Docket Number: EPA-HQ-OPP-2009-0724 www.regulations.gov

United States Chemical Safety June 2010

Environmental Protection and Pollution Prevention Agency (7510P)



# 2,2-dibromo-3-nitrilopropionamide (DBNPA)

Final Work Plan Registration Review

June 2010Docket Number: EPA-HQ-OPP-2009-0724 www.regulations.gov



### TABLE OF CONTENTS

DBNPA Registration Review Team ................................................................................ 4

I. INTRODUCTION ..................................................................................................... 5

II. SUMMARY OF COMMENTS RECE IVED ON PRELIMINARY WORK

PLAN .......................................................................................................................... 5

III. RISK ASSESSMENT AND DATA NEEDS ........................................................... 6

IV. TIMELINE .............................................................................................................. 11

V. GLOSSARY of TERMS & ABBREVIATIONS .................................................. 12Docket Number: EPA-HQ-OPP-2009-0724 www.regulations.gov

DBNPA Registration Review Team

Human Health & Environmental Effects Timothy Dole

Srinivas Gowda

Risk Management
Eliza Blair
Lance Wormell

Office of General Counsel Philip Ross

1Docket Number: EPA-HQ-OPP-2009-0724 www.regulations.gov

I. INTRODUCTION

This is the Environmental Protection Agency’s (EPA or “the Agency”) Final Work Plan (FWP) for the registration revi ew of DBNPA (Case 3056). The FWP includes the expected registration review timeline. Th e work plan also addresses public comments received concerning the Preliminary Work Plan in the Summary Document which was posted in the DBNPA registrati on review docket, and any other comments concerning the initial docket postings. The Summary Do cument provided information on what EPA knows about the pesticide and what additional ri sk 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 year s 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 registrati on review program is intended to make sure that, as the ability to assess risk evolve s and as policies and practices change, all registered pesticides continue to meet th at 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 DBNPA Preliminary Work Plan was entered into the docket for this registration review on December 16, 2009. Th e 90-day comment period ended on March 16, 2010. The Preliminary Work Plan document is available on www.regulations.gov

, docket number EPA-HQ-OPP-2009-0724.

II. SUMMARY OF COMMENTS RE CEIVED ON PRELIMINARY WORK

PLAN

The Agency received two comments from The Dow Chemical Company and ICLIP America (formerly AmeriBrom Inc) that itemized data these companies have submitted or will submit to support their regist rations. In addition, the Agency received one comment from the FIFRA Endangered Specie s Task Force (FESTF). The work plan and timeline described in the Preliminary Work Plan remain as they were presented initially. The anticipated data needs have been updated to remove the requirement for (GLN 870.3250) Dermal Toxicity. This document makes final the work plan for the DBNPA registration re view process.

In the Preliminary Work Plan, the Agen cy solicited comments on three specific topics: environmental justice, water body impairment, and trade irritants. No comments or information were received during the comment period concerning these issues.

Comment : The FIFRA Endangered Species Task Force (FESTF) submitted a comment noting that it has data that will assist the Agency in conducting an endangered species risk assessment for DBNPA, and requesting th at any technical regi strant for DBNPA who is not a member of the FESTF (or a company having met its data compensation

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obligations) be asked to provi de a formal offer-to-pay to FESTF for reliance on their

data.

Response : The Agency thanks FESTF for its comment and will consider this information as it conducts the registrati on review and makes its regi stration review decisions.

Comment : Dow disputes the “unacceptable” designation given to a previously-submitted 90-Day Dermal Toxicity (Rat) study. The study was rated unacceptable because its

conditions deviated from curre nt guidelines. Dow contends th at at the time the study was conducted, it conformed to existing guidelines , and the data it generated should not be ignored simply because guideli nes have changed since then.

Response: Upon further review, the Agency be lieves that the study titled, “Human Panelist Studies of Dermal Cumulative Irritancy/Sensitization with 2-2- Dibromo-3-nitrilopropionamide” (MRID 45828101) will satisfy the need for this data requirement, pending its approval for use by th e Human Studies Revi ew Board. Should it not be approved, or should the Agency later determine that this study does not satisfy the need for this data requirement, the Agency w ill revisit its review of the disputed rat study and the need for a new study at that time.

III. RISK ASSESSMEN T AND DATA NEEDS

A Reregistration Eligibilit y Decision (RED) was issued for DBNPA in September 1994. Since then, data have been submitted to the Agency and reviewed. However, to complete registration review, additional data are needed to conduct the human health and ecological risk assessments.

DBNPA was first registered in the Unite d States in 1972 as a microbiocide. There are currently 37 products registered by the EPA that contain DBNPA as an active ingredient; these products are registered by 16 companies. DBNPA is a biocide registered for use in a variety of industrial water processes to cont rol algae, bacteria, fungi and yeasts; it is registered for use in paper mills, metalworking fluids containing water, enhanced oil recovery systems, industrial recircul ation water cooling systems, membrane systems for industrial water (rev erse osmosis), air washer systems, hydro testing systems, publicly owned treatment wo rks, brewery pasteurizer water systems, packer fluids, water floods, construction products and household pr oducts as material preservative, and for technical manufacturing use.

Human Health Risk

The Agency has reviewed the hazard a nd exposure databases for DBNPA and its degradates and anticipates that additional to xicity and exposure data will be needed for the registration review. Based on its reviews, the Agency believes risk assessments are needed to ensure that the DBNPA registra tion review case meets the FIFRA and FFDCA standards. The Agency will complete the human health risk assessments presented

below:

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• Dietary exposure from the use of DBNPA in food packaging.

• Occupational dermal and inhalation e xposure from the use of DBNPA in metalworking fluids.

• Occupational dermal and inhalation e xposure from the open pour application of DBNPA to high volume use sites such as cooling towers.

• Occupational and residential dermal and inhalation exposure from the use of DBNPA in paints. The inhalation asse ssment is expected to include both aerosols and vapors.

Metabolites and Degradates of Toxicological Concern

As discussed in the RED, the hydrolysis of DBNPA produces dibromoacetic acid (DBAA) as the major degradate at pH 5 (30.6% of applied) and dibromoacetonitrile (DBAN) at pH 7 and 9 (54.5% at pH 7 a nd 38.6% at pH 9). DBAA was also the degradate found at highest concentration in the aerobic aquatic metabolism study.

Studies conducted by the EPA National Institute of Environmental Health Sciences and the National Toxicity Program (NTP) have suggested that DBAA and DBAN may cause cancer. There is also ev idence which indicates that DBAA is a

neurotoxicant. These data will be consider ed in the risk assessment for DBNPA.

Human Studies

MRID 458281-01 “Human Panelist St udies of Dermal Cumulative Irritancy/Sensitization with 2-2-Dibromo- 3-nitrilopropionamide” was submitted for DBNPA after the RED was published and was re viewed for scientific validity. This study is classified as Acceptable/Non-guideline because there are no guidelines for this type of study.

The Agency will consider this study in th e course of registration review, and will consider as well any other res earch brought to its attention in volving intentional exposure of human subjects to DBNPA. If the Agency decides to rely on any of these studies, it will ensure that all applicable regulatory requ irements are met, including, but not limited to, the requirements for an EPA ethics revi ew and Human Studies Review Board review of certain research involving inten tional exposure of human subjects.

Further discussion of this issue is av ailable in “Summary of Human Health Effects Data for the DBNPA Registration Re view Decision Document,” dated December 15, 2009.

Dietary and Drinking Water Exposure

DBNPA is FDA-approved for use in as an indirect food additive in Adhesives and Components of Coatings (21 CFR 175) and Paper and Paperboard Components (21 CFR 176). Use of DBNPA in food-contact articles is considered by EPA to be a food use;

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therefore, a dietary risk assessment will be ne eded to determine if there are any potential dietary concerns from indirect food exposures to DBNPA.

Occupational and Residential Exposure

An occupational handler risk assessme nt was conducted in 1994 for the DBNPA RED and one scenario (open pour liquids for cooling towers) was determined to be of concern. This risk was mitigated by the RED-specified chemical-resistant gloves. There were also potential risks of concern for handling of th e solid soluble concentrate formulations, but these concerns have been mitigated by water soluble packaging.

Occupational handler dermal and inha lation exposures can also occur for machinists using metalworking fluid treate d with DBNPA and pain ters using paints treated with DBNPA. These exposures were not evaluated in the RED and will need to be assessed during registration review.

Residential inhalation and dermal e xposures to DBNPA aerosols can occur during the airless sprayer app lication of DBNPA-treated pain t. Inhalation exposure to DBNPA vapor can also occur during and afte r paint application because DBNPA has a vapor pressure of 8 x 10 -4 mm Hg at 25 o C. These exposures we re not evaluated in the

RED and will need to be asse ssed during registration review.

Anticipated Human Health Data Needs

While the Agency already possesses some toxicity data for DBNPA itself, because DBNPA has two metabolites/degradate s of potential toxicological concern, the Agency anticipates needing the following t oxicity and exposure studies to perform a complete human health risk assessment for antimicrobial products containing DBNPA:

Human Health Toxicity:

o (GLN 870.3700) Developmental Toxicity – Rat

o (GLN 870.3465) 90 Day Inhalation – Rat

o (GLN 870.4100) Chronic Oral – Rodent

o (GLN 870.6200) 90-Day Neurotoxicity – Rat

o (GLN 870.6200) Acute Ne urotoxicity – Rat

Occupational and Residential Exposure:

o (GLN 875.1200) Dermal Exposure

o (GLN 875.1400) Inhalation Exposure

o (GLN 875.1600) Data Repor ting & Calculations

o (GLN 875.1700) Product Use Information

Once the Agency receives and reviews these studies, additional occupational, dietary and aggregate assessments may be needed.

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Further information is available in “Summary of Human Health Effects Data for the DBNPA Registration Review Decisi on Document,” dated December 15, 2009.

Anticipated Physical/ Chemic al Property Data Needs

All product chemistry data requirements have been fulfilled for the active ingredient DBNPA. Therefore, the Agency doe s not anticipate needing additional product chemistry data at this time.

Further information is available in “Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the DBNPA Registration Review Summary Document”, dated December 7, 2009.

Environmental Fate

No environmental fate assessment has been performed for DBNPA. The Agency has reviewed eight environmental fate studies for DBNPA that were received after the completion of the 1993 RED and has found th ese studies to be acceptable. An

environmental fate assessment will be needed for material preserva tives, and industrial

slimicides used in recirculat ing water cooling towers that potentially pass through waste water treatment plants (WWTPs) and may be discharged into terrestrial and aquatic

environments.

Ecological Risk

No ecological assessment has been performed for DBNPA. The Agency has reviewed thirty ecotoxicology studies for DBNPA that were received after the completion

of the 1993 RED and has found these studies to be acceptable. An ecological assessment will be needed for materials preservatives, i ndustrial slimicides us ed in recirculating water cooling towers, and pa per mills discharges that potentially pa ss through waste water treatment plants (WWTPs) and may be discharged into terrestrial and aquatic

environments.

Anticipated Environmental Fate and Ecological Data Needs for DBNPA

The Agency anticipates needing the followi ng data in order to conduct a complete environmental fate and ecotoxicity asse ssment, including an endangered species

assessment for all uses:

Environmental Fate Risk Assessment Data Needs :

o (GLN 850.6800) modified activated sludge respiration inhibition

o (GLN 835.1110) activated sl udge sorption isotherm

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Ecological Risk Assessment Data Needs :

o (GLN 850.5400) algal toxicity (Tier II) using fr eshwater green alga, Selenastrum capricornutum

Further information is available in “Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the DBNPA Registration Review Summary Document”, dated December 7, 2009.

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p) , EPA has developed the Endocrine Disruptor Screening Program (EDSP) to dete rmine whether certain substances (including pesticide active and other ingred ients) may have an effect in humans or wildlife similar to an effect produced by a “natur ally occurring estrogen, or othe r such endocrine effects as the Administrator may designate.” The ED SP 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 substa nce 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 inte ract with E, A, or T hormonal systems will proceed to the next stage of the EDSP wher e EPA will determine which, if any, of the Tier 2 tests are necessary based on the avai lable data. Tier 2 te sting is designed to identify any adverse endocrine related eff ects caused by the substance, and establish a dose-response relationship between th e dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which c ontains 58 pesticide ac tive ingredients and 9 inert ingredients. This list of chemicals was selected based on the potential for human exposure through pathways such as food and wa ter, residential activity, and certain postapplication agricultural s cenarios. This list should not be construed as a list of known or likely endocrine disruptors.

DBNPA is not among the group of 58 pestic ide active ingredients on the initial

list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates issuing future EDSP test orders/data call-ins for all pesticide active ingredients.

For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, please visit our

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

.

7Docket Number: EPA-HQ-OPP-2009-0724 www.regulations.gov

IV. TIMELINE

EPA has created the following estimated timeline for the completion of the DBNPA registration review.



### Registration Review for DBNPA Projected Registration Review Timeline

Activities Time

Opening Docket
Open Docket Completed December 2009

Close Public Comment Period Completed March 2010
Case Development

Final Work Plan Completed June 2010

Issue DCI June 2011

Data Submission June 2012
Preliminary Risk Assessment June 2014

Close Public Comment Period September 2014

Registration Review Decision
Proposed Registration Review Decision December 2014

Public Comment Period March 2015 Final Registration Review Decision & Begin Post-Decision Follow-up 2015 Total (years) 5

Next Steps:

A Data Call-In (DCI) will be developed regarding the data gaps listed under the

“Risk Assessment and Data Needs” section. Also, human health and ecological risk

assessments will be conducted for all uses.

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V. GLOSSARY of TERMS & ABBREVIATIONS

ai Active Ingredient AR Anticipated Residue ASTM American Society for Testing and Materials

AWPA American Wood Preserver’s Association

CFR Code of Federal Regulations cPAD Chronic Population Adjusted Dose

CSF Confidential Statement of Formula CSFII USDA Continuing Surveys for Food Intake by Individuals

DCI Data Call-In DEEM Dietary Exposure Evaluation Model DFR Dislodgeable Foliar Residue DNT Developmental Neurotoxicity DWLOC Drinking Water Level of Comparison

EC Emulsifiable Concentrate Formulation EDWC Estimated Drinking Water Concentration

EEC Estimated Environmental Concentration EPA Environmental Protection Agency

EUP End-Use Product FDA Food and Drug Administration FIFRA Federal Insecticide, Fungicide, and Rodenticide Act FFDCA Federal Food, Drug, and Cosmetic Act FQPA Food Quality Protection Act FOB Functional Observation Battery GENEEC Tier I Surface Water Computer Model

IR Index Reservoir

LC 50 Median Lethal Concentration. A statistically derived concentration of a substance that can be expected to cause death in 50% of test animals. It is usually expressed as the weight of substance per weight or volume of water, air or feed, e.g., mg/l, mg/kg or ppm.

LD 50 Median Lethal Dose. A statistically deri ved single dose that can be expected to

cause death in 50% of the test animals when administered by the route indicated (oral, dermal, inhalation). It is expressed as a weight of substance per unit weight of animal, e.g., mg/kg.

LOC Level of Concern

LOAEL Lowest Observed Adverse Effect Level μg/g Micrograms Per Gram μg/L Micrograms Per Liter mg/kg/day Milligram Per Kilogram Per Day mg/L Milligrams Per Liter MOE Margin of Exposure

MRID Master Record Identifi cation (number). EPA's system of recording and tracking

submitted studies. MUP Manufacturing-Use Product

NA Not Applicable NAWQA USGS National Ambient Water Quality Assessment NPDES National Pollutant Discharge Elimination System

NR Not Required

NOAEL No Observed Adverse Effect Level

OPP EPA Office of Pesticide Programs OPPTS EPA Office of Prevention, Pesticides and Toxic Substances PAD Population Adjusted Dose PAIRA Pure Active Ingredient Radiolabelled PCA Percent Crop Area

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10 PDP USDA Pesticide Data Program PHED Pesticide Handler's Exposure Data

PHI Preharvest Interval ppb Parts Per Billion

PPE Personal Protective Equipment

ppm Parts Per Million PRZM/EXAMS Tier II Surface Water Computer Model Q 1 * The Carcinogenic Potential of a Compound, Quantified by the EPA's Cancer

Risk Model RAC Raw Agriculture Commodity RASSB Risk Assessment and Science Support Branch RED Reregistration Eligibility Decision

REI Restricted Entry Interval

RfD Reference Dose RQ Risk Quotient SCI-GROW Tier I Ground Water Computer Model

SAP Science Advisory Panel SF Safety Factor

SLN Special Local Need (Registrati ons Under Section 24©) of FIFRA) TGAI Technical Grade Active Ingredient

TEP Typical End-Use Product USDA United States Department of Agriculture UF Uncertainty Factor

WPS Worker Protection Standard