### Page 2 of 70 Sodium and Potassium Dimethyldithiocarbamate Salts Registration Review Team

Human Health Timothy Dole
Steve Malish
Zo ё Layton

Environmental Fate and Effects
Srinivas Gowda James Breithaupt
William Erickson Siroos Mostaghimi

Risk Management
Sandra O’Neill

Office of General Counsel Philip Ross

### Page 3 of 70 ABBREVIATIONS AND SYMBOLS

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

atm

- m 3 

### /mole a tmospheric pressure

- cubic meter per mole
BCF b ioconcentration f actor °C d egrees Celsius
CaSO 4 

### c alcium s ulfate
CaSO 3 

### c alcium s ulfite
CAS Chemical Abstracts Service
CCA c hromated c opper a rsenate CFR Code of Federal Regulations
CHO Chinese h amster o vary CMA Chemical Manufacturers Association
CO 2 

### c arbon dioxide
COC c oncentration

- of

- c oncern cPAD c hronic p opulation a djusted d ose CS 2 

### c arbon disulfide
DCI data call

- in
DEA d iethanol amine
DMA d imethylamine
DDC d imethyldithiocarbamate
EC 50 

### m edian (or 50 percent) e ffect c oncentration
EC 05 

### 5 p ercent e ffect c oncentration
ECOTOX ECOTOXicology
EDI e stimated daily i ntake
EDSP E ndocrine Disruptor Screening Program
E

- FAST Exposure and Fate Assessment Screening Tool
EPI Suite Estimation Program Interface Suite
EPA Environmental Protection Agency
FDA Food and Drug Administration
FFDCA Feder al Food, Drug, and Cosmetic Act
FGD f lue

- g as d esulfurization
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FQPA Food Quality Protection Act
FWP Final Work Plan g/mol g rams per mole
GLN guideline number
HPV h igh production v olume
IDS Incident Data System
K DDC potassium d imethyldithiocarbamate
Koc o rganic carbon normalized soil

- water partition coefficient
Kd s oil

- water partition coefficient
Kow o ctanol

- water partition coefficient
LC 50 

### m edian (or 50 percent) l ethal c oncentration
LD 50 

### m edian (or 50 percent) l e thal d ose LOAEC l owest

- o bserved

- a dverse

- e ffect

- c oncentration
LOEC l owest

- o bserved

- e ffect

- c oncentration
LOAEL lowest

- observed

- adverse

- e ffect

- l evel

### Page 4 of 70 Log K
ow 

### l ogarithm of the octanol

- water partition coefficient

μg m icrogram ml/g m illiliter p er g ram mg/kg m illigram p er k ilogram mg/kg/day m illigram p er k ilogram p er d ay mg/L m illigram p er l iter mm Hg m illimeter of mercury
MOE m argin of e xposure MRID Master Record Identification Number
MRL m aximum r esidue l imit
N/A n ot a pplicable
Na DDC s odium d imethyldithiocarbamate s alt

nm n anometers NOAEC no

- observed

- adverse

- effect

- c oncentration
NOAEL n o

- o bserved

- a dverse

- e ffect

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

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

- 10 logarithm of the acid
dissociation constant of a solution ppb p arts p er b illion

ppm p arts p er m illion
PWP Preliminary Work Plan QSAR q uantitative s tructure

- a ctivity r elationship
RED Rere gistration Eligibility Decision
SAR s tructure a ctivity r elationship
SF s afety f actor SSTS Section Seven Tracking System
SO2 s ulfur dioxide
TEP t ypical e nd

- u se p roduct
TGAI t echnical grade active i ngredient
TMDL total maximum daily l oads
TMTDS t etramethylthiuram disulfide (Thiram)
TMTMS t etramethyl thiomonosulfide
TMTU t etramethyl thiourea
UF uncertainty f actor UV/VIS ultraviolet/v isible light a bsorption
% w / w p ercent weight per weight.
WP w ettable powder
WWTPs w astewater treatment plants

### Page 5 of 70 

## Table of Contents

1 Introduction

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

................................ ................................ ................. 7
1.2 Case Overview

................................ ................................ ................................ ................. 9
1.3 Chemical Ide ntification and Properties

................................ ................................ ............ 9
1.4 Use/Usage Description

................................ ................................ ................................ ... 11
1.4.1 Registrations

................................ ................................ ................................ ........... 11
1.4.2 Summary of Registered Uses

................................ ................................ .................. 11
1.4.3 Usage Information

................................ ................................ ................................ .. 12
1.5 Regulatory History

................................ ................................ ................................ ......... 12
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 Ecologic al

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

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

................................ ................................ ........................... 19
3. 1 Existing Toxicological Endpoints

................................ ................................ .................. 19
3.2 Dietary Exposure

................................ ................................ ................................ ............ 20
3.2.1 Food

................................ ................................ ................................ ........................ 20
3.2.2 Drinking Water

................................ ................................ ................................ ....... 21
3.3 Occupational and Residential Exposures

................................ ................................ ....... 21
3.3.1 Occupational Exposures

................................ ................................ .......................... 21
3.3.2 Residential Exposures

................................ ................................ ............................. 23
3.4 Aggregate and Cumulative Exposure

................................ ................................ ............. 24
3.4.1 Aggregate Exposures

................................ ................................ .............................. 24
3.4.2 Cumulative Exposures

................................ ................................ ............................ 24
4 Envi ronmental Risk Assessment

................................ ................................ ........................... 24
4.1 Water Quality

................................ ................................ ................................ ................. 24
4.2 Environmental Conceptual Model Exposure Pathways

................................ ................. 25
4.3 Ecological Effects Assessment

................................ ................................ ....................... 31
4.3.1 Mode of Action

................................ ................................ ................................ ....... 31
4.3.2 Measures of Effect (Ecotoxicology Endpoints)

................................ ...................... 31
4.4 Exposure Analysis Plan

................................ ................................ ................................ .. 33
4.4.1 Aquatic and Terrestrial Wildlife Exposure Estimates

................................ ............ 33
4.4.2 Screening Level Down

- the

- Drain Analysis

................................ ............................ 33
4.5 Effects Analysis Plan

................................ ................................ ................................ ..... 34
5 Endocrine Disruptor Screening Program (EDSP)

................................ ................................ . 34
6 Guidance for Commenters

................................ ................................ ................................ .... 35
6.1 Preliminary Work Plan

................................ ................................ ................................ ... 35
6.1.1 Trade Irritants

................................ ................................ ................................ .......... 35
6.1.2 Water Quality

................................ ................................ ................................ .......... 35
6.1.3 Environmental Justice

................................ ................................ ............................. 35
6.1.4 Structure Activity Relationships

................................ ................................ ............. 35
6.1.5 Additional Information

................................ ................................ ........................... 36
7 Next Steps

................................ ................................ ................................ ............................. 37

### Page 6 of 70 8 References

................................ ................................ ................................ ............................. 38

Appendix A T oxicology Profile for Dimethyldithiocarbamate

................................ ............... 43 Appendix B Environmental Fate

................................ ................................ ............................. 51 Appendix C Ecotoxicology Profile

................................ ................................ .......................... 60 Appendix D Product Chemistry

................................ ................................ ............................... 69

List of Tables

Table 1

– Summary of Anticipated Risk Assessments and Data Needs: Dimethyldithiocarbamate

................................ ................................ ................................ ................................ ......................... 8
Table 2

– Anticipated Registration Review Schedule

................................ ................................ .... 9
Table 3

– Chemical Identification of Dimethyldithiocarbamate Sodium and Potassium Salts

...... 9
Table 4

– Physical

- Chemical and Fate Properties for Dimethyldithiocarbamate Salts

................ 10
Table 5

– Summary of the Registered Uses of D imethyldithiocarbamate

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

– Studies Anticipated as Needed for the Registration Review of Dimethyldithiocarbamate

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

– Toxicological Endpoints Used for the Dimethyldithiocarbamate RED

........................ 1 9
Table 8

– Occupational Exposure Scenarios for the Dimethyldithiocarbamate Salts

.................. 22
Table 9

– Residential Exposure Scenarios for DDC Salts

................................ ............................ 23

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

................................ ........................ 27 Figure 2

- Conceptual Model for Environmental Exposure of DDC Salts from Water S ystem and
Flue

- Gas Desulfurization (FGD) to Aquatic and Terrestrial Organisms

................................ ...... 28 Figure 3

– Conceptual Model for Aquatic (A) and Te rrestrial (B) Environmental Exposure of
DDC Salts in Recovered Water from Oil and Gas Use

................................ ................................ 29 Figure 4

- Conceptual Model for Aquati c (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

................................ .......... 30 Figure 5

- Conceptual Model for Aquatic Environmental Exposure of DDC Salts from Use in
Pressure Treated Wood

................................ ................................ ................................ ................. 31

### Page 7 of 70 

# 1 Introduction

This document is the United States Environmental Protection Agency’s ( USEPA, EPA or “the
A gency”) Preliminary Work Plan (PWP) for Sodium and Potassium Dimethyldithiocarbamat e Salts , herein referred to as d imethyldithiocarbamate or DDC salts . The PWP document explains
what EPA's Offi ce 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 PWP docum ent 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 a separate Registration
Review case ( 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 particip ation 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 helpf ul for the Agency to receive as it moves toward a
decision on dimethyldithiocarbamate

. The Agency encourages all interested stakeholders to review the PWP and to provide comments and additional information that will help the Agency’s
decision

- making proces s for this chemical.



# 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 ti me. 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 register ed pesticide every 15 years to determine whether it continues to meet the FIFRA standard for registration. The regulations governing registration review begin at 40 CF R 155.40. The Agency will consider benefits information and data as required by FIFRA. Th e 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. After reviewing and responding to comments and data received in the docket during this initial

### Page 8 of 70 comment period, the Agency will develop and commit to a F inal W ork P lan (FWP) and anticipated schedule for the Sodium an d Potassium Dimethyldithiocarbamate Salts Case.

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

- HQ

- OPP

- 20 13

- 0245 . Below is a summary of the issues relevant to this registration review case.

Tab le 1

– Summary of Anticipated Risk Assessments and Data Needs : Dimethyldithiocarbamate

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 detail s)

Dietary (food) Yes 7/14/2009 Updated Migration Studies 1

Dietary (drinking water) Yes 7/8/2009 Updated None

Occupational and
Residential Handler Yes 3/3/ 2009 Updated Inhalation Toxicity

– 90 Day Reproduction and Fertility Effects Chronic Toxicity/Carcinogenicity 3 , 4 Dermal Exposure Inhalation Exposure
Product Use Information

Residental Post Application

- Incidental
Oral and Dermal Yes 3/3/ 2009 Updated Surface Residue Data 3

Aggregate Yes N/A New Reproduction and Fertility Effects Chronic Toxicity/Carcinogenicity 3,4

Cumulative No (see 3.4.2 ) N/A None None

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

Ecological Effects and
Environmental Fate Yes 2009 New 2 Updated for
wood preservative Fish (chronic); Aquatic invertebrates (chronic); Aquatic and semi

- aquatic plants;
Beneficial Insect Studies 3

Aerobic soil metabolism 3 Leaching from treated wood 3 Activated Sludge Respiration Inhibition or Modified Activated Sludge Respiration Inhibition Ready biodegradab ility test or one of three biodegradation in activated sludge
simulation tests

1 R esidue chemistry data are anticipated to be needed to determine dietary exposure to DDC as a result of food contact with components of food packaging such as coatings, adhesives, paper

- making additives, and paper made from treated pulp

2 Commercial/Industrial Cooling Water, Pulp/Paper Mill Water Systems, Gas/Oil operations

3 EPA has received a request to cancel the only product with a wood preservative use. When the cancellation order becomes effective, this anticipated data require ment should no longer be needed

4 EPA has received a request to cancel the only product with a metal working flu id use. When the cancellation order becomes effective, this anticipated data requirement should no longer be needed

### Page 9 of 70 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 Preli minary Work Plan 2013

- 09 2013

- 09

- 18
Close Public Comment Period 2013

- 11 Phase 2: Case Development

Issue Final Work Plan 2014

- 03
Issue Data Call

- In (DCI) 2016

- 03
Receive Data to be Considered in Risk Assessment 2019

- 03 Open 30

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

- 09
Close Public Comment Period 2020

- 10 Phase 3: Registration Review Decision and Implementation Open 60

- Day Public Comment Period for Pro posed Decision 2021

- 03
Close Public Comment Period 2021

- 05

Issue Final Decision 2021

- 09 Begin Post

- Decision Followup 2021 Total (years) 8

* 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 ( Na DDC

, PC Code 034804); and Potassium Dimethyldithiocarbamate Salt ( K DDC

, PC Code 034803). T hese chemicals are herein refe rred to as dimethyldithiocarbamate or DDC salts

.

Table 3

– Chemical Identification of Dimethyldithiocarbamate Sodium and Potassium Salts

Chemical Name Sodium dimethyldithiocarbamate Potassium dimethyldithiocarbamate

Abbreviation Na DDC K DDC

Classification Dithiocarbamate Dithiocarbamate

PC Code 034804 034803

CAS No. 128

- 04

- 1 128

- 03

- 0

Molecular Formula C 3 

### H 6 

### NNaS 2 

### C 3 

### H 6 

### NKS 2 

### Molecular Weight 143.2 1 g rams per m ole 159.31 g ra ms per m ole

Purity 40 percent ( % ) w eight per w eight A 

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

### Page 10 of 70 Chemical Name Sodium dimethyldithiocarbamate Potassium dimethyldithiocarbamate

Molecular Structure

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



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

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 Na DDC was identified by UV/VIS spectra recorded at different pH values.

Result at pH < 2:
> 200 n ano m eters (nm)

, ε = 0 l mol - 1

cm - 1

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

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

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

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

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

### Page 11 of 70 Guideline
No. Physical and Chemical Properties Na DDC K DDC

830.7370 Dissociation Constant in

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

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

pKa value: Not applicable; product decomposes below pH 8.

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

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

830.7550 Partition coefficient ( n

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

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

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

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

N/A Henry's Law Constant 7.857 x 10 - 16 atm

- m 3 /mole (EPI Suite v4.1) 2.01 x 10 - 16 atm

- m 3 /mole (EPI Suite v4.1).

PAI

- Pure active ingredient
HPV

– High production volume



# 1.4 Use/Usage Description

1.4.1 Registrations

There are 18 registered K DDC products and 13 registered Na DDC products. There are no inert uses and no pending registrations.



## 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, p roducts 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 RED 1



### .
Several product labels have b een amended since the 2009 RED Amendment to voluntarily delete

uses

. Deleted u ses include sapstain treatment, paints and coatings, metalworking fluids, cotton fabrics, wood veneers and alginate pastes. T here are still some labels that include some of the se

uses , and the labels are noted in Table 5

.

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

### Page 12 of 70 Table 5

– Summary of the Registered Uses of D imethyldithiocarbamate

Use Site Application Rate in
Terms of Active Ingredient (A.I.) Label s (EPA Reg istration 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 labels 1 Reverse Osmosis Water Systems 10 to 51 ppm Several labels. Sewage Systems 5 to 14 ppm Two labels ( 1448

- 70, 34688

- 77 )
Material Preservative Adhesives, Coatings, Emulsions 1000 ppm One label ( 1022

- 563 ) 2

Fuels and Oils Bottom Water 58 ppm One label ( 1022

- 563 ) 2 Metal Working Fluids 1000 ppm One label ( 1022

- 563 ) 2 Paints and varnish (applied film) 1000 ppm One label ( 1022

- 563 ) 2 Papermaking Additives (Alum solutions, pigment slurries, coating formulations etc.) 200 ppm Two labels ( 1022

- 563 1

, 2

, 1448

- 70 )

Wood Pr eservative Wood, Pressure Treatment 1 pound per cubic foot One Label ( 1022

- 577 ) 2

1 Includes indirect food uses.

2 EPA has received a product cancellation request for 1022

- 563, 1022

- 577, and 1022

- 574. A cancellation order is anticipated to be
issued in late 2013.



## 1.4.3 Usage Information

According to the Specialty Biocides North America Report 2004

- 2005 (Kline, 200 6 ) the dithiocarbamates, which include Nabam (disodium ethylene bis dithiocarbamate), and
d imethyldithiocarbamate , are used primarily for paper production and industrial cooling water

treatments

, and to a lesser extent

, for leather production. The report does not distinguish the use patterns for Nabam and d imethyldithiocarbamate . With respect to wood preservation, the report
indicates that d imethyldithiocarbamate is not used.

Production volume data in the EPA Section Seven Tracking System (SSTS) for the years 2004 through 2008 indicate that no more than 2,000,000 kilograms of dimethyldithiocarbamate are sold per year in the United States 2



### .



# 1.5 Regulatory History

T he D imethyldithio carbamate S alts were previously included in RED C ase 2180 , with PC Codes 034801, 034803, 034804, 034805, and 034806

. K DDC (034803) and Na DDC (034804) have been split from Case 2180 and moved into Case 8100 for registration review ; case 8100 consists

2 As per EPA’s Section Seven Tracking System, data pulled on 3/12/13.

### Page 13 of 70 of only these two chemicals

. The Agency completed a n Amended RED for DDC salts in 200 9. Ziram (034805) and Ferbam (034801) each had individual REDs in 2003 and 2005 , respectively ; registration review docket s for these conventional chemicals are scheduled to o pen in FY 2015

. Zinc dimethyldithiocarbamate ( 034806 ) was canceled in 1992.

The first product containing Na DDC was registered in 1949, and the first product containing
K DDC was registered in 1980.

Na DDC and K DDC are registered for use as material preservatives for fuels, metalworking fluids, paints, coatings, adhesives, cloth, and paper/paperboard; they are also registered for use as antifoulants/slimicides in a variety of liquids including industrial/commercial cooling water, air
washe r water, sugar mill pulp/process water, marine heat exchangers, gas/oil recovery fluid, industrial wastewater treatment systems, industrial water purification systems, reverse osmosis water systems, and pasteurizer cooling water. Their main uses reportedly are as antifoulants in industrial cooling and air washer water systems, as well as pulp and paper mills and gas/oil drilling muds.



## 1.5.1 Recent/Pending Regulatory Actions

Several uses of dimethyldithiocarbamate are pending termination/ cancellation as of the

pu blication of this document, including all wood

- preservative / pressure treatment, as well as preservation of adhesives/coatings/emulsions, fuels and oils bottom water, metal working fluids, and paints and varnish (EPA registration numbers 1022

- 563, 1022

- 574 , and 1022

- 577). EPA anticipates issuing the Registration Review generic

- data call

- in ( G DCI) 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

res idues 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
17 6.300 );

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

• Rubber article intended for repeated use, used in producing, manufacturing, packing, processing, preparing, treating, packaging, transporting, or holding food (21 CFR
177.2600 )

### Page 14 of 70 

# 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, n o 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 70 

# 2 A nticipated 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

OCSPP GLN Study Name Test Substance Time
Frame 1 (Months) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable Exposure Scenario

Studies Anticipated to be Required through the Registration Review DCI
835.3110 4

835.3220 5

835.32 4 0 6

835.32 8 0 7 Ready biodegradability test or one of three biodegradation in activated sludge simulation tests TGAI 12 Activated sludge microorganisms All uses Transport to Industrial wastewater treatment plant

835.4100 3 ,16 Aerobic soil metabolism Ethanolami

ne (degradate) 24 Wood Preservatives Treated wood in terrestrial
environments Terrestrial exposure

OECD 209 or
850.3300 8 Activated Sludge Respiration
Inhibition or Modified Activated Sludge Respiration Inhibition TGAI 12 Activated sludge microorganisms All uses Transport to Industrial wastewater treatment plant

850.1300 Aquatic invertebrate life

- cycle toxicity, f reshwater TGAI 24 Aquatic organisms Industrial process water; Pulp and paper; Gas/oil, wood preservative 3 Transport to the aquatic environment

850.1350 Aquatic invertebrate life

- cycle toxicity, estuarine/marine TGAI 24 Aquatic organisms Industrial process water; Pulp and paper; Gas/oil, wood preservative 3 Transport to the aquatic environment

850.1400 Fish early

- life stage, freshwater TGAI 12 Aquatic organisms As above Transport to the aquatic environment
850.3020 3 Honeybee, acute contact toxicity TGAI 12 Wood preservatives Wood preservatives Treated wood
850.3030 3 Honeybee, toxicity of residues TGAI 12 Wood preservatives Wood preservatives Treated wood

850.4100 9 Seedling emergence, Tier II rice TGAI 12 Aquatic organisms Industrial process water; Pulp and paper; Gas/oil, wood preservative 3 Transport to the aquatic environment

850.4150 15 Vegetative vigor, Tier II rice TGAI 12 Aquatic organisms Gas/oil Transport to the aquatic environment

850.4400 Aquatic Plant Testing using
Lemna sp., Tier II TGAI 12 Aquatic organisms A s above Transport to the aquatic environment

850.4500 Algal Toxicity Tier II

– marine diatom, freshwater diatom, and green algae TGAI 12 Aquatic organisms A s above Transport to the aquatic environment

850.4550 Algal Toxicity Tier II

- Cyanobacteria TGAI 12 Aquatic organisms A s above Transport to the aquatic environment

### Page 16 of 70 OCSPP GLN Study Name Test Substance Time
Frame 1 (Months) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable Exposure Scenario

870.2345 Inhalation Toxicity

– 90 Day TGAI 24 Occupational/ Residential Exposure All Use Sites As listed 10

870.3800 11 Reproduction and Fertility
Effects TGAI 36 Human Health All Use Sites As listed 10 Dietary and drinking water exposures

.
870.4300 Combined Chronic Toxicity/Carcinogenicity TGAI 36 Human Health All Use Sites MWF and Wood Preservation 12

. Dietary and drinking water exposures

.
870.5395 Mammalian Erythrocyte
Micronucleus Test TGAI 12 Human Health All Use Sites All exposure scenarios.

870.7800 Immunotoxicity TGAI 12 Human Health All Use Sites All exposure scenarios

875.1200 1 3,14 Indoor Dermal Exposure TGAI 24 Occupational/
Residential Handler All Use Sites As Listed 10

875.1400 1 3,14 Indoor Inhalation Exposure TGAI 24 Occupational/
Residential Handler All Use Sites As Listed 10

875.1700 Product Use Information TGAI 12 Human Health All Use Sites All exposure scenarios.
875.2300 3 Indoor Surface Residues TGAI 12 Residential Exposure Wood Preservative Toddlers on Decks and Playsets
AWPA
E11

- 06 3 Leaching from treated wood TGAI 12 Wood preservatives Treated wood in terrestrial
environments Terrestrial exposure

Special Study Migration Studies TEP 24 Dietary and Aggregate Cane sugar and beet sugar Mills; Coatings, adhesives, paper

- making additives, and pulp/paper mill
slimicide use Dietary/Tier II

Data Needs No Longer Anticipated to be Required from the 2009 RED

GLN Study Name Test Substance Time
Frame 1 (Months) Reason the Study is No Longer Anticipated to be Required

835.2240 Photodegration in Water TGAI 12 Data were available from active ingredient Thiram, a dimer of DDC acid (MRID 45651201)
835.2410 Photodegradation on Soil TGAI 12 Data were available from active ingredient Thiram, a dimer of DDC acid (MRID 45724501)
835.4100 Aerobic Soil Metabolism TGAI 24 Data were available from active ingredient Thiram, a dimer of DDC acid (MRID 43734901)

835.6100 Terrestrial Field Dissipation TGAI 24 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. In addition, t he 158 W regulations do not require 835. 6100 data ( 1 40 CFR § 158.2282 )

.

875.1100 Outdoor Dermal Exposure TGAI 24 Exposure scenarios were added to the indoor studies.
875.1300 Outdoor Inhalation Exposure TGAI 24 Exposure scenarios were added to the indoor studies.

875.1600 Application exposure monitoring data reporting TGAI 12 This study will be addressed in the submission of the remaining anticipated exposure data requirements

### Page 17 of 70 OCSPP GLN Study Name Test Substance Time
Frame 1 (Months) Risk Assessment(s) Data Will Support Use Site(s) Triggering Anticipated Data Requirement Applicable Exposure Scenario

875.2700 Product Use Information TGAI 12 This study will be addressed in the submission of the Product Use Information Study 875.1700
875.2800 Description of Human Activity TGAI 12

- 24 This study will be addressed in the submission of the Product Use Information Study 875.1700
875.2900 Data Reporting and Calculations TGAI 12 This study will be addressed in the submission of the remaining anticipated exposure data requirements

1 The timeframe will be measured from the receipt of the anticipated DCI.

2 MRID 40220701 was submitted and found to be acceptable for parent compound, but degradates were not identified. As a result, another study is anticipated to be required to assess the formation and decline of degradates.

3 EPA has received a request to can cel the only product with a wood preservative use. When the cancellation order becomes effective

, this anticipated data requirement should no longer be needed.

4 EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0017

. The biodegradation study anticipated to be required is based on results of an Activated Slu dge Respiration Inhibition test.

5 EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0024 . The biodegradation study anticipated to be required is based on results of an Activated Sludge Respiration Inhibition test.

6 EPA has a published final guideline for this study: http://www.regulations.gov/#!documentDetail;D=EPA

- HQ

- OPPT

- 2009

- 0152

- 0034 . The biodegradation study anticipated to be required is based on results of an Activated Sludge Respiration Inhibition test.
7 The results of the ASRI test will determine which of these four biodegradation tests is/are anticipated to be required. If the ASRI test EC 50 is less than or equal to 20 mg/L, then either the (i)Biodegradation in Activated Sludge Study or (ii) Simulation Test

– Aerobic Sewage Treatment: A. Activate d Sludge Units or (iii) the Porous Pot Test is expected to be required. If the ASRI test EC 50 is greater than 20 mg/L, then the registrant would likely be required to conduct either: (i) Ready Biodegradability or (ii) a) Biodegradation in Activated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units or c) the Porous Pot Test. If the Ready Biodegradability study is conducted and passes, then no further testing would be expected to be required. If, however, the
antimicrobial fai ls the Ready Biodegradability study, then the a) Biodegradation in Activated Sludge or b) Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units, or c) the Porous Pot study would likely be required.

8 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 allow preparation of a
concentrated stock solution in water.

9 Test guidelines 850.4100 and 850.4225 were merged and harmonized into OCSPP 850.4100 in a Federal R egister Notice dated June 27, 2012 (FRL

- 9333

- 1).
10 Indoor exposure scenarios include Open Pour Liquids

, Open Pour Wettable Powder

, Brush/Roller Application

, Airless Spray Application, Wood Pressure
Treatment and Using Treated MWF

. 11 Results from a multi

- ge neration (EPA guideline 870.3800) or an extended one

- generation reproductive and fertility effects study using OECD Test Guideline 443 ( http://www.oecd

- ilibrary.org/environment/test

- no

- 443

- extended

- one

- generation

- reproductive

- toxicity

- study_9789264185371

- en ) will satisfy this requirement.

12 Only t he metal working fluid and wood preservation uses may result in long term exposures to workers.

1 3 Data reporting and calculations are anticipated to be required when handler exposure data are submitted

1 4 EPA has received request s to cancel the only product s with a paints and coatings use and a metal working fluid use . When th e cancellation order s become
effective

, this anticipated data requirement should no longer be needed for the brush/roller paint, airless sprayer paint and metal working fluid indoor exposure
scenarios that are listed in footnote 10

. 15 Test guidelines 850.4150 and 850.4250 were merged and harmonized into OCSPP 850.4150 in a Federal Register Notice dated June 27, 2012 (FRL

- 9333

- 1).

### Page 18 of 70 16 The registrant submitted MRID 43685901 for diethanolamine, a surrogate compound for the dimethylamine (DMA) degradate of NaDDC and KDDC. Until this study is reviewed and classified as appropriate for use in the risk assessment, it is included as an anticipated data re quirement for use in conducting the risk

assessment.

### Docket Number EPA

- HQ

- OPP

- 2013

- 0245 www.regulations.gov

Page 19 of 70 

# 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 e xisting 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 assessmen t in support of the 200 9 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 regis tration 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 t oxicity 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 ( Female s 13

- 50) Oral NOAEL = 13 mg/kg/day
UF = 100 A Rabbit developmental study (MRID 40995101) LOAEL = 38 mg/kg/day based on clinical signs (reddish

- colored material in cage trays) and possible increased maternal death and
abortions.

Acute Dietary (General population) Oral NOAEL = 20 mg/kg
UF = 100 A Co

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

Sub

- chronic neurotoxicity study (MRID 43550501)
LOAEL = 9 9 mg/kg/day based on salivation, oral staining and decreased body weight

. NOAEL = 2.0 mg/kg/day

Chronic Dietary (All population s ) Oral NOAEL = 2 mg/kg/day
UF = 1000 B 90

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

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

### Occupational and Residential Exposures

Incidental oral ( Short

- Term ) Oral NOAEL = 2 mg/kg/day
UF = 1000 B 90

- day subchronic oral study (MRID 42047201) Same study used for the chronic dietary scenario above.

### Page 20 of 70 Exposure Scenario Dose, UF Study and Toxicological Effects

Incidental Oral ( Intermediate

- Term ) Oral NOAEL = 2 mg/kg/day
UF = 1000 B 90

- day subchronic oral study (MRID 42047201) Same study used for chronic dietary above.

Dermal (S hort, intermediate
and long

- term ) Dermal NOAEL

= 60 mg/kg/day
UF = 1000 B 90

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

Inhalation (Short, intermediate
and long

- term ) Oral NOAEL = 2 mg/kg/day
UF = 1000 B 90

- day subchronic oral study (MRID 42047201) Same study used for chronic dietary above.

A. Uncertainty Factor (UF) i ncludes 10 X for interspecies extrapolation and 10x for intraspecies variation

. B. UF i ncludes 10 X for interspecies extrapolation, 10x for intraspecies variation and 10x for database uncertainty

.



# 3.2 Dietary Exposure

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

### . Uses of Na DDC and K DDC salts that may result in indirect dietary exposure include
their use as slimicide in paper mill pulp slurries, material preservatives (includin g adhesives, coatings, and 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 and in wood pressure treatment.

Dietary risk is characterized in terms of the Population Adjusted Dose (PAD), which reflects the reference dose (RfD), either acute or chronic, that has been adjusted to account for the FQPA Safety Factor (SF). This calculation is performed for each population subgroup for which an endpoint exists. A risk estimate that is less than 100% of the acute or chronic PAD is not of
concern. Acute and chronic dietary risk s for D DC 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

Na DDC 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 addi tive 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 ethylenediam ine for control of microorganisms in cane sugar and beet sugar mills (21 CFR §173.320) 4 

### . The Agency anticipates reassessing dietary risks attributable to the sugar cane and sugar beet uses of Na DDC

. T he Agency anticipates the need to require migration st udies in order to refine the risk assessment.

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

4 21 CFR §173.320

### Page 21 of 70 In 2009, the Agency assessed the risks associated with the use of DDC salts in adhesives and coatings that have the potential to be in food

- contact packaging. FDA guidance for migration
from food contact surfa ces was adapted in the risk assessment 5 

### . Based on this guidance, a DDC
salts dietary concentration of 7 ppb was assumed in calculating the Estimated Daily Intake (EDI). T he Agency anticipates updating the dietary (food) risk assessments for food

- contact

p aper/paperboard, paper additives and coatings. T he Agency anticipates the need to require migration studies in order to refine the risk assessment. Dietary exposures will be incorporated into the aggregate risk assessment.



## 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
D 359537 (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 us ing unit exposure data and transferable residue data that have underlying limitations and will need to be reassessed using updated values.



## 3.3.1 Occupational Exposure s
EPA anticipates the need to revise the occupational exposure assessment conducted in support o f
the 200 9 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 a ddition of liquids and water soluble package addition of WP because these addition methods are considered to be closed systems. T he risks from closed system addition methods were assumed to be mitigated by label language and were not assessed quantitative ly in the 2009 RED Amendment

. 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 we ttable powder formulations range d from
1 to 6000 and were of concern for most of the scenarios. The inhalation MOEs for handling wettable powder formulations range d from <1 to 2000 and were also of concern.

Machinist Exposure to Dimethyldithiocarbamate Tr eated Metal Working Fluids

5 FDA. Guidance for Industry: Preparation of Premarket Submissions for Food Contact Substances: Chemistry
Recommendations. December 2007. http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/IngredientsAdditivesGR ASPackaging/ucm081818.htm#aii8

### Page 22 of 70 DDC salts may be used to treat metal working fluids in accordance with one label ( EPA reg.
number 1022

- 563). There is a potential for dermal and inhalation exposure when machinists use metalworking fluids treated with DDC salts

. The dermal exposure was estimated in the 2009
RED Amendment using the film thickness approach and the resulting dermal MOE was 1200. The inhalation exposure was estimated in the 2009 RED Amendment using the OSHA PEL approach by adjusting the oil mist concentration by the a.i. concentration and the resulting MOE

was 2800. EPA has received a product cancellation request for EPA registration number 1022

- 563. A cancellation order is anticipated to be issued in late 2013.

Pressure T reatment Worker Exposures

DDC salts may be used to pressure treat wood used for decks, buildings, fences, poles, etc., in
accordance with one label ( EPA reg. number 1022

- 577). These exposures were assessed in the
2009 RED Amendment using data from a chrom ated copper arsenate (CCA) exposure study (MRID 455021

- 01 ) that was sponsored by Arsenical Wood Preservative Task Force of the American Chemistry Council. The arsenic portion of the results from this study w as used as a surrogate to assess DDC salts expo sures and these results were normalized to extrapolate the measured exposures in the CCA study (monitored at 0.438 to 0.595% arsenic in the CCA solution) to the maximum DDC salts treatment solution concentration (10% ai in solution). The resulting inhalat ion MOEs ranged from 400 to 7,600 and were of concern for two scenarios because they were less than the target MOE of 1000. The dermal MOEs range d from 19 to 2200
and were of concern for most of the scenarios because they were less than the target MOE of
1000

. EPA has received a voluntary cancellation request for EPA registration number 1022

- 5 77

. A cancellation order is anticipated to be issued in late 2013.

Occupational Risk Characterization

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 Scenario s Exposure Route(s) Duration

Open Pour Liquids for treatment of Cooling Water, Drilling Muds, Drilling Fluids, Paints and Coatings. 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

Using Treated Metal Working Fluids Dermal
Inhalation Long Term

Pressure Treatment of Wood Dermal
Inhalation Long Term

Airless Sprayer and Brush Roller Application of Treated Paints Dermal
Inhalation Intermediate
Term

### Page 23 of 70 

## 3.3.2 Residential Exposures

EPA anticipates the need to revise the residential exposure assessment s conducted in support of
the 2009 RED Amendment

. There is one product ( EPA reg. number 1022

- 563) that is labeled
for use as an in

- can preservative of water thinned paints and coatings

. There is one product ( EPA reg. number 1022

- 577) labeled for pressure treatment wood preservation. EPA has
received a voluntary cancellation request for both products . A cancellation order is anticipated to
be issued in late 2013.

Residential Handler Exposures for Painting

There is the potential for residential handler exposure during the brush/roller and airless sprayer application of paints treated with dimethyldithiocarbamate. Both dermal and inhalation exposures are anticipated and are assumed to be primarily short term because painting is done on an episodic basis. The risks were assessed in the 2009 RED Amendment using PHED data a n d

an application rate of 1000 ppm

. T he dermal MOEs were 910 and 350 for brush/roller and airless sprayer application, respectively, and were less than the target MOE of 1000 which means
that the risks were of concern

. The inhalation MOE s were 25,000 and 1,100, respectively, and were greater than the target MOE of 1000

.
Residential Post Application Exposures from Pressure Treated Wood

There is a potential for child exposure to dimethyldithiocarbamate residues when play ing on dimethyldithiocarbamate

- treated wood structures such as decks and children’s playsets. Both dermal and incidental oral exposures are anticipated. These exposures were assessed in the 2009
RED Amendment using a n assumed transferable residue value o f 1.0 ug/cm 2 

### that was higher
than the maximum residue seen for chromium and non

- chromium based wood preservatives (D330159, EPA, 2006). The dermal MOE was 440 and the incidental oral MOE was 360 , both
of which were less than the target MOE.

Scenarios that Need to be Assessed During Registration Review

T he residential handler scenario that w as 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

. The post application scenario will need to be revised during registration review upon receipt of the transferable residue data that are anticipated to be required to verify the assumption that was used in the 2009 RED Amendment . A listing of residential exposure
scenarios to be assessed is incl uded in Table 9

.

Table 9

– Residential Exposure Scenarios for DDC Salts

Scenario Exposure Route(s) Duration

Handler Exposures

Application of Preserved Paint (Brush/Roller and Airless Spray) Dermal
Inhalation Short T erm

Post Application Exposures

Toddlers Playing on Pressure Treated Decking and Playground Equipment Dermal
Incidental Oral Intermediate Term

### Page 24 of 70 

# 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 200 9
RED Amendment

. Upon a reevaluation and selection of toxicological endpoints, combined with the human health exposure assessments ex pected as a part of this registration review case, aggregate exposures will need to be assessed. This assessment will include dietary (food) exposures and residential exposures.



## 3.4.2 Cumulative Exposures

With respect to cumulative exposure, unlike other pesti cides 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 do es 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
che micals, see http://www.epa.gov/pesticides/cumulative/

.


# 4 Environmental Risk Assessment

A risk assessment was conducted for the Amended RED 6 

### (EPA 2009) that assessed acute risks to fish and aquatic inv ertebrates from the use of sodium dimethyldithiocarbamate salt as a wood preservative. LOCs were exceeded for acute risk to aquatic organisms for some applications. However, in April, 2013

, EPA received a request to cancel the only product with a wood

pr eservative use. The product cancellation order is expected to be issued in late 2013 . For currently registered uses, the ecological risk assessment planned during registration review will allow the Ag ency 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 use s include c ommercial /industrial cooling water, p ulp/ p aper mill w ater

s ystems, and gas/o il 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 effe ct' 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 w ill 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 Act 7 

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

6 http://www.epa.gov/oppsrrd1/REDs/ DDC salts

- red

- amended.pdf

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

### Page 25 of 70 potassium dimethyldithiocarbamate salts 8



### . More information on impaired water bodies and
TMDLs can be found at EPA’s website 9



### .



# 4.2 Environmental Conceptual Model Exposure Pathways

Na DDC and K DDC 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 p lant flue gas
desulfuriza tion thickeners )

.

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 begin ning of the aerobic aquatic metabolism study

. 10 

### The primary and major ( > 10 % of applied parent compound) degradates include dimethylamine ( DMA )

, carbon disulfide ( CS 2 ) 

### , 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 water fracking water is released into streams. The flue gas desul furization use is associated with coal

- burning power plants and there are two forms of waste, water which goes to a WWTP and sludge which goes to a landfill. 11 

### 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. 12



### 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 an d its degradates occur by both
abiotic 13 

### and biotic means 14



### . 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

t he E PI

- Suite 4.1 15 

### Henry’s Law constants of 10 - 10 

### to 10 - 9 

### atm m 3 

### mol - 1 

### , DMA and CS 2 

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

### to 10 - 2 

### atm m 3 

### mol - 1 

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

8 http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id=885& p_pollutant_ group_name=PESTICIDES

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

10 MRID 40365702

11 h ttp://water.epa.gov/scitech/wastetech/guide/steam

- electric/upload/Steam

- Electric_Detailed

- Study

Report_2009.pdf , EPA 821

- R

- 09

- 008

12 http://www.epa.gov/osw/nonhaz/municipal /landfill/criteria/landbig.pdf

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

14 A quatic metabolism , MRIDs 43865901 and 40365702

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

### Page 26 of 70 For all the following conceptual expo sure models for DDC salts and its degradates, the Agency is using solid lines to signify that surfac e 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 properties 16 

### 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.

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 SO 2 

### gas from the smokestacks of steam electric power plants that cons ume 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 pla ced in a landfill or other surface impoundment or applied to land as a fertilizer and consists of ash (including some heavy metals)

, CaSO 4 

### , and
CaSO 3



### . The water system and FGD uses contain air washers, reverse osmosis, and industrial wastewater systems. 17



### The conceptual models for the oil and ga s 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. T he conceptual model for the wood preservative uses of DDC salts is attached in Figure 5

. Th e wood preservative us e is based on the sole remaining registered label 18 

### th at includes wood preservati on

.

16 W ater solubility, log Kow, and low potential for sorption

17 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

- Study

Report_2009.pdf

18 http://www.epa.gov/pesticides/chem_search/ppls/001022

- 00577

- 19960423.pdf

### Page 27 of 70 Figure 1

– Conceptual Model for Cooling Tower Use of DDC Salts and Ecological Exposure and Effects of
DDC Salts 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 Cooling Towers (Once Through and Recirculating)

WWTP microorganisms Uptake or sorption

Population Respiration
inhibition Direct Discharge

### Page 28 of 70 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 29 of 70 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 30 of 70 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 31 of 70 Figure 5

- Conceptual Model for Aquatic Environmental Exposure of DDC Salts from Use
in Pressure Treated Wood



# 4.3 Ecological Effects Assessment

4.3.1 Mode of Action

Na DDC 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 determin ation that in animals they do not share a common mechanism of toxicity 19



### . The dithiocarbamates all release carbon disulfide (CS 2 

### ) , under acidic conditions , w hich 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

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



### 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 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 WWTP microorganisms Uptake or sorption

Population Respiration
inhibition Dip, Pad or Pressure
Treated Wood Process

Facility Drain Post

- Treated Wood Product Storage

Leaching and Run

- off In

- Use Service of Wood
Treated Wood Products

Leaching and Run

- off

Surface Water

Sediment

### Page 32 of 70 and animals. The ecotoxicity data requirements and a ll available ecotoxicity end points 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 t he DDC salts ecological risk assessment are p resented in Table
1 1. Anticipated d ata gaps for the TGAI also are indicated

. Data also are included for thiram, a major reaction product and also a registered active ingred ient (PC Code 079801)

.

Table 1 1

. 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 LC 50 = 60 μg ai/L 240946

Chronic Data gap N / A

Bluegill Thiram Acute 96

- h LC 50 = 42 μg ai/L 070801

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

Freshwater
invertebrates Waterflea NaDDC Acute 48

- h EC 50 = 52 μg ai/L 42504802

Chronic Data gap N / A

Thiram Acute 48

- h E C 50 = 210 μg ai/L 164662

Chronic Under Review N/A

Estuarine/marine
fish Sheepshead

minnow NaDDC Acute 96

- h LC 50 = 59,000 μg ai/L 41984701

Chronic Not a data gap: Mysid is

more acutely sensitive N/A

Thiram Acute 96

- h LC 50 = 540 μg ai/L 42514401

Chronic Not a data gap: Mysid is

more acutely sensitive N/A

Estuarine/marine

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

Chronic Data gap N/A

Thiram Acute LC 50 = 3.36 μg ai/L 42488302

Chronic Will use generated ACRs N/A

Aquatic non

vascular plants Green algae,
Freshwater

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

Green algae Thiram Non

- listed I C 50 = 45 μ g a.i/L

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

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

Thiram Non

- listed I C 50 = 1 ,600,000 μ g a.i/L 45441202

### Page 33 of 70 Receptor

Group Surrogate Species Test

material Risk

Scenario Toxicity Endpoint EPA

ID

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

Semi

- aquatic plants (seedling

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

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

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

Ring

- necked

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

Mallard Thiram (97.5) Chronic NOAEC = 9.6 ppm 45441201

Beneficial insects Honeybee TGAI Acute Data gap 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 F ate Assessment Screening Tool) will be used to determine the potential for aquatic organisms downstream of the industrial wastewater treatment plan t s that receive discharges from the end

- use of K DDC and Na DDC to be exposed these chemicals or their degradates. Na DDC and K DDC salts are used in industrial water systems such as commercial/industrial cooling water, industrial wa stewater, pulp/paper mills, etc. Antimicrobials with these uses will eventually be released to industrial wastewater treatment plants whose effluents will reach surface water and aquatic organisms. The primary and major ( > 10 % of applied parent compound) degradates include the DMA, CS 2 

### , TMTDS, TMTMS, and TMTU. Chemicals that are released down

- the

- drain can typically take from a few to several hours to reach wastewater treatment plant intakes following their discharge and from several hours to roughly a da y following their discharge down

- the

- drain to subsequently be discharged from industrial wastewater treatment plants to surface water

. The half

- life of both
K DDC and Na DDC are long enough to enter the industrial wastewater treat ment 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 R egistration Review docket. The A gency does not anticipate requiring additional
data to assess down

- the

- drain exposures for this registration review.

### Page 34 of 70 

# 4.5 Effects Analysis Plan

Additional open literature studies will be identified through EPA’s ECOTOXicology (EC OTOX)
database 20 

### , 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 valu e s more sensitive than
available from the anticipated registrant

- submitted studies

. ECOTOX was created and is maintained by the USEPA, Office of Research an d 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, neurotoxicit y, 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 maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As par t 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).

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 eff ect 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 ass ays 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 sys tems 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 grou p of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. NaDDC and KDDC are not among the group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. Accordingly, as part of registration rev iew, EPA will issue future EDSP orders/data call

ins, requiring the submission of EDSP screening assays for NaDDC and KDDC

.

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

### Page 35 of 70 For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test gu idelines and the Tier 1 screening battery, please visit our
website: http://www.epa.gov/endo/

.


# 6 Guidance for Commenters

6.1 Preliminary Work Plan

The public is invited to comment on EPA’s Preliminary Work Plan and ratio nale. The Agency will carefully consider all comments as well as any additional information or data provided in a timely manner prior to issuing a final work plan for the Sodium and Potassium Dimethyldithiocarbamate S alts registration review case.



## 6.1.1 Trade Irritants

Through the registration review process, the Agency intends to solicit information on trade irritants and, to the extent feasible, take steps toward facilitating irritant resolution. The Agency
will work to harmonize tolerances and international maximum residue limits (MRLs) and may modify tolerance levels to do so, when possible. Stakeholders are asked to comment on any trade irritant issues resulting from lack of MRLs or disparities between U.S. tolerances and MRLs in key export markets, provid ing as much specificity as possible regarding the nature of
the concern.



## 6.1.2 Water Quality

See section 4.1. The Agency invites submission of water quality data for this pesticide. To the extent possible, data should conform to the quality standards in Append ix A of the OPP Standard Operating Procedure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and Management Process 21 

### in order to ensure they can be used quantitatively or qualitatively in pesticid e risk assessments.



## 6.1.3 Environmental Justice

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all people, regardless of race, color, national origin, or income, in the development, implementation,
and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of their location, cultural practices, or other factors, may have atypical, unusually high exposure to sodium and potassium dimethyldithiocarbamate salts compared to the general population. Please comment if you are aware of any sub

- populations that may have atypical, unusually high exposure compared to the general population.



## 6.1.4 Structure Activity Relationships

EPA must rely upon information of appropriate quality and reliability for each decision made by the Agency. In the Office of Pesticide Programs (OPP), the evaluation process for a pesticide

21 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm

### Page 36 of 70 chemical traditiona lly begins with the applicant’s submission of a set of studies conducted with the specific pesticide chemical of interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous process that identifies the physical, ch emical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in alternative techniques, i.e., techniques other than data generation that could significantly inform the Agency’s decision

- making process. Recently, OPP has made increasing use of structure activity relationship (SAR) as part of its regulatory
decision

- making process. In the SAR process, a chemical's molecular st ructure is compared to
that of other chemicals for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s physical, chemical, and biological properties. Thus, the chemical’s physical, chemical, and biological properties are a function of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured data on a single physical, chemical, or biological property is used to derive a model (an equation) to predict the value of that property.

Since SAR assessments and QSAR modeling are another set of tools that are available to Agency scientists, OPP has begun a process shift that envisions shifting from the current st udy

- by

- study approach to an approach in which the use of predicted data, generated using validated models, is considered along with information from open literature and studies specifically generated under Part 161 requirements. All relevant information wo uld be considered as part of a weight

- of

- the

evidence evaluation.

At this time, EPA believes that for certain endpoints, especially physical/chemical and fate properties, that SAR and QSAR might be effectively utilized to fulfill these data requirements
f

or many antimicrobial pesticide chemicals. When considering biological properties, at this time, EPA believes that SAR and QSAR can be most effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human health and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream

- lined, i.e., a screening

- level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predicted data can fulfill one of the data needs for the
Sodium and Potassium Dimethyldithiocarbamate Salts Case, then the Agency invites submission of this information. The submitter would be expected to supply a rationale describing the utility of the information and provide documentation on the scientific validity of the information. The
determination that th e predicted data fulfills the data requirement would be at the sole discretion of the Agency. Pre

- submission consultation with the Agency is encouraged.



## 6.1.5 Additional Information

Stakeholders are also specifically asked to provide available information and d ata that will assist the Agency in refining its risk assessments, including any species

- specific ecological effects determinations. The Agency is interested in receiving the following information:

1. Confirmation on the following label information:

### Page 37 of 70 A. Sites of application
B. Formulations
C. Application methods and equipment
D. Maximum application rates
E. Frequency of application, application intervals and maximum number of applications
F. Geographic limitations on use
2. Use or potential use distribution
3. Use hist ory 4. Usage/use information for non

- agricultural uses (e.g., materials preservation)
5. Typical application interval
6. State or local use restrictions
7. Ecological incidents (non

- target plant damage and avian, fish, reptilian, amphibian and
mammalian mortalitie s) not already reported to the Agency
8. Monitoring data



# 7 Next Steps

After the 60

- day comment period closes in November 2013 , the Agency will review and respond to any comments received in a timely manner, and then issue a Final Work Plan for the Sodium

and Potassium Dimethyldithiocarbamate Salts case.

### Page 38 of 70 

# 8 References

Allen, R. 1975

. Evaluation of Acute Toxicity of Vincide 31 to Fish Species. Unpublished study received Jul 7, 1975 under 9386

- 7; submitted by Vinings Chem Co., Atlanta, GA; CDL:
234870

- A

. MRID 00104057

.
Anonymous. 1978. Report of Laboratory Investigations. Unpublished study prepared by Sharpley Laboratories, Inc., Fredericksburg, VA. Acc. No. 240946.

Beavers, J. 1986

. S DDC : An Acute Oral Toxicity Study with the Bobwhite: Final Report: Projec t No. 211

- 106. Unpublished study prepared by Wildlife International Ltd. 18 p. MRID
00159788.

Bodden, R. 1982. Avian Single

- dose Oral LD 50 

### Bobwhite Quail: Study No. 6026

- 101. Unpublished study received Jun 3, 1982 under 1448

- 70; prepared by Hazleton Laboratories America, Inc., submitted by Buckman Laboratories, Inc., Memphis, TN;
CDL: 247734

- B . MRID 00 105155

.

Burke, K.; Patterson, S. 1990

. Physical and Chemical Characteristics of Aquatreat KM: Lab Project Number: D

- 08

- 004. Unpublished study prepared by National Starch and Chemical Co. 5 p. MRID 41609407

.

Burke, K.; Patterson, S. 1990

. Physical and Chemical Characteristics of Aquatreat SDM: Lab Project Number: D

- 08

- 004. Unpublished study prepared by National Starch and Chemical Co. 5 p. MRID 41609403

.

Coates, M. 1996

. Thiram: Algal Growth Inhibition: Addendum to MRID 426460

- 01: Lab Project Number: UCB 442/960953: UCB 442/921255. Unpubl ished study prepared by Huntingdon Life Sciences, Ltd. 10 p. MRID 44086101.

Cohen, S. 1994

. Sodium Dimethyldithiocarbamate (S DDC ): Hydrolysis of S DDC in Buffered Aqueous Solutions: Final Report: Lab Project Number: ME 9300155. Unpublished study prepared by Univ. of Pittsburgh Applied Research Center. 206 p. MRID 43180801.

Conzelmann, P. 1982

. Static 96

- hour Marine Bioassay Testing Vinings Antimicrobial Agent
AMA

- 31 on American Oyster: GSRI Project No. 415

- A60

- 41. Unpublished study received Apr 22, 1982 under 9386

- 7; prepared by Gulf South Research Institute, submitted by Vinings Chemical Co., Atlanta, GA; CDL:247417

- D . MRID 00100704.

Conzelmann, P. 1982

. Static 96

- hour Marine Bioassay Testing Vinings Antimicrobial Agent
AMA

- 31 on Blue Crab: GSRI Project No. 415

- A60

- 41. Unpublished study received Apr 22, 1982 under 9386

- 7; prepared by Gulf South Research Institute, submitted by Vinings Chemical Co., Atlanta, GA; CDL:247417

- C . MRID 00100703.

Conzelmann, P. 1982. Static 96

- hour Marine Bioassay Testing Vini ngs Antimicrobial Agent
AMA

- 31 on Grass Shrimp: GSRI Project No. 415

- A60

- 41. (Unpublished study received

### Page 39 of 70 Apr 22, 1982 under 9386

- 7; prepared by Gulf South Research Institute, submitted by Vinings Chemical Co., Atlanta, GA; CDL:247417

- A) MRID 00107905

Conz elmann, P. 1982. Static 96

- ho ur Marine Bioassay Testing Vin ings Antimicrobial Agent
AMA

- 31 o n Sheepshead Minnow: GSRI Proj ect No. 415

- A60

- 41. (Unpublished study received Apr 22, 1982 under 9386

- 7; prepared by Gulf South Research Institute, sub

mitted by V inings Chemical Co., Atlanta, GA; CDL:247417

- B) MRID 00107906

Croudace, C.; Caunter, J.; Johnson, P. 1992

. Thiram: Acute Toxicity to Sheepshead Minnow ( Cyprinodon variegatus ): Lab Project Number: W199/B. Unpublished study prepared by Imperial Chemical Industries PLC. 22 p. MRID 42514401.

Douglas, M. 1993

. Thiram: Algal Growth Inhibition ( Selenastrum capricornutum ): Lab Project Number: UCB 442/921255. Unpublished study prepar ed by Huntingdon Research Centre Ltd. 30 p. MRID 42646001.

Flynn, F. and Agahigian, H. 1990

. Physical and Chemical Characteristics of Sodium Dimethyldithiocarbamat e. Unpublished study pre pared by R. T. Vanderbilt Co., Inc. in
association with Baron Consul ting Co. 4 p. MRID 41651301.

Flynn, F. 1992

. Solubility of Sodium Dimethyldithiocarbamate. Unpublished study prepared by R.T. Vanderbilt Co., Inc. 6 p. MRID 42510401

.

Hinton, R. 1990

. Sodium Dimethyldithiocarbamate: Physical and Chemical Characteristics: Lab Project Number: S DDC V4

- 0790. Un

- published study prepared by Vinings Industries, Inc. 11 p. MRID 41586303

.
Husson, R. (1986) Letter sent to J. Rockwell date d Sept 17, 1986: Data r equested to complete
review of 48 hour LC50 study on Daphnia magna : thiram . Prepared by UCB Societe Anonyme. 3 p. MRID 00 164662

Knott, W.; Johnston, C. 1970

. Busperse 49 (SASE): Evaluation of Acute LC50 for Rainbow
Trout. Unpublished study received Nov 7 , 1974 under 1448

- 56; prepared by Woodard Research Corp., submitted by Buckman Laboratories, Inc., Memphis, TN; CDL: 240504

- A . MRID 00134589

Krueger, H.; Kendall, T. (2009) (Carbon 14)

- Th iram: A Flow

- Through Life

- Cycle Toxicity Test
with the Fathead Minno w ( Pimephales promelas ): Final Report. Project Number: 657A/103. Unpublished study prepared by Wildlife International, Ltd. 144 p. MRID
47824101

.

Lintott, D. 1992

. Sodium Dimethyldithiocarbamate (S DDC ): Acute Toxicity to Bluegill, Lepomis macrochirus Under Flow

- Through Conditions: Lab Project Number: J9203010B. Unpublished study prepared by Toxicon Environmental Sciences. 84 p. MRID 42504801

.

Lintott, D. 1992

. Sodium Dimethyldithiocarbamate (S DDC ): Acute Toxicity to the Water Flea, Daphnia magna Und er Flow

- Through Conditions: Lab Project Number: J9203010A. Unpublished study prepared by Toxicon Environmental Sciences. 85 p. MRID 42504802.

### Page 40 of 70 Lintott, D. 1992

. Sodium Dimethyldithiocarbamate (S DDC ): Acute Toxicity to the Mysid, Mysidopsis bahia , under Fl ow

- through Test Conditions: Lab Project Number: J9203010D. Unpublished study prepared by Toxikon Environmental Sciences. 93 p. MRID 42561901.

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

McCann, J.A. 1976. Bluegill sunfish ( Lepomis macrochirus ). Test No. 996 (U.S. EPA, Chemical and Biological Investigations Branch, Animal Biology Laboratory) Unpublished Study.
MRID 00 07 0801

.

McElwee, C.; Lintott, D. 1992

. Sodium Dimethyldithiocarbamate (S DDC ): Acute Effect on New Shell Growth of the Eastern Oyster, Crassostrea virginica : Lab Project Number: J9203010C. Unpublished study prepared by Toxikon Environmental Sciences. 82 p.
MRID 42561902.

Morgenroth, U.; Mueller

- Kallert, H. (1995) (Carbon 14)

- Thiram: Degradation and Metabolism in One Soil Incubated Under Aerobic Conditions: Lab Project Number: 326182. Unpublished study prepared by RCC Umweltchemie Ag. 114 p. MRID 43734901.

Obrist, J. 1986

. The Adsorption/Desorption of Dibam on Representative Agricultural Soils: Final Report: Study No. 6015

- 275. Un published study prepared by Hazleton Laboratories America, Inc. 71 p. MRID 00 164056.

Obrist, J. 1987. Aerobic Aquatic Metabolism of [Carbon 14]

- Dibam (Sodium N,N

Dimethyldithiocarbamate): Laboratory Project Identification: HLA 6015

- 279. Unpublished study prepared by Hazleton Laboratories America, Inc. 104 p. MRID
40365701

.
Obrist, J. 1987. Anaerobic Aquatic Metabolism of [Carbon 14]

- Dibam (Sodium N,N

Dimethyldithiocarbamate): Laboratory Project Identification: HLA

- 6015

- 271. Unpublished study prepared by Hazleton Laboratories America, Inc. 85 p. MRID
40365702.

Obrist, J. 1987. Photodegradation and Hydrolysis of [Carbon 14]

- Diba m (N,N,

- Dimethyldithiocarbamate) in Buffered Aqueous Solutions: Final Report: Lab Project ID:
HLA 6015

- 278. Unpublished study prepared by Hazleton Labs America, Inc. 182 p.
MRID 40220701

.

0 ’ Graney, R. 1982

. The Acute Toxicity of Busan 85 to Daphnia magna Straus: Project No. 82

- E

- 048

- D. Unpublished study received Jun 3, 1982 under 1448

- 70; prep ared by Biospherics, Inc., sub mitted by Buckman Laboratories, Inc., Memphis, TN; CDL:247734

- A . MRID 00 105154

.
Reynolds, J. 1995

. Aerobic Aquatic Metabolism of (car bon 14) (inert ingredient): Lab Project Number: XBL94084: RPT00216. Unpublished study prepared by XenoBiotic Lab., Inc. 120 p. MRID 48685902

.

### Page 41 of 70 Reynolds, J. 1995. Aerobic Soil Metabolism of (carbon 14) (inert ingredient): Lab Project
Number: XBL94082: RPT0 0214. Unpublished study prepared by XenoBiotic Lab., Inc. 118 p. MRID 43865901.

Shepler, K.; Runes, H. (2002) Photodegradation of (Carbon 14) Thiram in/on Soil by Artificial Light: Lab Project Number: 1043W: 1043W

- 1: 1042W

- 004. Unpublished study prepared by PTRL West, Inc. 115 p. MRID 45724501.

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

Sutherland, C.; Kendall, T.; Krueger, H. (2001) Thiram Technical: A 7

- Day Toxicity Test with Duckweed ( Lemna gibba G3): Final Report: Lab Project Number: 357A

- 101. Unpublished study prepared by Wildlife International. Ltd. 79 p. {OPPTS 850.4400} . MRID
45 441202.

Thompson, R.; Croudace, C.; Grinell, A. 1992

. Thiram: Acute Toxicity to Mysid Shrimp ( Mysidopsis bahia ): Lab Project Number: W199/D: BL4562/B. Unpublished study prepared by Imperial Chemical Industries PLC. 19 p. MRID 42488301.

U.S. EPA. March

, 1993. Criteria for Solid Waste Disposal Facilities: A Guide for Owner/Operators. EPA 530

- SW

- 91

- 089

. http://www.epa.gov/osw/nonhaz/municipal/landfill/criteria/landbig.pd f

U.S. EPA. September, 2004. Reregistration Eligibility Decision for Thiram

. EPA 738

- R

- 04

- 012. http://www.epa.gov/oppsrrd1/REDs/0122red_thiram.pdf

U.S. EPA

. 2009a. Sodium and Potassium Dimethyldithiocarbamate: Revised Occupational and Residential Exposure Assessment for the Registration Eligibility Decision (RED),
D 359537

, May 14, 2009

.

U.S. EPA. 2009b. Sodium and Potassium Dimethyldithiocarbamate Salts : Amendment to the Ferbam (PC C ode 034801) and Ziram (PC Code 034805) Rereg istration Eligibility
Decisions. List D

. CASE 2180 . June 2009. http://www.epa.gov/oppsrrd1/REDs/ DDC salts

- red

- amended.pdf

U.S. EPA. 2009c. “Dietary Risk Assessment for Potassium Dimethyldithiocarbamate for the RED Process”. Memorandum for Regulatory Management Branch II, from Najm Shamim, Chemist, Antimicrobials Division, Office of Pesticide Programs, Arlington, VA. July 14,
2009.

U. S. EPA. May 14, 2009. Environmental Fate Assessment of Sodium and Potassium Dimethyldithiocarbamate . Memorandum from James Breithaupt to Norm Cook.
D359533.

U.S. EPA. October, 2009. Steam Electric Power Generating Point Soucrce Category: Final Detailed Study Report. EPA 821

- R

- 09

- 008.

### Page 42 of 70 http://water.epa.gov/scitech/wastetech/guide/steam

- electric/upload/St eam

Electric_Detailed

- Study

- Report_2009.pdf

U

. S

. EPA. 201 3 . Estimation Programs Interface SuiteTM for Microsoft® Windows, v 4.11. United States Environmental Protection Agency, Washington, DC, USA. http://www.epa.gov/opptintr/exposure/pubs/episuite.htm

U.S. FDA. December, 2007. Guidance for Industry: Preparation of Premarket Submissions for Food Contact Substances: Chemistry Recommendations. http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformatio n/IngredientsAdditivesGRASPackaging/ucm081818.htm#aii8

Ward, G . (1991) Sodium Dimethyldithiocarbamate (S DDC ): Acute Toxicity to Sheepshead Minnow, Cyprinodon variegatus , under Flow

- Through Test Conditions: Lab Project Number: J9010004B. Unpublished study prepared by Toxikon Environmental Sciences. 54 p. MRID 41984701.

Wheat, J.; Ward, G. 1992

. Sodium Dimethyldithiocarbamate (S DDC ): Acute Toxicity t o Rainbow Trout, Oncorhynchus mykiss , Under Flow

- through Test Conditions: Lab Project Number: J9010004D. Unpublished study prepared by Toxikon Environmental Sciences. 59 p. MRID 42247901.

### Page 43 of 70 

# Appendix A T oxicology Profile for Dimethyldithiocarbamate

I. BACKGROUND

Both sodium dimethyldithiocarbamate and potassium d imethyldithiocarbam a te react with water readily and decompose into their respective salts. Due to their struct ural 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

Sod ium 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 inhal ation route of exposure study. There were no acceptable acute oral toxicity studies available; however, an unacceptable / guideline

upgradeable 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 44 of 70 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. LD 50 

### (M) = 2100 mg/kg
LD 50 

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

81

- 2 Acute Dermal 00160995, 92043009 LD 50 

### (M) = 1450 mg/kg
LD 50 

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

81

- 3 Acute Inhalation 00159769, 42327801,
92043010 LC 50 

### (M) > 2.22 mg/L
LD 50 

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

81

- 4 Primary Eye
Irritation 00161185, 92043011 Corrosive I

81

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

81

- 6 Dermal
Sensitization 00159783, 92043013 Negative

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



### B. Potassium dimethyldithiocarbamate

The acute toxicity summary table for potassium dimethyldithiocarbam a te 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. Acu te toxicity database for p otassium dimethyldithiocarbamate

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

81

- 1 Acute Oral 00132382,
92039001
00143448* LD 50 

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

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

81

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

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

81

- 3 Acute Inhalation No study available
81

- 4 Primary Eye
Irritation 00105157,
92039003 PIS: 32.2/110 unwashed,
PIS: 40.7/110 washed III **



### 81

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

81

- 6 Dermal
Sensitization 00132380,
92039005 Positive

Adapted from RED, Table 6, p. 10
* MRID s 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 45 of 70 III. Repeat Dose Toxicity

The toxicolo gical d atabase of repeat dose studies for dimethyldithiocarbamat e 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 D atabase of Repeat Dose Studies for D imethyldithiocarbam a te

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

870.3100 90

- Day Oral

- Rats Y es Y es 42047201 ( Na DDC )
870.3250 90

- Day Dermal

- Rats Y es Y es 40830801 ( K DDC )
870.3250 90

- Day Dermal

- Rabbit Y es Y es 40140101 ( Na DDC )
870.3700a Developmental Toxicity

- Rats Y es Y es 40140102 ( Na DDC ), 41005501 ( K DDC )
870.3700b Developmental Toxicity

- Rabbits Y es Y es 40165804 ( Na DDC ), 40995101 ( K DDC )
870.3800 Reproduction and Fertility Effects Y es N o 42905, 82096*
870.4100a Chronic Toxicity

– Rats Y es N o 82096*

870.4100b Chronic Toxicity

– Dogs No N o 82905*
870.5100 Bacterial Reverse Mutation Test Y es Yes 159688 ( Na DDC ), 40631103 ( K DDC )
870.5300 In vitro Mammalian Cell Gene Mutation Test Y es Yes 159779 ( Na DDC ), 4089901 ( K DDC )
870.5375 In vitro mammalian chromosome aberration

test Y es Yes 159681 ( Na DDC )

870.5550 Unscheduled DNA Synthesis in Mammalian
Cell Culture Y es Yes 40631101 ( K DDC )

870.5900 In vitro Sister Chromatid Exchange Assay Y es Yes 159778 ( Na DDC ), 40631102 ( K DDC )

870.6200 Neurotoxicity Screening Battery Y es Yes 43544201 ( Na DDC )

870.6200 Neurotoxicity Screening Battery Y es Yes 43550501 ( Na DDC )

Adapted from RED, Table 4, p. 7.

*MRID numbers not in references or profile

### Page 46 of 70 Table 5

. Toxicity Profile of Sodium Dimethyldithiocarbamate (excluding acute studies)

Guideline No./

Study Type MRID No./ Study
Classification Animal s 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

D ermal 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
G avage in water at 0, 2

, 20

, or 2 00 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
A dministered 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 C oncentrations of 4

, 40

, 1 33, 400

or 1 333 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

- c ytotoxic dose levels (lowest dose levels at which effects
occurred: 4 or 40 μg/plate ± S9).

### Page 47 of 70 870.5300
In Vitro
M ammalian 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

Si ngle 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

G avaged 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 = 9 9 mg/kg/day based on
S alivation

, oral staining and decreased body weight

.

Neurotoxicity NOAEL > 9 9 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 D imethyldithiocarbamate (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 study (MRID 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 48 of 70 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 post

implantation 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 a nd 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 de creased.
870.3700a Developmental Toxicity (Rabbit) MRID 40747002 Supplementary

– Pilot Study for the main study
MRID 40995101 6 female r abbits/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 post

implantation 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 49 of 70 870.3700a 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 incr eased 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, 90

- day inhalation toxicity study, and combined chronic toxicity/carcinogenicity study conducted with sodium dimethyldithiocarbamate were identified as data gaps and are anticipated to be required studies for an adequa te risk characterization

. S tructure activity relationship (SAR) analysis may be used to address the cancer 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 P art 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

- da ta

- requirement.pdf

.

### Page 50 of 70 References for Appendix A

US EPA, 2009

. Hazard Assessment for the Reregistration Eligibility Decision (RED) Document of Sodium Dimethyldithiocarbamate and Pot a ssium Dimethyldithiocarbamate. February 5,
2009

### Page 51 of 70 

# Appendix B Environmental Fate

Na DDC and K DDC 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 fat e studies indicate that both parent Na DDC 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) 22



### , log K ow values (

- 0.38

- 1.94) of less than 3, and
limited sorption to soil (Koc values of 312

- 445 ml/g ) 23



### . Although the half

- li ve s for Na DDC and its degradates in water are relatively short ( ranging up to 6.7 days) , th ese estimates of persistence

are not short enough to prevent residues from entering WWTPs. Data on the half

- life of Na DDC 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

. 24 

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

Abiotic

Hydrolysis

Parent Na DDC is composed of DMA and CS 2 

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

### ,
a re

- combination of DMA and CS 2 

### called TMTU

, TMTDS , which is also known as thiram , and
TMTMS

. A hydrolysis study 25 

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

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

### . Formation of oxidative degradates such as the disulfide appears to be more predominant in alkaline as opposed to acidic or neutral
conditions. The estimated abiotic hydrolysis half

- li ves of Na DDC are 16.5 min, 29.4 hours and 42.8 days at pH 5, 7 and 9, respectively.

Photodegra dation

A registrant

- submitted study for photodegradation of NaDDC in water 26 

### d id not track
d egradates. The photolytic half

- l ives at pH 5, 7 and 9 w ere 26 minutes, 17.6 hours and 21.2 hours, respectively. Two degradation products were observed in all samples and a third

22 http://www.epa.gov/opptintr/exposure/pubs/e pisuite.htm

23 MRID 00164056

24 MRIDs 43180801, 40220701, 40365701, and 40365702

25 MRID 43180801

26 835.2240, MRID 40220701

### Page 52 of 70 degradate was 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 45651201 27 

### , which is an acceptable study for the act ive 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). Thira m 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
hour s 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 p hotodegradation on soil 28 

### were not submitted for either Na DDC or K DDC salts. However, acceptable data on p hotodegradation 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. CO 2 

### was the only significant (formed at > 10 % of applied Thiram) degradate. T he only current use that requires photodegradation on soil data is wood preservation, and that use is expected to be cancelled. No additional data are expected to be req uired.

Soil Adsorption/Desorption (Kd) and Octanol

- Water Partition Coefficient (Koc)

In an adsorption/desorption study 29 

### on agricultural soils, the change in concentration of an

a queous Na DDC 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 (r 2 

### = 0.98) and pH (r 2 

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

Sludge Adsorption/Desorption

No data on sludge sorption ( OCSPP GLN 835.1110) have been submitted

. Sorption to sludge is

not a likely route of dissipation because the log Kow is less than three (3) . Therefore data are not anticipated to be required. 30

27 45651201, 835.2240

28 835.2410

29 835.1230, MRID 00164056

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

### Page 53 of 70 B iotic

Aquatic Metabolism

Aerobic and anaerobic aquatic metabolism also degrade Na DDC

. In an aerobic aquatic metabolism study (MRID 40365701), rapid degradation of Na DDC 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 h igh

p erformance l iquid c hromatography (HPLC)

. Under anaerobic conditions, Na DDC degraded into the same three degradates as seen under aerobic metabolism with TMTDS being the major degradate identified. Non

- linear half lives for TMT D S 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 ( CO 2 

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

Soil Metabolism

No aerobic soil metabolism data were submitted for parent NaDDC. However, an acceptable
aerobic soil metabolism study (MRID 43734901) was submitted for Thiram which degraded with

a non

- linear half

- life of 2.1 days in sandy loam soil . TMTU, TM U, TMTM, and CS 2 

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

### accounted for 9.0% of the applied radioactivity at 2 days post

- treatment and increased to a maximum of 7 5 % by 205 days. The
DT 50 

### , DT 75 

### , and DT 90 

### for thiram were approximately 1 .7, 4.8, and 9.8 days, respectively. No additional data are anticipated to be required for parent NaDDC.

The Agency also received registrant

- submitted aerobic soil metabolism ( OCSPP GLN 835.4100, MRID 43685901) and aerobic aquatic metabolism ( OCSPP GLN 8 35.4300, 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 f or DMA, there is no record of review for these studies. These studies will be formally reviewed prior to the risk assessment

. Until these studies are reviewed and classified as appropriate for use in the risk assessment, they are
included as anticipated data requirements

.
Terrestrial Field Dissipation

Data on terrestrial field dissipation ( OCSPP GLN 835.6100) were not submitted for either
Na DDC or K DDC salts. The Agency has reviewed the need for these data and determined that
the aerobic soi l 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.

### Page 54 of 70 Leaching from Treated Wood

Data on leaching from treated wood were no t submitted for either Na DDC or K DDC salts. This study is anticipated to be required. The preferred methods are AWPA E11

- 06 and E20

- 06 (see justification below)

. However, the only current use that requires data for leaching from treated wood is wood preservation, and that use is expected to be cancelled. If the use in wood preservation is cancelled, then this data requirement will no longer likely be needed.

Metab olism in Sewage Sludge and Activated Sludge Respiration Inhibition (ASRI)

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 an d determines the extent of impacts to WWTP organisms. If the ASRI test EC 50 

### 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 I C 50 

### is gre ater 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 CO 2 

### production for respirometric methods. These pass levels should be reached in a 10

- day window within the 28

- day period of
the test. If th e 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 55 of 70 Table B1

– Physical

- Chemical and Fate Properties for Sodium and Potassium Dimethyldithiocarbamate Salts and Degradates

Test Guideline Parent Compounds 31 Degradates 32

Na DDC K DDC 33 Dimethylamine (DMA) Carbon disulfide (CS 2 ) TMTDS (Thiram) 34 TMTMS 35 TMTU 36 TM U 37 Reference (MRID for Parent Compounds unless Stated, EPI

Suite for Degradates)

CAS Number 128

- 04

- 1 128

- 0 3

- 0 124

- 40

- 3 75

- 15

- 0 137

- 26

- 8 97

- 74

- 5 2782

- 91

- 4 632

- 22

- 4 EPI

- Suite 4.1 1

Molecular Formula C 3 H 6 N 1 S 2 Na 1 C 3 H 6 N 1 S 2 K 1 C 2 H 7 N 1 C 1 S 2 C 6 H 12 N 2 S 4 C 6 H 12 N 2 S 3 C 5 H 12 N 2 S 1 C 5 H 12 N 2 O 1 EPI

- Suite 4.11

Molecular weight 143.20 159.31 45.08 76.13 240.42 208.36 132.22 116.16 EPI

- Suite 4.11

Chemical Structure N/A

Physical

- Chemical Properties Melting Point ( o C) N/A 38 N/A 39

- 92.2

- 111.5 107 109.5 79.3

- 1.2 EPI

- Suite 4.1 1 Boiling Point ( o C) 102 >100 6.8 46 339 301.3 245 176.5 EPI

- Suite 4.1 1 Water Solubility (mg/L) 1.32 x 10 6 Easily soluble 1 x 10 6 2,160 30 1 x 10 6 350,000 1 x 10 6 EPI

- Suite 4.1 1

Dissociation Constant
in Water (pKa) 7.2 7.2 No data No data No data No data No data No data 41609403
EPI

- Suite 4.1 1

Octanol

- water Partition Coefficient (Log K
ow ) - 2.41 (EPI

- Suite 4.1) - 1.43 (EPI

- Suite 4.1) - 0.38 1.94 1.73 0.75 0.49 0.19 EPI

- Suite 4.1 1

31 Chemical and physical properties of parent compounds relative to environmental risk assessment are listed in Table 4 above. Values in this Table B1 are copied from Table 4.

32 Major degradates were formed at > 10 % of applied parent compound. Min or degradates were formed at <10 % of applied parent compound.

33 Environmental fate data were submitted for NaDDC but not KDDC. Both compounds are salts and therefore will readily disassoci ate in water to form the Na
or K cations and the DDC anion. As a result, NaDDC is an acceptable surrogate for KDDC.

34 DDC anion forms a cross

- linked dimer TMTDS, which is joined by two (2) sulfur molecules. This dimer is the active ingredient Thiram (PC Code 079801)

. 35 Cross

- linked DDC anions joined by one (1) sulfur instead of two sulfurs.

36 Tetramethyl thiourea (TMTU)

37 Tetramethyl urea (TMU)

38 Not applicable

39 Not applicable

### Page 56 of 70 Test Guideline Parent Compounds 31 Degradates 32

Na DDC K DDC 33 Dimethylamine (DMA) Carbon disulfide (CS 2 ) TMTDS (Thiram) 34 TMTMS 35 TMTU 36 TM U 37 Reference (MRID for Parent Compounds unless Stated, EPI

Suite for Degradates)

K
oc (ml/g) 312

- 445 No data 40 4.7 48 676 337.3 25.7 8.6 00164056
EPI

- Suite 4.1 1 Soil adsorption/ desorption (ml/g) 1.5

- 12.6 No data 41 3.2 No data No data No data No data No data 00164056
EPI

- Suite 4.1 1 Sludge adsorption/ desorption (%) <1.9 <1.9 1.74 0.6 1.6 1.5 0.63 0.62 EPI

- Suite 4.1 1

Bioconcentration Factor (BCF) No data No data 3.2 8.9 6.4 3.2 3.2 3.2 EPI

- Suite 4.1 1

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 10 +1 EPI

- Suite 4.1 1

Henry’s Law Constant (atm

- m 3 /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 10 - 5 EPI

- Suite 4.1 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 formed 43180801

Photodegradation in

water 835.2240 42 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 data 40220701

Photodegradation in

water 835.2240 43

for Thiram No data No data No data No data 6.6 hours (parent compound) No data No data No data 45651201

Photodegradation on
soil
835.2410 4 3

, for Thiram No data No data No data No data 1.2 days (parent compound) No data No data No data 45724501

40 Data for NaDDC were used as a surrogate for KDDC

41 Data for NaDDC were used as a surrogate for KDDC

42 Unknown degradate was formed at up t o 22

- 28 % of applied parent compound by 19 minutes, and declined to 1.4

- 3.3 % by 77 minutes. The 5/14/2009 environmental fate memorandum required another photodegradation in water study.

43 Thiram data used as a surrogate for NaDDC and KDDC

### Page 57 of 70 Test Guideline Parent Compounds 31 Degradates 32

Na DDC K DDC 33 Dimethylamine (DMA) Carbon disulfide (CS 2 ) TMTDS (Thiram) 34 TMTMS 35 TMTU 36 TM U 37 Reference (MRID for Parent Compounds unless Stated, EPI

Suite for Degradates)

Biotic Degradation Half

- lives (days unless specified)

Aerobic soil
metabolism
835.4100
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 major degradates

found 43734901

Aerobic soil

me tabolism for
diethanolamine (DEA) 44

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 major degradates

formed 43685901

Anaerobic soil
metabolism
835.4200 Not submitted Not
submitted Not submitted Not submitted Not submitted Not submitted Not
submitted Not submitted Not applicable

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 formed 40365702

Aerobic aquatic
metabolism of
Diethanolamine 45

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 major degradates

formed 43685902

Anaerobic aquatic
metabolism
835.4400 Not submitted Not
submitted Not submitted Not submitted Not submitted Not submitted Not
submitted Not submitted Not applicable

Biodegradation half

life in sludge (days) Not submitted Not
submitted Not submitted Not submitted Not submitted Not submitted Not
submitted Not submitted Not applicable

44 Aerobic soil metabolism data on diethanolamine (MRID 43685901) were submitted as a surrogate for the dimethylamine (DMA) degr adate.

45 Aerobic aquatic metabolism data on diethanolamine (MRID 43685902) were submitted as a surrogate for the dimethylamine (DMA ) degradate.

### Page 58 of 70 Table B2

– Physical

- Chemical and Fate Properties for Degradates of Sodium and Potassium Dimethyldithiocarbamate Salts from Photodegradation in Water 46

Test Guideline Thiram sulfone Thiram oxo Thiram oxo sulfone DDC sulfonic acid monomer (oxo) DDC sulfonic acid monomer (thio) Reference (MRID for Parent Compounds unless Stated, EPI

- Suite for Degradates)

CAS Number None None None None None EPI

- Suite 4.11
Molecular Formula C 6 H 13 N 2 S 4 C 6 H 12 N 2 OS 3 C 6 H 18 N 2 O 3 S 3 C 6 H 7 NO 4 S C 6 H 7 NO 3 S 2 EPI

- Suite 4.11 Molecular weight 241.42 224.36 262.40 153.15 169.21 EPI

- Suite 4.11

Chemical Structure 45651201

Melting Point ( o C) 190.38 110.35 155.43 101.39 98.02 EPI

- Suite 4.11 Boiling Point ( o C) 452.44 344.70 428.80 325.94 320.06 EPI

- Suite 4.11 Water Solubility (mg/L) 1 x 10 6 4.41 x 10 4 1 x 10 6 1 x 10 6 1 x 10 6 EPI

- Suite 4.11

Dissociation Constant in Water (pKa) N/A N/A N/A N/A N/A EPI

- Suite 4.11

Octanol

- water Partition Coefficient (Log K
ow ) - 2.5 1.03

- 1.58

- 3.14 - 2.47 EPI

- Suite 4.11

K
oc (ml/g) 113.5 57.02 16.9 7.7 1 EPI

- Suite 4.11

Soil adsorption/ desorption (ml/g) No data No data No data No data No data EPI

- Suite 4.11

Sludge adsorption/ desorption (%) 1.75 1.80 1.75 1.75 1.75 EPI

- Suite 4.11

Bioconcentration Factor (BCF) 3.16 2.21 3.16 3.16 3.16 EPI

- Suite 4.11

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 EPI

- Suite 4.11

Henry’s Law Constant (atm

- m 3 /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 EPI

- Suite 4.11

Abiotic Degradation Half

- lives (days unless specified)
Hydrolysis
835.2120 No data No data No data No data No data No data

46 Based on MRID 45651201, Photodegradation in water study for Thiram, a dimer of DDC acid.

### Page 59 of 70 Test Guideline Thiram sulfone Thiram oxo Thiram oxo sulfone DDC sulfonic
acid monomer (oxo) DDC sulfonic acid monomer (thio) Reference (MRID for Parent Compounds unless Stated, EPI

- Suite for Degradates)

Photodegradation in water
835.2240 47 Stable, did not decline Stable, did not
decline Stable, did not
decline Slight decline Slight decline 45651201

Photodegradation on soil
835.2410 No data No data No data No data No data Not applicable

Biotic Degradation Half

- lives (days unless specified)

Aerobic soil me tabolism for diethanolamine (DEA) 48

835.4100 Not formed Not formed Not formed Not formed Not formed 43685901

Aerobic soil metabolism
835.4100 No data No data No data No data No data Not applicable

Anaerobic soil metabolism
835.4200 No data No data No data No data No data Not applicable

Aerobic aquatic metabolism
835.4300 No data No data No data No data No data Not applicable

Aerobic aquatic metabolism of
Diethanolamine 49

835.4300 Not formed Not formed Not formed Not formed Not formed 43685902

Anaerobic aquatic metabolism
835.4400 No data No data No data No data No data Not applicable

Biodegradation half

- life in sludge (days) No data No data No data No data No data Not applicable

47 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 minutes. The 5/14/2009
enviro nmental fate memorandum required another photodegradation in water study.

48 Aerobic soil metabolism data on diethanolamine (MRID 43685901) were submitted as a surrogate for the dimethylamine (DMA) degr adate.

49 Aerobic aquatic metabolism data on diethanolam ine (MRID 43685902) were submitted as a surrogate for the dimethylamine (DMA) degradate.

### Page 60 of 70 

# 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 re quired.

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 Na DDC (40) LD 50 : 391 mg a.i./kg

bw/day ( 991mg ts /kg

- bw/day ) Moderately toxic 00159788 Acceptable

K DDC ( 50 ) LD 50 : 627 mg a.i./kg

bw ( 1255mg ts /kg

- bw/day ) Slightly toxic 00105155 Acceptable

Mallard Thiram (99) LD 50 : >2800 mg/kg

bw/day Practically
nontoxic 00 160000 Acceptable
Red

- winged

black bird Thiram (99) LD 50 : >100 mg/kg

bw/day Unknown 00073683 Supplemental Ring

- necked

pheasant Thiram (99) LD 50 : 673 mg/kg

bw/day Slightly toxic 00160000 Supplemental

Starling Thiram (95) LD 50 : > 50 00 mg/kg

bw/day Practically
nontoxic 00022923 Acceptable

Suba cute

– Avian Dietary
GLN 850.22 00 Northern
bobwhite K DDC (50) LC 50 : >2600 ppm a.i. ( >5200 ppm ts) ts Practically
nontoxic 00109244 Acceptable

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

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

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

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

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

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

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

- necked

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

– Avian Northern
bobwhite Thiram (97.5) NOAEL: 500 ppm NA 43612502 Acceptable

### Page 61 of 70 Study Type Species Test material (% ai) Toxicity Toxicity
Classification MRID & Status

GLN 850.2300

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

. Data ( OCSPP GLNs 850.3020, 850.3030) are expected to be required for the wood preservative use of the DDC salts. If the use in wood preservation is cancelled, then this data requirement will no longer likely be needed.

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

Honey bee (Apis mellifera), N.R.
GLN 850.3020 Thiram
Tech Dermal contact 48

- h LD 50 = 74 μg/bee Slightly toxic 00036935 Supplemental



# Toxicity to Aquatic Receptors

Freshwater Fish, acute

Acute toxicity data for freshwater fish are available for rainbow trout ( Oncorhynchus mykiss ), bluegill ( Lepomis macrochirus ) , and fathead minnow ( Pimephales promelas ). The potassium
DDC salt i s categorized as being highly to very highly toxic and the sodium DDC salt as slightly to moderately toxic. The combinatio n of sodium DDC salt and Nabam is m oderately 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 Na DDC (40.9) 96

- hr LC 50 : 6700 Moderately toxic 42247901 Acceptable
Na DDC (15) and Nabam (15) 96

- hr LC 50 : 1700 (as formulation) Moderately toxic 00104057 Supplemental

K DDC (50) 96

- hr LC 50 : 360 Highly toxic 00134589 Acceptable

Thiram (99) 96

- hr LC 50 : 126 Highly toxic McCann 1976
Test Number
1001 Acceptable

Thiram (99) 96

- hr LC 50 : 46 Highly toxic 46249301 Supplemental

Thiram (75) 96

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

### Page 62 of 70 Study Type Species Test material (% ai) Toxicity (μg ai/L) Toxicity Classification MRID & Status

Bluegill
sunfish NaDDC (40.5) 96

- hr LC 50 : 38,500 Slightly toxic 42504801 Acceptable NaDDC (15) and Nabam (15) 96

- hr LC 50 : 3400 (as formulation) Moderately toxic 00104057 Supplemental

Thiram (99) 96

- hr LC 50 : 42 Very highly
toxic 00 070801 Acceptable

Thiram (75) 96

- hr LC 50 : 280 (as formulation) Highly toxic 00090294 Supplemental
Fathead
minnow K DDC (50) 96

- hr LC 50 : 60 Very highly
toxic ACC240946 Acceptable

Harlequin fish Thiram (80)
formulation 96

- hr LC 50 : 7 Very highly
toxic 0 5020144 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

- c hronic ratio (ACR) method was used to calculate a chronic value for the bluegill sunfish. The Web

- based Interspecies Correlation Estimation (Web

- ICE 50 

### ) , 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 estima ted NOAEC of 0.36 ppb thiram.

Freshwater Fish Chronic Toxicity of Thiram

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

Chronic

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

LOAEC = 2.2 F 0 egg production; F 0 % spawning frequency; F 1 4

- week survival; F 1 time
to hatch 478241 01 Acceptable

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

### Page 63 of 70 Freshwater Invert ebrates, acute

Acute toxicity d ata 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 Degrada te

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

Acute

– Freshwater
Invertebrate
GLN 850.1010 Water flea Na DDC (40.5) 48

- hr EC 50 : 52 Very highly
toxic 42504802 Acceptable

K DDC (50) 48

- hr EC 50 : 340 Highly toxic 00105154 Acceptable

Thiram (98) 48

- hr EC 50 : 210 Highly toxic 00 164662 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 d a ta 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 Toxic ity of Sodium DDC Salt and Degradate

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

Acute

– Saltwater Fish
GLN 850.1075 Sheepshead
minnow Na DDC (48.3) 96

- hr LC 50 : 59,000 Slightly toxic 41984701 Acceptable

Na DDC (16) and
Nabam (15) 96

- hr LC 50 : 122 (as ts ) Highly toxic 00100706 Acceptable

Thiram (98) 96

- hr LC 50 : 540 Highly toxic 42514401 Acceptable

Acute

– Saltwater
Invertebrate
GLNs
850.1025/1055
850.1035 Eastern oyster Na DDC (39.6) 96

- hr EC 50 : 760 Highly toxic 42561902 Acceptable

Na DDC (16) and
Nabam (15) 96

- hr EC 50 : 300 (as ts ) Highly toxic 00100704 Supplemental

Thiram (98.3) I C 50 = 4.7 (embryo/larval development) Very highly
toxic 424883 01 Acceptable

### Page 64 of 70 Study Type Species Test material (% ai) Toxicity (μ g ai/L) Toxicity
Classification MRID & Status

Mysid Na DDC (39.6) 96

- hr LC 50 : 88 Very highly
toxic 42561901 Acceptable

Thiram (98.3) LC 50 : 3.36 Very highly
toxic 424883 02 Acceptable

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

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



### ts: test substance

Aquatic and terrestrial plants

Plant toxicity data are anticipated to be required for the DDC salt s 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, Navi cula pelliculosa, and (4) bluegreen cyanobacteria, Anabaena flos

- aquae. A s eedling 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 DD C 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

us es 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. U ses that potentially result in spray drift, such as an anti

- sapstain spray application, may result in exposure of non

- target 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%) I C 50 = 1

, 600 ,000
NOAEC < 57 ,000 45441202 Acceptable

Aquatic plants

- green algae

, Selenastrum capricornutum
GLN 850.4500 Thiram (99%) I C 50 = 45
NOAEC < 57 (will

calculate IC 05 ) 42646001 Acceptable

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



### Mesocosm

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

### Page 65 of 70 400, and 1250 ppb Thir am 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 attri buted 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. trea tment 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 zooplank ton 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 treatmen t 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 durati on 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 pos t

- 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. Addit ionally there was no true replication of treatment levels. Conclusions, provided in this study may be useful for
characterization.

### Page 66 of 70 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

R 2 : 0.825954

p - value: 0.000000

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

Minimum value of surrogate (log value): 0.671479 (

- 0.172967)

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

Mean Square Error (MSE): 0.372276

Sum of Squares (S

xx ): 176.91

### Page 67 of 70 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 68 of 70 Degrees of Freedom (N

- 2): 66

R 2 : 0.790938

p - value: 0.000000

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

Minimum value of surrogate (log value): 0.407815 (

- 0.389536)

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

Mean Square Error (MSE): 0.431786

Sum of Squares (S

xx ): 150.09

Cross

- validation Success (%): 75.00

Taxonomic Distance: 4

### Page 69 of 70 

# 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

– P roduct 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 sulfur

containing compounds Mild characteristic of sulfur

containing 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 70 of 70 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, ε = 0 l mol - 1 cm - 1

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

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

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

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

Result a t pH > 11: 254 nm, ε = 12714 l mol - 1 cm - 1
279 nm, ε = 13120 l mol - 1 cm - 1

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

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

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

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

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

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

pKa value: Not applicable; product decomposes below pH 8.

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

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

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

830.7550 Partition coefficient ( n

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

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

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

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

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