants to be exposed to DCOIT and its degradates. The Down

- the

- Drain module uses daily per capita release of household wastewaters, stream dilution factors, and wastewater treatment plant removal efficiency to provide both high

- end and median (average) time

- averaged surface wa ter concentrations of chemicals discharged by domestic wastewater treatment plants. The high

- end scenario uses surface water concentrations downstream of domestic wastewater treatment plants based on the 10th percentile stream dilution factor (SDF); the a verage scenario uses surface water concentrations based on the 50th percentile SDF. SDF is defined as the ratio of the stream flow downstream of a wastewater treatment plant to the wastewater treatment plant flow. Inputs used to run the DtD module includ ed concentrations of concern (COCs) for aquatic organisms, percent removal during wastewater treatment, and hypothetical wastewater treatment plant influent volumes. The results of the DtD module are expressed as number of days of exceedance of COCs for aq uatic organisms. COCs are grouped into 3 categories: acute, endangered/listed, and chronic. Acute COCs for freshwater fish and invertebrates were derived by dividing LC 50 values for freshwater organisms by 2. Endangered/listed COCs for freshwater fish an d invertebrates were derived by dividing LC50 values by 20. EC 50 values for plants were used to establish acute COCs for plants. NOAEC values for plants were used to establish endangered/listed COCs for plants. Chronic COCs for freshwater fish and inver tebrates are based on NOAEC values. For acute and endangered listed COCs, there may be potential concern for freshwater organisms if the COC is exceeded for 1 day or more. For chronic COCs, there may be potential concern for freshwater organisms if the C OC is exceeded 20 days or more.

The Down

- the

- Drain module was first run using a high

- end scenario to determine whether the model predicted exceedances of concentrations of concern. The average

– case scenario was run when exceedences were observed with the h igh end scenario results.

Page 73 of 77

# Appendix E Product Chemistry

3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

- product chemistry informat ion is summarized in Table E1 (S ource: MRIDs 40808501, and 41351601 ).

Table E1

– Product Chemistry of Octhilinone

Guideline No. Ph ysical and Chemical Properties 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

830.1550 Product identity and composition Refer to Table 3

. 830.1600 Description of materials used to produce the product Confidential Business Information (CBI)

830.1620 Description of production process CBI

830.1650 Description of Formulation Process CBI

830.1670 Discussion of Formation of Impurities CBI

830.1700 Preliminary analysis CBI 830.1750 Certified limits CBI

830.1800 En forcement analytical method GC/MS

830.1900 Submittal of samples CBI 830.6302 Color tan to brown 830.6303 Physical State waxy solid 830.6304 Odor pungent aromatic

830.6313 Stability to normal and elevated temperature, metals/metal ions Acceler ated the rm al stability testing of RH

- 287 Technical (55°C

- 3 months) showed no evidence of decomposition of RH

- 25,287 or appearance of new impurities. By

- products RH

- 27,610 and RH

- 34,227 gradually decomposed to give unknown non

- volatile products and < 0.05

w t

. % HCL. 830.6314 Oxidation/Reduction None 830.6315 Flammability Not applicable 830.6316 Explodability Not applicable

830.6320 Corrosion Characteristic RH

- 287 Technical is corrosive to steel and stainless steel. It is stored in fluorinated high

- densit y polyethylene containers or glass containers. 830.7000 pH Not applicable 830.7050 UV/Visible Absorption Not reported 830.7100 Viscosity Not applicable 830.7200 Melting point 40

- 41 C 830.7220 Boiling point not applicable 830.7300 Density 1.28 g/ml at 25C (melted and solidified) 830.7370 Dissociation Constant Not applicable

830.7550 Partition coefficient ( n

octanol/water) 2.8

830.7840 Solubility in water 14 ppm

830.7860 Solubility in organic solvents Acetone 40% Ethanol 35%

Page 74 of 77Guideline No. Ph ysical and Chemical Properties 3(2H)

- isothiazolone, 4,5

- dichloro

- 2

- octyl

Cellosol ve

- 40% 830.7950 Vapor pressure 4.5 x 10

- 6 mm Hg

Page 75 of 77

# Appendix F Public Comments Received on the Pr eliminary Work Plan

During the public comment period following posting of the Preliminary Work Plan to the docket
, t he agency received comments from the FIFRA Enda ngered Species Task Force (FE STF) and Dow Chemical Company. The following comments or requests were made.

Comment 1 (FESTF) : The FESTF has noted that 3(2H)

- Isothiazolo ne, 4.5

- dichloro

- 2

- octyl (DCOIT) h as not had a complete endangered species determination performed to allow the agency to determine whether the uses have “no effect” or “may effect” federally listed species or their designated critical habitats. At such time as an endangered species evaluation is conducted by EPA, the data developed by FESTF , in response to the agency’s endangered species data requirements, will address species proximity to 3(2H)

- Isothiazolone, 4,5

- dichloro

- 2

- octyl (DCOIT) uses.

EPA response: The agency will review the information submitted by the FESTF as part of the regist ration review process.
Comment 1 (Dow Chemical Company): The Application Rates (listed in Table 5) are not representative of the maximum use rates which appear on all of the EPA approved labels for DCOIT containing products.

EPA response 1 : The values wer e corrected in Table 5.
Comment 2: The Application Rates (listed in Table 5) for the use of DCOIT in Architectural Paints and Marine Antifoulant Paints vary such that we suggest these be sp l it into two separate entries.

EPA r esponse 2 : Table 5 has been updated to reflect two entries for the two paints.

Comment 3: The Resid ential Handler Exposure Scenario (listed in Table 9) for the use of DCOIT in do

- it

- yourself antifoulant paints should be removed as DCOIT is only approved for use in paints solely fo r commercial applications.

EPA response 3: EPA confirmed that labels require antifoulant paint applications to be made by commercial applicators and are not expected to be used by residential users. The do

- it

- yourself antifoulant paints use scenario has been removed. The term “latex” has been added in section 3.3.2 Residential Handler Exposure to “for the application of treated ‘ latex ’ paints and stains

. ” This scenario will have a n exposure assessment done.

Page 76 of 77Comment 4: EPA is required to evaluate all uses as part of regis tration review. Review of the wood preservative uses of DCOIT is premature and unnecessary.
EPA Response 4: The agency is expecting a wood pressure treatment study from the Antimicrobial Exposure Assessment Task Force ( AEATF )

. Upon receipt, the agency wi ll assess all uses of DCOIT in registration review.
Comment 5: The request for additional toxicity studies is not warranted given the wealth of information available for the isothiazolinone family of preservatives.
EPA response 5: DCOIT is one active ing redient in the isothiazolinone group. EPA encourages the submission of existing data and/or bridging rationale that a company believes satisfy the data needs identified.
Comment 6: DCOIT should be regulated as an irritant.

Comment 7: The choice of un certainty factors is not appropriate given the MOA of the isothizolinones.

C omment 8: The choice of NOAEL is overly conservative in some instances.

Comment 9: Systemic NOAELs cannot be derived from isothiazolinones.

Comment 10 : Rejection of guideline studies despite justified modification is not acceptable.

EPA response s 6, 7, 8, 9 and 10 : DCOIT toxicity concerns mentioned in comments 6

- 10 above will be presented to the agency’s toxicity science advisory committee (TOXSAC) in the near future. Appropr iate toxicological endpoints will be selected as part of risk assessments planned for this registration review.

Page 77 of 77