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 ReviewDocket Number: EPA-HQ-OPP-2009-0726 www.regulations.gov

2-Bromo-4’-hydroxyacetohenone (BHA P) 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 exp ected 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 wh at EPA knows about the pesticide and what additional risk analyses a nd data or information the Agency believes are needed to make a regist ration review decision.

The Agency is implementing the Registration Review program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodentic ide Act (FIFRA) and w ill review each registered pesticide every 15 year s to determine whether it continues to meet the FIFRA standard for regist ration. Changes in science, public policy and pesticide use practices will occur over time. The registra tion 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/

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The BHAP Preliminary Work Plan (PWP) was entered into the docket for this registration review on December 16, 2009. Th e 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 trad e irritants. No comm ents or information were received during the public comme nt period concerning these issues.

During the public comment period, the EP A 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 initi ally in the PWP. Further, this document makes final the work plan for the B HAP registration review process.

The following comment was submitted by the FIFRA Endangered Species Task Force (FESTF) in response to the BHAP PW P. The Agency’s response follows the

comment.

Comment : The FIFRA Endangered Species Task Force (FESTF) submitted a comment requesting that any technical regi strant 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 Laboratorie s is not a FESTF me mber. Therefore, the technical registrant must offer to pay FESTF to rely on FESTF submitted data or develop substantial si milar data on their own.

Response : The Agency thanks FESTF for its comment and will consider this information as it conducts the registra tion review and makes its registration

review decisions.

Risk Assessment & Anticipated Data Needs

BHAP was first registered in the Un ited 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 manufactur ing-use product and four end- use products). BHAP is registered as a broad spectrum microbioc ide/microbiostat for use to control slimeforming bacteria and fungi in industrial processes and water systems (pulp and paper mills, emulsions, slurries, cooling tower wa ter systems, oil drilling and secondary recovery systems, etc). BHAP is also regi stered for use as a ma terials preservative (incan preservation of emulsion pa ints, adhesives, waxes, polis hes, slurries and emissions, coating formulations and papermak ing chemicals, leather, etc).

In support of this registration review the Agency will conduct residential, occupational, indirect dietary (food) and aggregate exposure ri sk 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, EP A anticipates that additional toxicity data and exposure data will be needed to complete this registration review case. It is anticipated that inhala tion toxicology data will be ne eded to properly characterize possible inhalation hazards resulting from th e use of BHAP (application of preserved paint and open pouring use scenarios). Al so, 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 scenar ios (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 ri sk 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 doc ument 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. Th e 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) reside ntial 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 antici pated routes of exposure to occupational

handlers are dermal and inhalation.

Toxicity

Acute Toxicity

BHAP is of moderate toxici ty (Toxicity Category II) via inhalation and oral routes of exposure and is slightly toxic (Toxicity Ca tegory 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, l ungs, 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 to xicity data are not av ailable. The Agency believes that establishing toxicological e ndpoints based on the curre nt sub-chronic oral toxicity study may not be prot ective of adverse inhalation expos ure effects. Therefore, to properly characterize the hazards posed by B HAP via the inhalation route of exposure, the Agency anticipates that a 90-day rat i nhalation toxicity study will be needed. The exposure scenarios that trigge r the need for a 90-day rat inhalation toxicity study are

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painting by residential and occupational ha ndlers and open-pouring use scenarios for occupational handlers. A quantitative asse ssment of inhalation risks is needed.

Chronic toxicity data are not available fo r BHAP and are not an ticipated as being needed because the currently registered uses ofBHAP 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 indica tive of adverse effects on male fertility or some other reproductive para meter. The possible effects of BHAP on mammalian reproduction and fertility are unknow n because a reproductive toxicity study is not available. Therefore, the Agency anticipates needing a two-generation rat reproductive toxicity study to determin e possible effects of BHAP on mammalian reproduction and fertility.

Dietary and Drinking Wa ter 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 chemical s. Indirect dietar y (food) exposure could potentially occur because BHAP is used to inhibit slime-forming bacteria and fungi in paper process water systems involved in the pr oduction 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 co atings, inks, etc., which may be used for food contact. Migration of BH AP from paper packaging to food contents may occur, resulting in indirect dietar y (food) exposure. Therefore, an indirect dietary (food) exposure risk assessment is needed.

Dietary Drinking Water Exposure

The registered uses of BHAP are not lik ely to result in contamination of surface water and ground water and as a result dri nking water exposure is not expected. However, the need for a dietary drinking water exposure assessment for BHAP will be determined upon review of environmental fa te data, which the Agency anticipates requiring. The Agency anticipates that envi ronmental fate data will be useful to determine if BHAP can pass through waste-wate r 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 dri nking 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 w ith no specified maximum use concentration (21 CFR 176.300); and to preserve paper-maki ng chemicals that may be used for foodcontact at a use c oncentrations of ≤ 60 ppm (21 CFR 176.170).

Aggregate and Cumulative Exposure and Risk

In examining aggregate exposure, EPA ta kes into account available and reliable information concerning exposures to pesticid e 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 microbi ocide/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 handl er (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 us es of BHAP may resu lt in residential and occupational exposure. Therefore, the Ag ency will conduct residential (handler) and occupational (handler) risk assessments to as sess 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 (han dler) 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 Re view Decision,” dated December 7, 2009.

Anticipated Toxicity Data Needs

• (GLN 870.3465) 90-day inhala tion toxicity in rats

• (GLN 870.3800) Reproduction and fertility effects

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Anticipated Residential and Occupa tional 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 I nhalation Exposure

• (GLN 875.1600) Applicator Exposure Moni toring Data Reporting for Dermal

and Inhalation Data

• (GLN 875.2900) Data Reporti ng and Calculations

Environmental Fate and Ecologi cal 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 Bromohydroxy acetophenone 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 pres ervative and as an i ndustrial slimicide in recirculating water cooling towers and paper mills could potentially result in environmental exposure. These uses may re sult in waste water treatment plant (WWTP) discharges into terrestrial and aquatic environments. Therefore, the Agency will conduct environmental fate and ecological risk a ssessments to assess environmental exposure resulting from possible discharges into terres trial and aquatic environments. The Agency also anticipates that environmental fate a nd 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 eco logical risk assessment planned during registration review will allow the Agency to determine whether use of BHAP has “no effect” or “may affect” federally listed threat ened or endangered sp ecies (listed species) or their designated critical ha bitats. When an assessment c oncludes that a pesticide’s use “may affect” a listed species or its designate d 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 envi ronmental fate and ecological risk

assessments for BHAP based on its use as a materials preservative and as an industrial slimicide in recirculating water cooling to wers 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 produc ts that are of poten tial concern. The environmental fate and ecological toxicity da ta listed below are anticipated as being

needed to conduct environm ental fate and ecological risk assessments.

The Agency anticipates that the following data will be needed to conduct complete environmental fate and ecological ri sk assessments for the registered uses of

BHAP:

Anticipated Environmental Fate Data Needs

• (GLN 850.6800) Modified activated sludge respiration inhibition

• (GLN 835.1110) Activated sl udge sorption isotherm

• (GLN 835.3110) Ready biodegradability

Anticipated Ecological Data Needs

• GLN 850.4400) Aquatic Plant Gr owth (aquatic vascular plant toxicity), Tier II dose response study on floating macrophyte ( Lemna gibba )

• (GLN 850.5400) Aquatic Plant Growth (alg al 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 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

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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.

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/

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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 fo r 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 registra tion review case regarding the data needs

listed under the “Risk Assessment and Data N eeds” section of this document. The Agency expects to i ssue the DCI in 2011.

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