United States Chemical Safety October 2012

Environmental Protection and Pollution Prevention

Agency (7510P)

Dibromodicyanobutane

Registration Review: 

Final Work Plan

October 2012
Docket Number: EPA-HQ-OPP-2012-0342 

www.regulations.gov 

Dibromodicyanobutane 

Registration Review: 

Final Work Plan 

October 2012 

Case# 2780 

Approved By: 

~~ Director> Antimicrobials Division 

Date: 

2 ofll 
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

3 of 11

Dibromodicyanobutane Registration Review Team

Human Health & Environmental Effects

Timothy Dole

Jenny Tao

Jonathan Chen

Srinivas Gowda

David Bays

James Breithaupt

Risk Management

Seiichi Murasaki

Lance Wormell

Office of General Counsel

Philip Ross

________________________________________

Supporting documents for the Dibromodicyanobutane Case may be found in the registration 

review docket EPA-HQ-OPP-2012-0342 located on the internet at www.regulations.gov.
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

4 of 11

Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the 

Agency”) for the registration review of Dibromodicyanobutane (Case 2780). The work plan 

includes the expected registration review timeline. The work plan also addresses public 

comments received concerning the Preliminary Work Plan (PWP) in the Summary Document 

which was posted in the Dibromodicyanobutane registration review docket, and any other 

comments concerning the initial docket postings. The Summary Document provided information 

on what EPA knows about the pesticide and what additional risk analyses and data or 

information the Agency believes are needed to make a registration review decision. 

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

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

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

registration. Changes in science, public policy and pesticide use practices will occur over time. 

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 that 

statutory standard. The public phase of registration review begins when the initial docket is 

opened for each case. Information on this program is provided at: 

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

The Dibromodicyanobutane Preliminary Work Plan (PWP) (PC Code 111001) was published on 

July 6, 2012 and the 60-day comment period ended on September 10, 2012. The Preliminary 

Work Plan document is available on www.regulations.gov docket number EPA-HQ-OPP-2012-

0342.

The first product containing 1-Bromo-1-(bromomethyl)-1,3-propanedicarbonitrile 

(Dibromodicyanobutane or DBDCB) (PC Code 111001) as an active ingredient was registered in 

the United States in 1980. Currently, there are 16 products containing DBDCB as an active 

ingredient registered with EPA. Dibromodicyanobutane is registered for use in materials 

preservation, industrial recirculating cooling water treatment, oil production, and paper mill 

water treatment. The material preservation uses include adhesives, caulks, household cleaning

solution, paints and coatings, metal working fluids and non-apparel textiles. DBDCB is regulated 

by the FDA as an indirect food additive. Tolerances have been established for DBDCB as a 

preservative in food grade adhesives (see 21 CFR § 175.105) and as a slimicide in the 

manufacture in food grade paper and paperboard at a maximum level of 0.005% of dry weight 

fiber (see 21 CFR § 176.300).

The Agency completed a Reregistration Eligibility Decision (RED) for DBDCB in 1996. 

Comments Received on the Preliminary Work Plan

The Agency received one comment during the public comment period on the initial docket, 

described below. In the PWP, the Agency solicited comments on specific topics: environmental 

justice, water body impairment, trade irritants, and structure activity relationships. No comments 

or information were received during the public comment period concerning these issues.

Comment: The Physicians Committee for Responsible Medicine (PCRM) suggests the registrant 

use Organisation for Economic Cooperation and Development (OECD) Technical Guidance 443 
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

5 of 11

Extended One-Generation Reproductive Toxicity Study (EOGRTS) instead of the EPA

guideline. 

Response: The Agency agrees with PCRM that an extended one-generation reproductive and 

fertility effects study will provide the Agency with sufficient information to support the risk 

assessment planned for the DBDCB registration review. The Agency will accept a 

multigeneration or an extended one-generation reproductive and fertility effects study.

The comment received during the initial public comment period did not affect the data needs, 

work plan and timeline described in the PWP and they remain as they were presented initially in 

the PWP. Further, this document makes final the work plan for the DBDCB registration review 

process.

Risk Assessments and Anticipated Data Needs

The Agency will conduct a comprehensive ecological risk assessment, including an endangered 

species risk assessment, for all uses of DBDCB. If endpoints of concern are identified from 

toxicological studies expected to be required for the registration review of DBDCB, the Agency 

anticipates the need to conduct quantitative dietary, residential, occupational, and, if appropriate, 

aggregate assessments. The Agency expects to require additional data for use in conducting the 

registration review for DBDCB.

Ecological Risk Assessment Status and Anticipated Data Needs

• The most recent ecological risk assessment for DBDCB was performed to support the 1996

RED

• The Agency anticipates the need to require the following additional ecological data for use in 

the registration review of DBDCB.

850.4400 -- Aquatic plant toxicology test using Lemna spp.1

850.5400 -- Algal Toxicity (Tier II)2

• The Agency anticipates the need to require the following additional environmental fate data 

for use in the registration review of DBDCB.

850.3300 -- Activated sludge, respiration inhibition test3

 1 If data indicate the IC50 for Selenastrum capricornutum is greater than 1000 ppb, the Agency will consider waiver 

requests for the Aquatic vascular plant toxicology test (850.4400). 2 Algal Toxicity Tier II data using Selenastrum capricornutum (Green Algae), Anabaena flos-aquae (Blue-Green 

Cyanobacteria), Navicula pelliculosa (Freshwater Diatom), and Skeletonema costatum (Marine Diatom) are 

expected to be required. If data indicate the IC50 for Selenastrum capricornutum is greater than 1000 ppb, the 

Agency will consider waiver requests for studies conducted with the other three algal species. 3 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine 

which of these four biodegradation tests would be anticipated to be required. If the ASRI test EC50 is less than or 

equal to 20 mg/L, then either the Biodegradation in Activated Sludge Study or Simulation Test – Aerobic Sewage 

Treatment: A. Activated Sludge Units or the Porous Pot Test would be anticipated to be required. If the ASRI test 

EC50 is greater than 20 mg/L, then the applicant would choose 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 fails the Ready Biodegradability study, then the 

Biodegradation in Activated Sludge or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or 

the Porous Pot study would be expected to be required.
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

6 of 11

835.3110 -- Ready Biodegradability3

835.3220 -- Porous Pot Test3

835.3280 -- Simulation Tests to Assess the Biodegradability of Chemicals Discharged to 

Wastewater3

835.3240 -- Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units3

• For more information, please refer to Product Chemistry, Environmental Fate, and 

Ecological Effects Scoping Document in Support of Registration Review of 

Dibromodicyanobutane, located in the docket.

Human Health Risk Assessment Status and Anticipated Data Needs

• The most recent qualitative human health risk assessment for DBDCB was performed to 

support the 1996 RED.

• Toxicological endpoints of concern were not identified at the time of the RED. If endpoints 

of concern are identified from toxicological studies expected to be required for the 

registration review of DBDCB, the Agency anticipates the need to conduct quantitative 

dietary, residential, occupational, and, if appropriate, aggregate assessments.

Dietary Assessment

• Dietary (food) exposure to DBDCB is possible since it is used as a slimicide in food contact 

paper and paperboard production and to preserve paper-making chemicals and migration of 

DBDCB from paper packaging to the food contents may occur.

• Material preservative uses of DBDCB may lead to contamination of human and livestock 

drinking water through the discharge of waste water. DBDCB and/or its degradates could 

potentially pass through wastewater treatment plants (WWTPs). The Agency will determine 

the need for a dietary drinking water risk assessment following the submission and review of 

environmental fate data that are anticipated to be required

Tolerances and International Harmonization

• DBDCB is regulated by the FDA as an indirect food additive. Tolerances have been 

established for DBDCB as a preservative in food grade adhesives (see 21 CFR § 175.105) 

and as a slimicide in the manufacture in food grade paper and paperboard at a maximum 

level of 0.005% of dry weight fiber (see 21 CFR § 176.300).

Occupational and Residential Assessment and Risk

• Occupational dermal and inhalation exposures to DBDCB could occur during open pouring 

of liquids and wettable powders for material preservation and during the use of treated paints, 

metal working fluids, and cleaning solutions.

• Residential dermal and inhalation exposures to DBDCB could occur during use of treated 

paints and household cleaners. Residential incidental oral exposures could occur for toddlers 

playing on floors cleaned with treated cleaning solutions.

Aggregate and Cumulative Exposure and Risk
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

7 of 11

• EPA has not conducted an aggregate risk assessment for DBDCB. In examining aggregate 

exposure, EPA takes into account the available and reliable information concerning 

exposures to pesticide residues in food and drinking water, as well as non-occupational 

pesticide exposures. The Agency may need to conduct an aggregate assessment based on 

residential and dietary exposures.

• EPA does not have, at this time, available data to determine whether DBDCB has a common 

mechanism of toxicity with other substances or how to include this pesticide in a cumulative 

risk assessment. For the purposes of this Registration Review, EPA has assumed that 

DBDCB does not have a common mechanism of toxicity with other substances when used as 

an antimicrobial as registered. 

Human Health Anticipated Data Needs

• The Agency anticipates the need to require the following additional human health data for 

use in conducting the registration review of DBDCB.

870.3465 -- 90-day inhalation toxicity4

870.3800 – Two-Generation Reproduction5

875.1200 -- Dermal indoor exposure6

875.1400 -- Inhalation indoor exposure6

875.1600 -- Application exposure data reporting and calculations6

875.1700 -- Product use information

875.2300 -- Indoor surface residue dissipation7

Special Study -- Nature of Residue on Surfaces8

Special Study -- Migration Study8

• For more information, please refer to 1,2-Dibromo-2,4-dicyanobutane (DBDCB): Human 

Health Registration Review Scoping Document, located in the docket.

Product Chemistry Anticipated Data Needs

 4 Study is anticipated as being needed for following scenarios: open-pour liquids; open-pour wettable powders; 

application of preserved paints using brush/roller or airless sprayer; use of treated metalworking fluids; and trigger 

sprayer, wipe, and mop application of preserved cleaners.

5 Study is anticipated as being needed for all uses that can result in dietary and drinking water exposures. 6 Exposure studies are anticipated as being needed for following scenarios: open-pour liquids; open-pour wettable 

powders; application of preserved paints using brush/roller or airless sprayer; use of treated metalworking fluids; 

and trigger sprayer, wipe, and mop application of preserved cleaners. If labels are amended to require closed 

mixing/loading, then any required exposure study for open-pour liquid scenarios can likely be waived. If labels are 

amended to require water soluble packaging, then any required exposure study for open-pour wettable powder 

scenarios can likely be waived. It may be possible to use proprietary surrogate exposure data if data compensation 

issues are adequately addressed. 7 Study is anticipated as being needed for following scenario: residential post application dermal and incidental oral 

exposure to floors cleaned with preserved household cleaning solutions. The anticipated DCI will provide that a 

protocol must be submitted for review and approval by the Agency prior to initiating this study. 8 Study is anticipated as being needed for following scenarios: dietary exposures from countertops cleaned with 

preserved household cleaning solution; and dietary exposures from DBDCB treated paper products used in food 

packaging. The anticipated DCI will provide that a protocol must be submitted for review and approval by the 

Agency prior to initiating this study. In the absence of additional data, a default transfer factor of 100% would be 

expected to be used.
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

8 of 11

• The Agency does not anticipate the need to require additional product chemistry data for the 

registration review at this time.

• For more information, please refer to Product Chemistry, Environmental Fate, and 

Ecological Effects Scoping Document in Support of Registration Review of 

Dibromodicyanobutane, located in the docket.

Incidents:

Ecological:

• No DBDCB incidents have been reported in the Agency’s Ecological Incident Information 

System (EIIS).

Human Health:

• No DBDCB human poisoning incidents have been reported in the OPP’s Incident Data 

System (IDS).

Endangered Species

The Agency has not conducted a risk assessment that supports a complete endangered species 

determination for DBDCB. The ecological risk assessment planned during registration review 

will allow the Agency to determine whether DBDCB’s use has 'no effect' or 'may affect' 

federally listed threatened or endangered species (listed species) or their designated critical 

habitats. When an assessment concludes that a pesticide’s use 'may affect' a listed species or its 

designated critical habitat, the Agency will consult with the U.S. Fish and Wildlife Service 

and/or National Marine Fisheries Services (the Services), as appropriate.

Endocrine Disruptor Screening Program

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

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

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

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

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

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

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

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

taxonomic groups. A human health risk assessment identifying the most sensitive endpoints has 

not been conducted for the Dibromodicyanobutane Case. As required by FFDCA section 408(p), 

DBDCB is subject to the endocrine screening part of the Endocrine Disruptor Screening Program 

(EDSP). 

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

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

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

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

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

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

9 of 11

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

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

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

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

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

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

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

which contains 58 pesticide active ingredients and 9 inert ingredients. DBDCB is not among the 

group of 58 pesticide active ingredients on the initial list to be screened under the EDSP. 

Accordingly, as part of registration review, EPA will issue future EDSP orders/data call-ins, 

requiring the submission of EDSP screening assays for DBDCB. For further information on the 

status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test 

guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/.

Timeline

EPA has created the following estimated timeline for the completion of the DBDCB registration 

review:

Anticipated Schedule

Activities Estimated Month/Year

Phase 1: Opening the docket

Open Public Comment Period for Docket Completed

July 2012

Close Public Comment Period for Docket Completed

September 2012

Phase 2: Case Development

Develop Final Work Plan (FWP) Completed 

October 2012

Issue DCI December 2013

Data Submission December 2015

Open Public Comment Period for Preliminary Risk Assessments June 2017

Close Public Comment Period for Preliminary Risk Assessments July 2017

Phase 3: Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision December 2017

Close Public Comment Period for Proposed Reg. Review Decision February 2018

Final Decision and Begin Post-Decision Follow-up June 2018

Total (years) 6

Next Steps

A DCI will be developed regarding the data needs listed under the “Risk Assessments and 

Anticipated Data Needs” section of this document. The Agency expects to issue the DCI in 

December 2013. Environmental fate and ecological hazard assessments will be conducted for all 

uses. If endpoints of concern are identified from toxicological studies, the Agency will conduct 

quantitative dietary, residential, occupational, and, if appropriate, aggregate assessments.
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

10 of 11

Summary of Anticipated Data Requirements – DBDCB

The table below summarizes anticipated data needs for the Dibromodicyanobutane Case in this 

document (Final Work Plan), Product Chemistry, Environmental Fate, and Ecological Effects 

Scoping Document in Support of Registration Review of Dibromodicyanobutane, and 1,2-

Dibromo-2,4-dicyanobutane (DBDCB): Human Health Registration Review Scoping Document.

Guideline

Number Anticipated Data Requirement Test Material

Estimated Timeframe (Measured 

in months from DCI Receipt)

850.4400 Aquatic plant toxicology test using Lemna spp.9 TGAI 12

850.5400 Algal Toxicity (Tier II)10 TGAI 12

850.3300 Activated sludge, respiration inhibition test11 TGAI 12

835.3110 Ready Biodegradability11 TGAI 12

835.3220 Porous Pot Test11 TGAI 12

835.3280 Simulation Tests to Assess the Biodegradability of 

Chemicals Discharged to Wastewater11 TGAI 12

835.3240 Simulation Test – Aerobic Sewage Treatment: A. 

Activated Sludge Units11 TGAI 12

870.3465 90-day inhalation toxicity12 TGAI 24

870.3800 Two-Generation Reproduction13 TGAI 48

875.1200 Dermal indoor exposure14 TGAI 12

 9 If data indicate the IC50 for Selenastrum capricornutum is greater than 1000 ppb, the Agency will consider waiver 

requests for the Aquatic vascular plant toxicology test (850.4400). 10 Algal Toxicity Tier II data using Selenastrum capricornutum (Green Algae), Anabaena flos-aquae (Blue-Green 

Cyanobacteria), Navicula pelliculosa (Freshwater Diatom), and Skeletonema costatum (Marine Diatom) are 

expected to be required. If data indicate the IC50 for Selenastrum capricornutum is greater than 1000 ppb, the 

Agency will consider waiver requests for studies conducted with the other three algal species.

11 The results of the Activated Sludge Respiration Inhibition Test (ASRI) expected to be required will determine 

which of these four biodegradation tests would be anticipated to be required. If the ASRI test EC50 is less than or 

equal to 20 mg/L, then either the Biodegradation in Activated Sludge Study or Simulation Test – Aerobic Sewage 

Treatment: A. Activated Sludge Units or the Porous Pot Test would be anticipated to be required. If the ASRI test 

EC50 is greater than 20 mg/L, then the applicant would choose 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 fails the Ready Biodegradability study, then the 

Biodegradation in Activated Sludge or Simulation Test – Aerobic Sewage Treatment: A. Activated Sludge Units, or 

the Porous Pot study would be expected to be required.

12 Study is anticipated as being needed for following scenarios: open-pour liquids; open-pour wettable powders; 

application of preserved paints using brush/roller or airless sprayer; use of treated metalworking fluids; and trigger 

sprayer, wipe, and mop application of preserved cleaners.

13 Study is anticipated as being needed for all uses that can result in dietary and drinking water exposures. 14 Exposure studies are anticipated as being needed for following scenarios: open-pour liquids; open-pour wettable 

powders; application of preserved paints using brush/roller or airless sprayer; use of treated metalworking fluids; 

and trigger sprayer, wipe, and mop application of preserved cleaners. If labels are amended to require closed 

mixing/loading, then any required exposure study for open-pour liquid scenarios can likely be waived. If labels are 

amended to require water soluble packaging, then any required exposure study for open-pour wettable powder 

scenarios can likely be waived. It may be possible to use proprietary surrogate exposure data if data compensation 

issues are adequately addressed.
Docket Number: EPA-HQ-OPP-2012-0342

www.regulations.gov

11 of 11

875.1400 Inhalation indoor exposure14 TGAI 12

875.1600 Application exposure data reporting and 

calculations14 TGAI 12

875.1700 Product use information TGAI 12

875.2300 Indoor surface residue dissipation15 TGAI 24

Special 

Study Nature of Residue on Surfaces16 TGAI 24

Special 

Study Migration Study16 TGAI 24

 15 Study is anticipated as being needed for following scenario: residential post application dermal and incidental oral 

exposure to floors cleaned with preserved household cleaning solutions. The anticipated DCI will provide that a 

protocol must be submitted for review and approval by the Agency prior to initiating this study. 16 Study is anticipated as being needed for following scenarios: dietary exposures from countertops cleaned with 

preserved household cleaning solution; and dietary exposures from DBDCB treated paper products used in food 

packaging. The anticipated DCI will provide that a protocol must be submitted for review and approval by the 

Agency prior to initiating this study. In the absence of additional data, a default transfer factor of 100% would be 

expected to be used.