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Sodium and Potassium Dimethyldithiocarbamate 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-m3

/mole atmospheric pressure-cubic meter per mole 

BCF bioconcentration factor 

°C degrees Celsius 

CaSO4 calcium sulfate 

CaSO3 calcium sulfite 

CAS Chemical Abstracts Service 

CFR Code of Federal Regulations 

CHO Chinese hamster ovary 

CMA Chemical Manufacturers Association 

CO2 carbon dioxide 

COC concentration-of-concern 

cPAD chronic population adjusted dose 

CS2 carbon disulfide 

DCI data call-in 

DEA diethanol amine 

DMA dimethylamine 

DDC dimethyldithiocarbamate 

EC50 median (or 50 percent) effect concentration

EC05 5 percent effect concentration

ECOTOX ECOTOXicology 

EDI estimated daily intake 

EDSP Endocrine Disruptor Screening Program 

E-FAST Exposure and Fate Assessment Screening Tool 

EPI Suite Estimation Program Interface Suite 

EPA Environmental Protection Agency 

FDA Food and Drug Administration 

FFDCA Federal Food, Drug, and Cosmetic Act 

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 

LC50 median (or 50 percent) lethal concentration 

LD50 median (or 50 percent) lethal dose 

LOAEC lowest-observed-adverse-effect-concentration 

LOEC lowest-observed-effect-concentration 

LOAEL lowest-observed-adverse-effect-level 

Log Kow logarithm of the octanol-water partition coefficient
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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 

 
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Table of Contents 

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

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

1.2 Case Overview ............................................................................................................... 10

1.3 Chemical Identification and Properties .......................................................................... 10

1.4 Use/Usage Description ................................................................................................... 12

1.4.1 Registrations ........................................................................................................... 12

1.4.2 Summary of Registered 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 ............................................................................................................ 19

3.2.1 Food ........................................................................................................................ 19

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 Model 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 Wildlife Exposure Estimates ............................................ 29

4.4.2 Screening Level Down-the-Drain Analysis ............................................................ 29

4.5 Effects Analysis Plan ..................................................................................................... 30

5 Endocrine Disruptor Screening 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 the Preliminary Work Plan ............................ 65
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List of Tables 

Table 1 – Summary of Anticipated Risk Assessments and Data Needs: Dimethyldithiocarbamate 

Salts ................................................................................................................................................. 9

Table 2 – Anticipated Registration Review Schedule .................................................................... 9

Table 3 – Chemical Identification of Dimethyldithiocarbamate Sodium and Potassium Salts .... 10

Table 4 – Physical-Chemical and Fate Properties for Dimethyldithiocarbamate Salts ................ 11

Table 5 – Summary of the Registered Uses of Dimethyldithiocarbamate Salts ........................... 12

Table 6 – Studies Anticipated as Needed for the Registration Review of 

Dimethyldithiocarbamate Salts ..................................................................................................... 15

Table 7 –Toxicological Endpoints Used for the Dimethyldithiocarbamate RED ........................ 18

Table 8 – Occupational Exposure Scenarios for 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 Aquatic and Terrestrial Organisms ...................................... 25

Figure 3 – Conceptual Model for Aquatic (A) and Terrestrial (B) Environmental Exposure of 

DDC Salts in Recovered Water from Oil and Gas Use ................................................................ 26

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, Secondary, and Tertiary (Enhanced Oil) Fluids .......................................... 27

 
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1 Introduction 

This document is the United States Environmental 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, identifying 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. This FWP document does not include disodium 

ethylene bis dithiocarbamate (Nabam which is also a dimethyldithiocarbamate). Nabam was 

included in its own Registration Eligibility Decision (RED) rather than the 2009 

Dimethyldithiocarbamate RED Amendment and is being addressed in Registration Review case 

0641 (docket number EPA-HQ-OPP-2012-0339). Additionally, Nabam produces ethylene thio 

urea (ETU) as a degradate, whereas DDC salts do not. 

The registration review process was designed to include a public participation component to 

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

docket, to inform the public of what it knows about dimethyldithiocarbamate and what types of 

new data or other information would be helpful for the agency to receive as it moves toward a 

decision on dimethyldithiocarbamate. 

1.1 Statutory and Regulatory Authority 

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

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

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

the environment when used as directed on product labeling. The registration review program is 

intended to make sure that, as the ability to assess risk evolves and as policies and practices 

change, all registered pesticides continue to meet the statutory standard of no unreasonable 

adverse effects to human health or the environment. Changes in science, public policy, and 

pesticide use practices will occur over time. Through the registration review program, the agency 

periodically reevaluates pesticides to make sure that as change occurs, products in the 

marketplace can be used safely. Information on this program is provided at 

http://www.epa.gov/oppsrrd1/registration_review/. 

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

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

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

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

will consider benefits information and data as required by FIFRA. The public phase of 

registration review begins when the initial docket is opened for each case. The docket is the 

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. Public comments received concerning the PWP 

and documents associated with this registration 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, the EPA has made the following updates: 

 Corrected formatting and typographical errors. 

 Updated the dietary risk assessment in sections 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 Anticipated Registration Review Schedule. 

 Corrections made to Table 6 – Studies Anticipated as Needed for the Registration Review 

of Dimethyldithiocarbamate Salts: 

o Test substances 

o Corrected guideline number of the 90 day inhalation toxicity study from 870.2345 

to 870.3465 

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

20131

. Updates made to sections 1.5.1, 3, 4; Appendices 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 the agency no longer anticipates assessing 

residential exposure as residential exposures are not expected to occur. 

 In section 5, the Endocrine Disruption Screening Program (EDSP) language was updated 

to include discussion of the second list of chemicals identified for EDPS screening. 

The agency received one comment from the Physician Committee for Responsible Medicine 

(PCRM) during the public comment period on the initial 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 Appendix E for the agency’s responses to PCRM’s 

comments. 

Though the product cancellations mentioned in the bullets 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 document 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 registration 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 Risk 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 New1

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/Paper Mill Water Systems, Gas/Oil operations 

Table 2 – Anticipated Registration Review Schedule 

Anticipated Activity Target Date* Completion Date

Phase 1: Opening the Docket 

Open Docket and 60-Day Comment Period for Preliminary Work Plan 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 Preliminary 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 Dimethyldithiocarbamate 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 Dimethyldithiocarbamate 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 C3H6NNaS2 C3H6NKS2 

Molecular Weight 143.21 grams per mole 159.31 grams per mole 

Purity 40 percent (%) weight per weightA

(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 environmental fate properties are discussed in 

Appendix B and product chemistry information in Appendix D. 

Table 4 – Physical-Chemical and Fate Properties 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 (noctanol/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-m3

/mole 

(EPI Suite v4.1) 

2.01 x 10-16 atm-m3/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 directions, products that contain 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 ingredient Nabam and these products require 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 based on label specifications in the Nabam RED2. 

Several product labels have been amended since the 2009 RED Amendment to voluntarily delete 

uses. Deleted uses include sapstain treatment, paints and coatings, metalworking fluids, cotton 

fabrics, wood veneers and alginate pastes. 

Table 5 – Summary of the Registered Uses 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, Secondary 4 to 394 ppm Several labels. 

Pulp and Paper Mill Water Systems 113 to 250 ppm Several labels1

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 North America Report 2004-2005 (Kline, 2006) the 

dithiocarbamates, which include Nabam (disodium ethylene bis dithiocarbamate), and 

dimethyldithiocarbamate, are used primarily for paper production 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 production. The report does not distinguish the use 

patterns for Nabam and dimethyldithiocarbamate. With respect to wood preservation, the report 

indicates that dimethyldithiocarbamate 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 individual REDs in 2003 and 2005, respectively; 

registration review dockets for these conventional chemicals are scheduled to open in FY 2015. 

Zinc dimethyldithiocarbamate (034806) was canceled in 1992. 

The first product containing NaDDC was registered in 1949, and 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 1022-577 were cancelled on October 30, 20131. These 

labels accounted for the following use sites: material preservative for 

adhesives/coatings/emulsions, fuels and oils bottom water, metal working fluids, paints and 

varnish (applied film), and wood preservative 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 Registration Review generic-data call-in (GDCI) as noted in the 

anticipated schedule in Table 2. 

1.5.2 Tolerance Information 

EPA has not established a tolerance or exemption from the requirement of a tolerance for 

residues of dimethyldithiocarbamate in food. The Food & Drug Administration (FDA) has 

established a number of food additive regulations for NaDDC. No food additive 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 intended 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, manufacturing, packing, 

processing, preparing, treating, 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 signed, to the present (search conducted on 

6/18/2013). 

1.6.2 Ecological 

As of August 6, 2013, no incidents have been reported in the Incident Data System (v. 1.8).
Docket Number EPA-HQ-OPP-2013-0245 

www.regulations.gov 

Page 15 of 66

2 Anticipated Data Needs Table 6 presents a summary of the data anticipated as being needed to support this registration review. Table 6 – Studies Anticipated as Needed for the Registration Review of Dimethyldithiocarbamate Salts 

OCSPP GLN Study Name Test Substance Time Frame1 (Months) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable 835.31102

835.32203835.32404835.32805

Ready biodegradability test or one of three biodegradation in activated sludge simulation tests 

TGAI 12 Activated sludge microorganisms All uses Transport to 

treatment p

OECD 209 or 850.33006

Activated Sludge Respiration Inhibition or Modified Activated Sludge Respiration Inhibition 

MP; PAI; 

TGAI 12 Activated sludge microorganisms All uses Transport to 

treatment p

850.1300 Aquatic invertebrate life-cycle toxicity, freshwater TGAI 24 Aquatic organisms Industrial process water; Pulp and paper; Gas/oil Transport to 850.1350 Aquatic invertebrate life-cycle toxicity, estuarine/marine TGAI 24 Aquatic organisms Industrial process water; Pulp and paper; Gas/oil Transport to 850.1400 Fish early-life stage, freshwater TGAI 12 Aquatic organisms As above Transport to 850.41007 Seedling emergence, Tier II rice TEP 12 Aquatic organisms Industrial process water; Pulp and paper; Gas/oil Transport to 850.415010 Vegetative vigor, Tier II rice EP; TGAI 12 Aquatic organisms Gas/oil Transport to 850.4400 Aquatic Plant Testing using Lemna sp., Tier II TGAI 12 Aquatic organisms As above Transport to 850.4500 

Algal Toxicity Tier II –marine diatom, freshwater diatom, and green algae 

TEP; TGAI 12 Aquatic organisms As above Transport to 

850.4550 Algal Toxicity Tier II - Cyanobacteria TEP; TGAI 12 Aquatic organisms As above Transport to 870.3465 Inhalation Toxicity – 90 Day TGAI 24 Occupational Exposure All Use Sites Open pour 870.38008 Reproduction and Fertility Effects TGAI 36 Human Health All Use Sites All exposur870.4300 Combined Chronic Toxicity/Carcinogenicity TGAI 36 Human Health All Use Sites Dietary and 
Page 16 of 66

OCSPP GLN Study Name Test Substance Time Frame1 (Months) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable 870.5395 Mammalian Erythrocyte Micronucleus Test TGAI 12 Human Health All Use Sites All exposur870.7800 Immunotoxicity TGAI 12 Human Health All Use Sites All exposur875.12009 Indoor Dermal Exposure TEP 24 Occupational Handler All Use Sites Open pour 875.14009 Indoor Inhalation Exposure TEP 24 Occupational Handler All Use Sites Open pour 875.1700 Product Use Information TEP 12 Human Health All Use Sites All exposur Data Needs No Longer Anticipated to be Required from the 2009 RED GLN Study Name Test Substance Time Frame1 (Months) Reason the Study is No Longer Anticipated to be Required 835.2240 Photodegradation in Water TGAI 12 Data were available from active ingredient Thiram, a dimer of DDC acid (M

40220701) 

835.2410 Photodegradation on Soil TGAI 12 Data were available from active ingredient Thiram, a dimer of DDC acid (M835.4100 Aerobic Soil Metabolism TGAI 24 Data were available from active ingredient Thiram, a dimer of DDC acid (M835.6100 Terrestrial Field Dissipation TGAI 24 

The agency has reviewed the need for these data and determined that the aeof approximately two days indicates limited potential for leaching to grounwater. In addition, the 158 W regulations do not require terrestrial field dis

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. 875.1600 Application exposure monitoring data reporting TGAI 12 This study will be addressed in the submission of the remaining anticipated 875.2700 Product Use Information TGAI 12 This study will be addressed in the submission of the Product Use Informat875.2800 Description of Human Activity TGAI 12-24 This study will be addressed in the submission of the Product Use Informat875.2900 Data Reporting and Calculations TGAI 12 This study will be addressed in the submission of the remaining anticipated 

1 The timeframe will be measured from the receipt of the anticipated DCI. 2 EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-001study anticipated to be required is based on results of an Activated Sludge Respiration Inhibition test. 3 EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-002study anticipated to be required is based on results of an Activated Sludge Respiration Inhibition test. 4 EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0152-003study anticipated to be required is based on results of an Activated Sludge Respiration Inhibition test. 5 The results of the ASRI test will determine which of these four biodegradation tests is/are anticipated to be required. If the ASRI test 

to 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test – Aerobic Sewage Treatment: A. Activa

the Porous Pot Test is expected to be required. If the ASRI test EC50 is greater than 20 mg/L, then the registrant would likely be require
Page 17 of 66

Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic Sewage Treatment: A. Activated 

Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. antimicrobial fails the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test – Aerobic SActivated Sludge Units, or c) the Porous Pot study would likely be required. 

6 The anticipated DCI will provide that 850.3300 may be used in place of OECD 209 if the test substance is not sufficiently soluble to a

concentrated stock solution in water. 

7 Test guidelines 850.4100 and 850.4225 were merged and harmonized into OCSPP 850.4100 in a Federal Register Notice dated June 28 Results from a multi-generation (EPA guideline 870.3800) or an extended one-generation reproductive and fertility effects study using 

443 (http://www.oecd-ilibrary.org/environment/test-no-443-extended-one-generation-reproductive-toxicity-study_9789264185371-en) 

requirement. 9 Data reporting and calculations are anticipated to be required when handler exposure data are submitted 10 Test guidelines 850.4150 and 850.4250 were merged and harmonized into OCSPP 850.4150 in a Federal Register Notice dated June 11 Data are expected to be required to conduct the dietary exposure assessments based on a screening level analysis that indicates residu
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 human health risk assessment for DDC salts. The 

agency expects to require additional data for use in conducting the registration review. 

3.1 Existing Toxicological Endpoints 

EPA anticipates the need to revise the existing toxicological endpoints as part of this registration 

review. Table 7 presents a summary of the endpoints used in EPA’s most recent human health 

risk assessment in support of the 2009 RED Amendment. As previously stated, toxicological 

studies were identified as data gaps in the 2009 RED Amendment and identified in the 

registration review as anticipated data needs based on currently registered uses. All available 

information including existing toxicology studies, valid scientific literature, and the studies that 

are expected to be required for registration review will be considered in establishing the 

endpoints to be used in the registration 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 = 100A 

Rabbit developmental study (MRID 40995101) 

LOAEL = 38 mg/kg/day based on clinical signs (reddish-colored 

material in cage trays) and possible increased maternal death and 

abortions. 

Acute Dietary 

(General population) 

Oral NOAEL = 

20 mg/kg 

UF = 100A 

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 = 1000B

90-day subchronic oral study (MRID 42047201) 

LOAEL = 100 mg/kg/day and NOAEL = 2 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. 

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 = 1000B 

90-day subchronic oral study (MRID 42047201) 

Same study used for the chronic 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 = 1000B

90-day subchronic oral study (MRID 42047201) 

Same study used for chronic dietary above. 

Dermal 

(Short, intermediate 

and long-term)

Dermal NOAEL 

= 60 mg/kg/day 

UF = 1000B 

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 = 1000B 

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 

20093. Uses of NaDDC and KDDC salts that may result in indirect dietary exposure include 

their use as slimicide in paper mill pulp slurries, 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 mills. 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 performed for each population subgroup for which an 

endpoint exists. A risk estimate that is less than 100% of the acute or chronic PAD is not of 

concern. Acute and chronic dietary risks for DDC salts will be assessed by comparing dietary 

exposure estimates expressed in mg/kg/day to the acute Population Adjusted Dose (aPAD) and 

chronic Population Adjusted Dose (cPAD), respectively. 

The agency also anticipates the need to conduct an aggregate 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 beets. 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 bisdithiocarbamate 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 dietary (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 determine if additional residue data would be required 

to conduct these assessments and to determine toxicology data needs, a screening level analysis 

was conducted for the paper/pulp use. This screen used FDA methodology (FDA, 1993) where 

appropriate as well as relied on high-end assumptions 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 from a subchronic oral toxicity 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 variation 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 assessment indicates that 

residues exceeded the 200 ppb level that the agency uses to determine toxicology data 

requirements for indirect food uses of antimicrobial pesticides. The exposure contribution from 

this scenario will be considered in the aggregate assessment conducted during registration 

review. It is important to note that if the toxicological point of departure for either the acute or 

chronic scenario changes during the registration review process, additional residue chemistry 

data may be 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 passing through WWTPs (see 

Appendix B ). Any drinking water risks will be incorporated into the aggregate risk assessment. 

3.3 Occupational and Residential Exposures 

The occupational and residential exposures to dimethyldithiocarbamate were last assessed in 

D359537 (EPA, 2009b) which was written for the 2009 RED Amendment. The agency 

anticipates the need to revise the occupational 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 occupational exposure assessment conducted in support of 

the 2009 RED Amendment. There is the potential for both dermal and inhalation exposures 

during the open pouring of dimethyldithiocarbamate 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 assessed quantitatively in the 2009 RED Amendment. 
Page 21 of 66

The Chemical Manufacturers Association (CMA) unit exposure data were used for the open pour 

liquid handling scenarios and the Pesticide Handlers 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 were all greater than the target MOE of 1000 and 

were not of concern. The dermal MOEs for handling 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 Assessed During Registration Review 

All of the handler scenarios that 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 exposure data that were used in the 2009 RED 

Amendment. Occupational handler scenarios to be assessed are presented in Table 8. 

Table 8 – Occupational Exposure Scenarios 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 exposure 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 only 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 residential exposure concerns. 

3.4 Aggregate and Cumulative Exposure 

3.4.1 Aggregate Exposures 

EPA anticipates the need to revise the aggregate assessment conducted in support of the 2009 

RED Amendment. Upon a reevaluation and selection of toxicological endpoints, 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 analysis. 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 mechanism of toxicity, the agency made a 2001 

final determination that there is insufficient data to show a common mechanism of toxicity with 

other substances and dimethyldithiocarbamate does not appear to produce a toxic metabolite 

produced by other substances. For information regarding EPA’s efforts to determine which 

chemicals have a common mechanism of toxicity and to evaluate the cumulative effects of such 

chemicals, see http://www.epa.gov/pesticides/cumulative/. 

4 Environmental Risk Assessment 

For currently registered uses, the ecological risk 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 commercial/industrial cooling water, pulp/paper mill 

water systems, and gas/oil operations. The agency has not conducted a risk assessment that 

supports a complete endangered species determination for DDC salts. The ecological risk 

assessment planned during registration review will 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 critical habitat, the agency will consult with the U.S. 

Fish and Wildlife Service and/or National Marine Fisheries Services (the Services), as 

appropriate. 

4.1 Water Quality 

Sodium and potassium dimethyldithiocarbamate salts are not identified as a cause of impairment 

for any water bodies listed as impaired under section 303(d) of the Clean Water Act5

. In addition, 

no Total Maximum Daily Loads (TMDL) have been developed for sodium and potassium 

dimethyldithiocarbamate salts6

. More information on impaired water bodies and TMDLs can be 

found at EPA’s website7

. 

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, and industrial, cane and beet sugar mills in cane 

juice and beet pulp press water, commercial/industrial cooling water, industrial wastewater, 

pulp/paper mills (pulp), gas and oil (drilling muds/packer fluids, recovery injection water, 

fracturing fluids, workover and completion fluids), 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 water 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 initial exposures will be from a mixture of parent 

compounds and degradates which are impurities because the major degradates were present at 

the beginning of the aerobic aquatic metabolism study.8

 The primary and major (>10 % of 

applied parent compound) degradates include dimethylamine (DMA), carbon disulfide (CS2), 

tetramethylthiuram disulfide (TMTDS), tetramethyl thiomonosulfide (TMTMS), and tetramethyl 

thiourea (TMTU). The oil and gas uses can create 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 desulfurization 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 and its degradates were based on 

the results of submitted studies. Degradation of DDC salts and its degradates occur by both 

abiotic11 and biotic means12. Parent DDC salts and its degradates 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 potential to volatilize from water based on estimated values using 

the EPI-Suite 4.113 Henry’s Law constants of 10-10 to 10-9 atm m3 mol-1, DMA and CS2

degradates have Henry’s Law constants of 10-5 to 10-2 atm m3 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 exposure and attribute changes can occur, but the 

potential for bioconcentration and secondary exposure is unlikely or insignificant 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 properties14 of DDC salts and its degradates, all lines in Figure 1 are solid with the 

exception of ingestion and bioconcentration in aquatic organisms. Water from cooling towers 

will eventually be released to surface water directly 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/municipal/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 environmental 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 (SO2) gas from the smokestacks of steam electric power plants that 

consume fossil fuels (e.g. coal). The waste water 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 ash (including some heavy metals), 

calcium sulfate (CaSO4), and calcium sulfite (CaSO3). The water system and FGD uses contain 

air washers, reverse osmosis, and 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 and 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 Environmental Exposure of DDC Salts from Water System and Flue-Gas 

Desulfurization (FGD) to Aquatic 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, Secondary, 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, Hydraulic, 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 amino 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 toxicity16. 

The dithiocarbamates all release carbon disulfide (CS2), 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 direct and indirect effects of the DDC salts and degradates to plants 

and animals. The ecotoxicity data requirements and all available ecotoxicity 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 ecological risk assessment are presented in Table 

11. Anticipated data gaps for the TGAI also are indicated. Data also are included for thiram, a 

major reaction product and also a registered active ingredient (PC Code 079801). 

Table 11. Selected Ecological Effects Endpoints for Risk Assessment 

Receptor 

Group 

Surrogate 

Species 

Test 

material 

Risk 

Scenario 

Toxicity 

Endpoint 

EPA 

ID 

Freshwater fish 

Fathead minnow KDDC 

Acute 96-h LC50 = 60 μg ai/L 240946 

Chronic Data gap N/A 

Bluegill 

Thiram Acute 96-h LC50 = 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 EC50 = 52 μg ai/L 42504802 

Chronic Data gap N/A 

Thiram 

Acute 48-h EC50 = 210 μg ai/L 164662 

Chronic Under Review N/A 

Estuarine/marine 

fish 

Sheepshead 

minnow 

NaDDC 

Acute 96-h LC50 = 59,000 μg ai/L 41984701 

Chronic Not a data gap: Mysid is 

more acutely sensitive N/A 

Thiram 

Acute 96-h LC50 = 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 LC50 = 88 μg ai/L 42561901 

Chronic Data gap N/A 

Thiram 

Acute LC50 = 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 IC50 and 

NOAEC Data gap N/A 

Green algae Thiram 

Non-listed IC50 = 45 μg a.i/L 

42646001 

Listed NOAEC <57 μg a.i/L (will 

calculate IC05) 

Aquatic vascular 

plants Lemna sp. 

TGAI IC50 and 

NOAEC Data gap N/A 

Thiram 

Non-listed IC50 = 1,600,000 μg a.i/L 

45441202 

Listed species NOAEC <57,000 μg a.i/L 

(will calculate IC05) 

Semi-aquatic 

plants (seedling 

emergence) 

Rice TGAI IC50 and 

NOAEC Data gap N/A 

Vegetative Vigor Multiple species TGAI IC50 and 

NOAEC Data gap N/A 

Birds 

Northern 

bobwhite 

NaDDC 

(40) Acute LD50 = 391 mg ai/kg bw 00159788 

Ring-necked 

pheasant Thiram (99) Acute LD50 = 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 hypothesis, the potential for adverse effects on the environment will 

be estimated. For down-the-drain (DtD) risk estimates, an approach that estimates the number of 

days a concentration-of-concern (COC) is exceeded, also referred 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 the potential for aquatic organisms downstream of the industrial 
Page 30 of 66

wastewater treatment plants that receive discharges 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 cooling water, industrial wastewater, pulp/paper 

mills, etc. Antimicrobials with these uses will eventually be released to industrial wastewater 

treatment plants whose effluents will reach surface water and aquatic organisms. The primary 

and major (>10 % of applied parent compound) degradates include the DMA, CS2, 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 discharge down-the-drain to subsequently be 

discharged from industrial wastewater treatment plants to surface water. The half-life of both 

KDDC and NaDDC are long enough to enter the industrial wastewater treatment plants and 

subsequently be discharged to surface waters. 

This analysis plan will be revisited and may be revised depending upon a full review of the data 

available in the open literature and the information 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 exposures for this registration review. 

4.5 Effects Analysis Plan 

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

database17, which employs a literature search engine for locating chemical toxicity data for 

aquatic life, terrestrial plants, and wildlife. The 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 values 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 Laboratory's Mid-Continent Ecology Division. 

5 Endocrine Disruptor Screening Program (EDSP) 

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

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

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

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

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

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

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

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

taxonomic groups. As part of the 2009 Amended RED, 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 Screening Program (EDSP). 

 

17 http://cfpub.epa.gov/ecotox/
Page 31 of 66

EPA has developed the EDSP to determine whether certain substances (including pesticide 

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

produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator 

may designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

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

testing is designed to identify any adverse endocrine-related effects caused by the substance, and 

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

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

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

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

identified for EDSP screening was published on June 14, 201318 and includes some pesticides 

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors. 

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

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website19. 

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

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Page 37 of 66

Appendix A Toxicology Profile for 

Dimethyldithiocarbamate 

I. BACKGROUND 

Both sodium dimethyldithiocarbamate and potassium dimethyldithiocarbamate react with water 

readily and decompose into their respective salts. Due 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 database of both sodium dimethyldithiocarbamate 

and potassium dimethyldithiocarbamate in the ADTC endpoint selection meeting (US EPA, 

2009). However, the acute toxicological database could not be bridged 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 and causes mild or slight irritation to skin. The 

toxicity study with sodium dimethyldithiocarbamate yielded a Toxicity Category II with dermal 

route of exposure and a Toxicity Category IV with inhalation route of exposure study. There 

were no acceptable acute oral toxicity studies available; however, an unacceptable / guidelineupgradeable study’s (MRID 00160993, 00160994) results were considered. An acute oral study 

for the sodium salt is anticipated to be required for the product specific data call in (PDCI). 
Page 38 of 66

Table 2. Acute toxicity database for sodium dimethyldithiocarbamate 

Guideline 

No. 

Study Type MRID number (s) Results Toxicity 

Category

81-1 Acute Oral No acceptable study 

available. 

LD50 (M) = 2100 mg/kg 

LD50 (F) = 2500 mg/kg 

III 

81-2 Acute Dermal 00160995, 92043009 LD50 (M) = 1450 mg/kg 

LD50 (F) = 1020 mg/kg 

II 

81-3 Acute Inhalation 00159769, 42327801, 

92043010 

LC50 (M) > 2.22 mg/L 

LD50 (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 sensitizer 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 was assigned to both acute oral 

and dermal toxicity studies. No inhalation study was provided. An acute inhalation toxicity 

study for the potassium dimethyldithiocarbamate is anticipated to be required for the PCDI. 

Table 3. Acute toxicity database for potassium dimethyldithiocarbamate 

Guideline 

No. 

Study Type MRID (s) Results Toxicity 

Category

81-1 Acute Oral 00132382, 

92039001 

00143448* 

LD50 (M) = 2196 mg/kg 

(LD50 (F) = 1867 mg/kg 

III 

81-2 Acute Dermal 00146768, 

92039002 

00132381* 

00143449* 

LD50 (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 the table, but included in toxicology profile 

** An unacceptable primary eye irritation study (MRID 00143448) was assigned a Toxicity Category II. 
Page 39 of 66

III. Repeat Dose Toxicity 

The toxicological database of repeat dose studies for dimethyldithiocarbamate is listed in Table 

3. All of these studies were included in the hazard 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. Summaries 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 Dimethyldithiocarbamate (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 Dimethyldithiocarbamate (excluding 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-day inhalation toxicity study conducted with 

sodium dimethyldithiocarbamate were 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 should be submitted by the registrant, and the 

Agency will consider the validity of the approach. 

An in vivo mutagenicity study such as an erythrocyte micronucleus assay is anticipated to be 

required. 

An immunotoxicity study is a data requirement for all antimicrobial pesticide chemicals under 40 

CFR Part 158W, Data Requirements for Antimicrobial Pesticides. The registrant can address 

this data requirement by submitting a study according to the OCSPP 870.7800 guideline, citing 

information from the scientific literature that addresses immunotoxicity of DDC salts, or 

submitting a request for waiver of this study using the agency’s published guidance, available at: 

http://www.epa.gov/pesticides/regulating/part158-tox-data-requirement.pdf. 
Page 44 of 66

References for Appendix A 

US EPA, 2009. Hazard Assessment for the Reregistration Eligibility Decision (RED) Document 

of Sodium Dimethyldithiocarbamate and Potassium Dimethyldithiocarbamate. February 5, 

2009 

 
Page 45 of 66

Appendix B Environmental Fate 

NaDDC and KDDC salts are active ingredients in antimicrobials that can be used as material 

preservatives in water systems (air washer, reverse osmosis, and industrial), 

commercial/industrial cooling water, industrial wastewater, pulp/paper mills, gas and oil (drilling 

muds/packer fluids, recovery injection 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 indicate 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 (ranging up to 6.7 days), these estimates of persistence 

are not short enough to prevent residues from entering 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 wastewater treatment process in which conditions 

are present that tend to promote removal of chemical substances from WWTPs, particularly via 

processes such as biodegradation and sorption.22 Table B1 and Table B2 contain the chemical, 

physical, and environmental fate properties of the DDC salts and degradates. 

Abiotic 

Hydrolysis 

Parent NaDDC is composed of DMA and CS2 moieties. When hydrolyzed it forms DMA, CS2, a 

re-combination of DMA and CS2 called TMTU, TMTDS, which is also known as thiram, and 

TMTMS. A hydrolysis study23 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 CS2 increased with decreasing pH. Hence acidic conditions will favor the 

decomposition of the DDC anion into DMA and CS2. 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 photodegradation of NaDDC in water24 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 observed 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. Though these degradates were not identified , the 

photodegradation in water study is satisfied with the combination of MRIDs 40220701 and 

4565120125, which is an acceptable study for the active ingredient 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-life of 6.6 hours and 

formed four degradates that reached significant (>10 % of applied parent Thiram) 

concentrations. Three of the four degradates were 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 parent compound by 24 hours (end 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 groups) reached up to 15.3 % by 12 hours and 

decreased to 9 % by 24 hours. The fourth degradate was a mixture of sulfonic acid monomers of 

DDC in either an oxo form or a thio (sulfur-containing) form. The sum of these sulfonic acid 

degradates increased to 17-21 % of applied thiram by 24 hours. Table B2 below contains the 

chemical and physical properties of these four degradates. No additional data are anticipated to 

be required. 

Data on photodegradation on soil26 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 were 0.72 days for the irradiated 

treatment and 1.78 days for the dark control treatment, with a dark-control adjusted half-life of 

1.2 days. CO2 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 study27 on agricultural soils, the change 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. Desorption of adsorbed DDC salts generally 

ranged from 0-25% but no desorption values were calculated. Sorption of DDC salts to soil 

particles increases with increasing organic carbon (OC) content (r2

 = 0.98) and pH (r2 = 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 because the log Kow is less than three (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 also degrade NaDDC. In an aerobic aquatic 

metabolism study (MRID 40365701), rapid degradation of NaDDC was observed with an 

estimated half-life of 6 days. Three 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 conditions, NaDDC degraded 

into the same three degradates as seen under aerobic metabolism with TMTDS being the major 

degradate identified. Non-linear half-lives for TMTDS and TMTMS were 67 days and 15 days, 

respectively under the conditions of the study. Complete mineralization of the parent compound 

was evident under both aerobic and anaerobic conditions as indicated by the amount of carbon 

dioxide (CO2) 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 submitted for Thiram which degraded with 

a non-linear half-life of 2.1 days in sandy loam soil. TMTU, TMU, TMTM, and CS2 were minor 

(<10 % of applied Thiram) degradates. Evolved CO2 accounted for 9.0% of the applied 

radioactivity at 2 days post-treatment and increased to a maximum of 75% by 205 days. The 

DT50, DT75, and DT90 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- submitted aerobic soil metabolism (OCSPP GLN 835.4100, 

MRID 43685901) and aerobic aquatic metabolism (OCSPP GLN 835.4300, MRID 43685902) 

studies for DEA, a surrogate compound for the degradate DMA. The half-lives of DEA in the 

studies were 1.7 and 11 days, respectively. No major degradates were formed in the studies. 

While DEA is an appropriate surrogate compound for DMA, there is no record of review for 

these studies. However, the only use site triggering 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 are anticipated to be required. 

Terrestrial Field Dissipation 

Data on terrestrial field dissipation (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 approximately 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 sludge have been submitted but are anticipated to 

be required. The results of the ASRI test determine which of four tests are required and 

determines the extent of impacts to WWTP organisms. If the ASRI test EC50 is equal to or less 

than 20 mg/L, then one of three simulation tests would be anticipated to be required: OCSPP 

GLNs 835.3220, 835.3240, or 835.3280. If the ASRI test IC50 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 percent removal of dissolved organic carbon and 60 

percent removal of theoretical oxygen demand or theoretical CO2 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 biodegradability study, then the 

applicant should conduct one of the three biodegradation in activated sludge simulation tests 

mentioned previously. 
Docket Number EPA-HQ-OPP-2013-0245 

www.regulations.gov 

Page 49 of 66

Table B1 – Physical-Chemical and Fate Properties for Sodium and Potassium Dimethyldithiocarbamate S

Test Guideline 

Parent Compounds29 Degradates30

NaDDC KDDC31 Dimethylamine (DMA) Carbon disulfide (CS2) TMTDS (Thiram)32 TMTMS33 TMTU34 TMU

CAS Number 128-04-1 128-03-0 124-40-3 75-15-0 137-26-8 97-74-5 2782-91-4 632-2Molecular Formula C3 H6 N1 S2 Na1 C3 H6 N1 S2 

K1 C2 H7 N1 C1 S2 C6 H12 N2 S4 C6 H12 N2 S3 C5 H12 N2 S1 C5 H12 N

Molecular weight 143.20 159.31 45.08 76.13 240.42 208.36 132.22 116.Chemical Structure 

Physical-Chemical Properties

Melting Point (oC) N/A36 N/A37 -92.2 -111.5 107 109.5 79.3 -1.2 Boiling Point (oC) 102 >100 6.8 46 339 301.3 245 176.Water Solubility (mg/L) 1.32 x 106 Easily soluble 1 x 106 2,160 30 1 x 106 350,000 1 x 1Dissociation Constant in Water (pKa) 7.2 7.2 No data No data No data No data No data No daOctanol-water Partition Coefficient (Log Kow) 

-2.41 

(EPI-Suite 4.1) 

-1.43 

(EPI-Suite 

4.1) 

-0.38 1.94 1.73 0.75 0.49 0.19 

29 Chemical and physical properties of parent compounds relative to environmental risk assessment are listed in Table 4 above. Values 

copied from Table 4. 

30 Major degradates were formed at >10 % of applied parent compound. Minor degradates were formed at <10 % of applied parent co31 Environmental fate data were submitted for NaDDC but not KDDC. Both compounds are salts and therefore will readily disassociat

or K cations and the DDC anion. As a result, NaDDC is an acceptable surrogate for KDDC. 

32 DDC anion forms a cross-linked dimer TMTDS, which is joined by two (2) sulfur molecules. This dimer is the active ingredient Thi33 Cross-linked DDC anions joined by one (1) sulfur instead of two sulfurs. 34 Tetramethyl thiourea (TMTU) 35 Tetramethyl urea (TMU) 36 Not applicable 37 Not applicable 
Page 50 of 66

Test Guideline 

Parent Compounds29 Degradates30

NaDDC KDDC31 Dimethylamine (DMA) Carbon disulfide (CS2) TMTDS (Thiram)32 TMTMS33 TMTU34 TMU

Koc (ml/g) 312-445 No data38 4.7 48 676 337.3 25.7 8.6 Soil adsorption/ desorption (ml/g) 1.5-12.6 No data39 3.2 No data No data No data No data No daSludge adsorption/ desorption (%) <1.9 <1.9 1.74 0.6 1.6 1.5 0.63 0.62 Bioconcentration Factor (BCF) No data No data 3.2 8.9 6.4 3.2 3.2 3.2 Vapor Pressure (mm Hg) 4.2 x 10-9 8.2 x 10-10 1.5 x 10+3 359 1.7 x 10-5 2.7 x 10-4 1.1 x 10-2 1.4 x 1Henry’s Law Constant (atm-m3/mole) 7.9 x 10-16 2.0 x 10-16 4.5 x 10-5 1.2 x 10-2 3.8 x 10-10 8 x 10-10 5.2 x 10-9 5.0 x 1

Abiotic Degradation Half-lives (days unless specified)

Hydrolysis 835.2120 

17 min (pH 5) 

29 hours (pH 7) 

43 days (pH 9) 

No data Stable, did not decline Stable Minor degradate Minor Not formed Not for

Photodegradation in water 835.224040

3 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 da

Photodegradation in water 835.224041

for Thiram 

No data No data No data No data 

6.6 hours 

(parent 

compound) 

No data No data No da

Photodegradation on soil 835.241043, for Thiram 

No data No data No data No data 1.2 days (parent compound) No data No data No da

38 Data for NaDDC were used as a surrogate for KDDC 39 Data for NaDDC were used as a surrogate for KDDC 40 Unknown degradate was formed at up to 22-28 % of applied parent compound by 19 minutes, and declined to 1.4-3.3 % by 77 minut

environmental fate memorandum required another photodegradation in water study. 

41 Thiram data used as a surrogate for NaDDC and KDDC 
Page 51 of 66

Test Guideline 

Parent Compounds29 Degradates30

NaDDC KDDC31 Dimethylamine (DMA) Carbon disulfide (CS2) TMTDS (Thiram)32 TMTMS33 TMTU34 TMU

Biotic Degradation Half-lives (days unless specified)

Aerobic soil metabolism 835.410041

for Thiram 

No data No data 

No major 

degradate 

formed 

No major 

degradates 

formed 

2.1 days 

(parent 

compound) 

No major 

degradates 

formed 

No major 

degradates 

formed 

No ma

degrad

foun

Aerobic soil metabolism for diethanolamine (DEA)42

835.4100 

No data No data 1.7 day (diethanolamine) No major degradates formed No major degradates formed No major degradates formed No major degradates formed No ma

degrad

form

Anaerobic soil metabolism 835.4200 

Not submitted Not submitted Not submitted Not submitted Not submitted Not submitted Not submitted Not subm

Aerobic aquatic metabolism 835.4300 

5.6 days No data Not formed Not formed 7 days Stable, did not decline 24 % at day zero, <4.3 % after Not for

Aerobic aquatic metabolism of Diethanolamine43

835.4300 

No data No data 7 days (diethanolamine) No major degradates formed No major degradates formed No major degradates formed No major degradates formed No ma

degrad

form

Anaerobic aquatic metabolism 835.4400 

Not submitted Not submitted Not submitted Not submitted Not submitted Not submitted Not submitted Not subm

Biodegradation halflife in sludge (days) Not submitted Not submitted Not submitted Not submitted Not submitted Not submitted Not submitted Not subm

42 Aerobic soil metabolism data on diethanolamine (MRID 43685901) were submitted as a surrogate for the dimethylamine (DMA) deg43 Aerobic aquatic metabolism data on diethanolamine (MRID 43685902) were submitted as a surrogate for the dimethylamine (DMA) 
Page 52 of 66

Table B2 – Physical-Chemical and Fate Properties for Degradates of Sodium and Potassium Dimethyldithfrom Photodegradation in Water44

Test Guideline Thiram sulfone Thiram oxo Thiram oxo sulfone

DDC sulfonic 

acid monomer 

(oxo) 

DDC sulfonic acid 

monomer (thio)

CAS Number None None None None None Molecular Formula C6H13N2S4 C6H12N2OS3 C6H18N2O3S3 C6H7NO4S C6H7NO3S2 Molecular weight 241.42 224.36 262.40 153.15 169.21 Chemical Structure Melting Point (oC) 190.38 110.35 155.43 101.39 98.02 Boiling Point (oC) 452.44 344.70 428.80 325.94 320.06 Water Solubility (mg/L) 1 x 106 4.41 x 104 1 x 106 1 x 106 1 x 106 Dissociation Constant in Water (pKa) N/A N/A N/A N/A N/A Octanol-water Partition Coefficient (Log Kow) -2.5 1.03 -1.58 -3.14 -2.47 Koc (ml/g) 113.5 57.02 16.9 7.7 1 Soil adsorption/ desorption (ml/g) No data No data No data No data No data Sludge adsorption/ desorption (%) 1.75 1.80 1.75 1.75 1.75 Bioconcentration Factor (BCF) 3.16 2.21 3.16 3.16 3.16 Vapor Pressure (mm Hg) 7.9 x 10-9 2.55 x 10-5 1.85 x 10-10 4.55 x 10-6 7.22 x 10-6 Henry’s Law Constant (atm-m3/mole) 2.51 x 10-15 1.71 x 10-10 6.38 x 10-17 9.17 x 10-13 1.61 x 10-12 

Abiotic Degradation Half-lives (days unless specified)

Hydrolysis 835.2120 No data No data No data No data No data 

44 Based on MRID 45651201, Photodegradation in water study for Thiram, a dimer of DDC acid. 
Page 53 of 66

Test Guideline Thiram sulfone Thiram oxo Thiram oxo sulfone

DDC sulfonic 

acid monomer 

(oxo) 

DDC sulfonic acid 

monomer (thio)

Photodegradation in water 835.224045 Stable, did not decline Stable, did not decline Stable, did not decline Slight decline Slight decline Photodegradation on soil 835.2410 No data No data No data No data No data 

Biotic Degradation Half-lives (days unless specified)

Aerobic soil metabolism for diethanolamine (DEA)46

835.4100 

Not formed Not formed Not formed Not formed Not formed 

Aerobic soil metabolism 835.4100 No data No data No data No data No data Anaerobic soil metabolism 835.4200 No data No data No data No data No data Aerobic aquatic metabolism 835.4300 No data No data No data No data No data Aerobic aquatic metabolism of Diethanolamine47

835.4300 

Not formed Not formed Not formed Not formed Not formed 

Anaerobic aquatic metabolism 835.4400 No data No data No data No data No data Biodegradation half-life in sludge (days) No data No data No data No data No data 

45 Unknown degradate was formed at up to 22-28 % of applied parent compound by 19 minutes, and declined to 1.4-3.3 % by 77 minut

environmental fate memorandum required another photodegradation in water study. 

46 Aerobic soil metabolism data on diethanolamine (MRID 43685901) were submitted as a surrogate for the dimethylamine (DMA) deg47 Aerobic aquatic metabolism data on diethanolamine (MRID 43685902) were submitted as a surrogate for the dimethylamine (DMA) 
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 salts as being slightly to practically nontoxic 

to birds. Thiram, a degradate, is slightly to practically nontoxic 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 northern 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) 

LD50: 391 mg a.i./kgbw/day 

(991mg ts/kg-bw/day) 

Moderately toxic 00159788 

Acceptable 

KDDC (50) 

LD50: 627 mg a.i./kgbw 

(1255mg ts/kgbw/day) 

Slightly toxic 00105155 

Acceptable 

Mallard Thiram (99) LD50: >2800 mg/kgbw/day 

Practically 

nontoxic 

00160000 

Acceptable 

Red-winged 

black bird Thiram (99) LD50: >100 mg/kgbw/day Unknown 00073683 Supplemental 

Ring-necked 

pheasant Thiram (99) LD50: 673 mg/kgbw/day Slightly toxic 00160000 Supplemental 

Starling Thiram (95) LD50: >5000 mg/kgbw/day 

Practically 

nontoxic 

00022923 

Acceptable 

Subacute – 

Avian Dietary 

GLN 

850.2200 

Northern 

bobwhite 

KDDC (50) LC50: >2600 ppm a.i. 

(>5200 ppm ts) 

ts Practically 

nontoxic 

00109244 

Acceptable 

NaDDC (40) LC50: >2248 ppm a.i. 

(>5620 ppm ts) 

ts Practically 

nontoxic 

00159786 

Supplemental 

Mallard 

KDDC (50) LC50: >2500 ppm a.i. 

(>5000 ppm ts) 

ts Practically 

nontoxic 

00105156 

Acceptable 

NaDDC (38.9) LC50: >2475 ppm a.i. 

(>6363 ppm ts) 

ts Practically 

nontoxic 

42561802 

Acceptable 

NaDDC (40) LC50: 1874 ppm a.i. 

(4688 ppm ts) ts Slightly toxic 00159787 

Supplemental 

Thiram (95) LC50: 3950 ppm Slightly toxic 00022923 

Supplemental 

Thiram (95) LC50: 5000 ppm Slightly toxic 00022923 

Supplemental 

Japanese quail Thiram (95) LC50: >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) LC50: >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 salts 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 LD50 = 74 μg/bee Slightly toxic 00036935 

Supplemental 

Toxicity to Aquatic Receptors 

Freshwater Fish, acute 

Acute toxicity data for freshwater fish 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 sodium 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 Sodium 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 LC50: 6700 Moderately 

toxic 

42247901 

Acceptable 

NaDDC (15) and 

Nabam (15) 

96-hr LC50: 1700 

(as formulation) 

Moderately 

toxic 

00104057 

Supplemental 

KDDC (50) 96-hr LC50: 360 Highly toxic 00134589 

Acceptable 

Thiram (99) 96-hr LC50: 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 LC50: 46 Highly toxic 46249301 

Supplemental 

Thiram (75) 96-hr LC50: 320 

(as formulation) Highly toxic Supplemental 

Bluegill 

sunfish 

NaDDC (40.5) 96-hr LC50: 38,500 Slightly toxic 42504801 

Acceptable 

NaDDC (15) and 

Nabam (15) 

96-hr LC50: 3400 

(as formulation) 

Moderately 

toxic 

00104057 

Supplemental 

Thiram (99) 96-hr LC50: 42 Very highly 

toxic 

00070801 

Acceptable 

Thiram (75) 96-hr LC50: 280 

(as formulation) Highly toxic 00090294 

Supplemental 

Fathead 

minnow KDDC (50) 96-hr LC50: 60 Very highly 

toxic 

ACC240946 

Acceptable 

Harlequin fish Thiram (80) 

formulation 96-hr LC50: 7 Very highly 

toxic 

05020144 

Supplemental 

Freshwater Fish, chronic 

No data are available for the DDC salts. However, a flow-through life-cycle toxicity 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 generation were as sensitive as reproductive effects 

(reduced egg production and reduced spawning frequency). An early-life stage study (850.1400) 

with the DDC salts is anticipated to be required for 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-ICE48), version 3.2.1, application was first used to estimate acute 

toxicity of thiram to the fathead minnow from existing rainbow trout and bluegill sunfish data 

(results are provided at the end of this appendix). 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 fathead minnow full life cycle study provides an 

ACR of 127. Applying this ACR to the rainbow trout acute data provides 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 

F0 egg production; F0 % 

spawning frequency; F1

4-week survival; F1 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 EC50: 52 Very highly 

toxic 

42504802 

Acceptable 

KDDC (50) 48-hr EC50: 340 Highly toxic 00105154 

Acceptable 

Thiram (98) 48-hr EC50: 210 Highly toxic 00164662 

Acceptable 

Freshwater Invertebrates, chronic 

No data are available for the DDC salts. However, 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 invertebrates 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 moderately to very highly toxic. The degradate 

thiram is highly to very highly toxic. No additional 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 LC50: 

59,000 Slightly toxic 41984701 Acceptable 

NaDDC (16) and 

Nabam (15) 

96-hr LC50: 122 

(as ts) Highly toxic 00100706 

Acceptable 

Thiram (98) 96-hr LC50: 540 Highly toxic 42514401 

Acceptable 

Acute – 

Saltwater 

Invertebrate 

GLNs 

850.1025/1055 

850.1035 

Eastern oyster 

NaDDC (39.6) 96-hr EC50: 760 Highly toxic 42561902 

Acceptable 

NaDDC (16) and 

Nabam (15) 

96-hr EC50: 300 

(as ts) Highly toxic 00100704 

Supplemental 

Thiram (98.3) 

IC50 = 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 LC50: 88 Very highly 

toxic 

42561901 

Acceptable 

Thiram (98.3) LC50: 3.36 Very highly 

toxic 

42488302 

Acceptable 

Grass shrimp NaDDC (16) and 

Nabam (15) 

LC50: 17 

(as ts) 

Very highly 

toxic 

00100705 

Supplemental 

Blue crab NaDDC (16) and 

Nabam (15) 

LC50: 9100 

(as ts) 

Moderately 

toxic 

00100703 

Supplemental 

ts: test substance 

Aquatic and terrestrial plants 

Plant toxicity data are anticipated to be required 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 rooted aquatic macrophyte. 

Data are not available for the DDC salts. Green 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 biocides in waste water used for irrigation and from 

uses resulting in spray drift. Use patterns, such as the oil and gas uses, have the potential for 

waste water from the process to be used in irrigation. There are no vegetative vigor data for 

thiram or DDC salts. Uses that potentially result 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%) IC50 = 1,600,000 

NOAEC < 57,000 

45441202 

Acceptable

Aquatic plants - green algae, 

Selenastrum capricornutum 

GLN 850.4500 

Thiram (99%) 

IC50 = 45 

NOAEC < 57 (will 

calculate IC05) 

42646001 

Acceptable 

Thiram (99%) IC50 = 140 

IC05 = 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 field 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 three replicate mesocosm ponds for the negative 

control group and a single replicate mesocosm pond per treatment 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 level) 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 period 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 meaningfully identified during the treatment period. 

However, these significant reductions in the above community parameters were attributed by the 

authors to treatment related reductions in zooplankton grazers and the subsequent rapid 

population growths, as supported by significant phytoplankton biomass, of those phytoplankton 

taxa with the most rapid population development/growth rates at the nominal 320 and 1000 ppb 

a.i. Therefore, true treatment-related negative effects as a result of Thiram 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 also at the nominal 320 

and 1000 ppb a.i. treatment levels. Treatment-related effects on specific taxa were never 

discussed within the study report. 

Due to the significant negative concentration-effect relationship 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 significantly affected during the treatment period. Similarity 

analysis of the treated zooplankton communities 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. (measured; 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 following 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 community structure compared to the structure from 

untreated or post-treatment years. This study provides 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 guideline requirement. Additionally there was no 

true replication of treatment levels. Conclusions, 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

μg/L 

(1.66) 

140.16 μg/L (2.14) 

Select Confidence Interval: Lower Limit Upper Limit 

 95% 92.35 μg/L 212.71 μg/L 

Model Information 

Intercept: 0.669768 

Slope: 0.888200 

Degrees of Freedom (N-2): 79 

R2

: 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 (Sxx): 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

μg/L 

(1.62) 

109.55 μg/L (2.03) 

Select Confidence Interval: Lower Limit Upper Limit 

 95% 66.32 μg/L 180.97 μg/L 

Model Information 

Intercept: 0.663875 

Slope: 0.847538 
Page 62 of 66

Degrees of Freedom (N-2): 66 

R2: 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 (Sxx): 150.09 

Cross-validation Success (%): 75.00 

Taxonomic Distance: 4 

 
Page 63 of 66

Appendix D Product Chemistry 

Sodium dimethyldithiocarbamate and Potassium 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 and Potassium Dimethyldithiocarbamate 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 (noctanol/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 comment period on the initial docket. PCRM is 

encouraging the agency to consider using non-testing approaches to fulfill the carcinogenicity 

study that had been anticipated to be required. 

Comments received did not result in a modification to the anticipated 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 for Responsible Medicine (PCRM) 

1. Comment: “GLN 870.4300 Combined Chronic Toxicity/Carcinogenicity Study 

The EPA has indicated, in the documents for this docket and in previous guidance, that it 

is willing to accept information obtained using 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 where these approaches can provide enough 

information to assess the potential carcinogenicity 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 entries 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 conduct a read-across for the carcinogenicity 

endpoint, is available. 

It should be noted that, according to data found in the QSAR 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/carcinogenicity study was triggered by the 

wood preservative and metalworking fluid uses which are now cancelled (EPA Reg. 

No.’s 1022-563 and 1022-577 were cancelled on October 30, 2013). As a result of these 

cancellations, the agency no longer anticipates the need to require the combined chronic 

toxicity/carcinogenicity study.