### Page 2 of 66 Sodium and Potassium Dimethyldithiocarba mate Salts Registration Review Team

Human Health Timothy Dole
Zoe Cavinder
Don Wilbur
Steve Malish

Environmental Fate and Effects James Breithaupt
William Erickson Siroos Mostaghimi

Risk Management
Sandra O’Neill
James Parker

Office of General Counsel Philip Ross

### Page 3 of 66 ABBREVIATIONS AND SYMBOLS

AD Antimicrobials Division A.I. or a.i. active ingredient aPAD acute population adjusted dose ASRI activated sludge respiration inhibition

atm-m 3 

### /mole atmospheric pressure-cubic meter per mole
BCF bioconcentration factor °C degrees Celsius
CaSO 4 

### calcium sulfate
CaSO 3 

### calcium sulfite
CAS Chemical Abstracts Service CFR Code of Federal Regulations CHO Chinese hamster ovary
CMA Chemical Manufacturers Association
CO 2 

### carbon dioxide
COC concentration-of-concern cPAD chronic population adjusted dose
CS 2 

### carbon disulfide
DCI data call-in
DEA diethanol amine DMA dimethylamine DDC dimethyldithiocarbamate
EC 50 

### median (or 50 percent) effect concentration
EC 05 

### 5 percent effect concentration ECOTOX ECOTOXicology EDI estimated daily intake EDSP Endocrine Disruptor Screening Program E-FAST Exposure and Fate Assessment Screening Tool EPI Suite Estimation Program Interface Suite EPA Environmental Protection Agency FDA Food and Drug Administration FFDCA Federal Food, Dr ug, and Cosmetic Act FGD flue-gas desulfurization FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act
FWP Final Work Plan g/mol grams per mole GLN guideline number HPV high production volume IDS Incident Data System KDDC potassium dimethyldithiocarbamate Koc organic carbon normalized soil-water partition coefficient
Kd soil-water partition coefficient Kow octanol-water partition coefficient
LC 50 

### median (or 50 percent) lethal concentration

LD 50 

### median (or 50 percent) lethal dose
LOAEC lowest-observed-adverse-effect-concentration
LOEC lowest-observed-effect-concentration
LOAEL lowest-observed-adverse-effect-level Log K ow 

### logarithm of the octanol-water partition coefficient

### Page 4 of 66 μg microgram ml/g milliliter per gram mg/kg milligram per kilogram mg/kg/day milligram per kilogram per day mg/L milligram per liter mm Hg millimeter of mercury MOE margin of exposure
MRID Master Record Identification Number
MRL maximum residue limit N/A not applicable NaDDC sodium dimethyldithiocarbamate salt

nm nanometers NOAEC no-observed-adverse-effect-concentration
NOAEL no-observed-adverse-effect-level OCSPP Office of Chemical Safety and Pollution Prevention OECD Organization for Economic Co-operation and Development OPP Office of Pesticide Programs PAD population adjusted dose PAI pure active ingredient
PDM Probabilistic Dilution Model % percent
PC Code Pesticide Chemical Code PCF pounds per cubic foot pH power of hydrogen or power of the concentration of the hydrogen ion PHED Pesticide Handler’s Exposure Data PIS primary irritation score pKa power of the acid dissociation constant or negative base-10 logarithm of the acid
dissociation constant of a solution ppb parts per billion ppm parts per million PWP Preliminary Work Plan QSAR quantitative structure-activity relationship RED Reregistration Eligibility Decision SAR structure activity relationship SF safety factor SSTS Section Seven Tracking System
SO2 sulfur dioxide TEP typical end-use product TGAI technical grade active ingredient TMDL total maximum daily loads TMTDS tetramethylthiuram disulfide (Thiram) TMTMS tetramethyl thiomonosulfide TMTU tetramethyl thiourea UF uncertainty factor UV/VIS ultraviolet/visible light absorption % w/w percent weight per weight. WP wettable powder WWTPs wastewater treatment plants

### Page 5 of 66 

## Table of Contents

1 Introduction .................................................................................................................. ........... 7
1.1 Statutory and Regulatory Authority ................................................................................. 7
1.2 Case Overview ............................................................................................................... 1 0
1.3 Chemical Identification and Properties .......................................................................... 10
1.4 Use/Usage Description ................................................................................................... 12
1.4.1 Registrations ........................................................................................................... 12
1.4.2 Summary of Regist ered Uses .................................................................................. 12
1.4.3 Usage Information .................................................................................................. 12
1.5 Regulatory History ......................................................................................................... 13
1.5.1 Recent/Pending Regulatory Actions ....................................................................... 13
1.5.2 Tolerance Information ............................................................................................ 13
1.6 Incidents ..................................................................................................................... .... 14
1.6.1 Human Health ......................................................................................................... 14
1.6.2 Ecological ............................................................................................................... 14
2 Anticipated Data Needs ........................................................................................................ 15
3 Human Health Risk Assessment ........................................................................................... 18
3.1 Existing Toxicological Endpoints .................................................................................. 18
3.2 Dietary Exposure ............................................................................................................ 1 9
3.2.1 Food ........................................................................................................................ 1 9
3.2.2 Drinking Water ....................................................................................................... 20
3.3 Occupational and Residential Exposures ....................................................................... 20
3.3.1 Occupational Exposures.......................................................................................... 20
3.3.2 Residential Exposures ............................................................................................. 21
3.4 Aggregate and Cumulative Exposure ............................................................................. 21
3.4.1 Aggregate Exposures .............................................................................................. 21
3.4.2 Cumulative Exposures ............................................................................................ 22
4 Environmental Risk Assessment........................................................................................... 22
4.1 Water Quality ................................................................................................................. 22
4.2 Environmental Conceptual M odel Exposure Pathways ................................................. 22
4.3 Ecological Effects Assessment ....................................................................................... 28
4.3.1 Mode of Action ....................................................................................................... 28
4.3.2 Measures of Effect (Ecotoxicology Endpoints) ...................................................... 28
4.4 Exposure Analysis Plan .................................................................................................. 29
4.4.1 Aquatic and Terrestrial Wild life Exposure Estimates ............................................ 29
4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 29
4.5 Effects Analysis Plan ..................................................................................................... 30

5 Endocrine Disruptor Screen ing Program (EDSP) ................................................................. 30
6 Next Steps .................................................................................................................... ......... 31
7 References .................................................................................................................... ......... 32

Appendix A Toxicology Profile for Dimethyldithiocarbamate ............................................... 37 Appendix B Environmental Fate ............................................................................................. 45 Appendix C Ecotoxicology Profile .......................................................................................... 54 Appendix D Product Chemistry ............................................................................................... 63 Appendix E Comments Received Concerning th e Preliminary Work Plan ............................ 65

### Page 6 of 66 List of Tables

Table 1 – Summary of Anticipated Risk Assessments and Data Needs: Dimethyldithiocarbamate
Salts ......................................................................................................................... ........................ 9 Table 2 – Anticipated Regist ration Review Schedule .................................................................... 9 Table 3 – Chemical Identification of Dimethyld ithiocarbamate Sodium and Potassium Salts .... 10 Table 4 – Physical-Chemical a nd Fate Properties for Dimethyldithiocarbamate Salts ................ 11 Table 5 – Summary of the Registered Uses of Dimethyldithiocarbamate Salts ........................... 12 Table 6 – Studies Anticipated as Need ed for the Registration Review of Dimethyldithiocarbamate Salts ................................................................................................. .... 15 Table 7 –Toxicological E ndpoints Used for the Dimethyldithiocarbamate RED ........................ 18 Table 8 – Occupational Exposure Scenarios fo r the Dimethyldithiocarbamate Salts .................. 21

List of Figures

Figure 1 – Conceptual Model for Cooling Tower Use of DDC Salts and Ecological Exposure and Effects of DDC Salts to Aquatic and Terrestrial Organisms ........................................................ 24 Figure 2 - Conceptual Model for Environmental Exposure of DDC Salts from Water System and Flue-Gas Desulfurization (FGD) to A quatic and Terrestrial Organisms ...................................... 25 Figure 3 – Conceptual Model for Aquatic (A) a nd Terrestrial (B) Envi ronmental Exposure of
DDC Salts in Recovered Water from Oil and Gas Use ................................................................ 26 Figure 4 - Conceptual Model for Aquatic (A) a nd Terrestrial Environmental Exposure (B) of DDC Salts from Use in Oil and Gas Extraction, Drilling Muds/Fluids, Hydraulic Fracturing Fluids, and Primary, Secondary, and Te rtiary (Enhanced Oil) Fluids .......................................... 27

### Page 7 of 66 

# 1 Introduction

This document is the United States Environmen tal Protection Agency’s (USEPA, EPA or “the agency”) Final Work Plan (FWP) for Sodium and Potassium Dimethyldithiocarbamate Salts, herein referred to as dimethyldithiocarbamate or DDC salts. The FWP document explains what EPA's Office of Pesticide Programs (OPP) knows about dimethyldithiocarbamate, highlighting anticipated data and assessment needs, identify ing the types of information that would be especially useful to the agency in conducting the review, and providing an anticipated timeline for the dimethyldithiocarbamate review. Th is FWP document does not include disodium ethylene bis dithiocarbamate (Nabam which is also a dimethyldithiocarbamate). Nabam was included in its own Regist ration Eligibility Decision (RED) rather than the 2009 Dimethyldithiocarbamate RED Amendment and is being addressed in Regi stration Review case 0641 (docket number EPA-HQ-OPP-2012-0339). Add itionally, Nabam produces ethylene thio urea (ETU) as a degradate, whereas DDC salts do not.

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



# 1.1 Statutory and Regu latory Authority

The Food Quality Protection Act (FQPA) of 1996 mandated a regi stration review program. All pesticides distributed or sold in the United St ates generally must be registered by the USEPA based on scientific data showing that they will not cause unreasonable risk s to human health or the environment when used as directed on produc t labeling. The registra tion review program is intended to make sure that, as the ability to assess risk evolves and as policies and practices change, all registered pesticides continue to meet the statutory standard of no unreasonable
adverse effects to human health or the environm ent. Changes in scien ce, public policy, and pesticide use practices will occur over time. Th rough the registration review program, the agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Inform ation on this program is provided at http://www.epa.gov/oppsrr d1/registration_review/

.
The agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and will review each registered pesticide every 15 years to determine whether it continues to meet th e FIFRA standard for registration. The regulations governing registra tion review begin at 40 CFR 155.40. The agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the agency’s opportunity to state what it knows about the pesticide and what additional risk analyses
and data or information it believes are needed to make a registration review decision. The DDC Salts Preliminary Work Plan (PWP) was published on September 25, 2013 and the 60-day comment period ended on November 25, 2013. Pub lic comments received concerning the PWP
and documents associated with this re gistration review can be viewed at http://www.regulations.gov in docket EPA-HQ-OPP-2013-0245. Updates to the Work Plan

### Page 8 of 66 Since the publication of the PWP, th e EPA has made the following updates:

 Corrected formatting and typographical errors.

 Updated the dietary risk assessment in secti ons 1 and 3 to reflect that the agency no longer anticipates the need to require a migration study, though a combined toxicity/carcinogenicity study is anticipated to be required. Tables 1 and 6 were also updated.

 Corrected dates in Table 2 – the Anti cipated Registration Review Schedule.

 Corrections made to Table 6 – Studies Anticip ated as Needed for the Registration Review of Dimethyldithiocarbamate Salts:

o Test substances

o Corrected guideline number of the 90 day inhalation toxi city study from 870.2345
to 870.3465

 EPA Reg. No.’s 1022-563, 1022-574, and 1022- 577 were cancelled on October 30,
2013 1 

### . Updates made to sections 1.5.1, 3, 4; Appe ndices A, B, and C; and Tables 1 and 6.
These labels accounted for the use sites that triggered the following data requirements which are now no longer anticipated to be required:

o 835.4100 Aerobic Soil Metabolism

o 850.3020 Honeybee, acute contact toxicity

o 850.3030 Honeybee, toxicity of residues

o 

### 875.2300 Surface Residue Data

o AWPA E11-06 Leaching from Treated Wood

 Section 3.4.1 was updated to reflect that th e agency no longer anticipates assessing residential exposure as re sidential exposures are not expected to occur.

 In section 5, the Endocrine Disruption Sc reening Program (EDSP) language was updated
to include discussion of the second list of chemicals identified fo r EDPS screening.

The agency received one comment from the Physician Committee for Responsible Medicine (PCRM) during the public commen t period on the initia l docket. PCRM is encouraging the agency to consider using non-testing approaches to fulfill the carcinogenicity study that had been anticipated to be required. Please see Appendi x E for the agency’s responses to PCRM’s

comments.

Though the product cancellations mentioned in the bu llets above resulted in a modification to the anticipated data needs, comments received did not result in a modification to the anticipated data
needs detailed in the DDC Salts PWP. This do cument makes final the work plan for the DDC Salts registration review process. Tables 1-2 below summarize the issues relevant to this registration review case and the anticipated regist ration review schedule.

1 The product cancellation order for EPA Reg. No.’s 1022-563, 1022-574, and 1022-577 can be found on regulations.gov, in docket EPA-HQ-OPP-2009-1017-0045.

### Page 9 of 66 Table 1 – Summary of Anticipated Ri sk Assessments and Data Needs: Dimethyldithiocarbamate Salts

Risk Assessment Assessment Necessary to

Support Registration
Review Date of
Most
Recent
Assessment Type of
Assessment

Required (New/Updated) Data Anticipated as Needed (See Table 6 for details)

Dietary (food) Yes 7/14/2009 Updated Reproduction and Fertility Effects Chronic Toxicity/Carcinogenicity

Dietary (drinking water) Yes 7/8/2009 Updated Reproduction and Fertility Effects Chronic Toxicity/Carcinogenicity

Occupational Handler Yes 3/3/2009 Updated Inhalation Toxicity – 90 Day Reproduction and Fertility Effects Dermal Exposure Inhalation Exposure
Product Use Information

Residential Handler No (see) 3/3/2009 None None

Residential Post Application Dermal and
Incidental Oral No (see 3.3.2) 3/3/2009 None None

Aggregate Yes N/A New Reproduction and Fertility Effects

Cumulative No (see 3.4.2) N/A None None

Tolerance Review (EPA) No (see 1.5.2) 7/14/2009 N/A None

Ecological Effects and
Environmental Fate Yes 2009 New 1

Fish (chronic); Aquatic invertebrates (chronic); Aquatic and semi-aquatic plants; Activated Sludge Respiration Inhibition or Modified Activated Sludge Respiration Inhibition; Ready biodegradability test or one of three biodegradation in activated sludge
simulation tests

1 Commercial/Industrial Cooling Water, Pulp/Pap er Mill Water Systems, Gas/Oil operations



### Table 2 – Anticipated Regi stration Review Schedule

Anticipated Activity Target Date* Completion Date Phase 1: Openin g the Docket Open Docket and 60-Day Comment Period for Preliminary Work Plan 2013-09 2013-09-25
Close Public Comment Period 2013-11 2013-11-25 Phase 2: Case Development
Issue Final Work Plan 2014-06 2014-06

### Page 10 of 66 Anticipated Activity Target Date* Completion Date Issue Data Call-In (DCI) 2015-06
Receive Data to be Considered in Risk Assessment 2018-06 Open 30-Day Public Comment Period for Pr eliminary Risk Assessment(s) 2019-12
Close Public Comment Period 2020-01 Phase 3: Registration Review Decision and Implementation Open 60-Day Public Comment Period for Proposed Decision 2020-06
Close Public Comment Period 2020-08
Issue Final Decision 2020-12 Begin Post-Decision Followup 2020 Total (years) 7

*The anticipated schedule will be revised as necessary ( e.g ., need arising under the Endocrine Disruptor Screening Program with respect to the active ingredients in this case).



# 1.2 Case Overview

The docket for the Sodium and Potassium Dimet hyldithiocarbamate Salts Case (Case 8100) has
been established at http://www.regulations.gov in docket number EPA-HQ-OPP-2013-0245.



# 1.3 Chemical Identification and Properties

Table 3 presents the active ingredients to be assessed in Case 8100: Sodium Dimethyldithiocarbamate Salt (NaDDC, PC Code 034804); and Potassium Dimethyldithiocarbamate Salt (KDDC, PC Code 034803). These chemicals are herein referred to as dimethyldithiocarbamate or DDC salts.

Table 3 – Chemical Identification of Dimeth yldithiocarbamate Sodium and Potassium Salts

Chemical Name Sodium dimethyldithiocarbamate Potassium dimethyldithiocarbamate

Abbreviation NaDDC KDDC

Classification Dithiocarbamate Dithiocarbamate

PC Code 034804 034803

CAS No. 128-04-1 128-03-0

Molecular Formula C 3 

### H 6 

### NNaS 2 

### C 3 

### H 6 

### NKS 2 

### Molecular Weight 143.21 grams per mole 159.31 grams per mole

Purity 40 percent (%) weight per weight A 

### (w/w) as aqueous solution 50% w/w as aqueous solution

Molecular Structure

A % w/w is the number of grams of solute per 100 grams of solutions.



### NaDDC and KDDC salts product chemistry information (source: MRIDs 41586303, 41609403, 41651301, 42510401, and 41609407 and EPI Suite v4.1) relevant to risk assessment is

### Page 11 of 66 summarized in Table 4 and details of the envi ronmental fate properties are discussed in Appendix B and product chemistry information in Appendix D.

Table 4 – Physical-Chemical and Fate Prop erties for Dimethyldithiocarbamate Salts

Guideline
No. Physical and Chemical Properties NaDDC KDDC

830.7000 pH As measured 13.3 at 20 degrees Celsius (°C)

10.1 (1% aqueous solution) - HPV 12.6 (32% aqueous solution) - HPV 9-14 (50% solution)

830.7050 Ultraviolet (UV)/Visible Absorption NaDDC was identified by UV/VIS spectra recorded at different pH values.

Result at pH < 2: > 200 nanometers (nm),  = 0 l mol -1

cm -1

Result at pH 7: 254 nm,  = 12792 l mol -1 cm -1
279 nm,  = 13127 l mol -1 cm -1
295 nm,  = 1863 l mol -1 cm -1

Result at pH > 11: 254 nm,  = 13388 l mol -1 cm -1
279 nm,  = 13687 l mol -1 cm -1
295 nm,  = 1803 l mol -1 cm -1 KDDC was identified by UV/VIS spectra recorded at different pH values.

Result at pH < 2: 207 nm,  = 12713 l mol -1 cm -1

Result at pH 7: 253 nm,  = 26409 l mol -1 cm -1
279 nm,  = 28187 l mol -1 cm -1
495 nm,  = 3562 l mol -1 cm -1

Result at pH > 11: 254 nm,  = 12714 l mol -1 cm -1
279 nm,  = 13120 l mol -1 cm -1

830.7200 Melting point PAI: > 300 °C with decomposition. PAI: > 300 °C with decomposition.

830.7220 Boiling point Not required since PAI is solid Boiling point of 32% solution: 102°C Not required since PAI is solid. Boiling point of 50% solution:
>100°C 830.7300 Density 1.17 g/ml (40% solution) 1.25 g/ml (50% solution)

830.7370 Dissociation Constant in

water pKa = 5.4 for the organic portion/ Estimated/(40% w/w aqueous solution).

6.5 x 10 -8 at 20°C. Performed on PAI.

pKa value: Not applicable; product decomposes below pH 8. – HPV pKa = 5.4 for the organic portion/ Estimated/(40% w/w aqueous solution).

6.5 x 10 -8 at 20°C. Performed on PAI.

830.7550 Partition coefficient ( n

octanol/water) Performed on PAI. Estimated to be less than 1 based on solubility at 20°C.

− 2.41 (EPI Suite v4.1) − 1.43 (EPI Suite v4.1)

830.7840 Solubility in water Complete 132 g/100 ml of water at 20 °C
Performed on PAI. Complete. Easily soluble in water.

830.7950 Vapor pressure Solid: 4.17 x 10 -9 mm Hg at 25°C (EPI Suite v4.1). Solid: 8.15 x 10 -10 mm Hg at 25°C (EPI Suite v4.1).

N/A Henry's Law Constant 7.857 x 10 -16 atm-m 3 /mole (EPI Suite v4.1) 2.01 x 10 -16 atm-m 3 /mole (EPI Suite v4.1).
PAI - Pure active ingredient HPV – High production volume

### Page 12 of 66 

# 1.4 Use/Usage Description

1.4.1 Registrations

There are 15 registered KDDC products and 11 registered NaDDC products.



## 1.4.2 Summary of Registered Uses

Table 5 presents a summary of the registered uses of DDC salts that will be assessed in this registration review. Per label di rections, products that contai n only DDC salts can be open poured or metered into the system being treated or the product being preserved. Some products also contain the active ingredie nt Nabam and these products requi re closed system loading for certain uses such as industrial cooling towers, oil drilling fluids, paper mills, beet sugar mill and cane sugar mills. These requirements are base d on label specifications in the Nabam RED 2



### .

Several product labels have been amended sin ce the 2009 RED Amendment to voluntarily delete uses. Deleted uses include sapstain treatment, paints and coatings, metalworking fluids, cotton fabrics, wood veneers an d alginate pastes.

Table 5 – Summary of the Registered Us es of Dimethyldithiocarbamate Salts

Use Site Application Rate in
Terms of Active Ingredient (A.I.) Labels (EPA Registration no.)

Industrial Processes and Water Systems Air Washer Water Systems 6 to 29 ppm Several labels. Beet and Cane Sugar Mills 3 ppm Several labels. Beet Sugar Mills 12 ppm One label (45728-29) Coal Slurry Systems 75 ppm One label (34688-76) Commercial/Industrial Cooling Water Systems 6 to 59 ppm Several labels. Evaporative Condenser Water Systems 6 to 59 ppm Several labels. Food Processing Water Systems 3 to 12 ppm Several labels. Oil Recovery Drilling Muds and Packer Fluids 77 to 1214 ppm Several labels. Oil Recovery Injection Water, Seco ndary 4 to 394 ppm Several labels. Pulp and Paper Mill Water Systems 113 to 250 ppm Several labels 1 Reverse Osmosis Water Systems 10 to 51 ppm Several labels. Sewage Systems 5 to 14 ppm Two labels (1448-70, 34688-77)

Material Preservative Papermaking Additives (Alum solutions, pigment slurries, coating formulations etc.) 200 ppm One label (1448-70)

1 Includes indirect food uses.



## 1.4.3 Usage Information

According to the Specialty Biocides No rth America Report 2004-2005 (Kline, 2006) the dithiocarbamates, which include Nabam (dis odium ethylene bis dithiocarbamate), and dimethyldithiocarbamate
, are used primarily for paper product ion and industrial cooling water

2 PC Code 014503, http://www.epa.gov/oppsrrd1/REDs/0641.pdf

### Page 13 of 66 treatments, and to a lesser extent, for leather pr oduction. The report does not distinguish the use patterns for Nabam and dimethyldithiocarbamate. With respect to wood preservation, the report indicates that dimethyldith iocarbamate is not used.



# 1.5 Regulatory History

The Dimethyldithiocarbamate Salts were previously included in RED Case 2180, with PC Codes 034801, 034803, 034804, 034805, and 034806. KDDC (034803) and NaDDC (034804) have been split from Case 2180 and moved into Case 8100 for registration review; case 8100 consists of only these two chemicals. The agency completed an Amended RED for DDC salts in 2009. Ziram (034805) and Ferbam (034801) each had i ndividual REDs in 2003 and 2005, respectively; registration review dockets for these conventio nal chemicals are scheduled to open in FY 2015. Zinc dimethyldithiocarbamate (034806) was canceled in 1992.

The first product containing Na DDC was registered in 1949, a nd the first product containing KDDC was registered in 1980.



## 1.5.1 Recent/Pending Regulatory Actions

EPA Reg. No.’s 1022-563, 1022-574, and 1022-5 77 were cancelled on October 30, 2013 1 

### . These labels accounted for the following use sites: material preservative for adhesives/coatings/emulsions, fuels and oils bo ttom water, metal working fluids, paints and varnish (applied film), and wood pr eservative uses. As a result of these cancellations, the agency no longer anticipates the need to require the following data and has removed these data requirements from Tables 1 and 6:

 835.4100 Aerobic Soil Metabolism

 850.3020 Honeybee, acute contact toxicity

 850.3030 Honeybee, toxicity of residues

 

### 875.2300 Surface Residue Data

 AWPA E11-06 Leaching from Treated Wood

EPA anticipates issuing the Regi stration Review generic-data cal l-in (GDCI) as noted in the anticipated schedule in Table 2.



## 1.5.2 Tolerance Information

EPA has not established a tolerance or exemp tion from the requirement of a tolerance for residues of dimethyldithiocarbamate in f ood. The Food & Drug Administration (FDA) has established a number of food additive regulations for NaDDC. No food addi tive regulations have been established for KDDC. In the case of NaDDC, regulations have been established as a (an):

 Chemical for controlling microorganisms in cane-sugar and beet-sugar mills (21 CFR 173.320);

 Slimicide used in the manufacture of paper and paperboard that contact food (21 CFR 176.300);

 Adhesive used as components of articles in tended for use in packaging, transporting, or holding food (21 CFR 175.105);

### Page 14 of 66  Rubber article intended for repeated use, used in producing, manu facturing, packing, processing, preparing, treati ng, packaging, transporting, or holding food (21 CFR 177.2600)



# 1.6 Incidents

1.6.1 Human Health

There have been no incidents reported in the OPP Incident Database System for the period 6/30/2009, when the RED Amendment was signe d, to the present (search conducted on 6/18/2013).



## 1.6.2 Ecological

As of August 6, 2013, no incidents have been repo rted in the Incident Data System (v. 1.8).Docket Number EPA-HQ-OPP-2013-0245www.regulations.govPage15of662Anticipated Data NeedsTable 6 presents a summary of the data anticipated asbeing needed to supportthis registration review.Table 6 – Studies Anticipated as Needed for the Registration Review of Dimethyldithiocarbamate SaltsOCSPP GLNStudy NameTestSubstanceTimeFrame1(Months)Risk Assessment(s)Data Will SupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure Scenario835.31102835.32203835.32404835.32805Ready biodegradability test orone of three biodegradation inactivated sludge simulation testsTGAI 12Activated sludgemicroorganismsAll usesTransport to Industrial wastewatertreatment plantOECD 209 or850.33006Activated Sludge RespirationInhibition or Modified ActivatedSludge Respiration InhibitionMP; PAI;TGAI12Activated sludgemicroorganismsAll usesTransport to Industrial wastewatertreatment plant850.1300Aquatic invertebrate life-cycletoxicity, freshwaterTGAI 24 Aquatic organismsIndustrial process water; Pulp andpaper; Gas/oilTransport to the aquatic environment850.1350Aquatic invertebrate life-cycletoxicity, estuarine/marineTGAI 24 Aquatic organismsIndustrial process water; Pulp andpaper; Gas/oilTransport to the aquatic environment850.1400 Fish early-life stage, freshwater TGAI 12 Aquatic organisms As above Transport to the aquatic environment850.41007Seedling emergence, Tier II rice TEP 12 Aquatic organismsIndustrial process water; Pulp andpaper; Gas/oilTransport to the aquatic environment850.415010Vegetative vigor, Tier II rice EP; TGAI 12 Aquatic organisms Gas/oil Transport to the aquatic environment850.4400Aquatic Plant Testing usingLemnasp., Tier IITGAI 12 Aquatic organisms As above Transport to the aquatic environment850.4500Algal Toxicity Tier II –marinediatom, freshwater diatom, andgreen algaeTEP; TGAI 12 Aquatic organisms As above Transport to the aquatic environment850.4550Algal Toxicity Tier II -CyanobacteriaTEP; TGAI 12 Aquatic organisms As above Transport to the aquatic environment870.3465 Inhalation Toxicity – 90 Day TGAI 24 Occupational Exposure All Use Sites Openpour liquids and wettablepowders870.38008Reproduction and FertilityEffectsTGAI 36 Human Health All UseSites All exposure scenarios.870.4300Combined ChronicToxicity/CarcinogenicityTGAI 36 Human Health All Use Sites Dietary and drinking water exposures11Page16of66OCSPP GLNStudy NameTestSubstanceTimeFrame1(Months)Risk Assessment(s)Data Will SupportUse Site(s) Triggering AnticipatedData RequirementApplicable Exposure Scenario870.5395Mammalian ErythrocyteMicronucleus TestTGAI 12 Human Health All UseSites All exposure scenarios.870.7800 Immunotoxicity TGAI 12 Human Health All Use Sites All exposure scenarios875.12009Indoor Dermal Exposure TEP 24 Occupational Handler All Use Sites Open pour liquids and wettablepowders.875.14009Indoor Inhalation Exposure TEP 24 Occupational Handler All Use Sites Open pour liquids and wettablepowders.875.1700 Product Use Information TEP 12 Human Health All Use Sites All exposure scenarios.Data Needs No Longer Anticipated to be Required from the 2009 REDGLNStudy NameTestSubstanceTimeFrame1(Months)Reason the Study is No Longer Anticipated to be Required835.2240 Photodegradation in Water TGAI 12Data were available from active ingredient Thiram, a dimer of DDC acid (MRID 45651201 and MRID40220701)835.2410 Photodegradation on Soil TGAI 12 Data were available from active ingredient Thiram, a dimer of DDC acid (MRID 45724501)835.4100 Aerobic Soil Metabolism TGAI 24 Data were available from active ingredient Thiram, a dimer of DDC acid (MRID 43734901)835.6100 Terrestrial Field Dissipation TGAI 24The agency has reviewed the need for these data anddetermined that the aerobic soil metabolism half-lifeof approximately two days indicateslimited potential for leaching toground water or runoff to surfacewater. In addition, the 158 W regulations do notrequire terrestrial field dissipation data (140 CFR §158.2282).875.1100 Outdoor Dermal Exposure TGAI 24 Exposure scenarios were added to the indoor studies.875.1300 Outdoor Inhalation Exposure TGAI 24 Exposure scenarios were added to the indoor studies.875.1600Application exposure monitoringdata reportingTGAI 12 This study will be addressed in the submissionof the remaining anticipated exposure data requirements875.2700 Product Use Information TGAI 12 This study will be addressed in the submission of the Product Use Information Study 875.1700875.2800 Description of Human Activity TGAI 12-24 This study willbe addressed in the submission of the Product Use InformationStudy 875.1700875.2900 Data Reporting and Calculations TGAI 12 This study willbe addressed in the submission of the remaining anticipated exposure data requirements1The timeframe will be measured fromthe receipt of the anticipated DCI.2EPA has a published final guideline for this study:http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0017. The biodegradationstudy anticipated to be required is based on resultsof an Activated Sludge Respiration Inhibition test.3EPA has a published final guideline for this study:http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0024. The biodegradationstudy anticipated to be required is based on resultsof an Activated Sludge Respiration Inhibition test.4EPA has a published final guideline for this study:http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-0034. The biodegradationstudy anticipated to be required is based on resultsof an Activated Sludge Respiration Inhibition test.5The results of the ASRI test will determine which of these four biodegradation tests is/are anticipated to be required. If theASRI test EC50is less than or equalto 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test– Aerobic Sewage Treatment: A.Activated Sludge Units or (iii)the Porous Pot Test is expected to be required. If the ASRI test EC50is greater than 20 mg/L, then the registrantwould likely be required to conduct either: (i)Page17of66Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units or c) thePorous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, theantimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A.Activated Sludge Units, or c) the Porous Pot study would likely be required.6The anticipated DCI will provide that 850.3300 may be used in placeof OECD 209 if the test substance is not sufficiently soluble to allow preparation of aconcentrated stock solution in water.7Test guidelines 850.4100 and 850.4225 were merged and harmonized into OCSPP 850.4100 in a Federal Register Notice dated June 27, 2012 (FRL-9333-1).8Results from a multi-generation (EPA guideline 870.3800) or anextended one-generation reproductive and fertility effects studyusing OECD Test Guideline443 (http://www.oecd-ilibrary.org/environment/test-no-443-extended-one-generation-reproductive-toxicity-study_9789264185371-en) will satisfy thisrequirement.9Data reporting and calculations are anticipated to berequired when handler exposure data are submitted10Test guidelines 850.4150 and 850.4250 were merged and harmonized into OCSPP 850.4150 in a Federal Register Notice dated June 27, 2012 (FRL-9333-1).11Data are expected to be required to conduct the dietary exposure assessments basedon a screening level analysis that indicates residues exceed 200 ppb.

### Docket Number EPA-HQ-OPP-2013-0245 www.regulations.gov

Page 18 of 66 

# 3 Human Health Risk Assessment

The agency anticipates the need to conduct a hu man health risk assessment for DDC salts. The agency expects to require additional data fo r use in conducting the registration review.



# 3.1 Existing Toxicological Endpoints

EPA anticipates the need to revise the existing t oxicological endpoints as pa rt of this registration review. Table 7 presents a summary of the endpoi nts used in EPA’s most recent human health risk assessment in support of the 2009 RED Amendment. As prev iously stated, toxicological
studies were identified as data gaps in the 2009 RED Ame ndment and identified in the registration review as anticipated data needs based on currently registered uses. All available information including existing toxi cology studies, valid scientific lit erature, and the studies that are expected to be required for registration review will be considered in establishing the endpoints to be used in the regi stration review risk assessment. A summary listing of all of the available toxicity studies is provided in Appendix A .

Table 7 –Toxicological Endpoints Used for the Dimethyldithiocarbamate RED

Exposure
Scenario Dose, UF Study and Toxicological Effects



### Dietary Exposures
Acute Dietary ( Females 13-50) Oral NOAEL = 13 mg/kg/day
UF = 100 A Rabbit developmental study (MRID 40995101) LOAEL = 38 mg/kg/day based on clinical signs (reddish-colored material in cage trays) and possi ble increased maternal death and
abortions.

Acute Dietary (General population) Oral NOAEL = 20 mg/kg

UF = 100 A Co-critical studies: Acute neurotoxicity study (MRID 43544201) LOAEL = 790 mg/kg/day based on clinical signs of toxicity, numerous functional observational battery parameter effects, and decreased motor activity. NOAEL = 20 mg/kg/day

Sub-chronic neurotoxicity study (MRID 43550501) LOAEL = 99 mg/kg/day based on salivation, oral staining and decreased body weight. NOAEL = 2.0 mg/kg/day

Chronic Dietary (All populations) Oral NOAEL = 2 mg/kg/day

UF = 1000 B 90-day subchronic oral study (MRID 42047201) LOAEL = 100 mg/kg/day and NOAEL = 2 mg/kg/day based on decreased erythrocyte counts, incr eased glucose concentration, and increased alkaline phosphatase activity in females, and exocrine pancreatic atrophy with fibrosis in males.

Note: This study had a very wide dose range of 0, 0.2, 2 and 100 mg/kg/day which resulted in the 50 fold difference between the LOAEL of 100 mg/kg/day and the NOAEL of 2 mg/kg/day. 

### Occupational and Residential Exposures

Incidental oral ( Short-Term) Oral NOAEL = 2 mg/kg/day

UF = 1000 B 90-day subchronic oral study (MRID 42047201) Same study used for the chro nic dietary scenario above.

### Page 19 of 66 Exposure
Scenario Dose, UF Study and Toxicological Effects

Incidental Oral ( Intermediate-Term) Oral NOAEL = 2 mg/kg/day
UF = 1000 B 90-day subchronic oral study (MRID 42047201) Same study used for ch ronic dietary above.

Dermal (Short, intermediate and long-term) Dermal NOAEL

= 60 mg/kg/day

UF = 1000 B 90-Day Dermal toxicity study (MRID 40140101) LOAEL = 120 mg/kg/day Based on decreased leukocyte and platelet counts.

Inhalation (Short, intermediate and long-term) Oral NOAEL = 2 mg/kg/day

UF = 1000 B 90-day subchronic oral study (MRID 42047201) Same study used for chronic dietary above.

A. Uncertainty Factor (UF) includes 10X for interspecies extrapolation and 10x for intraspecies variation. B. UF includes 10X for interspecies extrapolation, 10x for intraspecies variation and 10x for database uncertainty.



# 3.2 Dietary Exposure

The agency anticipates the need to revise the previous dietary risk assessment conducted in
2009 3 

### . Uses of NaDDC and KDDC salts that may re sult in indirect di etary exposure include their use as slimicide in paper mill pulp slurri es, material preservatives (including papermaking additives that have the potential to be in food-contact packaging) , and their use in water process systems for beet sugar mills and cane sugar m ills. Additionally, drinking water exposure may
occur as a result of DDC salts ’ use in various industrial process water systems.

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

The agency also anticipates the need to conduct an aggr egate risk assessment.



## 3.2.1 Food

NaDDC is considered to be a food additive by the U.S. Food and Drug Administration (FDA) under 21 CFR, when used in raw cane and sugar b eets. Use limitations for the additive are 3.0 ppm on a raw cane basis combined with disodium ethylenebisdithiocarbamate for control of microorganisms in cane sugar mills and 3.0 ppm on a raw cane or sugar beets basis when combined with disodium ethylene bisdithiocar bamate and ethylenediamine for control of microorganisms in cane sugar and beet sugar mills (21 CFR §173.320) 4



### .

3 Dietary Risk Assessment for Potassium Dimethyldithiocarbamate for the RED Process ,” dated July 14, 2009.

4 21 CFR §173.320

### Page 20 of 66 Since the use of DDC salts as slimicide in paper mill pulp slurries and as a material preservative (papermaking additives) can contribute to diet ary (food) exposure, the agency will need to conduct both acute and chronic dietary exposure assessments for all population subgroups to support registration review. In an effort to dete rmine if additional residue data would be required
to conduct these assessments and to determine toxi cology data needs, a sc reening level analysis was conducted for the paper/pulp use. This screen used FDA met hodology (FDA, 1993) where appropriate as well as relied on high-end assumpti ons to be protective of human health. These include: all of the daily food consumed will come into contact with paper treated with the active ingredient and 100% of the residue on the paper will transfer to food items. The toxicological point of departure used for the analyses is fr om a subchronic oral t oxicity study with a NOAEL of 2 mg/kg/day (MRID 42047201 ) . A 1000x uncertainty factor was applied in order to account for intra- and interspecies vari ation and database uncertainty.

The screening level analyses based on use in paper products indicates that residues exceed 200 ppb. No further residue data is anticipated to be required because the screening level analysis did not identify risks of concern. However, a chronic toxicity/carcinogenicity study is anticipated to be required to conduct the risk assessment because the screening level a ssessment indicates that residues exceeded the 200 ppb le vel that the agency uses to determine toxicology data requirements for indirect food uses of antimicr obial pesticides. The exposure contribution from
this scenario will be considered in the a ggregate assessment conducted during registration review. It is important to note that if the toxico logical point of departure for either the acute or chronic scenario changes during the registration review process, additional residue chemistry data may be required.



## 3.2.2 Drinking Water

EPA expects to conduct a Tier I screening-level drinking water analysis to estimate dietary exposure from uses that are expected to result in DDC salts pa ssing through WWTPs (see Appendix B ). Any drinking water ri sks will be incorporated into th e aggregate risk assessment.



# 3.3 Occupational and Residential Exposures

The occupational and residential exposures to di methyldithiocarbamate were last assessed in D359537 (EPA, 2009b) which was written for the 2009 RED Amendment. The agency anticipates the need to revise the occupationa l and residential assessments conducted in support
of the 2009 RED Amendment since the Margins of Exposure (MOE)s were calculated using unit exposure data and transferable residue data that have underlying limitations and will need to be reassessed using updated values.



## 3.3.1 Occupational Exposures

EPA anticipates the need to revise the occupa tional exposure assessment conducted in support of the 2009 RED Amendment. There is the potenti al for both dermal and inhalation exposures during the open pouring of dimethyldithio carbamate liquid and wettable powder (WP) formulations. There is a much lower potential for exposure during metering pump addition of liquids and water soluble package addition of WP because these addition methods are considered to be closed systems. The risks from closed system addition methods were assumed to be mitigated by label language and were not assess ed quantitatively in the 2009 RED Amendment.

### Page 21 of 66 The Chemical Manufacturers Asso ciation (CMA) unit exposure data were used for the open pour liquid handling scenarios and the Pesticide Hand lers Exposure Database (PHED) unit exposure data were used for the open pour WP scenarios. The dermal and inhalation MOEs for handling liquid formulations of dimethyldithiocarbamate we re all greater than th e target MOE of 1000 and
were not of concern. The dermal MOEs for ha ndling wettable powder formulations ranged from
1 to 6000 and were of concern for most of the scenarios. The inhalation MOEs for handling wettable powder formulations ranged from <1 to 2000 and were also of concern.

Scenarios that Need to be A ssessed During Registration Review

All of the handler scenarios th at were assessed in the 2009 RED Amendment will need to be revised during registration review upon receipt of the unit exposure data that is anticipated to be required to supplement or replace the unit expos ure data that were used in the 2009 RED Amendment. Occupational handler scenarios to be assessed are presented in Table 8.

Table 8 – Occupational Exposure Scenario s for the Dimethyldithiocarbamate Salts

Handler Scenarios Exposure Route(s) Duration

Open Pour Liquids for treatment of Cooling Water, Drilling Muds, Drilling
Fluids. Dermal
Inhalation Intermediate

Term Open Pour Wettable Powder for treatment of Cooling Water, Drilling Muds, Drilling Fluids and Pulp and Papers Dermal
Inhalation Intermediate

Term



## 3.3.2 Residential Exposures

EPA does not anticipate the need to revise the residential ex posure assessments conducted in support of the 2009 RED Amendment. Since the DDC Salts Preliminary Work Plan posted, the products with uses that had triggered the need to revise the residential exposure assessment have been cancelled: EPA reg. number 1022-563 was the onl y product with an in-can preservative of water thinned paints and coatings use and EPA reg. number 1022-577 was the only product with a pressure treatment wood preservations use (see section 1.5.1). The remaining use sites for the DDC Salts case do not trigger re sidential exposure concerns.



# 3.4 Aggregate and Cumulative Exposure

3.4.1 Aggregate Exposures

EPA anticipates the need to revise the aggr egate assessment conducted in support of the 2009 RED Amendment. Upon a reevaluation and selecti on of toxicological endpoi nts, combined with the human health exposure assessments expected as a part of this registration review case, aggregate exposures will need to be assessed. This assessment will include dietary (food) exposures and drinking water anal ysis. Residential exposures are not expected and thus are not anticipated to be aggregated.

### Page 22 of 66 

## 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 me chanism of toxicity, the agency made a 2001
final determination that there is insufficient data to show a common mechan ism of toxicity with other substances and dimethyldithiocarbamate does not appear to produce a toxic metabolite produced by other substances. For informati on regarding EPA’s efforts to determine which chemicals have a common mechanism of toxicity a nd to evaluate the cumulative effects of such chemicals, see http://www.epa.gov/pesticides/cumulative/

.


# 4 Environmental Risk Assessment

For currently registered uses, the ecological ri sk assessment planned during registration review will allow the agency to determine potential acute and chronic risks to aquatic organisms exposed to dimethyldithiocarbamate salts that are transported from treatment sites into the aquatic environment. Such uses include comm ercial/industrial cooling water, pulp/paper mill water systems, and gas/oil operations. The ag ency has not conducted a risk assessment that supports a complete endangered species determ ination for DDC salts. The ecological risk assessment planned during registration review w ill allow the agency to determine whether DDC salts’ use has 'no effect' or 'may affect' federally listed threatened or endangered species (listed species) or their designated critical habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its designated criti cal habitat, the agency will consult with the U.S.
Fish and Wildlife Service and/or National Mari ne Fisheries Services (the Services), as appropriate.



# 4.1 Water Quality

Sodium and potassium dimethyldithiocarbamate sa lts are not identified as a cause of impairment for any water bodies listed as impaired unde r section 303(d) of the Clean Water Act 5 

### . In addition, no Total Maximum Daily Loads (TMDL) have been developed for sodium and potassium dimethyldithiocarbamate salts 6 

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



### .



# 4.2 Environmental Conceptual Model Exposure Pathways

NaDDC and KDDC salts are active ingredients in antimicrobials that can be used in water process systems (air washer, reverse osmosis, a nd industrial, cane and be et sugar mills in cane juice and beet pulp press water, commercial/indust rial cooling water, industrial wastewater, pulp/paper mills (pulp), gas and oil (drilling mu ds/packer fluids, recovery injection water, fracturing fluids, workover and completion fl uids), and coal powered plant flue gas desulfurization thickeners).

5 http://iaspub.epa.gov/tmdl_waters10/attains_nation_cy.cause_detail_303d?p_cause_group_id=885

6 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl _pollutant_detail?p_pollutant_group_id=885&p_pollutant_ group_name=PESTICIDES

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

### Page 23 of 66 Antimicrobials with the above uses will eventually be released to wastewater treatment plants (WWTPs) whose effluents will reach surface wate r and aquatic organisms. The exposure to parent compounds is limited because of ready disassociation of the sodium and potassium
cations from the acid of the DDC salts. The ini tial exposures will be from a mixture of parent compounds and degradates which are impurities becau se the major degradates were present at the beginning of the aerob ic aquatic metabolism study. 8 

### The primary and major (>10 % of applied parent compound) degradates includ e dimethylamine (DMA), carbon disulfide (CS 2) 

### , tetramethylthiuram disulfide (TMTDS), tetramet hyl thiomonosulfide (TMTMS), and tetramethyl thiourea (TMTU). The oil and gas uses can crea te environmental exposure of ground water to impurities and degradates if well casing is not intact or to surface water if treated fracking water is released into streams. The flue gas desulfur ization use is associated with coal-burning power plants and there are two forms of waste, 1) water which goes to a WWTP and 2) sludge which goes to a landfill. 9 

### As a result, the agency is assessing the WWTP exposure from the desulfurization use but not the landfill disposal because it is assumed that landfills are lined and will not create exposure. 10



### Except as noted, the environmental fate properties of DDC salts a nd its degradates were based on the results of submitted studies. Degradation of DDC salts and its degradates occur by both
abiotic 11 

### and biotic means 12 

### . Parent DDC salts and its degrad ates are water soluble and will be
associated with water in the presence of soil, sediment, and sewage sludge. While most DDC salts compounds have limited poten tial to volatilize from water based on estimated values using
the EPI-Suite 4.1 13 

### Henry’s Law constants of 10 -10 

### to 10 -9 

### atm m 3 

### mol -1 

### , DMA and CS 2 

### degradates have Henry’ s Law constants of 10 -5 

### to 10 -2 

### atm m 3 

### mol -1 

### and are likely to volatilize from water and create aerial exposure, especially from the cooling tower use (Table B1).

For all the following conceptual exposure models for DDC salts and its degradates, the agency is using solid lines to signify that surface water ex posure and attribute changes can occur, but the potential for bioconcentration and secondary exposure is unlikely or insign ificant as indicated by
the dashed lines.

Figure 1 contains the conceptual model for the environmental exposure from the cooling tower
use of DDC salts. Based on the lack of data on the persistence in cooling towers and chemical and physical properties 14 

### of DDC salts and its degradates, all lines in Figure 1 ar e solid with the exception of ingestion and biocon centration in aquatic organisms. Water from cooling towers will eventually be released to surface water dire ctly or to a WWTP where it will be present in water and not be sorbed to the sludge. Treated water from a WWTP will then be released to
surface water.

8 MRID 40365702

9 http://water.epa.gov/scitech/wastetech/guide/steam -electric/upload/Steam-Electric_Detailed-StudyReport_2009.pdf , EPA 821-R-09-008

10 http://www.epa.gov/osw/nonhaz/muni cipal/landfill/criteria/landbig.pdf

11 Hydrolysis (MRID 43180801) and photolysis in water (MRID 40220701)

12 Aquatic metabolism, MRIDs 43865901 and 40365702

13 http://www.epa.gov/opptintr/exposure/pubs/episuite.htm

14 Water solubility, log Kow, and low potential for sorption

### Page 24 of 66 Figure 2 contains the conceptual model for enviro nmental exposure of DDC salts from the water system and flue-gas desulfurization ( 

### FGD) uses. The water system and FGD uses involve scrubbing of sulfur dioxide (SO 2) 

### gas from the smokestacks of steam electric power plants that consume fossil fuels (e.g. coal). The waste wa ter will eventually pass through a WWTP where it will reach surface water. The solid waste (sludge ) will be placed in a landfill or other surface impoundment or applied to land as a fertilizer and consists of as h (including some heavy metals), calcium sulfate (CaSO 4) 

### , and calcium sulfite (CaSO 3) 

### . The water system and FGD uses contain air washers, reverse osmosis, a nd industrial wastewater systems. 15 

### The conceptual models for the oil and gas uses may be seen in Figures 3 and 4. These uses include potential for waste water to be used in irrigation and exposure of terrestrial plants.

Figure 1 – Conceptual Model for Cooling Tower Use of DDC Salts and Ecological Exposure and Effects of DDC Salts to Aquatic an d Terrestrial Organisms

15 EPA 821-R-09-008. October, 2009. Steam Electric Power Generating Point Source Category: Final Details Study Report. http://water.epa.gov/scitech/wastetech/guide/steam -electric/upload/Steam-Electric_Detailed-StudyReport_2009.pdf 

### Stressor

Source

Receptors
and Exposure

Routes

Attribute Change(s) Individual organisms
Reduced survival

Reduced growth

Reduced reproduction Food chain

Reduction in algae

Reduction in prey Modification of PCEs related

to prey availability Habitat integrity
Reduction in primary productivity

Reduced cover Community change
Modification of PCEs related to
habitat Surface Water

Aquatic Animals

Invertebrates

Vertebrates 

### Exposure
Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants

Non

‐ vascular

Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous*

Invertebrates

Vertebrates Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc.) Ingestion Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway contributing to risk

Low likelihood of contributing to risk Use of DDC in Cooling Towers (Once Through and Recirculating)

WWTP microorganisms Uptake or sorption

Population Respiration
inhibition Direct Discharge

### Page 25 of 66 Figure 2 

### - Conceptual Model for Environmen tal Exposure of DDC Salts from Water System and Flue-Gas Desulfurization (FGD) to Aqua tic and Terrestrial Organisms



### Stressor

Source

Receptors
and Exposure

Routes

Attribute Change(s) Individual organisms
Reduced survival

Reduced growth

Reduced reproduction Food chain

Reduction in algae

Reduction in prey Modification of PCEs related

to prey availability Habitat integrity
Reduction in primary productivity

Reduced cover Community change
Modification of PCEs related to
habitat Surface Water

Aquatic Animals

Invertebrates

Vertebrates 

### Exposure
Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants

Non

‐ vascular

Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous*

Invertebrates

Vertebrates Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc.) Ingestion Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway contributing to risk

Low likelihood of contributing to risk Use of DDC in Water Systems and Flue

‐ Gas Desulfurization

WWTP microorganisms Uptake or sorption

Population Respiration
inhibition

### Page 26 of 66 Figure 3 – Conceptual Model for Aquatic (A ) and Terrestrial (B) Environmental Exposure
of DDC Salts in Recovered Water from Oil and Gas Use

Stressor

Source

Receptors
and Exposure

Routes

Attribute Change(s) Individual organisms
Reduced survival

Reduced growth

Reduced reproduction Food chain

Reduction in algae

Reduction in prey Modification of PCEs related

to prey availability Habitat integrity
Reduction in primary productivity

Reduced cover Community change
Modification of PCEs related to
habitat Surface Water

Aquatic Animals

Invertebrates

Vertebrates Exposure
Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants

Non

‐ vascular

Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous*

Invertebrates

Vertebrates Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc. ) Ingestion Waste Water Treatment Plant (WWTP)

Key

Most likely

exposure pathway contributing to risk

Low likelihood of contributing to risk Use of DDC in Hydraulic Fracturing (Fracking) Process for Oil and Gas Exploration

WWTP microorganisms Uptake or sorption

Population Respiration
inhibition Recovered Water (Flowback and Produced) Disposal Migration into
Groundwater (A)

Deep Well Injection

Migration into
Groundwater

Exposed Groundwater from

Soil Applications see Figure (B)

Stressor

Source/
Exposure
Media

Receptors
and Exposure

Routes

Attribute Change(s) Individual organisms
Reduced survival (emergence*)

Reduced growth

Reduced reproduction** Food chain

Reduction in prey Modification of PCEs related

to prey availability Habitat integrity
Reduction in primary productivity

Reduced cover Community change
Modification of PCEs
related to habitat Terrestrial Animals

Birds (Reptiles, Amphibians)

Mammals

Ingestion (B)

Key Most likely

exposure pathway contributing to risk
Low likelihood of contributing to risk Recovered Water (Flowback and Produced) Open Pit Storage or Evaporation Pond Use of DDC in Hydraulic Fracturing (Fracking) Process for Oil and Gas Exploration in Recovered Water

Irrigation Water Recovered Water (Flowback and Produced) Disposal

Terrestrial plants Grasses/forbs, fruit, seeds, trees, shrubs Contact/Uptake leaves, stems Soil

Root uptake

Ingestion

*Refers to seedling emergence **Vegetative vigor and seedling emergence endpoints are assumed to be as sensitive or more sensitive than reproduction endpoint and plant reproduction s not explicitly evaluated. Soil Leaching

Groundwater

See Figure (A) for aquatic exposure pathways

### Page 27 of 66 Figure 4 - Conceptual Model for Aquatic (A) and Terrestrial Environmental Exposure (B) of DDC Salts from Use in Oil and Gas Extraction, Drilling Muds/Fluids, Hydraulic Fracturing Fluids, and Primary, Secondar y, and Tertiary (Enhanced Oil) Fluids

Stressor

Source

Receptors
and Exposure

Routes

Attribute Change(s) Individual organisms
Reduced survival

Reduced growth

Reduced reproduction Food chain

Reduction in algae

Reduction in prey Modification of PCEs related

to prey availability Habitat integrity
Reduction in primary productivity

Reduced cover Community change
Modification of PCEs related to
habitat Surface Water /Sediment

Aquatic Animals

Invertebrates

Vertebrates Exposure
Media

Ingestion Ingestion Uptake/gills

or integument

Aquatic Plants

Non

‐ vascular

Vascular Uptake or sorption/cell, roots, leaves,

Piscivorous*

Invertebrates

Vertebrates Phytoplanktivore/

Herbivore

Invertebrates

Vertebrates

*As used here this term refers to animals (terrestrial or aquatic) that eat not just fish but any aquatic animal ( e.g ., amphibians, mollusks, crustaceans, etc. ) Ingestion Deep Well Injection

Key

Most likely

exposure pathway contributing to risk

Low likelihood of contributing to risk Use of DDC in Oil and Gas Extraction Drilling Muds/Fluids, Hydraulic, Fracking Fluids, Primary, Secondary and Tertiary (Enhanced Oil) Recovery Fluids

WWTP microorganisms Uptake or sorption

Population Respiration
inhibition Recovered Water/Fluids (Flowback

and Produced), Muds Disposal Migration into
Groundwater (A)

Waste Water Treatment Plant (WWTP) Migration into
Groundwater

Exposed Groundwater from

Soil Applications see Figure (B)

Stressor

Source/ Exposure
Media

Receptors
and Exposure
Routes

Attribute Change(s) Individual organisms
Reduced survival (emergence*) Reduced growth Reduced reproduction** Food chain Reduction in prey
Modification of PCEs related to prey availability Habitat integrity Reduction in primary productivity
Reduced cover Community change
Modification of PCEs
related to habitat Terrestrial Animals Birds (Reptiles, Amphibians)
Mammals

Ingestion (B)

Key Most likely

exposure pathway contributing to risk
Low likelihood of contributing to risk Recovered Water (Flowback and Produced) Open Pit Storage or Evaporation Pond Use of DDC in Oil and Gas Extraction Drilling Muds/Fluids, Hydrau lic, Fracking Fluids, Primary, Secondary and Tertiary (Enhanced Oil) Recovery Fluids

Irrigation Water Recovered Water (Flowback and Produced) Disposal

Terrestrial plants Grasses/forbs, fruit, seeds, trees, shrubs Contact/Uptake leaves, stems

Ingestion

*Refers to seedling emergence **Vegetative vigor and seedling emergence endpoints are assumed to be as sensitive or more sensitive than reproduction endpoint and plant reproduction s not explicitly evaluated. Soil

Root uptake Soil Leaching

Groundwater

See Figure (A)

for aquatic

exposure pathways

### Page 28 of 66 

# 4.3 Ecological Effects Assessment

4.3.1 Mode of Action

NaDDC and KDDC are synthetic broad-spectrum antimicrobial agents. Dithiocarbamate fungicides inhibit sulfhydryl (-SH) groups in am ino acids, proteins and enzymes of fungal and bacterial cells. While these salts are a subgroup of the carbamate pesticides, the agency made a 2001 final determination that in animals they do not share a common mechanism of toxicity 16



### . The dithiocarbamates all re lease carbon disulfide (CS 2 

### ), under acidic conditions, which is toxic to the central and peripheral nervous systems.



## 4.3.2 Measures of Effect (Ecotoxicology Endpoints)

Ecological effects data are used as measures of direct and indirect effects to aquatic and terrestrial organisms. Acute and chronic toxicity data from registrant-submitted studies will be used to evaluate the potential dir ect and indirect effect s of the DDC salts and degradates to plants and animals. The ecotoxicity data requirement s and all available ecot oxicity endpoints from studies submitted by registrants are tabulated in Appendix C .

OPP uses the most sensitive toxicity values for assessing risk to each receptor group. The endpoints that will be used for the DDC salts eco logical risk assessment are presented in Table 11. Anticipated data gaps for the TGAI also are indicated. Data also ar e included for thiram, a major reaction product and also a regist ered active ingredient (PC Code 079801).

Table 11. Selected Ecological Effect s Endpoints for Risk Assessment

Receptor

Group Surrogate Species Test

material Risk

Scenario Toxicity Endpoint EPA

ID

Freshwater fish Fathead minnow KDDC Acute 96-h LC 50 = 60 μg ai/L 240946

Chronic Data gap N/A

Bluegill Thiram Acute 96-h LC 50 = 42 μg ai/L 070801

Thiram
estimated using ACR Chronic NOAEC = 0.36 μg ai/L See Appendix
C

Freshwater
invertebrates Waterflea NaDDC Acute 48-h EC 50 = 52 μg ai/L 42504802

Chronic Data gap N/A

Thiram Acute 48-h EC 50 = 210 μg ai/L 164662

Chronic Under Review N/A

Estuarine/marine
fish Sheepshead

minnow NaDDC Acute 96-h LC 50 = 59,000 μg ai/L 41984701

Chronic Not a data gap: Mysid is more acutely sensitive N/A

Thiram Acute 96-h LC 50 = 540 μg ai/L 42514401

Chronic Not a data gap: Mysid is more acutely sensitive N/A

16 http://epa.gov/pesticides/cumulative/

### Page 29 of 66 Receptor

Group Surrogate Species Test

material Risk

Scenario Toxicity Endpoint EPA

ID

Estuarine/marine

invertebrates Mysid NaDDC Acute LC 50 = 88 μg ai/L 42561901

Chronic Data gap N/A

Thiram Acute LC 50 = 3.36 μg ai/L 42488302

Chronic Will use generated ACRs N/A

Aquatic nonvascular plants Green algae,
Freshwater

diatom,
Estuarine/marine diatom, and Cyanobacteria DDC salts IC 50 and
NOAEC Data gap N/A

Green algae Thiram Non-listed IC 50 = 45 μg a.i/L

42646001
Listed NOAEC <57 μg a.i/L (will
calculate IC 05 )

Aquatic vascular plants Lemna sp. TGAI IC 50 and
NOAEC Data gap N/A

Thiram Non-listed IC 50 = 1,600,000 μg a.i/L

45441202 Listed species NOAEC <57,000 μg a.i/L (will calculate IC 05 )

Semi-aquatic plants (seedling

emergence) Rice TGAI IC 50 and
NOAEC Data gap N/A

Vegetative Vigor Multiple species TGAI IC 50 and
NOAEC Data gap N/A

Birds Northern
bobwhite NaDDC (40) Acute LD 50 = 391 mg ai/kg bw 00159788

Ring-necked

pheasant Thiram (99) Acute LD 50 = 673 mg ai/kg bw 00160000

Mallard Thiram (97.5) Chronic NOAEC = 9.6 ppm 45441201

Beneficial insects Honeybee TGAI Acute Not Required (wood preservative use cancelled) NA



# 4.4 Exposure Analysis Plan

4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

In order to address the risk hypot hesis, the potential for adverse effects on the environment will be estimated. For down-the-drain (DtD) risk estim ates, an approach that estimates the number of days a concentration-of-concern (COC) is exceeded, also referre d to as a probabilistic dilution model (PDM) approach is used to assess risk to aquatic organisms.



## 4.4.2 Screening Level Down-the-Drain Analysis

The Industrial Releases Module of the E-FAST (Exposure and Fate Assessment Screening Tool)
will be used to determine th e potential for aquatic organism s downstream of the industrial

### Page 30 of 66 wastewater treatment plants that receive disc harges from the end-use of KDDC and NaDDC to be exposed these chemicals or their degradates . NaDDC and KDDC salts are used in industrial water systems such as commercial/industrial coo ling water, industrial wa stewater, pulp/paper mills, etc. Antimicrobials with these uses will eventually be released to industrial wastewater treatment plants whose effluents will reach surf ace water and aquatic organisms. The primary and major (>10 % of applied parent co mpound) degradates include the DMA, CS 2 

### , TMTDS, TMTMS, and TMTU. Chemicals that are released down-the-drain can typically take from a few
to several hours to reach wastewater treatment plant intakes following their discharge and from several hours to roughly a day following their di scharge down-the-drain to subsequently be discharged from industrial wastewater treatment pl ants to surface water. The half-life of both KDDC and NaDDC are long enough to enter the i ndustrial wastewater treatment plants and subsequently be discharged to surface waters.

This analysis plan will be re visited and may be revised dependi ng upon a full review of the data available in the open literature and the inform ation submitted by the public in response to the opening of the Registration Review docket. The agency does not anticipate requiring additional data to assess down-the-drain expos ures for this registration review.



# 4.5 Effects Analysis Plan

Additional open literature studies will be identified through EPA’s ECOTOXicology (ECOTOX)
database 17 

### , which employs a literature search engine for locating chemical toxicity data for aquatic life, terrestrial plants, and wildlife. Th e ECOTOX database will be searched when the risk assessment for the DDC salts is prepared. Open literature studies will be reviewed that potentially provide data for missing endpoint valu es or provide values more sensitive than available from the anticipated registrant-submitted studies. ECOTOX was created and is maintained by the USEPA, Office of Research and Development, and the National Health and
Environmental Effects Research Labora tory's Mid-Continent Ecology Division.



# 5 Endocrine Disruptor Screening Program (EDSP)

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include e ndpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of the 2009 Amended RE D, for DDC salts, 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), DDC salts are subject to the endocrine screening part of the Endocrine Disruptor Screenin g Program (EDSP).

17 http://cfpub.epa.gov/ecotox/

### Page 31 of 66 EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine-related eff ects 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 scr een all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/dat a call-ins for the firs t group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredient s. A second list of chemicals identified for EDSP screening was published on June 14, 2013 18 

### 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 ED SP, the policies and procedures, the list of chemicals, future lists, the test guidelines and the Tier 1 screening ba ttery, please visit our
website 19



### .


# 6 Next Steps

A DCI will be developed regarding the data needs listed under the “Risk Assessments and Anticipated Data Needs” section of this document. The agency expects to issue the DCI in June

of 2015.

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

chemicals.

19 http://www.epa.gov/endo/

### Page 32 of 66 

# 7 References

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Anonymous. 1978. Report of Laboratory Inve stigations. Unpublished study prepared by Sharpley Laboratories, Inc., Fr edericksburg, VA. Acc. No. 240946.

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Bodden, R. 1982. Avian Single-dose Oral LD 50 

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Conzelmann, P. 1982. Static 96- hour Marine Bioassay Testing Vinings Antimicrobial Agent AMA-31 on American Oyster: GSRI Pr oject No. 415-A60-41. Unpublished study received Apr 22, 1982 under 9386-7; prepared by Gulf South Research Institute, submitted by Vinings Chemical Co., Atlanta, GA; CDL:247417-D. MRID 00100704.

Conzelmann, P. 1982. Static 96- hour Marine Bioassay Testing Vinings Antimicrobial Agent AMA-31 on Blue Crab: GSRI Project No. 415-A60-41. Unpublished study received Apr 22, 1982 under 9386-7; prepared by Gulf South Re search Institute, submitted by Vinings Chemical Co., Atlanta, GA; CDL:247417-C. MRID 00100703.

Conzelmann, P. 1982. Static 96- hour Marine Bioassay Testing Vinings Antimicrobial Agent AMA-31 on Grass Shrimp: GSRI Project No. 415-A60-41. (Unpublished study received

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Croudace, C.; Caunter, J.; Johnson, P. 1992. Thiram : Acute Toxicity to Sheepshead Minnow ( Cyprinodon variegatus ): Lab Project Number: W199/B. Unpublished study prepared by Imperial Chemical Industries PLC. 22 p. MRID 42514401.

Douglas, M. 1993. Thiram: Algal Growth Inhibition ( Selenastrum capricornutum ): Lab Project Number: UCB 442/921255. Unpublished study prep ared by Huntingdon Research Centre Ltd. 30 p. MRID 42646001.

Flynn, F. and Agahigian, H. 1990. Physical a nd Chemical Characte ristics of Sodium Dimethyldithiocarbamate. Unpublished study prepared by R. T. Vanderbilt Co., Inc. in
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Flynn, F. 1992. Solubility of Sodium Dimethyl dithiocarbamate. Unpublished study prepared by R.T. Vanderbilt Co., Inc. 6 p. MRID 42510401.

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Knott, W.; Johnston, C. 1970. Busperse 49 (SASE): Evaluation of Acute LC50 for Rainbow Trout. Unpublished study received N ov 7, 1974 under 1448-56; prepared by Woodard Research Corp., submitted by Buckman Laborat ories, Inc., Memphis, TN; CDL: 240504-
A. MRID 00134589

Krueger, H.; Kendall, T. (2009) (Carbon 14)-Thira m: A Flow-Through Life-Cycle Toxicity Test with the Fathead Minnow ( Pimephales promelas ): Final Report. Project Number: 657A/103. Unpublished study prepared by Wild life International, Ltd. 144 p. MRID
47824101.

Lintott, D. 1992. Sodium Dimethyldithiocarba mate (SDDC): Acute Toxicity to Bluegill, Lepomis macrochirus Under Flow-Through Conditions: Lab Project Number: J9203010B. Unpublished study prepared by Toxicon E nvironmental Sciences. 84 p. MRID 42504801.

Lintott, D. 1992. Sodium Dimethyldithiocarbamate (SDDC): Acute Toxicity to the Water Flea, Daphnia magna Under Flow-Through Conditions: Lab Project Number: J9203010A. Unpublished study prepared by Toxicon E nvironmental Sciences. 85 p. MRID 42504802.

### Page 34 of 66 Lintott, D. 1992. Sodium Dimethyldithiocarba mate (SDDC): Acute Toxicity to the Mysid, Mysidopsis bahia , under Flow-through Test Conditions : Lab Project Number: J9203010D. Unpublished study prepared by Toxikon Environmental Sciences. 93 p. MRID 42561901.

McCann, J.A. 1976. Rainbow Trout (Salmo gairdneri ). Test No. 1001. (U.S. EPA, Chemical and Biological Investigations Branch, Anim al Biology Laboratory), Unpublished study.

McCann, J.A. 1976. Bluegill sunfish ( Lepomis macrochirus ). Test No. 996 (U.S. EPA, Chemical and Biological Investigations Branch, Anim al Biology Laboratory) Unpublished Study.
MRID 00070801.

McElwee, C.; Lintott, D. 1992. Sodium Dime thyldithiocarbamate (SDDC): Acute Effect on New Shell Growth of the Eastern Oyster, Crassostrea virginica : Lab Project Number: J9203010C. Unpublished study prepared by Toxikon Environmental Sciences. 82 p.
MRID 42561902.

Morgenroth, U.; Mueller-Kallert, H. (1995) (C arbon 14)-Thiram: Degradation and Metabolism
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Obrist, J. 1987. Aerobic Aquatic Meta bolism of [Carbon 14]-D ibam (Sodium N,NDimethyldithiocarbamate): Laboratory Project Identification: HLA 6015-279. Unpublished study prepared by Hazleton Labor atories America, Inc. 104 p. MRID
40365701.

Obrist, J. 1987. Anaerobic Aquatic Meta bolism of [Carbon 14]-D ibam (Sodium N,NDimethyldithiocarbamate): Laboratory Project Identification: HLA-6015-271. Unpublished study prepared by Hazleton Labor atories America, Inc. 85 p. MRID
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Obrist, J. 1987. Photodegradation and Hydrolysis of [Carbon 14]- Dibam (N,N,- Dimethyldithiocarbamate) in Buffered Aqueous Solutions: Final Report: Lab Project ID: HLA 6015-278. Unpublished study prepared by H azleton Labs America, Inc. 182 p.
MRID 40220701.

0’Graney, R. 1982. The Acute Toxicity of Busan 85 to Daphnia magna Straus: Project No. 82- E-048-D. Unpublished study received Jun 3, 1982 under 1448-70; prepared by Biospherics, Inc., submitted by Buckman Labor atories, Inc., Memphis, TN; CDL:247734-
A. MRID 00105154.

Reynolds, J. 1995. Aerobic Aquati c Metabolism of (carbon 14) (ine rt ingredient): Lab Project Number: XBL94084: RPT00216. Unpublished st udy prepared by XenoBiotic Lab., Inc. 120 p. MRID 48685902.

### Page 35 of 66 Reynolds, J. 1995. Aerobic Soil Metabolism of ( carbon 14) (inert ingred ient): Lab Project Number: XBL94082: RPT00214. Unpublished st udy prepared by XenoBiotic Lab., Inc. 118 p. MRID 43865901.

Shepler, K.; Runes, H. (2002) Photodegradati on of (Carbon 14) Thiram in/on Soil by Artificial Light: Lab Project Number: 1043W: 1043W- 1: 1042W-004. Unpublished study prepared by PTRL West, Inc. 115 p. MRID 45724501.

Shepler, K.; Runes, H. (2002) Photodegradation of (Carbon 14) Thiram in Sterilized Buffer at pH 5 by Artificial Light: Lab Project Number: 1042W. Unpub lished study prepared by PTRL West, Inc. 117 p. MRID 45651201.

Sutherland, C.; Kendall, T.; Krueger, H. (2001) Th iram Technical: A 7-Day Toxicity Test with Duckweed ( Lemna gibba G3): Final Report: Lab Proj ect Number: 357A-101. Unpublished study prepared by Wildlife Interna tional. Ltd. 79 p. {OPPTS 850.4400}. MRID
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U.S. EPA. 2009b. Sodium and Potassium Dime thyldithiocarbamate Sa lts: Amendment to the Ferbam (PC Code 034801) and Ziram (PC Code 034805) Reregistration Eligibility
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U.S. EPA. 2009c. “Dietary Risk Assessment fo r Potassium Dimethyldithiocarbamate for the RED Process”. Memorandum for Regulatory Mana gement Branch II, from Najm Shamim, Chemist, Antimicrobials Division, Office of Pe sticide Programs, Arlington, VA. July 14,
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### Page 36 of 66 http://water.epa.gov/scitech/wastetech/ guide/steam-electric/upload/SteamElectric_Detailed-Study-Report_2009.pdf

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Ward, G. (1991) Sodium Dimethyldithiocarbama te (SDDC): Acute Toxicity to Sheepshead Minnow, Cyprinodon variegatus , under Flow-Through Test Conditions: Lab Project Number: J9010004B. Unpublished study prepared by Toxikon Environmental Sciences. 54 p. MRID 41984701.

Wheat, J.; Ward, G. 1992. Sodium Dimethyldi thiocarbamate (SDDC): Acute Toxicity to Rainbow Trout, Oncorhynchus mykiss , Under Flow-through Test Conditions: Lab Project Number: J9010004D. Unpublished study prepared by Toxikon Environmental Sciences. 59 p. MRID 42247901.

### Page 37 of 66 

# Appendix A Toxicology Profile for Dimethyldithiocarbamate

I. BACKGROUND

Both sodium dimethyldithiocarbamate and potassi um dimethyldithiocarbamate react with water readily and decompose into their respective salts. Du e to their structural and chemical similarities as shown in Table 1, the bridging of their toxicological databases was ascertained. A consensus was reached on bridging the repeat exposure data base of both sodium dimethyldithiocarbamate and potassium dimethyldithiocarbamate in th e ADTC endpoint selection meeting (US EPA, 2009). However, the acute toxicologi cal database could not be bridge d due to lack of data on the technical active ingredient on each of the chemicals.

Table 1. Chemical structures

Sodium dimethyldithiocarbamate Potassium dimethyldithiocarbamate

Adapted from RED, Table 1. p. 1



### II. Acute Toxicity

A. Sodium dimethyldithiocarbamate

The acute toxicity summary for sodium dimethyldithiocarbamate is provided in Table 2. Sodium dimethyldithiocarbamate is corrosive to the eye a nd causes mild or slight irritation to skin. The toxicity study with sodium dime thyldithiocarbamate yielded a Toxi city Category II with dermal route of exposure and a Toxicity Category IV with inhalation route of exposure study. There were no acceptable acute oral t oxicity studies available; however, an unacceptable / guidelineupgradeable study’s (MRID 00160993, 00160994) results were considere d. An acute oral study for the sodium salt is anticipated to be require d for the product specific data call in (PDCI).

### Page 38 of 66 Table 2. Acute toxicity database fo r sodium dimethyldithiocarbamate

Guideline
No. Study Type MRID number (s) Results Toxicity Category

81-1 Acute Oral No acceptable study
available. LD 50 

### (M) = 2100 mg/kg

LD 50 

### (F) = 2500 mg/kg III

81-2 Acute Dermal 00160995, 92043009 LD 50 

### (M) = 1450 mg/kg

LD 50 

### (F) = 1020 mg/kg II

81-3 Acute Inhalation 00159769, 42327801,
92043010 LC 50 

### (M) > 2.22 mg/L

LD 50 

### (F) > 2.22 mg/L IV

81-4 Primary Eye
Irritation 00161185, 92043011 Corrosive I

81-5 Primary Skin
Irritation 00159782, 43481501,
92043012 Mild or slight IV

81-6 Dermal
Sensitization 00159783, 92043013 Negative

Adapted from RED (2009), Table 5, p. 9



### B. Potassium dimethyldithiocarbamate

The acute toxicity summary table for potassium dimethyldithiocarbamate is provided in Table 2. Potassium dimethyldithiocarbamate is a dermal se nsitizer and causes moderate dermal irritation. The primary eye irritation study was assigned a Toxicity Category of III with the corneal
involvement reversible within 7 days. A Toxicity Category III wa s assigned to both acute oral and dermal toxicity studies. No inhalation study was provided. An acut e inhalation toxicity study for the potassium dimethyldithiocarbamate is anticipated to be required for the PCDI.

Table 3. Acute toxicity database fo r potassium dimethyldithiocarbamate

Guideline
No. Study Type MRID (s) Results Toxicity Category 81-1 Acute Oral 00132382,
92039001
00143448* LD 50 

### (M) = 2196 mg/kg (LD 50 

### (F) = 1867 mg/kg III

81-2 Acute Dermal 00146768,
92039002
00132381*
00143449* LD 50 

### (M) = 2990 mg/kg III

81-3 Acute Inhalation No study available 81-4 Primary Eye
Irritation 00105157,
92039003 PIS: 32.2/110 unwashed,
PIS: 40.7/110 washed III **



### 81-5 Primary Skin
Irritation 00105157,
92039004 Primary Irritation Index:
3.08 after 72 hours III

81-6 Dermal
Sensitization 00132380,
92039005 Positive

Adapted from RED, Table 6, p. 10 * MRIDs 00143448, 00132381, and 00143449 not included in th e table, but included in toxicology profile ** An unacceptable primary eye irritation study (M RID 00143448) was assigned a Toxicity Category II.

### Page 39 of 66 III. Repeat Dose Toxicity

The toxicological database of re peat dose studies for dimethyldith iocarbamate is listed in Table
3. All of these studies were included in the ha zard assessment that was written for the RED (US EPA, 2009). No new studies have been submitted since the publication of the RED, and no data are anticipated to be required. Summar ies of the toxicity profiles for Sodium dimethyldithiocarbamate and Potassium dimethyl -dithiocarbamate are included in Tables 4 and 5, respectively.

Table 4. Toxicological Database of Repeat Dose Studies for Dimethyldithiocarbamate

Guideline
Number Study Required Satisfied MRID Number(s) (Chemical)

870.3100 90-Day Oral - Rats Yes Yes 42047201 (NaDDC) 870.3250 90-Day Dermal -Rats Yes Yes 40830801 (KDDC) 870.3250 90-Day Dermal -Rabbit Yes Yes 40140101 (NaDDC) 870.3700a Developmental Toxicity- Rats Yes Yes 40140102 (NaDDC), 41005501 (KDDC) 870.3700b Developmental Toxicity- Rabbits Yes Yes 40165804 (NaDDC), 40995101 (KDDC) 870.3800 Reproduction and Fertility Effects Yes No 42905, 82096* 870.4100a Chronic Toxicity – Rats Yes No 82096*

870.4100b Chronic Toxicity – Dogs No No 82905*
870.5100 Bacterial Reverse Mutation Test Yes Yes 159688 (NaDDC), 40631103 (KDDC)

870.5300 In vitro Mammalian Cell Gene Mutation Test Yes Yes 159779 (NaDDC), 4089901 (KDDC)

870.5375 In vitro mammalian chromosome aberration

test Yes Yes 159681 (NaDDC)

870.5550 Unscheduled DNA Synthesis in Mammalian
Cell Culture Yes Yes 40631101 (KDDC)

870.5900 In vitro Sister Chromatid Exchange Assay Yes Yes 159778 (NaDDC), 40631102 (KDDC) 870.6200 Neurotoxicity Screening Battery Yes Yes 43544201 (NaDDC)

870.6200 Neurotoxicity Screening Battery Yes Yes 43550501 (NaDDC)

Adapted from RED, Table 4, p. 7.

*MRID numbers not in references or profile

### Page 40 of 66 Table 5. Toxicity Profile of Sodium Dimethyl dithiocarbamate (excluding acute studies)

Guideline No./

Study Type MRID No./ Study
Classification Animals Tested and Dose
Administered Results

Subchronic Toxicity

870.3100 90-Day Oral
Subchronic (Rat) MRID 42047201 Acceptable
Core-Minimum 10 Sprague-Dawley rats/sex/dose

Gavage dose at 0.2, 2, or 100 mg/kg/day for 13 weeks. LOAEL = 100 mg/kg/day, based on decreased erythrocyte counts, increased glucose concentration, and increased alkaline phosphatase activity in females, and exocrine pancreatic atrophy with
fibrosis in males.

NOAEL = 0.2 mg/kg/day
870.3250 90-Day Dermal (Rabbit) MRID 40140101 Acceptable/
Guideline 10 New Zealand White
rabbits/sex/dose

Dermal dose to the clipped unabraded dorsal surfaces at 0, 20, 60, or 120 mg/kg/day, 6 hours/day, 5 days/week for 13
weeks. Systemic Toxicity LOAEL = 120 mg kg/day , based on decreased leukocyte and platelet counts. NOAEL = 60 mg/kg/day

Dermal Irritation LOAEL = 20 mg/kg/day, based on redness, edema, and/or desquamation at
the treatment site.
NOAEL Not Determined 

### Developmental Toxicity

870.3700a Developmental Toxicity (Rat) MRID 40140102 Acceptable 22 Female Sprague-Dawley
rats/dose Gavage in water at 0, 2, 20, or 200 mg/kg/day on gestation days 6-15, inclusive. On GD 20, dams were sacrificed and necropsied. Maternal Toxicity LOAEL = 2 mg /kg/day based on decreased corrected body weights.
NOAEL Not Determined

Developmental Toxicity
LOAEL Not determined
NOAEL ≥ 200 mg/kg/day
No treatment related effects
870.3700b Developmental Toxicity (Rabbit) MRID 40165804 Acceptable 18 New Zealand White
rabbits/dose Administered by gavage in distilled water at doses of 0, 0.4, 4, or 40 mg/kg/day on gestation days 7-19, inclusive. On GD 29, surviving does were sacrificed and necropsied. Maternal Toxicity LOAEL = 40 mg/kg/day , based on decreased body weights. NOAEL = 4 mg/kg/day

Developmental Toxicity
LOAEL Not Determined
NOAEL ≥ 40 mg/kg/day
There were no treatment related effects 

### Mutagenicity

870.5100
Bacterial Reverse
Mutation Test MRID 00159688 Acceptable Concentrations of 4, 40, 133, 400 or 1333 μg ai/plate. Positive Positive results (frequencies of revertants greater than twice solvent control) were registered in three strains (TA100, TA1535, and TA1537), both with/without metabolic activation at non-cytotoxic dose levels (lowest dose levels at which effects occurred: 4 or 40 μg/plate ± S9).

### Page 41 of 66 870.5300
In Vitro
Mammalian Cell
Gene Mutation

Test MRID 00159779 Acceptable Chinese Hamster Ovary Cells Negative

870.5375
In Vitro
mammalian
chromosome
aberration test MRID 00159681 Acceptable Chinese Hamster Ovary Cell
Cultures Positive in the presence of S9

870.5900
In Vitro Sister
Chromatid Exchange Assay MRID 00159778 Acceptable Chinese Hamster Ovary Cell
Cultures Negative



### Neurotoxicity

870.6200 Neurotoxicity Screening Battery MRID 43544201 Acceptable 17 Sprague-Dawley rats/sex/dose

Single gavage doses of 0, 20, 400, or 790 mg/kg/day. Neurotoxicity NOAEL = 20 mg /kg/day LOAEL = 400 mg /kg/day based on clinical signs of toxicity, numerous FOB parameter effects and decreased motor activity

ChE Inhibition NOAEL= 790 mg /kg/day (HDT)
There were no test material-related effects on plasma, RBC, or brain ChE activity for males or females at any dose level.

870.6200 Neurotoxicity Screening Battery MRID 43550501 Acceptable 15 Sprague-Dawley rats/sex/dose

Gavaged at daily doses of 0, 0.2, 2, or 99 mg/kg/day for 13 weeks. Systemic (Clinical) Toxicity NOAEL = 2 mg/kg/day. LOAEL = 99 mg/kg/day based on Salivation, oral staining and decreased body weight.

Neurotoxicity NOAEL > 99 mg/kg/day, except for
minor clinical effects at the HDT (salivation; wet-mouth staining; decreased body weight of 2% - 8% in males; 2% to 6% in females), no significant neurotoxic or other systemic effects were recorded.
Adapted from RED, Table A3, p. 46



### Table 6. Toxicity Profile of Potassium Dime thyldithiocarbamate (exc luding acute studies)

Guideline No./ Study Type MRID No./
Classification Dosing and Animal
Information Results

Subchronic Toxicity

870.3200 21-Day Dermal (Rat) MRID 40747003 Supplementary A pilot study for 90-day dermal Sprague-Dawley Rat (5/sex/dose) Doses of 0, 51.3, 128, 257, 385, or 513 mg/kg/day, respectively were applied 5 days/week for 3 Dermal Irritation NOAEL: 257 mg/kg/day LOAEL: 385 mg/kg/day , based on slight
dermal irritation in 2-3 females but not males. In addition, at 1000 mg/kg/day 3/5

### Page 42 of 66 study (MRID 40830801) weeks. A gauze patch was applied to the dosing area for 6 hours per day. males and 5/5 females exhibited slight
dermal irritation

Systemic Effects NOAEL: 257 mg/kg/day LOAEL: 385 mg/kg/day based on female body weight gain decrement and reduced food efficiency.

870.3250 90-Day Dermal (Rat) MRID 40830801 Acceptable
Core-Minimum 10 Sprague Dawley
Rats/sex/dose Doses of 0, 38.5, 180, or 385 mg/kg/day for 6 hr/day, 5 d/wk
for 13 weeks. Dermal Irritation LOAEL = 180 mg/kg/day, based on mild to moderate acanthosis, partial eschar, and ulceration, with ulceration occurring at 385 mg a.i./kg/day NOAEL: 38.5 mg/kg//day

Systemic Effects LOAEL = 385 mg/kg/day, based on reduced body weight in males, decreased erythrocyte count and hematocrit in males, and hemosiderosis in the spleens of both

sexes. NOAEL = 180 mg a.i./kg/day 

### Developmental Toxicity - Teratogenicity

870.3700a Developmental Toxicity (Rat) MRID 40747001 Supplementary - Pilot Study for the main study MRID
41005501 8 Sprague-Dawley Rats/dose

Doses via gavage to pregnant rats at 0, 51.3, 103, 205, 308, 410 mg/kg/day respectively from gestation days 6 through 15. Developmental Toxicity NOAEL = 51 mg/kg/day LOAEL = 205 mg/kg/day , based on postimplantation loss and fetal weight decrements at 600 mg/kg/day and above

Maternal Toxicity NOAEL < 51 mg/kg/day LOAEL <51 mg kg/day , based on body weight gain decrements. Salivation at 103 mg ai/kg/day and above.

870.3700a Developmental Toxicity (Rat) MRID 41005501 Acceptable 28 Sprague-Dawley Rats/dose

Doses via gavage in water at 0, 0, 12.8, 77, or 205 mg/kg/day, on gestation days 6-15, inclusive. On GD 20, dams were sacrificed and necropsied. Maternal Toxicity LOAEL: 77 mg/kg/day, based on reduced body weights and body weight gains and reduced food consumption. NOAEL: 12.8 mg/kg/day

Developmental Toxicity

NOAEL:  205 mg/kg/day(HDT) At 205 mg a.i./kg/day, mean fetal weight was marginally decreased.

870.3700a Developmental Toxicity (Rabbit) MRID 40747002 Supplementary –
Pilot Study for the main study
MRID 40995101 6 female rabbits/dose. Dose was via gavage to pregnant rats at doses of 0, 12.8, 26.6, 77, 154, or 256 mg/kg/day from gestation days 6 through 18. Developmental Toxicity
NOAEL: 75 mg/kg/day LOAEL: 77 mg/kg/day based on postimplantation loss and fetal weight
decreases.

Maternal Toxicity NOAEL: 26.6 mg/kg/day LOAEL: 77 mg/kg/day based on body weight gain decrements. Death occurred at 154 and 256 mg/kg/day

### Page 43 of 66 870.3700a Developmental Toxicity (Rabbit) MRID 40995101 Acceptable 20 inseminated female
Rabbits/dose

Dose by gavage in water at 0, 0, 12.8, 38, or 77 mg/kg/day on GD 6-18, inclusive. On GD 29, the
does were sacrificed and necropsied. Maternal Toxicity LOAEL: 38 mg/kg/day, based on clinical signs (reddish-colored material in cage trays), and possible increased maternal
death and abortions. NOAEL: 12.8 mg /kg/day

Developmental Toxicity LOAEL: 38 mg /kg/day, based on malalignment of sternebrae, increased early and total implantation losses, and decreased fetal weights. NOAEL: 12.8 mg /kg/day Mutagenicity

870.5100
Bacterial Reverse Mutation Test (Rat) MRID 40631103 Acceptable S. typhimurium strains TA98, TA100, TA1535, TA1537, and
TA1538 Positive

870.5300 In Vitro
Mammalian Cell
Gene Mutation Test MRID 40899001 Acceptable Chinese Hamster Ovary K1-BH4 (CHO) Cells Positive

870.5550
Unscheduled DNA Synthesis in
Mammalian Cell
Culture MRID 40631101 Acceptable Rat hepatocyte cultures Negative

870.5900
In Vitro Sister
Chromatid Exchange Assay MRID 40631102 Acceptable Chinese Hamster Ovary Cells Negative

Adapted from RED, Table A4, p. 53



### VI. Additional Data Gaps

A multi-generation reproduction study and a 90-da y inhalation toxicity study conducted with sodium dimethyldithiocarbamate we re identified as data gaps and are anticipated to be required studies for an adequate risk characterization. Structure activity relationship (SAR) analysis may be used to address the reproductive study concern. If the industry is interested in the SAR approach, a complete and valid SAR analysis sh ould be submitted by th e registrant, and the Agency will consider the validity of the approach.

An in vivo mutagenicity study such as an erythrocyt e micronucleus assay is anticipated to be required.

An immunotoxicity study is a data requirement fo r all antimicrobial pesticide chemicals under 40 CFR Part 158W, Data Requirements for Antimicrobi al Pesticides. The re gistrant can address this data requirement by submitting a study according to the OCSPP 870.7800 guideline, citing
information from the scientific literature th at addresses immunotoxic ity of DDC salts, or submitting a request for waiver of this study usin g the agency’s published guidance, available at: http://www.epa.gov/pesticides/regul ating/part158-tox- data-requirement.pdf

.

### Page 44 of 66 References for Appendix A

US EPA, 2009. Hazard Assessment for the Reregi stration Eligibility De cision (RED) Document of Sodium Dimethyldithiocarbamate and Pota ssium Dimethyldithioca rbamate. February 5,
2009

### Page 45 of 66 

# Appendix B Environmental Fate

NaDDC and KDDC salts are active ingredients in an timicrobials that can be used as material preservatives in water systems (air wa sher, reverse osmosis, and industrial), commercial/industrial cooling water, industrial wastewater, pulp/pap er mills, gas and oil (drilling muds/packer fluids, recovery inj ection water, fracturing fluids, workover and completion fluids), flue gas desulfurization thickeners in smokestacks at coal-fired power plants, and sugar mills (cane and beet).

The half-lives in environmental fate studies indi cate that both parent NaDDC and its degradates can reach WWTPs where they will be associated with water instead of sludge based on their water solubilities (260,000-1.63 million mg/l) 20



### , log Kow values (-0.38-1.94) of less than 3, and limited sorption to soil (Koc values of 312-445 ml/g) 21 

### . Although the half-lives for NaDDC and its degradates in water are relatively short (rangi ng up to 6.7 days), these estimates of persistence are not short enough to prevent residues from en tering WWTPs. Data on the half-life of NaDDC and its degradates in environmental media do not provide specific information on the potential for these compounds to be removed during the wast ewater treatment process in which conditions are present that tend to promote removal of chem ical substances from WWTPs, particularly via processes such as biodegradation and sorption. 22 

### Table B1 and Table B2 contain the chemical, physical, and environmental fate properti es of the DDC salts and degradates.

Abiotic

Hydrolysis

Parent NaDDC is composed of DMA and CS 2 

### moieties. When hydrolyzed it forms DMA, CS 2 

### , a re-combination of DMA and CS 2 

### called TMTU, TMTDS, which is also known as thiram, and TMTMS. A hydrolysis study 23 

### in buffered aqueous solutions demonstrated that abiotic hydrolysis of NaDDC is pH dependant. The rate of hydrolysis and the relative amounts of major degradates DMA and CS 2 

### increased with decreasing pH. He nce acidic conditions will favor the decomposition of the DDC anion into DMA and CS 2 

### . Formation of oxidative degradates such as the disulfide appears to be more predominant in alkaline as opposed to acidic or neutral conditions. The estimated abiotic hydrolysis half-lives of NaDDC are 16.5 min, 29.4 hours and 42.8 days at pH 5, 7 and 9, respectively.

Photodegradation

A registrant-submitted study for photode gradation of NaDDC in water 24 

### did not track degradates. The photolytic half- lives at pH 5, 7 and 9 were 26 minutes, 17.6 hours and 21.2 hours, respectively. Two degradation products were obser ved in all samples and a third degradate was

20 http://www.epa.gov/opptintr/exposure/pubs/episuite.htm

21 MRID 00164056

22 MRIDs 43180801, 40220701, 40365701, and 40365702

23 MRID 43180801

24 835.2240, MRID 40220701

### Page 46 of 66 observed in all pH 7 and pH 9 samples. T hough these degradates were not identified , the photodegradation in water study is satisfied with the combination of MRIDs 40220701 and
45651201 25 

### , which is an acceptable study for the active i ngredient Thiram. Thiram is a dimer of the DDC acid and therefore any degradates present are expected to be the same as for NaDDC. In MRID 45651201, parent Thiram photodegraded in water with a half-l ife of 6.6 hours and formed four degradates that reached si gnificant (>10 % of applied parent Thiram) concentrations. Three of the four degradates we re intact Thiram dimers with substitutions of oxygen for sulfur and additions of oxygens to sulfur. Thiram sulfone (addition of two oxygen molecules) reached up to 31 % of applied pare nt compound by 24 hours (e nd of study). Thiram oxo (oxygen substituted for a sulfur) reached 11 % of applied parent compound by 24 hours. Thiram oxo sulfone (both oxo and sulfone gr oups) reached up to 15.3 % by 12 hours and decreased to 9 % by 24 hours. The fourth degradat e was a mixture of sulfonic acid monomers of DDC in either an oxo form or a thio (sulfur-con taining) form. The sum of these sulfonic acid degradates increased to 17-21 % of applied th iram by 24 hours. Table B2 below contains the chemical and physical properties of these four degr adates. No additional data are anticipated to be required.

Data on photodegradation on soil 26 

### were not submitted for either NaDDC or KDDC salts. However, acceptable data on photodegradation on soil were submitted in MRID 45724501 for the active ingredient Thiram. The half-lives of parent Thiram we re 0.72 days for the irradiated treatment and 1.78 days for the dark control treatment, with a dark-c ontrol adjusted half-life of 1.2 days. CO 2 

### was the only significant (formed at >10 % of applied Thiram) degradate. No additional data are expected to be required.

Soil Adsorption/Desorption (Kd) and Octanol-Water Partition Coefficient (Koc)

In an adsorption/desorption study 27 

### on agricultural soils, the cha nge in concentration of an aqueous NaDDC solution was determined for four soil types: Plainfield sand, California sandy loam, Plano silt loam and Hagerstown silty clay loam. At approximately 25°C adsorption values (Kd) were observed to be 6.0, 12.6, 6.5 and 1.45 mL/g, respectively. Corresponding Koc values were 343, 367, 445 and 312 mL/g, respectively. Deso rption of adsorbed DDC salts generally ranged from 0-25% but no desorpti on values were calculated. Sorption of DDC salts to soil particles increases with increasi ng organic carbon (OC) content (r 2 

### = 0.98) and pH (r 2 

### = 0.56). No additional data are anticipated to be required.

Sludge Adsorption/Desorption

No data on sludge sorption (OCSPP GLN 835.1110) have been submitted. Sorption to sludge is not a likely route of dissipation be cause the log Kow is less than thre e (3). Therefore data are not anticipated to be required. 28

25 45651201, 835.2240

26 835.2410

27 835.1230, MRID 00164056

28 Final 158 W regulations, 40 CFR Part 158.2282, test note 19, at 78 FR 26991.

### Page 47 of 66 Biotic

Aquatic Metabolism

Aerobic and anaerobic aquatic metabolism al so degrade NaDDC. In an aerobic aquatic metabolism study (MRID 40365701), rapid degrada tion of NaDDC was observed with an estimated half-life of 6 days. Th ree major unidentified degradates (Peaks A, B, & C) which are most likely to be TMTMS, TMTDS, and TMTU , respectively, were detected using high performance liquid chromatography (HPLC). Under anaerobic conditio ns, NaDDC degraded into the same three degradates as seen under aerobic metabolism with TMTDS being the major degradate identified. Non-linear half-lives fo r TMTDS and TMTMS were 67 days and 15 days, respectively under the conditions of the study. Co mplete mineralization of the parent compound
was evident under both aerobic and anaerobic co nditions as indicated by the amount of carbon dioxide (CO 2 

### ) formed, 38% and 36%, respectively. No additional data are anticipated to be required.

Soil Metabolism

No aerobic soil metabolism data were submitted for parent NaDDC. However, an acceptable aerobic soil metabolism study (MRID 43734901) was s ubmitted for Thiram which degraded with a non-linear half-life of 2.1 days in sa ndy loam soil. TMTU, TMU, TMTM, and CS 2 

### were minor (<10 % of applied Thiram) degradates. Evolved CO 2 

### accounted for 9.0% of the applied radioactivity at 2 days post-t reatment and increased to a maximum of 75% by 205 days. The

DT 50 

### , DT 75 

### , and DT 90 

### for thiram were approximately 1.7, 4.8, and 9.8 days, respectively. No additional data are anticipated to be required for parent NaDDC.

The agency also received registrant- s ubmitted aerobic soil metabolism (OCSPP GLN 835.4100, MRID 43685901) and aerobic aquatic meta bolism (OCSPP GLN 835.4300, MRID 43685902) studies for DEA, a surrogate compound for the de gradate DMA. The half-lives of DEA in the studies were 1.7 and 11 days, respectively. No ma jor degradates were formed in the studies. While DEA is an appropriate su rrogate compound for DMA, there is no record of review for these studies. However, the only use site tr iggering a soil metabolism study is the wood preservative use and the sole product with that use has been cancelled (see section 1.5.1). No
additional soil metabolism studies ar e anticipated to be required.

Terrestrial Field Dissipation

Data on terrestrial field di ssipation (OCSPP GLN 835.6100) were not submitted for either NaDDC or KDDC salts. The agency has reviewed the need for these data and determined that the aerobic soil metabolism half-life of approxi mately two days indicates limited potential for leaching to ground water or runoff to surface water. No additional data are anticipated to be required.

Metabolism in Sewage Sludge and Activated Sludge Respiration Inhibition (ASRI)

### Page 48 of 66 No data on ASRI or on degradation in sewage sl udge have been submitted but are anticipated to be required. The results of the ASRI test de termine which of four tests are required and determines the extent of impacts to WW TP organisms. If the ASRI test EC 50 

### is equal to or less than 20 mg/L, then one of three simulation test s would be anticipated to be required: OCSPP GLNs 835.3220, 835.3240, or 835.3280. If the ASRI test IC 50 

### is greater than 20 mg/L, then the applicant can choose to conduct a ready biodegradability test (OCSPP GLN 835.3110) or one of the three simulation tests ( i.e. , OCSPP GLNs 835.3220, 835.3240, or 835.3280). Pass criteria for the ready biodegradability study are: 70 percen t removal of dissolved organic carbon and 60 percent removal of theoretical oxygen demand or theoretical CO 2 

### production for respirometric methods. These pass levels should be reached in a 10-day window within the 28-day period of
the test. If the antimicrobial passes the ready biodegradability study, then no further testing is anticipated to be required. If the antimicrobial fails the ready biodegrad ability study, then the applicant should conduct one of th e three biodegradation in activ ated sludge simulation tests mentioned previously.Docket Number EPA-HQ-OPP-2013-0245www.regulations.govPage49of66Table B1 – Physical-Chemical and Fate Properties for Sodiumand Potassium Dimethyldithiocarbamate Salts and DegradatesTest GuidelineParent Compounds29Degradates30NaDDCKDDC31Dimethylamine(DMA)Carbondisulfide (CS2)TMTDS(Thiram)32TMTMS33TMTU34TMU35Reference (MRIDfor ParentCompounds unlessStated, EPI-Suite forDegradates)CAS Number 128-04-1 128-03-0 124-40-3 75-15-0 137-26-8 97-74-5 2782-91-4 632-22-4 EPI-Suite 4.11Molecular Formula C3H6N1S2Na1C3H6N1S2K1C2H7N1C1S2C6H12N2S4C6H12N2S3C5H12N2S1C5H12N2O1EPI-Suite 4.11Molecular weight 143.20 159.31 45.08 76.13240.42 208.36 132.22 116.16 EPI-Suite 4.11Chemical StructureN/APhysical-Chemical PropertiesMelting Point (oC) N/A36N/A37-92.2 -111.5 107 109.5 79.3 -1.2 EPI-Suite 4.11Boiling Point (oC) 102 >100 6.8 46 339 301.3 245 176.5 EPI-Suite 4.11Water Solubility(mg/L)1.32 x 106Easilysoluble1 x 1062,160 30 1 x 106350,000 1 x 106EPI-Suite 4.11Dissociation Constantin Water (pKa)7.2 7.2 No data No data No data No data No data No data41609403EPI-Suite 4.11Octanol-waterPartition Coefficient(Log Kow)-2.41(EPI-Suite 4.1)-1.43(EPI-Suite4.1)-0.38 1.94 1.73 0.75 0.49 0.19 EPI-Suite 4.1129Chemical and physical properties of parent compounds relative toenvironmental risk assessmentare listed in Table 4 above. Values in this Table B1 arecopied from Table 4.30Major degradates were formed at >10 % of applied parent compound. Minor degradates were formed at <10 % of applied parent compound.31Environmental fate datawere submitted for NaDDCbut not KDDC. Both compounds are saltsand therefore will readily disassociate in water to form the Naor K cations and the DDC anion. As a result, NaDDC is an acceptable surrogate for KDDC.32DDC anion forms a cross-linked dimer TMTDS, which is joined bytwo (2) sulfur molecules. Thisdimer is the active ingredientThiram (PC Code 079801).33Cross-linked DDC anions joined by one (1) sulfur instead of two sulfurs.34Tetramethyl thiourea (TMTU)35Tetramethyl urea (TMU)36Not applicable37Not applicablePage50of66Test GuidelineParent Compounds29Degradates30NaDDCKDDC31Dimethylamine(DMA)Carbondisulfide (CS2)TMTDS(Thiram)32TMTMS33TMTU34TMU35Reference (MRIDfor ParentCompounds unlessStated, EPI-Suite forDegradates)Koc(ml/g) 312-445 No data384.7 48 676 337.3 25.7 8.600164056EPI-Suite 4.11Soil adsorption/desorption (ml/g)1.5-12.6 No data393.2 No data No data Nodata No data No data00164056EPI-Suite 4.11Sludge adsorption/desorption (%)<1.9 <1.9 1.74 0.6 1.6 1.5 0.63 0.62 EPI-Suite 4.11BioconcentrationFactor (BCF)No data No data 3.2 8.9 6.4 3.2 3.2 3.2EPI-Suite 4.11Vapor Pressure (mmHg)4.2 x 10-98.2 x 10-101.5 x 10+3359 1.7 x 10-52.7 x 10-41.1 x 10-21.4 x 10+1EPI-Suite 4.11Henry’s Law Constant(atm-m3/mole)7.9 x 10-162.0 x 10-164.5 x 10-51.2 x 10-23.8 x 10-108 x 10-105.2 x 10-95.0 x 10-5EPI-Suite 4.11Abiotic Degradation Half-lives (days unless specified)Hydrolysis835.212017 min (pH 5)29 hours (pH 7)43 days (pH 9)No dataStable, did notdeclineStableMinordegradateMinor Not formed Not formed 43180801Photodegradation inwater835.2240403 hours (pH 5)2.1 days (pH 7)1.7 days (pH 9)No data No data No data No data No data No data No data 40220701Photodegradation inwater835.224041for ThiramNo data No data No data No data6.6 hours(parentcompound)No data No data No data 45651201Photodegradation onsoil835.241043,for ThiramNo data No data No data No data1.2 days (parentcompound)No data No data No data 4572450138Data for NaDDC were used as a surrogate for KDDC39Data for NaDDC were used as a surrogate for KDDC40Unknown degradate was formed at up to 22-28 % of applied parent compound by 19 minutes, and declined to 1.4-3.3 % by 77 minutes. The 5/14/2009environmental fate memorandum required another photodegradation in water study.41Thiram data used as a surrogate for NaDDC and KDDCPage51of66Test GuidelineParent Compounds29Degradates30NaDDCKDDC31Dimethylamine(DMA)Carbondisulfide (CS2)TMTDS(Thiram)32TMTMS33TMTU34TMU35Reference (MRIDfor ParentCompounds unlessStated, EPI-Suite forDegradates)Biotic Degradation Half-lives (days unless specified)Aerobic soilmetabolism835.410041for ThiramNo data No dataNo majordegradateformedNo majordegradatesformed2.1 days(parentcompound)No majordegradatesformedNo majordegradatesformedNo majordegradatesfound43734901Aerobic soilmetabolism fordiethanolamine(DEA)42835.4100No data No data1.7 day(diethanolamine)No majordegradatesformedNo majordegradatesformedNo majordegradatesformedNo majordegradatesformedNo majordegradatesformed43685901Anaerobic soilmetabolism835.4200Not submittedNotsubmittedNot submitted Not submitted Not submitted Not submittedNotsubmittedNot submitted Not applicableAerobic aquaticmetabolism835.43005.6 days No data Not formed Not formed 7 daysStable, did notdecline24 % at dayzero, <4.3 %afterNot formed 40365702Aerobic aquaticmetabolism ofDiethanolamine43835.4300No data No data7 days(diethanolamine)No majordegradatesformedNo majordegradatesformedNo majordegradatesformedNo majordegradatesformedNo majordegradatesformed43685902Anaerobic aquaticmetabolism835.4400Not submittedNotsubmittedNot submitted Not submitted Not submitted Not submittedNotsubmittedNot submitted Not applicableBiodegradation halflife in sludge (days)Not submitted NotsubmittedNot submitted Not submitted Not submitted Not submittedNotsubmittedNot submitted Not applicable42Aerobic soil metabolism data on diethanolamine (MRID 43685901) were submitted as a surrogate for the dimethylamine (DMA) degradate.43Aerobic aquatic metabolism data on diethanolamine (MRID 43685902) were submitted as a surrogate for the dimethylamine (DMA) degradate.Page52of66Table B2 – Physical-Chemical and Fate Properties for Degradates of Sodium and PotassiumDimethyldithiocarbamate Saltsfrom Photodegradation in Water44Test GuidelineThiram sulfoneThiram oxoThiram oxo sulfoneDDC sulfonicacid monomer(oxo)DDC sulfonic acidmonomer (thio)Reference (MRID forParent Compounds unlessStated, EPI-Suite forDegradates)CAS Number None None None None None EPI-Suite 4.11Molecular Formula C6H13N2S4C6H12N2OS3C6H18N2O3S3C6H7NO4S C6H7NO3S2EPI-Suite 4.11Molecular weight 241.42 224.36 262.40 153.15 169.21 EPI-Suite 4.11Chemical Structure45651201Melting Point (oC) 190.38 110.35 155.43 101.39 98.02 EPI-Suite 4.11Boiling Point (oC) 452.44 344.70 428.80 325.94 320.06 EPI-Suite 4.11Water Solubility (mg/L) 1 x 1064.41 x 1041 x 1061 x 1061 x 106EPI-Suite 4.11Dissociation Constant inWater (pKa)N/A N/A N/A N/AN/AEPI-Suite 4.11Octanol-water PartitionCoefficient (Log Kow)-2.5 1.03 -1.58 -3.14-2.47EPI-Suite 4.11Koc(ml/g) 113.5 57.02 16.9 7.71EPI-Suite 4.11Soil adsorption/ desorption(ml/g)No data No data No data No dataNo dataEPI-Suite 4.11Sludge adsorption/ desorption(%)1.75 1.80 1.75 1.751.75EPI-Suite 4.11Bioconcentration Factor(BCF)3.16 2.21 3.16 3.163.16 EPI-Suite 4.11Vapor Pressure (mm Hg) 7.9 x 10-92.55 x 10-51.85 x 10-104.55 x 10-67.22 x 10-6EPI-Suite 4.11Henry’s Law Constant(atm-m3/mole)2.51 x 10-151.71 x 10-106.38 x 10-179.17 x 10-131.61 x 10-12EPI-Suite 4.11Abiotic Degradation Half-lives (days unless specified)Hydrolysis835.2120No data No data No data No dataNo dataNo data44Based on MRID 45651201, Photodegradation in water study for Thiram, a dimer of DDC acid.Page53of66Test GuidelineThiram sulfoneThiram oxoThiram oxo sulfoneDDC sulfonicacid monomer(oxo)DDC sulfonic acidmonomer (thio)Reference (MRID forParent Compounds unlessStated, EPI-Suite forDegradates)Photodegradation in water835.224045Stable, did not declineStable, did notdeclineStable, did notdeclineSlight decline Slight decline 45651201Photodegradation on soil835.2410No data No data No data No data No data Not applicableBiotic Degradation Half-lives (days unless specified)Aerobic soil metabolism fordiethanolamine(DEA)46835.4100Not formed Not formed Not formed Not formed Not formed 43685901Aerobic soil metabolism835.4100No dataNo dataNo dataNo dataNo data Not applicableAnaerobic soil metabolism835.4200No data No data No data No data No data Not applicableAerobic aquatic metabolism835.4300No data No data No data No data No data Not applicableAerobic aquatic metabolism ofDiethanolamine47835.4300Not formed Not formed Not formed Not formed Not formed 43685902Anaerobic aquatic metabolism835.4400No data No data No data No data No data Not applicableBiodegradation half-life insludge (days)No data No data No data No data No data Not applicable45Unknown degradate was formed at up to 22-28 % of applied parent compound by 19 minutes, and declined to 1.4-3.3 % by 77 minutes. The 5/14/2009environmental fate memorandum required another photodegradation in water study.46Aerobic soil metabolism data on diethanolamine (MRID 43685901) were submitted as a surrogate for the dimethylamine (DMA) degradate.47Aerobic aquatic metabolism data on diethanolamine (MRID 43685902) were submitted as a surrogate for the dimethylamine (DMA) degradate.

### Page 54 of 66 

# Appendix C Ecotoxicology Profile

Toxicity to Terrestrial Receptors

Avian acute-oral and dietary

Avian acute-oral and dietary toxicity data for the northern bobwhite ( Colinus virginianus ) and mallard ( Anas platyrhynchos ) categorize both DDC sa lts as being slightly to practically nontoxic to birds. Thiram, a degradate, is slightly to practically nonto xic based on acute-oral and dietary toxicity data for the northern bobwhite ( C. virginianus ) and mallard ( A. platyrhynchos ), Japanese quail ( Coturnix japonica ) and ring-necked pheasant ( Phasianus colchicus ). There are two avian reproduction studies with thiram, one with the nort hern bobwhite ( C. virginianus ) and one with the mallard ( A. platyrhynchos ). No additional avian data are anticipated to be required.

Avian Toxicity of Sodium and Potassium DDC Salts and Degradate

Study Type Species Test material (% ai) Toxicity Toxicity
Classification MRID & Status

Acute – Avian
Oral
GLN
850.2100 Northern
bobwhite NaDDC (40) LD 50 : 391 mg a.i./kgbw/day (991mg ts/kg-bw/day) Moderately toxic 00159788 Acceptable

KDDC (50) LD 50 : 627 mg a.i./kgbw(1255mg ts/kgbw/day) Slightly toxic 00105155 Acceptable

Mallard Thiram (99) LD 50 : >2800 mg/kgbw/day Practically
nontoxic 00160000 Acceptable Red-winged

black bird Thiram (99) LD 50 : >100 mg/kgbw/day Unknown 00073683 Supplemental Ring-necked

pheasant Thiram (99) LD 50 : 673 mg/kgbw/day Slightly toxic 00160000 Supplemental

Starling Thiram (95) LD 50 : >5000 mg/kgbw/day Practically
nontoxic 00022923 Acceptable

Subacute – Avian Dietary
GLN
850.2200 Northern
bobwhite KDDC (50) LC 50 : >2600 ppm a.i. (>5200 ppm ts) ts Practically
nontoxic 00109244 Acceptable

NaDDC (40) LC 50 : >2248 ppm a.i. (>5620 ppm ts) ts Practically
nontoxic 00159786 Supplemental

Mallard KDDC (50) LC 50 : >2500 ppm a.i. (>5000 ppm ts) ts Practically
nontoxic 00105156 Acceptable

NaDDC (38.9) LC 50 : >2475 ppm a.i. (>6363 ppm ts) ts Practically
nontoxic 42561802 Acceptable

NaDDC (40) LC 50 : 1874 ppm a.i. (4688 ppm ts) ts Slightly toxic 00159787 Supplemental

Thiram (95) LC 50 : 3950 ppm Slightly toxic 00022923 Supplemental

Thiram (95) LC 50 : 5000 ppm Slightly toxic 00022923 Supplemental

Japanese quail Thiram (95) LC 50 : >5000 ppm Practically
nontoxic 00022923 Acceptable

### Page 55 of 66 Study Type Species Test material (% ai) Toxicity Toxicity
Classification MRID & Status

Ring-necked

pheasant Thiram (95) LC 50 : >5000 ppm Practically
nontoxic 00022923 Acceptable

Reproduction
– Avian

GLN
850.2300 Northern
bobwhite Thiram (97.5) NOAEL: 500 ppm NA 43612502 Acceptable

Mallard Thiram (97.5) NOAEL: 9.6 ppm NA 45441201 Acceptable

Thiram (97.5) NOAEL <50 ppm NA 43612501 Supplemental 

### ts: test substance

Beneficial Insects

No data are available for the DDC salts, there is an acute dermal contact study with the degradate thiram. The wood preservative use of the DDC sa lts has been cancelled, no additional data are anticipated to be required.

Species, Age or size % Purity Design Exposure Type/ pH/ hardness/ temperature Endpoint Toxicity Category MRID & Status

Honey bee (Apis mellifera), N.R.
GLN 850.3020 Thiram
Tech Dermal contact 48-h LD 50 = 74 μg/bee Slightly toxic 00036935 Supplemental



# Toxicity to Aquatic Receptors

Freshwater Fish, acute

Acute toxicity data for freshwater fi sh are available for rainbow trout ( Oncorhynchus mykiss ), bluegill ( Lepomis macrochirus ), and fathead minnow ( Pimephales promelas ). The potassium DDC salt is categorized as being highly to very highly toxic and the sodium DDC salt as slightly to moderately toxic. The combination of sodi um DDC salt and Nabam is moderately toxic, and thiram, a degradate, is very highly toxic. No additional data are anticipated to be required.

Freshwater Fish Acute Toxicity of Sodi um and Potassium DDC Salts and Degradate

Study Type Species Test material (% ai) Toxicity (μg ai/L) Toxicity
Classification MRID &
Status

Acute -
Freshwater Fish
GLN 850.1075 Rainbow trout NaDDC (40.9) 96-hr LC 50 : 6700 Moderately
toxic 42247901 Acceptable NaDDC (15) and Nabam (15) 96-hr LC 50 : 1700 (as formulation) Moderately
toxic 00104057 Supplemental

KDDC (50) 96-hr LC 50 : 360 Highly toxic 00134589 Acceptable

Thiram (99) 96-hr LC 50 : 126 Highly toxic McCann 1976
Test Number
1001 Acceptable

### Page 56 of 66 Study Type Species Test material (% ai) Toxicity (μg ai/L) Toxicity
Classification MRID &
Status

Thiram (99) 96-hr LC 50 : 46 Highly toxic 46249301 Supplemental

Thiram (75) 96-hr LC 50 : 320 (as formulation) Highly toxic Supplemental

Bluegill
sunfish NaDDC (40.5) 96-hr LC 50 : 38,500 Slightly toxic 42504801 Acceptable NaDDC (15) and Nabam (15) 96-hr LC 50 : 3400 (as formulation) Moderately
toxic 00104057 Supplemental

Thiram (99) 96-hr LC 50 : 42 Very highly
toxic 00070801 Acceptable

Thiram (75) 96-hr LC 50 : 280 (as formulation) Highly toxic 00090294 Supplemental
Fathead
minnow KDDC (50) 96-hr LC 50 : 60 Very highly
toxic ACC240946 Acceptable

Harlequin fish Thiram (80)
formulation 96-hr LC 50 : 7 Very highly
toxic 05020144 Supplemental



### Freshwater Fish, chronic

No data are available for the DDC salts. However, a flow-through life-cycle t oxicity test with the fathead minnow ( Pimephales promelas ) is available for thiram. Time to hatch of the F1 generation and 4-week survival of the F1 gene ration were as sensitiv e as reproductive effects (reduced egg production and redu ced spawning frequency). An early-life stage study (850.1400) with the DDC salts is anticipated to be required fo r assessing chronic risk to fish. For thiram, as the more sensitive acute fish was the bluegill sunfish, an acute-to-chronic ratio (ACR) method
was used to calculate a chronic value for the bluegill sunfish. The Web-based Interspecies Correlation Estimation (Web-ICE 48 

### ), version 3.2.1, application was first used to estimate acute toxicity of thiram to the fathead minnow from existing rainbow trout a nd bluegill sunfish data (results are provided at the end of this appendi x). Web-ICE predicted a fathead minnow acute value for thiram 140 ppb based on the rainbow trout data; the rainbow trout correlation was used because it has a higher correlation than that for the bluegill sunfish, Comparing this fathead
minnow acute value to the NOAEC from the fa thead minnow full life cycle study provides an ACR of 127. Applying this ACR to the rainbow trout acute data provid es an estimated NOAEC of 0.36 ppb thiram.

Freshwater Fish Chronic Toxicity of Thiram

Study Type Species Test material (% ai) Toxicity (μg ai/L) Endpoints MRID &
Status

Chronic –
Freshwater Fish
GLN 850.1500 Fathead
minnow Thiram (98.7) NOAEC = 1.1

LOAEC = 2.2 F 0 egg production; F 0 % spawning frequency; F 1 4-week survival; F 1 time
to hatch 47824101 Acceptable

48 http://epa.gov/ceampubl/fchain/webice/

### Page 57 of 66 Freshwater Invertebrates, acute

Acute toxicity data for the water flea ( Daphnia magna ) categorize the sodium DDC salt as being very highly toxic and the potassium DDC salt as highly toxic. The degradate Thiram also is highly toxic. No additional data are anticipated to be required.

Freshwater Invertebrate Acute Toxicity of Sodium and Potassium DDC Salts and Degradate

Study Type Species Test material (% ai) Toxicity (μg ai/L) Toxicity
Classification MRID &
Status

Acute –
Freshwater
Invertebrate
GLN 850.1010 Water flea NaDDC (40.5) 48-hr EC 50 : 52 Very highly
toxic 42504802 Acceptable

KDDC (50) 48-hr EC 50 : 340 Highly toxic 00105154 Acceptable

Thiram (98) 48-hr EC 50 : 210 Highly toxic 00164662 Acceptable



### Freshwater Invertebrates, chronic

No data are available for the DDC salts. Ho wever, a thiram chronic study (MRID 47495001) is currently under review. A life cycle study (850.1300) is anticipated to be required for assessing chronic risk to aquatic invert ebrates with the DDC salts.

Estuarine/Marine Fish and Invertebrates

Acute data are available for fish (sheepshead minnow, Cyprinodon variegatus ) and the following invertebrates: Eastern oyster ( Crassostrea virginica ), mysid shrimp ( Mysidopsis bahia ), blue crab ( Callinectes sapidus ), and grass shrimp ( Palaemonetes pugio ). The data categorize sodium DDC salt as slightly toxic to fish and as highly to very highly toxic to invertebrates. The
combination of sodium DDC salt and Nabam is mode rately to very highly toxic. The degradate thiram is highly to very highly toxic. No a dditional data are anticipated to be required.

Estuarine/marine Acute Toxicity of Sodium DDC Salt and Degradate

Study Type Species Test material (% ai) Toxicity (μg ai/L) Toxicity
Classification MRID &
Status

Acute –
Saltwater Fish
GLN 850.1075 Sheepshead
minnow NaDDC (48.3) 96-hr LC 50 : 59,000 Slightly toxic 41984701 Acceptable

NaDDC (16) and Nabam (15) 96-hr LC 50 : 122 (as ts) Highly toxic 00100706 Acceptable

Thiram (98) 96-hr LC 50 : 540 Highly toxic 42514401 Acceptable

Acute –
Saltwater
Invertebrate
GLNs
850.1025/1055
850.1035 Eastern oyster NaDDC (39.6) 96-hr EC 50 : 760 Highly toxic 42561902 Acceptable
NaDDC (16) and Nabam (15) 96-hr EC 50 : 300 (as ts) Highly toxic 00100704 Supplemental

Thiram (98.3) IC 50 = 4.7 (embryo/larval development) Very highly
toxic 42488301 Acceptable

### Page 58 of 66 Study Type Species Test material (% ai) Toxicity (μg ai/L) Toxicity
Classification MRID &
Status

Mysid NaDDC (39.6) 96-hr LC 50 : 88 Very highly
toxic 42561901 Acceptable

Thiram (98.3) LC 50 : 3.36 Very highly
toxic 42488302 Acceptable

Grass shrimp NaDDC (16) and Nabam (15) LC 50 : 17 (as ts) Very highly
toxic 00100705 Supplemental

Blue crab NaDDC (16) and Nabam (15) LC 50 : 9100 (as ts) Moderately
toxic 00100703 Supplemental



### ts: test substance

Aquatic and terrestrial plants

Plant toxicity data are anticipated to be requi red for the DDC salts uses. Testing for aquatic plants is conducted with one species of aquatic vascular plant (duckweed, Lemna gibba ) and four species of algae: (1) freshwater green alga, Selenastrum capricornutum, (2) marine diatom, Skeletonema costatum, (3) freshwater diatom, Navicula pelliculosa, and (4) bluegreen cyanobacteria, Anabaena flos-aquae. A seedling emergence test (OCSPP GLN 850.4100) also is anticipated to be required for rice ( Oryza sativa ), representing a root ed aquatic macrophyte.
Data are not available for the DDC salts. Gree n algae and duckweed data are available for
thiram.

A vegetative vigor study (OCSPP GLN 850.4150) is anticipated to be required to support an assessment of risk from exposure to residual biocid es in waste water used for irrigation and from uses resulting in spray drift. Use patterns, such as the oil a nd gas uses, have the potential for waste water from the process to be used in i rrigation. There are no vegetative vigor data for thiram or DDC salts. Uses that potentially resu lt in spray drift may result in exposure of nontarget plants.

Aquatic Plants

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

ID Aquatic plants – vascular Duckweed, Lemna gibba
GLN 850.4400 Thiram (98.7%) IC 50 = 1,600,000 NOAEC < 57,000 45441202 Acceptable

Aquatic plants - green algae, Selenastrum capricornutum
GLN 850.4500 Thiram (99%) IC 50 = 45 NOAEC < 57 (will

calculate IC 05 ) 42646001 Acceptable

Thiram (99%) IC 50 = 140
IC 05 = NR 44086101 Acceptable



### Mesocosm

A mesocosm study was conducted to simulate the potential impact of Thiram 80 WG (a water dispersible formulation containing 81.2% of the a. i. Thiram) contamination via spray drift from agricultural applications on a freshwater ecosystem under fiel d conditions. There were seven treatment levels consisting of nominal Thiram 80 WG concentrations of 1.25, 4.0, 12.5, 40, 125,

### Page 59 of 66 400, and 1250 ppb Thiram 80 WG, which correspond to 1.0, 3.2, 10, 32, 100, 320, and 1000 ppb a.i. The mesocosm study design included thre e replicate mesocosm ponds for the negative control group and a single repl icate mesocosm pond per treatme nt group. Four applications, simulating direct over-spray or spray drift, were made at 7- day intervals with identical application rates. Thiram quickly degraded in the water/sediment systems with a half-life ranging from 0.7 to 1.9 days.

In general, phytoplankton (at the community le vel) taxa abundance, diversity (based on the Shannon-Weaver index), evenness, and similarity (Steinhaus' and Stander's similarity indices) were reported to be significantly reduced during the treatment peri od at the two highest treatment levels tested; i.e, nominal 320 and 1000 ppb a.i. No significant treatment -related reductions in any individual phytoplankton taxa were meani ngfully identified duri ng the treatment period. However, these significant reductions in the abov e community parameters were attributed by the
authors to treatment related reductions in zooplankton graz ers and the subsequent rapid population growths, as supported by significant phytoplankton bi omass, of those phytoplankton taxa with the most rapid population developm ent/growth rates at the nominal 320 and 1000 ppb a.i. Therefore, true treatment-related negative e ffects as a result of Thir am 80 WG application on the phytoplankton community can be excluded with high probability at least up to and including the nominal 100 ppb a.i. treatment level. Consequently, the NOAEC for individual phytoplankton taxa and the community as a whole was concluded to be 106.5 ppb a.i. (measured; nominally 100 ppb a.i.). Periphyton biomass was significantly reduced al so at the nominal 320 and 1000 ppb a.i. treatment levels. Treatment-re lated effects on specific taxa were never discussed within the study report.

Due to the significant negative c oncentration-effect relationshi p in zooplankton taxa abundance during the treatment period, the NOAEC for zooplankton taxa abundance was 2.1 ppb a.i. (measured; nominally 3.2 ppb a.i.). Zooplankton community diversity (based on ShannonWeaver Index) and evenness were not si gnificantly affected during th e treatment period. Similarity analysis of the treated zooplankton communitie s was compared to the control ponds using
Steinhaus' and Stander's indices. The NOAEC value for zooplankton community similarity during the treatment period was <1.0 ppb a.i. (measur ed; nominally <1.0 ppb a.i.); i.e. less than
the lowest treatment concentration tested.

Test material concentrations were not measured in all treatment ponds fo llowing each application
and did not allow for an exact determination of what concentrations the mesocosm flora and fauna were exposed. The overall short duration of the study, less than 1 year for the in-life portion of the study, also prevented the assessment of chronic effects of Thiram 80 WG and did not allow for the comparison of the treated commun ity structure compared to the structure from untreated or post-treatment years. This study pr ovides only supplemental data because only five
of the seven treatment levels were actually analytically verified during the study and because this study does not fulfill any current US EPA OPP guid eline requirement. Additionally there was no true replication of treatment levels. Conclusi ons, provided in this study may be useful for
characterization.

### Page 60 of 66 Test Species Test
Material

(% ai) Toxicity Endpoint EPA Study

ID

Mesocosm: Multiple species

Non-Guideline Thiram 80
WG (80) Zooplankton community similarity NOAEC < 1.0 ppb a.i.

Hexarthra mira/intermedia NOAEC was < 1.0 ppb a.i. (measured) Supplemental



# WebICE Results for Estimating Fathead Minnow Acute using Rainbow Trout

Surrogate Species: Rainbow trout ( Oncorhynchus mykiss )
Predicted Species: Fathead minnow ( Pimephales promelas )

Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

46 μ g/L

(1.66) 140.16 μ g/L (2.14)

Select Confidence Interval : Lower Limit Upper Limit

95% 92.35 μ g/L 212.71 μ g/L

Model Information

Intercept: 0.669768

Slope: 0.888200

Degrees of Freedom (N-2): 79

R 2 : 0.825954

p-value: 0.000000

Average value of surrogate (log value): 1077.24 (3.03)

Minimum value of surrogate (log value): 0.671479 (-0.172967)

Maximum value of surrogate (log value): 9800000.00 (6.99)

Mean Square Error (MSE): 0.372276

Sum of Squares (S xx ): 176.91

### Page 61 of 66 Cross-validation Success (%): 82.71

Taxonomic Distance: 4



# WebICE Results for Estimating Fathead Minnow Acute using Bluegill Sunfish

Surrogate Species: Bluegill ( Lepomis macrochirus )

Predicted Species: Fathead minnow ( Pimephales promelas )

Surrogate Acute Toxicity (log value) Predicted Acute Toxicity (log value)

42 μ g/L

(1.62) 109.55 μ g/L (2.03)

Select Confidence Interval : Lower Limit Upper Limit

95% 66.32 μ g/L 180.97 μ g/L

Model Information

Intercept: 0.663875

Slope: 0.847538

### Page 62 of 66 Degrees of Freedom (N-2): 66

R 2 : 0.790938

p-value: 0.000000

Average value of surrogate (log value): 1174.34 (3.06)

Minimum value of surrogate (log value): 0.407815 (-0.389536)

Maximum value of surrogate (log value): 7100000.00 (6.85)

Mean Square Error (MSE): 0.431786

Sum of Squares (S xx ): 150.09

Cross-validation Success (%): 75.00

Taxonomic Distance: 4

### Page 63 of 66 

# Appendix D Product Chemistry

Sodium dimethyldithiocarbamate and Potassi um dimethyldithiocarbamate salts product chemistry information is summarized in Table E1 (source: MRIDs 41586303, 41609403, 41651301, 42510401, and 41609407 and EPI Suite v4.1).

Table E1 – Product Chemistry of Sodium a nd Potassium Dimethyldi thiocarbamate Salts

Guideline
No. Physical and Chemical Properties Sodium dimethyldithiocarbamate Potassium dimethyldithiocarbamate

830.1550 Product identity and composition Refer to Table 3. Refer to Table 3.

830.1600 Description of materials used to produce the product Confidential Business Information (CBI) CBI

830.1620 Description of production

process CBI CBI

830.1650 Description of Formulation

Process CBI CBI

830.1670 Discussion of formulation of impurities CBI CBI

830.1700 Preliminary analysis CBI CBI

830.1750 Certified limits CBI CBI

830.1800 Enforcement analytical method Purity of dimethyldithiocarbamate is determined by acidic decomposition Purity of dimethyldithiocarbamate is determined by acidic decomposition 830.1900 Submittal of samples CBI CBI

830.6302 Color Yellow-green to amber liquid Pale yellowish green liquid. Clear light amber liquid. 830.6303 Physical State Liquid Liquid

830.6304 Odor Mild characteristic of sulfurcontaining compounds Mild characteristic of sulfurcontaining compounds. Slight sulfur odor. Pungent, ammoniacal odor.

830.6313 Stability to normal and elevated temperature,
metals/metal ions Stable under recommended storage
conditions.

Stable up to 70 °C for extended periods. Stable under recommended storage
conditions.

Stable up to 50 ± 2 C for a 30 day period.

830.6314 Oxidation/Reduction:

Chemical Incompatibility Does not contain an oxidizing or reducing agent.

Incompatible with strong acids, strong oxidizing agents. (40% w/w aqueous solution) Does not contain an oxidizing or reducing agent.

Incompatible with strong acids, strong oxidizing agents. (50% w/w aqueous solution)

830.7000 pH As measured 13.3 at 20°C.

10.1 (1% aqueous solution) -HPV 12.6 (32% aqueous solution) -HPV 9-14 (50% solution)

### Page 64 of 66 Guideline
No. Physical and Chemical Properties Sodium dimethyldithiocarbamate Potassium dimethyldithiocarbamate

830.7050 UV/Visible Absorption Sodium dimethyldithiocarbamate was identified by UV/VIS spectra recorded at different pH values.

Result at pH < 2: > 200 nm,  = 0 l mol -1 cm -1

Result at pH 7: 254 nm,  = 12792 l mol -1 cm -1
279 nm,  = 13127 l mol -1 cm -1
295 nm,  = 1863 l mol -1 cm -1

Result at pH > 11: 254 nm,  = 13388 l mol -1 cm -1
279 nm,  = 13687 l mol -1 cm -1
295 nm,  = 1803 l mol -1 cm -1 Potassium dimethyldithiocarbamate was identified by UV/VIS spectra recorded at different pH values.

Result at pH < 2: 207 nm,  = 12713 l mol -1 cm -1

Result at pH 7: 253 nm,  = 26409 l mol -1 cm -1
279 nm,  = 28187 l mol -1 cm -1
495 nm,  = 3562 l mol -1 cm -1

Result at pH > 11: 254 nm,  = 12714 l mol -1 cm -1
279 nm,  = 13120 l mol -1 cm -1

830.7100 Viscosity 20.2 centipoise (cps) at 20°C 20.2 cps at 20°C

830.7200 Melting point Not applicable. It is a liquid.
MP Performed on PAI: > 300 °C with decomposition. Not applicable. It is a liquid.
MP Performed on PAI: > 300 °C with decomposition.

830.7220 Boiling point Not required since PAI is solid Boiling point of 32% solution:
102°C Not required since PAI is solid. Boiling point of 50% solution:
>100°C

830.7300 Density 1.17 g/ml (40% solution) 1.25 g/ml (50% solution)

830.7370 Dissociation Constant in water pKa = 5.4 for the organic portion/ Estimated/(40% w/w aqueous solution).

6.5 x 10 -8 at 20°C. Performed on
PAI.

pKa value: Not applicable; product decomposes below pH 8. – HPV pKa = 5.4 for the organic portion/ Estimated/(40% w/w aqueous solution).

6.5 x 10 -8 at 20°C. Performed on
PAI.

830.7520 Particle size, fiber length, &
diameter distribution Not Applicable; soluble in water Not Applicable; soluble in water

830.7550 Partition coefficient ( n

octanol/water) Performed on PAI. Estimated to be less than 1 based on solubility at
20°C.

− 2.41 (EPI Suite v4.1) − 1.43 (EPI Suite v4.1)

830.7840 Solubility in water Complete 132 g/100 ml of water at 20 °C
Performed on PAI. Complete. Easily soluble in water.

830.7860 Solubility in organic solvents Methanol 89 g/100 g at 20°C Glycol 94 g/100 g at 20°C
Performed on PAI. Not reported (Not required).

830.7950 Vapor pressure Solid: 4.17 x 10 -9 mm Hg at 25°C (EPI Suite v4.1). 40% w/w as aqueous solution: 13 mm Hg at 25°C. Solid: 8.15 x 10 -10 mm Hg at 25°C (EPI Suite v4.1).

### Page 65 of 66 

# Appendix E Comments Received Concerning the Preliminary Work Plan

On September 25, 2013, EPA opened a 60-day public comment period on the preliminary work plan (PWP) for the registration review of halohydantoins. The comment period ended on November 25, 2013. The agency received one comment from the Physician Committee for Responsible Medicine (PCRM) during the public co mment period on the ini tial docket. PCRM is encouraging the agency to consider using non-tes ting approaches to fulfill the carcinogenicity study that had been anticipated to be required.

Comments received did not result in a modification to the anticipate d data needs detailed in the
DDC Salts PWP.

The Antimicrobials Division (AD) generally used an outline format to address the comments (with name of submitter, comment and AD response, in that order).

### Page 66 of 66 Comments Received on the Registration Review Preliminary Work Plan
for DDC Salts

Submitter: Physician Committee fo r Responsible Medicine (PCRM)

1. Comment: “ GLN 870.4300 Combined Chronic To xicity/Carcinogenicity Study The EPA has indicated, in the documents for th is docket and in previous guidance, that it is willing to accept information obtained us ing QSAR, weight-of-evidence, and other “non-testing” approaches in lieu of new in vivo data in some cases. We believe that Dimethyldithiocarbamate may be a case wh ere these approaches can provide enough information to assess the potential car cinogenicity of the chemical and avoid de novo testing.

We refer the registrant to the OECD QSAR Toolbox1, where one will find 786 entries for
‘carbamate’. While data from all of these en tries will not necessarily be informative, it may be possible to build a robust category to fulfill the carcinogenicity endpoint. Extensive guidance on the QSAR Toolbox site2, including detailed PowerPoint walkthroughs on how to build a category and conduc t a read-across for the carcinogenicity endpoint, is available.

It should be noted that, acco rding to data found in the QS AR Toolbox, the chemical does not appear to be genotoxic except in vitro in the absence of S9. We encourage the registrant to consider using this or other in silico tools with which it is familiar to investigate fulfilling the carcinogenicity endpoint.”

AD Response: The combined chronic toxicity/carci nogenicity study was triggered by the wood preservative and metalworking fluid us es which are now cancelled (EPA Reg.
No.’s 1022-563 and 1022-577 were cancelled on Oc tober 30, 2013). As a result of these cancellations, the agency no l onger anticipates the need to require the combined chronic toxicity/carcinogenicity study.