Docket Number: EPA-HQ-OPP-2009-0726 

www.regulations.gov 

 

 

United States Prevention, Pesticides May 2010 

Environmental Protection and Toxic Substances 

Agency (7510P)

2-Bromo-4’-hydroxyacetophenone (BHAP) 

Final Work Plan Registration Review 

Docket Number: EPA-HQ-OPP-2009-0726 

www.regulations.gov 

2-Bromo-4’-hydroxyacetohenone (BHAP) Registration Review Team

Human Health & Environmental Effects 

Srinivas Gowda 

William Hazel 

Risk Management

K. Avivah Jakob 

Lance Wormell 

Office of General Counsel

Philip Ross 

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Introduction

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

Work Plan (FWP) for the registration review of 2-Bromo-4’-hydroxyacetophenone 

(BHAP) (Case 3032). The FWP includes the expected registration review time-line. The 

FWP also addresses public comments received concerning the Preliminary Work Plan

(PWP) in the Summary Document which was posted in the BHAP registration review 

docket (EPA-HQ-OPP-2009-0726), and any other comments concerning 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 BHAP Preliminary Work Plan (PWP) was entered into the docket for this 

registration review on December 16, 2009. The 90-day comment period ended on March 

16, 2009. The Preliminary Work Plan document is available on www.regulations.gov, 

docket number EPA-HQ-OPP-2009-0726. 

Comments Received on the Preliminary Work Plan

In the PWP, the EPA solicited comments on three specific topics: environmental 

justice, water body impairment and potential trade irritants. No comments or information 

were received during the public comment period concerning these issues. 

During the public comment period, the EPA received one comment as described 

and discussed below. The comment received during the initial public comment period 

did not affect the anticipated 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 BHAP registration review process. 

The following comment was submitted by the FIFRA Endangered Species Task 

Force (FESTF) in response to the BHAP PWP. The Agency’s response follows the 

comment. 

Comment: The FIFRA Endangered Species Task Force (FESTF) submitted a 

comment requesting that any technical registrant for BHAP who is not a member 

of the FESTF (or a company having met its data compensation obligations) be 

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asked to provide a formal offer-to-pay to FESTF for reliance on their data. In their 

comment, FESTF also noted that Buckman Laboratories is the leading registrant 

for BHAP, and that Buckman Laboratories is not a FESTF member. Therefore, 

the technical registrant must offer to pay FESTF to rely on FESTF submitted data 

or develop substantial similar data on their own. 

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. 

Risk Assessment & Anticipated Data Needs

BHAP was first registered in the United States in 1964. A Reregistration 

Eligibility Decision (RED) for BHAP was issued in February 1995. The RED can be 

located at: http://www.epa.gov/pesticides/reregistration/status.htm

There are currently five EPA registered products that contain BHAP as an active 

ingredient (one manufacturing-use product and four end-use products). BHAP is 

registered as a broad spectrum microbiocide/microbiostat for use to control slimeforming bacteria and fungi in industrial processes and water systems (pulp and paper 

mills, emulsions, slurries, cooling tower water systems, oil drilling and secondary 

recovery systems, etc). BHAP is also registered for use as a materials preservative (incan preservation of emulsion paints, adhesives, waxes, polishes, slurries and emissions, 

coating formulations and papermaking chemicals, leather, etc). 

 In support of this registration review the Agency will conduct residential, 

occupational, indirect dietary (food) and aggregate exposure risk assessments as well as 

environmental fate and ecological exposure risk assessments for BHAP. Prior to 

conducting these risk assessments, the Agency anticipates requiring additional data. 

Human Health Risk Assessment Status 

 The Agency has reviewed the hazard and exposure databases for BHAP for this 

registration review case. As a result of this review, EPA anticipates that additional 

toxicity data and exposure data will be needed to complete this registration review case. 

It is anticipated that inhalation toxicology data will be needed to properly characterize 

possible inhalation hazards resulting from the use of BHAP (application of preserved 

paint and open pouring use scenarios). Also, the Agency anticipates needing a twogeneration rat reproductive toxicity study to determine possible effects of BHAP on 

mammalian reproduction and fertility. Exposure data are expected to be needed to 

estimate residential and occupational handler exposures (inhalation and dermal) resulting 

from the application of preserved paint; and occupational exposure (inhalation and 

dermal) resulting from open pouring use scenarios (open pouring into pulp and paper mill 

systems and secondary oil recovery sites, and open pouring to preserve materials). 

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Residential and occupational exposure risk assessments are needed to assess 

whether the BHAP registration review case continues to meet the FIFRA and FFDCA 

standards. The Agency will complete the human health risk assessments presented 

below. Further information and detailed justifications for the studies that are expected to 

be required are available in the document titled, “2-Bromo-4’-hydroxyacetophenone 

(BHAP). Human Health Effects Scoping Document for the Registration Review 

Decision,” dated December 7, 2009. 

• Residential Handler Risk Assessment (adults) - Exposure resulting from 

application of preserved paints. The anticipated routes of exposure to 

residential handlers are dermal and inhalation. 

• Dietary (Food) Risk Assessment - Indirect dietary (food) exposure resulting 

from the use of BHAP as a microbiocide/microbiostat which is used to control 

slime-forming bacteria and fungi in pulp and paper mills and as a materials 

preservative for paper-making chemicals. 

• Aggregate Risk Assessment - Needed to combine the following exposure 

scenarios: (1) indirect dietary exposure resulting from use as a 

microbiocide/microbiostat which is used to control slime-forming bacteria and 

fungi in pulp and paper mills and as a materials preservative for paper-making 

chemicals, and (2) residential handler exposure resulting from the application 

of preserved paint. 

• Occupational Handler Assessment - Exposure resulting from application of 

preserved paints; open-pouring of BHAP into pulp and paper mill systems and 

secondary oil recovery sites; and open-pouring of BHAP to preserve materials 

(paints, waxes, inks, etc.). The anticipated routes of exposure to occupational 

handlers are dermal and inhalation. 

Toxicity 

Acute Toxicity 

 

BHAP is of moderate toxicity (Toxicity Category II) via inhalation and oral routes 

of exposure and is slightly toxic (Toxicity Category III) via the dermal route. It is a 

severe eye irritant (Toxicity Category I) and a light dermal irritant (Toxicity Category 

III). BHAP is also a dermal sensitizer. 

Sub-chronic and Chronic Toxicity 

BHAP is extremely irritating to the eyes, lungs, and skin. It also induces systemic 

effects at relatively low oral doses. Sub-chronic dermal and oral toxicity data are 

available. However, sub-chronic inhalation toxicity data are not available. The Agency 

believes that establishing toxicological endpoints based on the current sub-chronic oral 

toxicity study may not be protective of adverse inhalation exposure effects. Therefore, to 

properly characterize the hazards posed by BHAP via the inhalation route of exposure, 

the Agency anticipates that a 90-day rat inhalation toxicity study will be needed. The 

exposure scenarios that trigger the need for a 90-day rat inhalation toxicity study are 

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painting by residential and occupational handlers and open-pouring use scenarios for 

occupational handlers. A quantitative assessment of inhalation risks is needed. 

Chronic toxicity data are not available for BHAP and are not anticipated as being 

needed because the currently registered uses of BHAP are not expected to result in longterm human exposure. 

Reproductive Toxicity 

 In the 90-day oral rat toxicity study (MRID 43327501) decreased testicular 

weight was an observed effect. This effect could be indicative of adverse effects on male 

fertility or some other reproductive parameter. The possible effects of BHAP on 

mammalian reproduction and fertility are unknown because a reproductive toxicity study 

is not available. Therefore, the Agency anticipates needing a two-generation rat 

reproductive toxicity study to determine possible effects of BHAP on mammalian 

reproduction and fertility. 

Dietary and Drinking Water Exposure and Risk 

Dietary Food Exposure 

 BHAP has no registered direct food uses and a dietary (food) exposure risk 

assessment has not been performed for BHAP. However, an indirect dietary (food) 

exposure and risk assessment is needed as a result of its use to treat pulp/paper water 

systems and to preserve paper-making chemicals. Indirect dietary (food) exposure could 

potentially occur because BHAP is used to inhibit slime-forming bacteria and fungi in 

paper process water systems involved in the production of paper and paperboard that may 

be used for food contact. Also, BHAP is used to preserve a number of paper-making 

chemicals as well as paper and paperboard coatings, inks, etc., which may be used for 

food contact. Migration of BHAP from paper packaging to food contents may occur, 

resulting in indirect dietary (food) exposure. Therefore, an indirect dietary (food) 

exposure risk assessment is needed. 

Dietary Drinking Water Exposure 

The registered uses of BHAP are not likely to result in contamination of surface 

water and ground water and as a result drinking water exposure is not expected. 

However, the need for a dietary drinking water exposure assessment for BHAP will be 

determined upon review of environmental fate data, which the Agency anticipates 

requiring. The Agency anticipates that environmental fate data will be useful to 

determine if BHAP can pass through waste-water treatment facilities into drinking water 

or migrate into residential groundwater wells as a result of its current use patterns. 

Therefore, the need for a dietary drinking water assessment will be revisited upon 

submission and review of the environmental fate data that are anticipated as being 

required. 

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Tolerances

 Tolerance exemptions have been established by the Food and Drug 

Administration (FDA) which regulates BHAP as an indirect food additive for use as a 

slimicide in pulp and paper water systems with no specified maximum use concentration 

(21 CFR 176.300); and to preserve paper-making chemicals that may be used for foodcontact at a use concentrations of ≤60 ppm (21 CFR 176.170). 

Aggregate and Cumulative Exposure and Risk

In examining aggregate exposure, EPA takes into account available and reliable 

information concerning exposures to pesticide residues in food and drinking water, as 

well as non-occupational pesticide exposures. Indirect food exposure is expected 

resulting from the use of BHAP as a microbiocide/microbiostat that is used to control 

slime-forming bacteria and fungi in pulp and paper mills and as a materials preservative 

for paper-making chemicals. Residential handler (painting) exposure of adults to BHAP 

is also likely to occur. Therefore, the Agency has determined that an aggregate 

assessment for BHAP will be needed to assess the combined exposure resulting from 

these uses. 

Occupational and Residential Exposure and Risk

The Agency reviewed all available data associated with BHAP and has 

determined that the currently registered uses of BHAP may result in residential and 

occupational exposure. Therefore, the Agency will conduct residential (handler) and 

occupational (handler) risk assessments to assess possible dermal and inhalation exposure 

to BHAP. 

Incidents

Three incidents related to the use of BHAP have been reported in the OPP 

Incident Database System (IDS). The following dermal exposure symptoms were 

reported: skin depigmentation and skin peel after a chemical burn. These incidents 

appear to be allergic reactions. 

Anticipated Human Health Data Needs 

The Agency anticipates that the following toxicity and exposure data will be 

needed to conduct residential (handler) and occupational (handler) exposure risk 

assessments for the registered uses of BHAP. For further information, please refer to the 

document titled “2-Bromo-4’-hydroxyacetophenone (BHAP). Human Health Effects 

Scoping Document for the Registration Review Decision,” dated December 7, 2009. 

Anticipated Toxicity Data Needs

• (GLN 870.3465) 90-day inhalation toxicity in rats 

• (GLN 870.3800) Reproduction and fertility effects 

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Anticipated Residential and Occupational Handler Exposure Data Needs

• (GLN 875.1700) Product Use Information- Outdoor 

• (GLN 875.2700) Product Use Information- Indoor 

• (GLN 875.2800) Descriptions of Human Activity 

• (GLN 875.1100) Outdoor Dermal Exposure 

• (GLN 875.1200) Indoor Dermal Exposure 

• (GLN 875.1300) Outdoor Inhalation Exposure 

• (GLN 875.1400) Indoor Inhalation Exposure 

• (GLN 875.1600) Applicator Exposure Monitoring Data Reporting for Dermal 

and Inhalation Data 

• (GLN 875.2900) Data Reporting and Calculations 

Environmental Fate and Ecological Risk Assessment Status 

The Agency reviewed the environmental fate and ecological hazard databases for 

BHAP. Based on its review, EPA believes risk assessments are needed to ensure that the 

BHAP registration review case meets the FIFRA standards. The Agency will complete 

the environmental fate and ecological hazard risk assessments presented below. Further 

information and detailed justifications for the studies that are expected to be required are 

available in the document titled “Summary of Product Chemistry, Environmental Fate, 

and Ecotoxicity Data for the Bromohydroxyacetophenone Registration Review Decision 

Document,” dated December 7, 2009. 

• Environmental fate 

• Ecological hazard 

• Endangered species assessment 

Environmental fate and ecological risk assessments have not been conducted for 

BHAP. The use of BHAP as a materials preservative and as an industrial slimicide in 

recirculating water cooling towers and paper mills could potentially result in 

environmental exposure. These uses may result in waste water treatment plant (WWTP) 

discharges into terrestrial and aquatic environments. Therefore, the Agency will conduct 

environmental fate and ecological risk assessments to assess environmental exposure 

resulting from possible discharges into terrestrial and aquatic environments. The Agency 

also anticipates that environmental fate and ecological data will be needed to conduct 

these assessments. 

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

endangered species determination. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether use of BHAP 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 Service (the 

Services), as appropriate. 

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Anticipated Physical/Chemical Property Data Needs 

All product chemistry data requirements have been fulfilled for the active 

ingredient BHAP. Therefore, it is anticipated that additional product chemistry data will 

not be needed for BHAP. 

Anticipated Environmental Fate and Ecological Data Needs 

The Agency anticipates conducting environmental fate and ecological risk 

assessments for BHAP based on its use as a materials preservative and as an industrial 

slimicide in recirculating water cooling towers and paper mills. These uses could 

potentially result in BHAP passing through waste water treatment plants (WWTPs), 

which may then be discharged into terrestrial and/or aquatic environments. Therefore, 

the Agency anticipates needing environmental fate and ecological toxicity data for BHAP 

and/or any of its major degradation products that are of potential concern. The 

environmental fate and ecological toxicity data listed below are anticipated as being 

needed to conduct environmental fate and ecological risk assessments. 

The Agency anticipates that the following data will be needed to conduct 

complete environmental fate and ecological risk assessments for the registered uses of 

BHAP: 

Anticipated Environmental Fate Data Needs

• (GLN 850.6800) Modified activated sludge respiration inhibition 

• (GLN 835.1110) Activated sludge sorption isotherm 

• (GLN 835.3110) Ready biodegradability 

Anticipated Ecological Data Needs

• GLN 850.4400) Aquatic Plant Growth (aquatic vascular plant toxicity), Tier 

 II dose response study on floating macrophyte (Lemna gibba) 

• (GLN 850.5400) Aquatic Plant Growth (algal toxicity), Tier II dose response 

 studies on Anabaena flos-aquae (blue-green cyanobacteria), Navicula 

 pelliculosa (freshwater diatom), and Skeletonema costatum (marine diatom) 

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 

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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. 

BHAP 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/. 

Timeline

The EPA has created the following estimated timeline for the completion of the 

BHAP registration review case. The Agency anticipates requiring additional data and 

will conduct residential, occupational and ecological exposure assessments for this 

registration review case. 

Anticipated Schedule

Registration Review for BHAP 

Projected Registration Review Timeline 

Activities 

Time 

Opening Docket 

Open Public Comment Period for BHAP Docket December 2009 

Close Public Comment Period March 2010 

Case Development 

Develop Final Work Plan (FWP) May 2010 

Issue DCI May 2011 

Data Submission May 2015 

Open Public Comment Period for Preliminary Risk Assessments September 2015 

Close Public Comment Period November 2015 

Registration Review Decision 

Open Public Comment Period for Proposed RR Decision February 2016 

Close Public Comment Period May 2016 

Final Decision August 2016 

Total (years) 7 years 

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Next Steps

A DCI will be developed for this registration review case regarding the data needs 

listed under the “Risk Assessment and Data Needs” section of this document. The 

Agency expects to issue the DCI in 2011. 

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