United States Chemical Safety October 2012 Environmental Protection and Pollution Prevention Agency (7510P)



# Dibromodicyanobutane Registration Review: Final Work Plan October 2012Docket 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 

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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

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.Docket Number: EPA

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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 p ublic 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 Sect ion 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 pestic ide 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 publi c 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 p ublished 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

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. The first product contai ning 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 registere d 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 Prelimin ary 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 i ssues.

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

use Organisation for Economic Cooperation and Development (OECD) Technical Guidance 443Docket Number: EPA

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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 assessm ent, 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 quantita tive 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 mo st 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. 330 0

-- A ctivated sludge, respiration inhibition test 3

1 If data indicate the IC 50 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 IC 50 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 Simula tion Test

– Aerobic Sewage Treatment: A. Activated Sludge Units, or the Porous Pot study would be expected to be required.Docket Number: EPA

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6 of 11 835.3110

-- Ready Biodegradability 3
835.3220

-- Porous Pot Test 3
835.3280

-- Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater 3
835.3240

-- Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units 3

• For more information, please refer to Product Chemistry, Envi ronmental 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 conta ct 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 throug h 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 environme ntal 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 c ould 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 trea ted 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 RiskDocket Number: EPA

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7 of 11 • EPA has not conducted an aggregate risk assessment for D BDCB. 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 a ggregate 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 assess ment. 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 toxicity 4
870.3800

– Two

- Generation Reproduction 5
875.1200

-- Dermal indoor exposure 6
875.1400

-- Inhalation indoor exposure 6
875.1600

-- Application exposure data reporting and calculations 6
875.1700

-- Product use information 875.2300

-- Indoor surface residue dissipation 7 Special Study

-- Nature of Residue on Surfaces 8 Special Study

-- Migration Study 8

• 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 preser ved 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 ex posures. 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 spray er, 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, the n 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 follo wing 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. T he 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

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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 Ecologi cal 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 DBDC B 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 habit ats. 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 appropri ate. 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 a ssessments 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 ef fects 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) hormonalDocket Number: EPA

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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 t he 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 fo r 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 registrati on 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 guidel ines 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

. E nvironmental fate and ecological hazard assessments will be con ducted 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

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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

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- 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. 33 00 A ctivated sludge, respiration inhibition test 11 TGAI 12

835.3110 Ready Biodegradability 11 TGAI 12

835.3220 Porous Pot Test 11 TGAI 12

835.3280 Simulation Tests to Assess the Biodegradability of Chemicals Discharged to Wastewater 11 TGAI 12

835.3240 Simulation Test

– Aerobic Sewage Treatment: A. Activated Sludge Units 11 TGAI 12

870.3465 90

- day inhalation toxicity 12 TGAI 24

870.3800 Two

- Generation Reproduction 13 TGAI 48

875.1200 Dermal indoor exposure 14 TGAI 12

9 If data indicate th e IC 50 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

- aq uae (Blue

- Green Cyanobacteria), Navicula pelliculosa (Freshwater Diatom), and Skeletonema costatum (Marine Diatom) are expected to be required. If data indicate the IC 50 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 fou r 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 Po rous 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 S ewage 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 s tudy, 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 fo r 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 spr ayer; 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

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11 of 11 875.1400 Inhalation indoor exposure 14 TGAI 12

875.1600 Application exposure data reporting and calculations 14 TGAI 12

875.1700 Product use information TGAI 12

875.2300 Indoor surface residue dissipation 15 TGAI 24
Special Study Nature of Residue on Surfaces 16 TGAI 24

Special Study Migration Study 16 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.