United States Chemical Safety December 2011

Environmental Protection and Pollution Prevention

Agency (7510P)

Bronopol

Registration Review:

Final Work Plan

December 2011

Docket Number: EPA-HQ-OPP-2011-0421

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Bronopol Registration Review Team

William Hazel

Human Health & Environmental Effects

Srinivas Gowda

Eliza Blair

Risk Management

Lance Wormell

Philip Ross

Office of General Counsel

________________________________________

Supporting documents for the Bronopol Case may be found in the registration review docket

EPA-HQ-OPP-2011-0421 located on the internet at www.regulations.gov.
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This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the 

Agency”) for the registration review of bronopol (Case 2770). 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 bronopol 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.

Introduction

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 Bronopol Preliminary Work Plan (PWP) (PC Code 216400) was published on June 29, 2011

and the 60-day comment period ended on August 29, 2011. The Preliminary Work Plan 

document is available on www.regulations.gov docket number EPA-HQ-OPP-2011-0421.

The first product containing 2-Bromo-2-nitro-1,3-propanediol (Bronopol) (PC Code 216400) as 

an active ingredient was registered in the United States in 1984. Currently, there are 42 products 

registered with EPA. Bronopol is a bacteriostat, fungicide, microbicide, microbiostat, 

antimicrobial, and algaecide contained in products registered for use as a materials preservative, 

in industrial process water systems, and in HVAC systems. Products containing bronopol are 

also registered for use to preserve adhesives, metalworking fluids, absorbent clay, starch slurries, 

pigment slurries, mineral slurries, paints, emulsion systems, water-based printing inks and 

fountain solutions, paper, and bulk pulp. The following water systems may be treated: paper 

mill process water systems, recirculating water cooling towers, evaporative condensers, air 

scrubber systems, air conditioning systems, humidifying systems, and oil and gas drilling fluids. 

In HVAC systems, the following may be treated: furnaces, air handlers, coils, fans, fan housings, 

sheet metal ducts, air supply and return ducts, humidifiers, dehumidifiers, and air intake and 

discharge devices. Bronopol has been widely used for decades as a preservative in 

pharmaceuticals, cosmetics, and other personal care products regulated by the Food & Drug 

Administration (FDA). Bronopol is exempt from the requirement of a tolerance when used at 

≤400 ppm as an inert ingredient in conventional pesticide products used on crops and animals.

Bronopol is approved by the FDA for indirect food contact under 21 CFR 175.105 (c)(5), 21 

CFR 176.170 (a)(5), 21 CFR 176.180 (b)(1), 21 CFR 176.300. A RED was completed for 

bronopol in 1995.
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The Agency received comments from one registrant 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.

Comments Received on the Preliminary Work Plan

Comment: The Agency indicated in its Summary Document that bronopol is not approved for 

any kind of food-contact use. In fact, bronopol is approved by the FDA for indirect food contact 

under the following: 21 CFR 175.105 (c)(5), 21 CFR 176.170 (a)(5), 21 CFR 176.180 (b)(1), 21 

CFR 176.300.

Response: The Agency thanks the registrant for this correction. Future documents, including this 

Final Work Plan, will include that corrected information.

Comment: The registrant has in the past submitted a study (MRID 47256605) that may satisfy 

the data requirement 835.3110 - Ready Biodegradability.

Response: The Agency will review this study as part of its risk assessment for bronopol and 

encourages the registrant to cite this study when responding to the data call-in (DCI) anticipated 

to be issued for this case.

Comment: Although it is not listed in the anticipated data requirements table, the Summary 

Document suggests that bystander formaldehyde exposure data will be required. Bystander 

exposure data are not applicable for industrial use sites.

Response:

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

work plan and timeline described in the PWP; however, the Agency expects to require two 

additional ecological studies that were not included in the anticipated the data needs section of 

the PWP. These additional studies that the Agency anticipates requiring are “835.3220 -- Porous 

Pot Test” and “835.3240 -- Simulation Test - Aerobic Sewage Treatment: A. Activated Sludge 

Units”. They were not included in the PWP because they were not required for down-the-drain 

exposure assessment at that time, and are being added to the FWP because they are now part of 

the standard suite of studies that the Agency anticipates needing to assess down-the-drain 

exposure.

The referenced phrase on page 15 of the Summary Document was 

"postapplication/bystander formaldehyde exposure". The Agency still anticipates needing 

postapplication formaldehyde exposure data.

This document makes final the work plan for the bronopol registration review process.

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

species risk assessment, for all uses of bronopol. The Agency will conduct a human health risk 

Risk Assessments and Anticipated Data Needs
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assessment. The Agency anticipates the need to require additional data for use in conducting the 

registration review for bronopol.

EPA believes that bronopol releases formaldehyde (HCHO) under certain conditions; therefore,

this Registration Review also addresses potential risks associated with formaldehyde exposure

from bronopol use. Products containing formaldehyde as an active ingredient will be evaluated

under registration review Case 0556. EPA’s formaldehyde RED is available in the formaldehyde

public docket at http://www.regulations.gov in docket number EPA-HQ-OPP-2008-0121.

Ecological Risk Assessment Status and Data Needs

• The most recent ecological risk assessment for bronopol was performed in 1995 in support of 

the bronopol RED.

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

conducting the registration review of bronopol.

850.1300 -- Daphnid chronic toxicity test

850.1400 -- Fish early-life stage toxicity test (freshwater)

850.4225 -- Seedling emergence, Tier II - dose response study on rice (Oryza sativa);

850.4250 -- Vegetative vigor, Tier II - dose response study on rice (Oryza sativa);

850.4400 -- Aquatic plant growth (aquatic vascular plant toxicity), Tier II - using 

Lemna gibba, Tier I

850.5400 -- Aquatic plant growth (algal toxicity), Tier II - dose response studies on 

four species

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

for use in conducting the registration review of bronopol.

850.6800 -- Modified activated sludge respiration inhibition test

835.3110 -- Ready biodegradability1

835.3220 -- Porous Pot Test1

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

to Wastewater1

835.3240 -- Simulation Test - Aerobic Sewage Treatment: A. Activated Sludge Units 1

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

which of these three 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) 

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

the Porous Pot Test. If the antimicrobial passes the ready biodegradability study, 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.
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• For more information, please refer to Summary of Product Chemistry, Environmental Fate, 

and Ecotoxicity Data for the Bronopol Registration Review Decision Document, located in 

the docket.

Human Health Risk Assessment Status and Data Needs

• The most recent human health risk assessment for bronopol was performed in 1995 in 

support of the bronopol RED.

• Dietary (food) exposure could potentially occur because bronopol is used as an in-can 

preservative or preservative during storage or use of materials including the following: bulk 

paper pulp, paper and paperboard water systems, water-based coatings, dishwashing liquids, 

and premoistened sponges and wipes. Residue transfer from these preserved materials to 

food may occur. The labels do not preclude food contact use of these materials. A dietary 

exposure and risk assessment addressing use of bronopol as an active ingredient has not been 

conducted in the past. However, a dietary (food source) risk assessment is now expected to 

be necessary.

Dietary Assessment

• A drinking water assessment has not been conducted for bronopol in the past. However, a 

number of the industries making use of bronopol periodically discharge waste water. 

Although the extent to which bronopol will survive waste water treatment is not known, it is 

fairly likely that bronopol could contaminate surface or ground water, and hence drinking 

water as a result of antimicrobial use patterns. Based on the present use scenarios on the 

bronopol labels, a drinking water assessment is warranted at this time.

• Bronopol is exempt from the requirement of a tolerance when used at ≤400 ppm as an inert 

ingredient in conventional pesticide products used on crops and animals. Additionally, 

bronopol is approved by the FDA for indirect food contact under 21 CFR 175.105 (c)(5), 21 

CFR 176.170 (a)(5), 21 CFR 176.180 (b)(1), and 21 CFR 176.300.

Tolerances and International Harmonization

• The most recent occupational and residential exposure assessment was performed in support 

of the bronopol RED in 1995.

Occupational and Residential Assessment and Risk

• Assessments of occupational risk are planned for this registration review because bronopol

products are added to preserve industrial materials during the manufacturing process using 

open-pour or metered pump application methods which may result in dermal and inhalation 

exposure to workers. 

• Bronopol hydrolyzes to release formaldehyde which may result in worker inhalation 

exposure. Because the conditions under which bronopol releases formaldehyde and the rate 

of release are unknown, postapplication formaldehyde exposure data are anticipated to be 
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needed to assess inhalation risks posed to workers in pulp and paper mills, machine shops, 

and other industrial facilities manufacturing preserved materials. In addition to the data 

expected to be required through registration review, a small chamber study could be 

substituted for the indoor inhalation exposure data the Agency anticipates needing. The 

Agency encourages registrants who wish to conduct a small chamber study in place of indoor 

inhalation exposure to discuss a protocol with the Agency. A small chamber study would 

allow the Agency to better estimate the magnitude of occupational (mixer/loader) 

formaldehyde inhalation exposure while using bronopol products as preserving materials in 

the manufacturing facility, using treated metalworking fluids, using products containing 

bronopol in paper and paperboard mill water systems, painting with preserved paint, and 

applying preserved coatings. 

• Assessments of residential risk are planned for registration review because materials 

preserved with Bronopol are intended for residential, commercial, and institutional use and 

may result in exposure of the general public and homeowners to the parent compound and 

formaldehyde. Such materials include latex paints, resin/latex/polymer emulsions, or 

detergent and polish suspensions. To help the Agency determine whether or not residential or 

other nonoccupational exposure to the parent compound or formaldehyde is likely to occur 

from its use as a preservative, the Agency encourages registrants to submit detailed 

information on physical and chemical properties and use information to elucidate the 

conditions, rates, and magnitude of formaldehyde release from Bronopol under various 

conditions and in various materials.

• The Agency has not conducted an aggregate risk assessment for bronopol. 

Aggregate and Cumulative Exposure and Risk

• 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. Assessments of aggregate risk are planned for 

registration review because dietary (food) and residential painter/postapplication exposures 

are expected to occur. In addition, bronopol residues may also reach drinking water as a 

result of industrial discharges. However, the potential need to include drinking water 

exposure in the aggregate assessment will be revisited upon receipt of the additional 

environmental fate data anticipated to be required through registration review. The specifics 

of necessary aggregate assessments will be determined during the risk assessment stage of this 

registration review.

• EPA does not have, at this time, available data to determine whether Bronopol 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 

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

as an antimicrobial as registered. 

Human Health Data Needs
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• The Agency anticipates the need to require the following additional human health data for 

use in conducting the registration review of Bronopol.

870.3465 -- 90-day inhalation toxicity (rat)

875.1700 -- Product use information (outdoor)

875.2700 -- Product use information (indoor)

875.2800 -- Description of human activity

875.1100 -- Dermal outdoor exposure

875.1200 -- Dermal indoor exposure

875.1300 -- Inhalation outdoor exposure (HRSB costs not included)

875.1400 -- Inhalation indoor exposure*

875.1600 -- Application exposure data reporting and calculations

875.2900 -- Data reporting and calculations

* The anticipated DCI will provide that the indoor inhalation exposure anticipated data requirement may also be 

met with a small chamber study to determine the level of human exposure to formaldehyde in residential and 

occupational settings. The anticipated DCI will provide that registrants seeking to conduct a small chamber study 

must discuss a protocol with the Agency to ensure that the study will meet EPA guidelines.

• For more information, please refer to 2-Bromo-2-nitropropane-1,3-diol. Human Health 

Effects Scoping Document for the Registration Review Decision, located in the docket.

Product Chemistry Data Needs

• 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 Summary of Product Chemistry, Environmental Fate, 

and Ecotoxicity Data for the Bronopol Registration Review Decision Document, located in 

the docket.

Ecological:

Incidents:

• No Bronopol ecological incidents have been reported in Agency's Ecological Incident 

Information System (EIIS).

Human Health:

• Four human poisoning incidents have been confirmed as being due to Bronopol exposure. 

These are summarized as follows: 

1. A residential use of a bronopol product to treat HVAC ducts resulted in the homeowner 

becoming sick. No more detailed information was provided. 

2. A worker was splashed on the upper arm with approximately 2 ml of a 25% solution of 

bronopol in water. The worker promptly washed the area with soap and water. The 
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worker experienced no immediate pain. The exposed area began to itch later that evening 

and then blister. The worker went to a doctor who said it was a second degree burn. 

3. A worker who uses a printing press claims that (s)he has developed a chemical allergy to 

bronopol. 

4. A man reported that he was sick after the HVAC system in his house was treated with a 

bronopol product. The person began having some adverse reactions to the chemical 

treatment immediately after re-entering the house. The reactions became more intense 

until he finally had to leave the house. 

Endangered Species

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

species determination for Bronopol. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether Bronopol’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. As part of its reregistration decision for bronopol, EPA reviewed these data 

and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), Bronopol 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 

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.
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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. Bronopol 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 Bronopol. 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/.
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Timeline

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

review:

Anticipated Schedule

Activities Estimated Month/Year

Phase 1: Opening the docket

Open Public Comment Period for Docket Completed

June 2011

Close Public Comment Period for Docket Completed

August 2011

Phase 2: Case Development

Develop Final Work Plan (FWP) Completed

December 2011

Issue DCI December 2012

Data Submission December 2014

Open Public Comment Period for Preliminary Risk Assessments June 2016

Close Public Comment Period for Preliminary Risk Assessments July 2016

Phase 3: Registration Review Decision

Open Public Comment Period for Proposed Reg. Review Decision December 2016

Close Public Comment Period for Proposed Reg. Review Decision February 2017

Final Decision and Begin Post-Decision Follow-up June 2017

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 2012. Human health and environmental fate and ecological hazard assessments will 

be conducted for all uses. 
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Summary of Anticipated Data Requirements – Bronopol

The table below summarizes anticipated data needs for the registration review of bronopol.

Table 1. Summary of Anticipated Data Requirements – Bronopol

Guideline

Number Anticipated Data Requirement Test Material

Estimated Timeframe 

(Measured in months from 

DCI Receipt)

835.3110 Ready biodegradabilityi TGAI 12

835.3220 Porous Pot Testi2 TGAI 12

835.3280

Simulation Tests to Assess the 

Biodegradability of Chemicals 

Discharged to Wastewateri

TGAI

12

835.3240 Simulation Test – Aerobic Sewage 

Treatment: A. Activated Sludge Unitsi2

TGAI 12

850.1300 Aquatic invertebrate life-cycle, 

freshwater species

TGAI 24

850.1400 Fish early-life stage toxicity test, 

freshwater species

TGAI 24

850.4225 Seedling emergence, Tier II - dose 

response study on rice (Oryza sativa)

TGAI 24

850.4250 Vegetative vigor, Tier II - dose response 

study on rice (Oryza sativa)

TGAI 24

850.4400 Aquatic plant toxicity test, vascular 

species

TGAI 24

850.5400 Aquatic plant toxicity test, non-vascular 

(4 species)

TGAI 12

850.6800 Modified Activated Sludge Respiration 

Inhibition

TGAI 24

870.3465 90-day inhalation toxicity (rat) TGAI 48

875.1100 Dermal outdoor exposure TGAI 24

875.1200 Dermal indoor exposure TGAI 24

875.1300 Inhalation outdoor exposure 

TGAI

24

875.1400 Inhalation indoor exposureii TGAI 24

 2 These two studies were not listed as anticipated data needs in the Bronopol Preliminary Work Plan; they are new 

additions to the standard suite of down-the-drain data that the Agency anticipates needing for risk assessment.
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875.1600 Application exposure data reporting and 

calculations

TGAI 24

875.1700 Product use information (outdoor) TGAI 24

875.2700 Product use information (indoor) TGAI 24

875.2800 Description of human activity TGAI 24

875.2900 Data reporting and calculations TGAI 24

 i

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

which of these three 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) 

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

the Porous Pot Test. If the antimicrobial passes the ready biodegradability study, 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.

ii The indoor inhalation exposure data requirement may also be met with a small chamber study to determine the 

level of human exposure to formaldehyde in residential and occupational settings. Registrants seeking to conduct a 

small chamber study must discuss a protocol with the Agency to ensure that the study will meet EPA guidelines.