United States Chemical Safety December 2010 Environmental Protection and Pollution Prevention Agency (7510P)



# Benzoic Acid Summary Document: Registration Review December 2010Docket Number: EPA-HQ-OPP-2010-0692 www.regulations.gov



## Benzoic Acid Registration Review: Initial Docket December 2010

Case # 

## 5107

Approved By:

Jo Harrigan-Farrelly

irector, Antimicrobials Division

Date:



### 7 I 

## (2 /; 5' /,Uj!tJ

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### TABLE OF CONTENTS

Benzoic Acid Registration Review Team ............................................................................4 I. Preliminary Work Plan .....................................................................................................5 II. Fact Sheet ......................................................................................................................11 III. Summary of Anticipated Data Requirements ..............................................................15 IV. Appendix A ..................................................................................................................16

________________________________________
Please Note

This Preliminary Work Plan and Fact Sheet su mmarize the Environmental Protection Agency's current position based on the following documents:

1. Summary of Product Chemistry, Environmenta l Fate, and Ecotoxicity Data for the Benzoic acid Registration Review Decision Document. November 3, 2010

2. Benzoic acid. Human Health Effects Scopi ng Document for the Registration Review Decision. October 19, 2010

Additional supporting documents for benzoic acid may be found in the registration review docket EPA-HQ-OPP-2010-0692 located on the internet at www.regulations.gov

.

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Benzoic Acid Registration Review Team

Human Health & Environmental Effects William Hazel Srinivas Gowda

Risk Management Seiichi Murasaki Lance Wormell

Office of General Counsel Philip Ross

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I. Preliminary Work Plan -- Benzoic Acid

Introduction:

The Food Quality Protection Act (F QPA) of 1996 mandated a regist ration review program. All pesticides distributed or sold in the United St ates generally must be registered by the U.S. Environmental Protection Agency (USEPA, EPA, or the Agency ) based on scientific data showing that they will not cause unreasonable ri sks to human health or the environment when used as directed on product labeling. The regist ration 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 th e statutory standard of no unreas onable adverse effects to human health or the environment. Changes in science, public policy, and pesticide use practices will occur over time. Through the registration review program, the Agency periodically reevaluates pesticides to make sure that as change occurs, products in the marketplace can be used safely. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

. The Agency is implementing the registration revi ew 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 th e FIFRA standard for registration. The Agency will consider benefits information and data as required by FIFRA. The public phase of registration review begins when the initial docket is opened for each case. The docket is the Agency’s opportunity to state whatit knows about the pesticide and what additional risk analyses and data or information it belie ves are needed to make a registration review decision. After reviewing and responding to comments and data received in the docket during this initial comment period, the Agency will de velop and commit to a final work plan and schedule for the Benzoic Acid Case.

Benzoic acid (PC Code 009101) is registered as an antimicrobial pest icide in one end-use product (EP), MICROL Preservative, registered to Petro-Canada Lubricants (EPA Reg. No. 82076-1). MICROL Preservative is a soluble concentrate/soli d (SC/S) containing 99.98% benzoic acid. Currently, there are no registered conventional pesticide uses and the only registered antimicrobial use is for the preser vation of food-grade lubr icating oils used in commercial food-handling establishments. EPA has granted exemptions from the requirement of a tolerance for use of benzoic acid as an inert in gredient (preservative) in pesticide formulations (40 CFR 180.910 and 40 CFR 180.930). Human dietary exposure to residues of benzoic acid from pesticidal sources, however, is expected to be minimal compared to naturally-occurring levels in food (especially in fruits), as well as the direct food-additive uses, pharmaceutical uses, and cosmetic uses regulated by the Food a nd Drug Administration (F DA). Between 1989 and December 2005, there were no registered uses for benzoic acid as a pesticide. Because the current product (used in lubricati ng oil) was registered after the risk assessments were completed for the Benzoic Acid and Derivatives (Case 4013) Reregistration Eligib ility Decision (RED), uses for benzoic acid were assigned to be reevaluated under Registra tion Review Case 5107. Derivatives of benzoic acid will be reev aluated under Registration Review Case 4013.

Documents associated with the registration review of benzoic acid can be viewed at www.regulations.gov in docket EPA-HQ-OPP-2010-0692. Belo w is a summary of the issues relevant to the registration review case.

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Anticipated Risk Assessment and Data Needs:

The Agency does not anticipate the need to condu ct an ecological risk assessment. The Agency anticipates the need to conduct a human health risk assessment. The Agency anticipates needing additional data to conduct the regist ration review for benzoic acid.

Ecological Risk:

• No ecological risk assessment has b een performed for benzoic acid.

• Based on the low hazard and exposure, the Agency concludes that the registered uses of benzoic acid will have 'no effect' (NE) on enda ngered or threatened terrestrial or aquatic species, or their designated critical habitats , as listed by the U. S. Fish and Wildlife Service (USFWS) and the National Oceanic and Atmospheric Administration's (NOAA) National Marine Fisheries Se rvice (NMFS). EPA anticipates conducting no further analysis of potential risks to endangered or threatened species unless public comment provides data or information that would othe rwise inform the Agency's determination.

• The Agency does not anticipate the need to require additional ecological data at this time.

• The Agency does not anticipate the need to re quire additional environmental fate data at this time.

• For more information, please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Benzoic acid Registration Revi ew Decision Document
, dated November 3, 2010.

Human Health Risk:

• The most recent human health risk assessments for benzoic acid were completed in 1993, for EPA’s Integrated Risk Information System (IRIS) report. Risk assessments were not conducted to support the 2007 RED because ther e were no registrations at the time the RED risk assessments were completed.

• The Agency anticipates the need to require the following additional human health data to support an occupational inhalati on risk assessment to be con ducted during the registration review of benzoic acid.

o 875.2700 -- Product use information

o 875.2800 -- Description of human activity

• For more information, please refer to Benzoic acid. Human Health Effects Scoping Document for the Registration Review Decision ,” dated October 19, 2010.

Product Chemistry:

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• The Agency anticipates the need to require the following additional product chemistry data to support an occupati onal inhalation risk assessmen t to be conducted during the registration review of benzoic acid.

o 830.7520 -- Particle size distribution

• For more information, please refer to Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Benzoic acid Registration Revi ew Decision Document
, dated November 3, 2010.

Endocrine Disruptor Screening Program

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar 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 ap proach 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 estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, and establish a quantitative relationship betw een 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 pesticid e active ingredients and 9 inert ingredients. This list of chemicals was selected based on th e potential for human exposure through pathways such as food and water, residen tial activity, and certain post-app lication agricultural scenarios. This list should not be construed as a lis t of known or likely e ndocrine disruptors.

Benzoic acid was not among the group of 58 pesticid e active ingredients on th e initial list to be screened under the EDSP. Under FFDCA sec. 408(p) the Agency must screen all pesticide chemicals. Accordingly, EPA anticipates i ssuing future EDSP orders/data call-ins for all Registration Review cases, including those for which EPA has already opened a Registration Review docket for a pestic ide active ingredient.

For further information on the status of the ED SP, the policies and procedures, the list of 67 chemicals, the test guidelines and the Tier 1 screening battery, pl ease visit our website: http://www.epa.gov/endo/.

Timeline

EPA has created the following estimated time line for the completion of the benzoic acid registration review:

Anticipated Schedule

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Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Benz oic Acid Docket December 2010 Close Public Comment Period for Benz oic Acid Docket February 2011 Phase 2: Case Development Develop Final Work Plan (FWP) June 2011 Issue DCI June 2012 Data Submission June 2013 Open Public Comment Period for Prelim inary Risk Assessments September 2014
Close Public Comment Period for Prelim inary Risk Assessments December 2014 Phase 3: Registration Review Decision Open Public Comment Period for Propos ed Reg. Review Decision March 2016 Close Public Comment Period for Pro posed Reg. Review Decision June 2016 Final Decision and Begin Post-Decision Follow-up 2016 Total (years) 6

Guidance for Commenters:

The public is invited to comme nt on EPA’s preliminary regist ration review work plan and rationale. The Agency will carefully consid er all comments as well as any additional information or data provided in a timely manner pr ior to issuing a final wo rk plan for the benzoic acid registration review case.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any tr ade irritant issues resulting from lack of Maximum Residue Limits (MRLs) or disparitie s between U.S. tolerances and MRLs in key export markets, providing as much specificity as possible regarding the na ture of the concern.

Water Quality:

Benzoic acid is not identified as a cause of impa irment for any water bodies listed as impaired under section 303(d) of the Clean Water Act, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation_cy.cause_detail_303d?p_cause_group_id=88 5. In addition, no Total Maximum Daily Loads (TMDL) have been developed for benzoic acid, based on information provided at http://iaspub.epa.gov/tmdl_waters10/attains_ nation.tmdl_pollutant_de tail?p_pollutant_group_id =885&p_pollutant_group_name=PESTICIDES.

More information on impaired wate r bodies and TMDLs can be found at http://www.epa.gov/owow/tmdl/ . The Agency invites submission of water quality data for this

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pesticide. To the extent possible, data should conform to the quality standards in Appendix A of the OPP Standard Operating Procedure: Inclus ion of Impaired Water Body and Other Water Quality Data in OPP’s Registration Revi ew Risk Assessment and Management Process (see: http://www.epa.gov/oppsrrd1/regist ration_review/water_quality_sop.htm ), in order to ensure the data can be used quantitatively or qual itatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulations, and policies. To help address potential environmental justice issues, the Agency seeks information on any groups or segments of the population who, as a result of thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to benzoic acid compared to the general population. Please comment if you are aware of any sub-populatio ns that may have atypical, unusually high exposure compared to th e general population.

Structure Activity Relationships:

EPA must rely upon information of appropriate qual ity and reliability for each decision made by the Agency. In the Office of Pesticide Program s (OPP), the evaluation process for a pesticide chemical traditionally begins with the applicant’ s submission of a set of studies conducted with the specific pesticide chemical of interest. The use of the results of such testing (measured data) is a logical, scientifically rigorous proce ss that identifies the physical, chemical, and environmental fate properties of the pesticide, as well as the dose and endpoints at which an adverse effect can occur in various animal species.

Today, there is significant interest in alternat ive techniques, i.e., tech niques other than data generation that could significantly inform th e Agency’s decision-making process. Recently, OPP has made increasing use of structure activity relationship (S AR) as part of its regulatory decision-making process. In the SAR process, a chemical's molecular structure is compared to that of other chemicals for which data are available. These structural similarities are then used to make predictive judgments about a chemical’s p hysical, chemical, and bi ological properties. Thus, the chemical’s physical, chemical, and biol ogical properties are a f unction of (or directly related to) the chemical’s molecular structure. Quantitative SAR is referred to as QSAR. To develop a QSAR, a selected set of measured da ta on a single physical, chemical, or biological property is used to derive a model (an equatio n) to predict the valu e of that property.

Since SAR assessments and QSAR modeling are anothe r set of tools that are available to Agency scientists, OPP has begun a proce ss shift that envisions shifting from the current study-by-study approach to an approach in which the use of pr edicted data, generated us ing validated models, is considered along with information from open litera ture and studies specifically generated under Part 161 requirements. All relevant information w ould be considered as pa rt of a weight-of-theevidence evaluation.

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At this time, EPA believes that for certain e ndpoints, especially physi cal/chemical and fate properties, that SAR and QSAR might be effect ively utilized to fulfill these data requirements for many antimicrobial pesticide chemicals. Wh en considering biologica l properties, at this time, EPA believes that SAR and QSAR can be mo st effectively utilized in the evaluation of chemicals that exhibit lower toxicity for human h ealth and/or ecotoxicity parameters. This is appropriate because the risk assessment for lower toxicity chemicals can be stream-lined, i.e., a screening-level assessment procedure rather than multiple tiers of assessments with progressively more data requirements.

If stakeholders believe that submission of predic ted data can fulfill one of the data needs for the Benzoic Acid Case, then the Agency invites s ubmission of this inform ation. The submitter would be expected to supply a ra tionale describing the utility of the information and provide documentation on the scientific valid ity of the information. The de termination that the predicted data fulfills the data requiremen t would be at the sole discretio n of the Agency. Pre-submission consultation with the Agency is encouraged.

Additional Information:

Stakeholders are also specifically asked to provid e available information a nd data that will assist the Agency in refining the risk assessments. Th e Agency is interested in receiving the following information:

1. Confirmation on the following label information:

a. Sites of application b. Formulations

c. Application methods and equipment d. Maximum application rates

e. Frequency of application, applicatio n intervals and maximum number of applications f. Geographic limitations on use 2. Use or potential use distribution 3. Use history 4. Usage/use information for non-agricultura l uses (e.g., materials preservation) 5. Typical application interval 6. State or local use restrictions 7. Ecological incidents (non-target plant dama ge and avian, fish, reptilian, amphibian and mammalian mortalities) not already reported to the Agency 8. Monitoring data 9. Structure Activity Relationships

Next Steps:

After the 60-day comment period closes in February 2011, the Agency will review and respond to any comments received in a timely manne r, and then issue a Final Work Plan for the Benzoic Acid Case.

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II. Fact Sheet

Background Information:

• Active Ingredient: benzoic acid

• Registration review case nu mber for benzoic acid: 5107

• PC Code: 009101

• CAS#: 65-85-0

• Technical registrants: Petr o-Canada Lubricants, Inc.

• First approved for use in a registered product: 1987

• EPA has granted exemptions from the requireme nt of a tolerance for use of benzoic acid as an inert ingredient (pre servative) in pesticide form ulations (40 CFR 180.910 and 40 CFR 180.930).

• A Reregistration Eligibilit y Decision (RED) was completed for Benzoic Acid and Derivatives (Case 4013) in June 2007. Because the current product (used in lubricating oil) was registered after the risk assessments were completed for the Benzoic Acid and Derivatives (Case 4013) Reregist ration Eligibility Decision (RED ), uses for benzoic acid were assigned to be reevaluated under Re gistration Review Case 5107. Derivatives of benzoic acid will be reevaluated unde r Registration Review Case 4013.

• Antimicrobials Division Chemical Review Manager (CRM): Seiichi Murasaki, murasaki.seiichi@epa.gov

• Antimicrobials Division Product Manager (PM): Velma Noble, noble.velma@epa.gov

Use & Usage Information:

• Antimicrobial use of benzoic acid is currently registered only for us e as a preservative of food-grade lubricating oils in industrial settings.

Ecological Risk Assessment Status:

Please refer to Summary of Product Chemistry, Environm ental Fate, and Ecotoxicity Data for the Benzoic acid Registrati on Review Decision Document , located in the docket, for a detailed discussion of the ecological risk assessments.

• Based on available environmental fate and ecotoxicity data for benzoic acid, EPA believes that the currently registered use patter n of benzoic acid as a material preservative in the mineral oil component of lubricants will not cause unreasona ble adverse effects on the environment, and is not anticipated to cause adverse effects on fish, invertebrates, plants or other wildlife.

Human Health Risk Assessment Status:

The following are key findings of the recent huma n health risk assessments for benzoic acid. Please refer to Benzoic acid. Human Health Effects Scoping Document for the Registration Review Decision , located in the docket, for a detailed discussion of the human health risk
assessment.

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Hazard Characterization:

• Benzoic acid exhibits low to moderate acute oral toxicity (toxicity category III and IV) based on acute oral, dermal, and inhalati on studies in animals. The soluble concentrate/solid (SC/S) is a se vere eye irritant (Category I).

• The carcinogenic potential of benzoic aci d has been classified as Group D, not classifiable as to human carcinogenicity.

Dietary (Food and Water):

• A quantitative assessment of dietary (food) risk has not been deemed necessary as part of this Registration Review because human diet ary exposure to residues of benzoic acid from pesticidal sources will be minimal compared to naturally-occurring levels in food (especially in fruits), as well as the dire ct food-additive uses, pharmaceutical uses, and cosmetic uses regulated by the FDA.

• A dietary (drinking water) risk assessment is not required because human dietary exposure to residues of benzoic acid in drinki ng water is not expecte d. Benzoic acid is used to preserve food-grade lubricants for equipment in commercial food-handling establishments (an indoor use) and discharge or disposal of treated lubricant into aquatic environments is expected to be minimal.

Residential:

• The product is registered for use only in indus trial settings; residen tial exposure is not expected and assessment of residential ri sk is not planned for the benzoic acid registration review at this time.

Aggregate:

• In examining aggregate exposure, EPA take s into account the available and reliable information concerning exposures to pesticid e residues in food and drinking water, as well as non-occupational pesticide exposures. An aggregate risk assessment has not been deemed necessary for benzoic acid because any non-occupational exposure from pesticidal uses of benzoic acid (i.e., dietary food) is expected to be minimal compared to levels of benzoic acid that occur naturally in food. Additionally, the FDA has classified benzoic acid (21 CFR 184.1021) as Generally Recognized as Safe (GRAS) for use as a food additive. Furthermore, following diet ary exposure, benzoic acid is rapidly metabolized and excreted.

Occupational:

• Dermal and inhalation routes of occupational applicator e xposure are likely to occur during open-pour loading and mixing of the product with food-grade indust rial lubricants.

• Occupational dermal risk is not recommended for assessment because of the low dermal hazard, the label requirement that gloves be worn, and the rapid ra te of excretion.

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• Quantitative occupational inhalation risk assessments are expected to be needed as benzoic acid is a crystalline solid, is somewhat volatile, and may be loaded via the openpour method.

• A 28-day rat inhalation toxicity study is av ailable. The Agency will have this study scientifically evaluated for use during the risk assessment stage of the benzoic acid registration review.

• Modeling will be used to estimate worker inhalation exposure once the product use, description of human activity, and particle size distribution data anticipated as needed have been received.

• Current label instructions requiring that handlers wear protect ive eye covering are sufficient to protect workers from the eye irri tation effects of expos ure to benzoic acid.

Cumulative:

• EPA does not have, at this time, available data to determine whether benzoic acid has a common mechanism of toxicity w ith other substances or how to include this pesticide in a cumulative risk assessment.

• For the purposes of this Registration Review , EPA has assumed that benzoic acid does not have a common mechanism of toxicity w ith other substances when used as an antimicrobial as registered.

Incidents:

Ecological:

• No benzoic acid ecological inci dents have been reported in the OPP incident database.

Human Health:

• No benzoic acid human poisoning incidents ha ve been reported in the OPP incident database.

Tolerances and International Harmonization:

• EPA has granted exemptions from the requireme nt of a tolerance for use of benzoic acid as an inert ingredient (pre servative) in pesticide form ulations (40 CFR 180.910 and 40 CFR 180.930).

Data Call-In Status:

• There are no outstanding data call-in (DCI) requirements for benzoic acid.

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Labels:

Registered active products, includi ng EPA registration numbers are provided in Table 1 below. For future reference, during registration review a list of product registration numbers will be included in the docket. Product registration labe ls may be obtained from the Pesticide Product Label System (PPLS) website at: http://oaspub.epa.gov/pestlabl/ppls.home

. Table 1. Registered Active Products – Benzoic Acid Registration # Registration Name Company Name Formulation Type % A.I.

82076-1 MICROL Preservative Petro-Canada Lubricants Division End-use product 99.98

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III. Summary of Anticipated Data Requirements – Benzoic Acid

The table below summarizes anticipated data ne eds for benzoic acid in Section I of this document (Preliminary Work Plan), Summary of Product Chemistry, Environmental Fate, and Ecotoxicity Data for the Benzoic acid Registration Review Decision Document , and Benzoic acid. Human Health Effects Scoping Docume nt for the Registration Review Decision.

Table 2. Summary of Anticipated Data Requirements – Benzoic Acid

Guideline Number Anticipated Data Requirement Test Material Est. Timeframe

(months) (Measured from DCI Receipt)

830.7520 Particle size distribution TEP 12

875.2700 Product use information TEP 12

875.2800 Description of human activity TEP 12

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16 of 16 IV. Appendix A: Use Patterns – Benzoic Acid

Use Site Formulation/ EPA Reg. no. Method of Application Application Rate/ No. of applications Materials Preservative Food Grade Lubricating Oils Food use mineral oils Ready-to-Use Solution / 82076-1 Open Pour 1.0% maximum