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 2010 

 

 

Docket Number: EPA-HQ-OPP-2009-0724 

www.regulations.gov 

TABLE OF CONTENTS

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

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

II. SUMMARY OF COMMENTS RECEIVED ON PRELIMINARY WORK 

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

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

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

V. GLOSSARY of TERMS & ABBREVIATIONS.................................................. 12 

 
Docket 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 

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I. INTRODUCTION

This is the Environmental Protection Agency’s (EPA or “the Agency”) Final 

Work Plan (FWP) for the registration review of DBNPA (Case 3056). The FWP includes 

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

received concerning the Preliminary Work Plan in the Summary Document which was 

posted in the DBNPA 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 DBNPA Preliminary Work Plan was entered into the docket for this 

registration review on December 16, 2009. The 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 RECEIVED 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 registrations. In addition, the Agency received 

one comment from the FIFRA Endangered Species 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 review process. 

In the Preliminary Work Plan, the Agency 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 that any technical registrant 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 provide 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 registration review and makes its registration 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 current guidelines. Dow contends that at the time the study was 

conducted, it conformed to existing guidelines, and the data it generated should not be 

ignored simply because guidelines have changed since then. 

Response: Upon further review, the Agency believes 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 the Human Studies Review 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 will revisit its review of the disputed rat study 

and the need for a new study at that time. 

III. RISK ASSESSMENT AND DATA NEEDS

A Reregistration Eligibility 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 United 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 control algae, bacteria, 

fungi and yeasts; it is registered for use in paper mills, metalworking fluids containing 

water, enhanced oil recovery systems, industrial recirculation water cooling systems, 

membrane systems for industrial water (reverse osmosis), air washer systems, hydro 

testing systems, publicly owned treatment works, brewery pasteurizer water systems, 

packer fluids, water floods, construction products and household products as material 

preservative, and for technical manufacturing use. 

Human Health Risk 

 

The Agency has reviewed the hazard and exposure databases for DBNPA and its 

degradates and anticipates that additional toxicity 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 registration 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 exposure from the use of DBNPA in 

metalworking fluids. 

• Occupational dermal and inhalation exposure 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 assessment 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 and 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 evidence which indicates that DBAA is a 

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

Human Studies

MRID 458281-01 “Human Panelist Studies of Dermal Cumulative 

Irritancy/Sensitization with 2-2-Dibromo-3-nitrilopropionamide” was submitted for 

DBNPA after the RED was published and was reviewed 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 the course of registration review, and will 

consider as well any other research brought to its attention involving 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 requirements are met, including, but not limited 

to, the requirements for an EPA ethics review and Human Studies Review Board review 

of certain research involving intentional exposure of human subjects. 

Further discussion of this issue is available in “Summary of Human Health 

Effects Data for the DBNPA Registration Review 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 needed to determine if there are any potential 

dietary concerns from indirect food exposures to DBNPA. 

Occupational and Residential Exposure

An occupational handler risk assessment 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 the solid soluble concentrate 

formulations, but these concerns have been mitigated by water soluble packaging. 

 Occupational handler dermal and inhalation exposures can also occur for 

machinists using metalworking fluid treated with DBNPA and painters 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 exposures to DBNPA aerosols can occur 

during the airless sprayer application of DBNPA-treated paint. Inhalation exposure to 

DBNPA vapor can also occur during and after paint application because DBNPA has a 

vapor pressure of 8 x 10-4 mm Hg at 25o

 C. These exposures were not evaluated in the 

RED and will need to be assessed during registration review. 

Anticipated Human Health Data Needs 

 

 While the Agency already possesses some toxicity data for DBNPA itself, 

because DBNPA has two metabolites/degradates of potential toxicological concern, the 

Agency anticipates needing the following toxicity 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 Neurotoxicity – Rat 

Occupational and Residential Exposure:

o (GLN 875.1200) Dermal Exposure 

o (GLN 875.1400) Inhalation Exposure 

o (GLN 875.1600) Data Reporting & 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 Decision Document,” dated December 15, 2009. 

Anticipated Physical/ Chemical Property Data Needs 

All product chemistry data requirements have been fulfilled for the active 

ingredient DBNPA. Therefore, the Agency does 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 these studies to be acceptable. An 

environmental fate assessment will be needed for material preservatives, and industrial 

slimicides used in recirculating 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, industrial slimicides used in recirculating 

water cooling towers, and paper mills discharges that potentially pass 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 following data in order to conduct a complete 

environmental fate and ecotoxicity assessment, 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 sludge sorption isotherm 

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Ecological Risk Assessment Data Needs: 

o (GLN 850.5400) algal toxicity (Tier II) using freshwater 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 determine whether certain substances (including 

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

an effect produced by a “naturally occurring estrogen, or other such endocrine effects as 

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

the statutorily required determinations. Tier 1 consists of a battery of 11 screening assays 

to identify the potential of a chemical substance to interact with the estrogen, androgen, 

or thyroid (E, A, or T) hormonal systems. Chemicals that go through Tier 1 screening 

and are found to have the potential to interact with E, A, or T hormonal systems will 

proceed to the next stage of the EDSP where EPA will determine which, if any, of the 

Tier 2 tests are necessary based on the available data. Tier 2 testing is designed to 

identify any adverse endocrine related effects caused by the substance, and establish a 

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

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. This list of chemicals was selected based on the potential for human 

exposure through pathways such as food and water, residential activity, and certain postapplication agricultural scenarios. This list should not be construed as a list of known or 

likely endocrine disruptors. 

DBNPA is not among the group of 58 pesticide 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/.

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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 

LC50 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. 

LD50 Median Lethal Dose. A statistically derived 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 Identification (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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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 

Q1* 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 (Registrations 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