United States Chemical Safety September 2012 Environmental Protection and Pollution Prevention Agency (7510P)



# Pine Oil Registration Review : Final Work Plan September 2012Docket Number: EPA-HQ-OPP-2012-0005 www.regulations.gov



## Pine Oil Registration Review: Final Work Plan September 2012

Case# 3113

Approved By:

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Date:

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3 of 12 Pine Oil Registration Review Team

Human Health & Environmental Effects Nathan Mottl Talia Lindheimer Michelle Centra Srinivas Gowda William Erickson James Breithaupt

Risk Management Rebecca von dem Hagen Lance Wormell

Office of General Counsel Philip Ross

________________________________________ S upporting documents for the Pine Oil Case may be found in the registration review docket EPA

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- 0005 located on the internet at www.regulations.gov

.Docket Number: EPA

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4 of 12 Introduction

This is the Final Work Plan (FWP) of the Environmental Protection Agency (EPA or “the Agency”) for the registration review of Pine oil (Case 3113 )

. 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 Pine oil registration review docket , and any other comments concerning the initial docket postings. The Summary Document provided information on wh at 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 Fe deral 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 registr ation 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 Pine Oil Case (Case Number 3113) includes one active ingredient, PC Code 067002. The
act ive ingredient pine oil consists of a mixture of cyclic t erpene alcohols and may contain terpene hydrocarbons, ethers, and esters . Registered products can be composed of slightly different blends of these components. The first product containing pine oil ( 1

- Methyl

- 4

- isopropyl

- 1

- cyclo

- hexen

- 8

- ol ) as an active ingredient was registered in the United States in 1947. Currently, there are 57 product s registered with EPA

. Products containing pine oil are registered for use as antimicrobial pesticides for use as sanitizers, fungicides, mildewstats, deodorizers, disinfectants, virucides, and microbicide/microbistats. Registered use sites include eating establishments, food processing plants, commercial/institutional/industrial premises and equipment, household or domestic dwellings and contents, and medical sites. In addition, one pine oil product currently contains directions for use as a dog wash. The registrant has indicated the intent to submit updated product labeling to terminate that use. Upon receipt o f the registrant's formal request to terminate the dog wash use, the Agency will initiate the

use termination process pursuant to FIFRA Section 6(f). If the use termination request is not received or is withdrawn, the dog wash use will be assessed as part of this registration review and the anticipated data needs and risk assessments will be revised accordingly.
The Agency completed a Reregistration Eligibility Decision (RED ) for pine oil in 2006

. Pine oil is currently exempted from the requirement of a tolerance under 40 CFR 180.1035 for use in honey and honeycomb. In the 2006 RED, the Agency recommended that this exemption from the requirement of a tolerance b e revoked be cause there were no registered products for this use at that time. Because no new registrations have been granted utilizing this tolerance exemption since the 2006 RED, on May 9, 2012, the Agency published a Proposed Rule in the Federal Register announcin g the proposal to revoke the pine oil tolerance exemption. The 60

- day comment period closed on July 9, 2012 and no comments were received regarding pine oil; therefore, the Agency intends to publish a Final Rule revoking the pine oil tolerance exemptionDocket Number: EPA

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5 of 12 i n the near future. The proposed tolerance action is available at regulations.gov in docket EPA

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- 0171. Pine oil and its major components alpha

- terpineol and alpha

- and beta

pinene are high production volume (HPV) chemicals 1 regulated under the Toxics Substances Control Act (TSCA).
The Agency anticipates issuing a post

- RED data call

- in (DCI) for pine oil and intends to review any data received in response to the post

- RED DCI prior to conducting the registration review risk assessments anticipated as being needed in this document

. Also, the Agency intends to conduct this registration review based on updated labels submitted in response to the post

- RED DCI that reflect the label changes specified by the Agency in the 2006 RED

.

Documents associated with the registration review of pine oil can be viewed at www.regulations.gov in docket EPA

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- 0005 . Document associated with the reregistration of pine oil can be viewed at regulations.gov in d ocket EPA

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- 0302. Below is a summary of the issues relevant to th is registration review case.
Comments Received on the Preliminary Work Plan
The Agency received two comments during the public comment period on the initial docket, described belo w. In the PWP, the Agency solicited comments on specifi c topics: environmental justice, water body impairment
, trade irritants , and structure activity relationships

. One comment was received during the public comment period concerning these issues
, described below.

Comment: The Consumer Specialty Products Association , Pine Oil Steering Committee/Joint Venture re

- submitted comments originally submitted on the 2006 draft RED . The comments address issues from the RED such as toxicity endpoints, uncerta inty factors, risk calculations
, models used to conduct the risk assessments and label change requirements

. The commenters also requested that the Agency make available the list of post

- RED data requirements anticipated to be included in the post

- RED DCI.
Response: As stated in the PWP, for the registration review of pine oil the Agency anticipates updating the dietary, residential, occupational and aggregate risk assessments conducted in the RED and selecting new toxicological endpoints. The updated risk assessments will be conducted with the most appropriate models and will include a review of al l uncertainty factors applied in the RED. T he Agency is committed to working with the pine oil registrants to clarify issues related to the label changes specif ied in the RED. In response to the request for clarification of the post

- RED data requirements, the Agency has updated Table 1 in this document to include the anticipated post

- RED data requirements.

Comment: The Physicians Committee for Responsible Medicine ( PCRM ) submitted a comment stating that “ Because of the indications of neurotoxic effects already exhibited in the prenatal study, the potential for pine oil

- associated neurotoxicity

-- and the suffering of animals used in additional studies

-- is cle ar. Therefore we hope that the registrants will submit food residue data before undertaking any testing. If food residue data shows a lack of transfer to food from treated

1 High production volume (HPV) chemicals are classified as those chemicals produced or imported in the United States in quantities of 1 million pounds or more per year.Docket Number: EPA

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6 of 12 surfaces, further testing might be waived. We also suggest information from related substances can be brought to bear for this risk assessment. ”

Response: The Agency intends to call in food residue data through the post

- RED DCI. In the event that the data indicate that pine oil and its degradation products do not transfer from treated

s urfaces to food, then the Agency would encourage the registrants to submit waiver requests for the applicable anticipated studies.
The comments received during the initial public comment period did not affect the data needs and work plan described in the P WP. The Agency has updated Table 1 to include the data anticipated to be required by the post

- RED DCI, reconciled the anticipated registration review data requirements with the anticipated post

- RED data requirements to remove redundant requirements, and h as corrected the timeline to allow the standard time frame for the Agency to develop preliminary risk assessments once data submission is complete. Further, this document makes final the work plan for the pine oil registration review process.

Risk Assessm ents and Anticipated Data Needs
The Agency does not anticipate the need to conduct an ecological risk assessment. The Agency anticipates the need to conduct a human health risk assessment. The Agency anticipates needing additional data for use in conducti ng the registration review for pine oil.
Anticipated Ecological Risk Assessment and Data Needs :

• The most recent qualitative ecological risk assessment for pine oil was completed in support of the 2006 RED.

• The Agency does not anticipate the need for an ecological risk assessment for the registration review of pine oil due to the low likelihood of exposure from the indoor use patterns. In the event that pine oil is released into a waste stream, the Agency believes that pine oil will volatilize rapidly and readily degrade biotically and abiotically and therefore, not reach waste water treatment plants (WWTPs), surface water or ground
water.

• Based on the low likelihood of exposure to surface or ground water, the Agency intends to conclude that the regis tered uses of pine oil will have ' no effect' (NE) on endangered 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 Administra tion's (NOAA) National Marine Fisheries Service (NMFS). EPA anticipates conducting no further analysis of potential risks to endangered or threatened species unless public comment or other submissions provide data or information that would otherwise infor m the Agency's determination.

• The Agency does not anticipate the need to require additional ecological effects or environmental fate data for th is registration review case at this time.Docket Number: EPA

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7 of 12 • F or more information
, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Pine oil
, located in the docket

. Anticipated Human Health Risk Assessment and Data Needs :

• The most recent human health risk assessment for pine oil was completed in support of the 2006 RED.

• Based on the availability of new data and additional exposure scenarios, the Agency anticipates selecting new toxicological endpoints for the registration review risk assessment on pine oil.

• The Agency anticipates the need to conduct a dietary risk assessment based on indirect food exposure from pine oil products used to treat surfaces with food contact. The Agency does not anticipate the need to conduct a drinking water assessment due to the low likelihood of exposure to surf ace and ground water.

• Residential handler and post

- application risk assessments are expected to be needed based on dermal, inhalation and incidental oral exposure. Post

- application scenarios anticipated to be assessed include children’s inhalation exposu re to cleaned floors, incidental oral exposure to cleaned toys and dermal exposure to laundered clothing. Adult post

- application dermal exposure to laundered clothing is also expected to be assessed.

• The Agency anticipates the need to revise to the aggr egate assessment performed for the RED to include additional scenarios for dietary and residential exposures and to include short

- and intermediate

- term exposure durations.

• The Agency anticipates the need to update the occupational exposure assessment conducted in support of the RED to include additional handler exposure scenarios and post

- application exposure.

• The Agency anticipates the need to require the following additional human health data for use in the registration review of pine oil.

870.3100

-- 90

- day oral (feeding) 2
, 3

2 The Agency will accept a combined 90

- day oral and 90

- day ne urotoxicity study. The combined study would need to be a 90

- day (oral) subchronic toxicity study with additional neurotoxicity evaluations. These studies are anticipated because of the lack of a repeat

- dose, route

- specific (oral) study conducted with pin e oil, evidence of neurotoxicity in the existing pine oil toxicity data base and the documented neurotoxicity of other chemicals belonging to the same class (i.e., terpenoids) as the active ingredient. Data obtained from the individual studies or combined study will provide critical scientific information (potential systemic toxicities/neurotoxic effects) via the oral route of exposure and may result in the selection of new toxicological endpoints for quantification of risks from the indirect

- food uses of pine oil

- containing pesticide products. The anticipated DCI will provide that a protocol must be submitted for review and approval by the Agency prior to initiating the studies or the combined study.Docket Number: EPA

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8 of 12 870.6200

– 90

- day neurotoxicity (oral) 2
, 3 870.3465

-- 90

- day inhalation toxicity (rat) 875.2500

-- Inhalation exposure 875.2300

-- Indoor surface residue dissipation 3 875.2900

-- Data reporting and calculations 875.1700

-- Prod uct use information 875.2700

-- Product use information

• F or more information
, please refer to Pine Oil: Human Health Risk Assessment Scoping Document in Support of Registration Review
, located in the docket

. Product Chemistry:

• The Agency does not anticipate the need to require additional product chemistry data for this registration review case at this time.

• F or more information
, please refer to Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Pine oil
, located in the docket

.
Incidents:
Ecological:

• No pine oil ecological incidents have been reported in the OPP incident database.

Human Health:

• There are 283 pine oil related human incidents that have been reported to the EPA’s Office of Pesticide Program’s Incident Database (IDS).

• The most common symptoms reported for oral exposure following accidental ingestion of pine oil include: coughing, c hoking, vomiting, nausea, abdominal pain, shortness of breath, drowsiness, lethargy, and loss of consciousness. In IDS, there have been 13 reported death incident cases as a result of ingestion of pine oil containing products.

• The most common symptoms reported for cases involving dermal exposure were skin irritation/burning, rash, itching, skin discoloration/redness. Symptoms associated with allergic skin reactions include blisters and hives.

• The most common symptoms reported for cases involving inha lation exposure were coughing, choking, sneezing, respiratory irritation/burning, asthma/difficult breathing, shortness of breath, and respiratory depression. Reported incidents for inhalation also include headaches, shaking, numbness, drowsiness, letharg y and unconsciousness.

3 The anticipated DCI will provide that a protocol mu st be submitted for review and approval by the Agency prior to initiating this study

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9 of 12 • Ocular effects including eye irritation (burning and redness), corneal abrasion, eye swelling, eye discharge/infection and visual defect/blurred vision are common symptoms that have been reported with use of pine oil

- containing pro ducts.
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 evaluate s acute tests and chronic studies that assess growth, developmental and reproductive effects in different taxonomic groups. As part of the 2006 reregistration eligibility decision for pine oil , EPA reviewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database

. However, as required by FFDCA section 408(p), pine oil 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 test s 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.

Under FFDCA section 40 8(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. Pine oil 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 pine o il

. 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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10 of 12 Timeline

EPA has create d the following estimated timeline for the completion of the p ine oil registration review:

Activities Estimated Month/Year Phase 1: Opening the docket Open Public Comment Period for Docket Completed March 2012 Close Public Comment Period for Docket Completed May 2012 Phase 2: Case Development Develop Final Work Plan (FWP) Completed September 2012 Issue DCI September 2013 Data Submission September 2015 Open Public Comment Period for Preliminary Risk Assessments March 2017 Close Public Comment Period for Preliminary Risk Assessments April 2017 Phase 3: Registration Review Decision Open Public Comment Period for Proposed Reg. Review Decision September 2017 Close Public Comment Period for Proposed Reg. Review Decision November 2017 Final Decision and Begin Post

- Decision Follow

- up March 2018 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 September 2013

. Human health assessments are anticipated to be conducted for all uses.Docket Number: EPA

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11 of 12 Summary of Anticipated Data Requirements

– P ine O il

The table below summarizes anticipated data needs for the Pine Oil Case in this document (Final Work Plan), Product Chemistry, Environmental Fate, and Ecological Effects Scoping Document in Support of Registration Review of Pine oil

, and Pine Oil: Human Health Risk Assessment Scoping Document in Support of Registration R eview

. Table 1. Summary of Anticipated Data Requirements

– Pine Oil

Guideline Number Anticipated Data Requirement Test Material Estimated Timeframe (Measured in months from DCI Receipt)

870.3100 90

- day oral (feeding) 4 TGAI 24

870.6200 90

- day neurotoxicity 4 TGAI 24

870.3465 90

- day inhalation toxicity (rat) TGAI 24

875.2500 Inhalation exposure TGAI 12

875.2300 Indoor surface residue dissipation 5 TEP 24

875.2900 Data reporting and calculations TGAI 12

875.1700 Product use information (handler) TGAI 12

875.2700 Product use information (post

- application) TGAI 12 The studies listed below are anticipated to be required through the post

- RED generic data call

- in. These studies are listed in this document as background; they will NOT be included in the anticipated Registration Review DCI.

875.1200 Dermal exposure

-- Indoor TGAI 12

875.1400 Inhalation exposure

-- indoor TGAI 12

875.1600 Application exposure monitoring data reporting TGAI 12

4 The Agency will accept a combined 90

- day oral and 90

- day neurotoxicity study. The combined study would need to be a 90

- day (oral) subchronic toxicity study with addi tional neurotoxicity evaluation s. These studies are anticipated because of the lack of a repeat

- dose, route

- specific (oral) study conducted with pine oil, evidence of neurotoxicity in the existing pine oil toxicity data base and the documented neurotoxici ty of other chemicals belonging to the same class (i.e., terpenoids) as the active ingredient. Data obtained from th e individual studies or combined study will provide critical scientific information (potential systemic toxicities/neurotoxic effects) via the oral route of exposure and may result in the selection of new toxicological endpoint s for quantification of risks from the indirect

- food uses of pine oil

- containing pesticide products. The anticipated DCI will provide that a protocol must be submitte d for review and approval by the Agency prior to initiating th e studies or the combined study

. 5 Anticipated study would need to be conducted with toys and textiles treated with pine oil. The anticipated DCI will provide that a protocol must be submitted for review and approval by the Agency prior to initiating this study.Docket Number: EPA

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12 of 12 875.2800 Description of human activity TGAI 12

870.2600 Skin sensitization TGAI 12

870.5375 In vitro mammalian chromosome aberration test TGAI 12
Special Study Food Residue Study 6 TGAI 24

6 Dietary

- Residues on Food from Treating Countertops with Pine Oil (FDA Wipe Study Methodology) . Anticipated study would need to be conducted with pine oil pr oducts used on hard non

- porous surfaces in food settings such as kitchen countertops. The anticipated DCI will provide that a protocol must be submitted for review and approval by the Agency prior to initiating this study.