United States Chemical Safety September 2012

Environmental Protection and Pollution Prevention

Agency (7510P)

Pine Oil

Registration Review:

Final Work Plan

September 2012
Docket Number: EPA-HQ-OPP-2012-0005 

www.regulations.gov 

Pine Oil 

Registration Review: 

Final Work Plan 

September 2012 

Case# 3113 

Approved By: 

a d-oan Harrig:;an:ell ~ML~ Duector, Anttmtcrobtals Dtv1s1on 

Date: 

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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

________________________________________

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

EPA-HQ-OPP-2012-0005 located on the internet at www.regulations.gov.
Docket Number: EPA-HQ-OPP-2012-0005

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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 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 Pine Oil Case (Case Number 3113) includes one active ingredient, PC Code 067002. The 

active ingredient pine oil consists of a mixture of cyclic terpene 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 products 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 of 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 be revoked because 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 announcing 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 exemption 
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in the near future. The proposed tolerance action is available at regulations.gov in docket EPAHQ-OPP-2012-0171. Pine oil and its major components alpha-terpineol and alpha- and betapinene are high production volume (HPV) chemicals1 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-HQ-OPP-2012-0005. Document associated with the 

reregistration of pine oil can be viewed at regulations.gov in docket EPA-HQ-OPP-2004-0302. 

Below is a summary of the issues relevant to this 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 below. In the PWP, the Agency solicited comments on specific 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, uncertainty 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 all uncertainty factors applied in

the RED. The Agency is committed to working with the pine oil registrants to clarify issues 

related to the label changes specified 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 clear. 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.
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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 

surfaces 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 PWP. 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 has 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 Assessments 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 conducting 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 registered 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 

Administration'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 inform the Agency's determination.

• The Agency does not anticipate the need to require additional ecological effects or 

environmental fate data for this registration review case at this time.
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• For 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 surface 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 exposure 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 aggregate 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 neurotoxicity 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 pine 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.
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870.6200 – 90-day neurotoxicity (oral)2,3

870.3465 -- 90-day inhalation toxicity (rat)

875.2500 -- Inhalation exposure

875.2300 -- Indoor surface residue dissipation3

875.2900 -- Data reporting and calculations

875.1700 -- Product use information

875.2700 -- Product use information

• For 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.

• For 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, choking, 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 inhalation 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, lethargy and unconsciousness. 

 3 The anticipated DCI will provide that a protocol must be submitted for review and approval by the Agency prior to 

initiating this study. 
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• 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 products.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of the 2006 reregistration eligibility decision for pine oil, EPA 

reviewed these data and selected the most sensitive endpoints for relevant risk assessment 

scenarios from the existing hazard database. However, as required by FFDCA section 408(p), 

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 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.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. 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 oil. For further information on the 

status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test 

guidelines and the Tier 1 screening battery, please visit our website: http://www.epa.gov/endo/.
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Timeline

EPA has created the following estimated timeline for the completion of the pine 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. 
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Summary of Anticipated Data Requirements – Pine Oil

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 Review.

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 neurotoxicity4 TGAI 24

870.3465 90-day inhalation toxicity (rat) TGAI 24

875.2500 Inhalation exposure TGAI 12

875.2300 Indoor surface residue dissipation5 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 additional neurotoxicity evaluations. 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 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. 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.
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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 Study6 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 products 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.