Docket Number: EPA-HQ-OPP-2010-0673 

www.regulations.gov 

d-Limonene Summary Document 

 Registration Review: Initial Docket 

 September 2010 

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TABLE OF CONTENTS 

I. Preliminary Work Plan (PWP) 4 

II. Fact Sheet 10 

________________________________________ 

Please Note 

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's 

current position based on the following documents: 

1. Registration Review – Problem Formulation for d-Limonene. June 30, 2010 

2. d-Limonene. Human-Health Assessment Scoping Document in Support of Registration 

Review. August 13, 2010 

3. Limonene: Review of Human Incidents. May 20, 2010 

4. Appendix A for Limonene. June 16, 2009

Supporting documents for Limonene may be found in the docket (EPA-HQ-OPP-2010-0673) 

located on the internet at www.regulations.gov. 
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I. Preliminary Work Plan – d-Limonene 

Introduction:

The Food Quality Protection Act of 1996 mandated a registration review program. All pesticides 

sold or distributed in the United States (U.S) generally must be registered by the Environmental 

Protection Agency (EPA or the Agency), based on scientific data showing that they will not 

cause unreasonable risks to human health or the environment when used as directed on product 

labeling. 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 the 

statutory standard of no unreasonable 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 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. 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 what it knows about the pesticide and what additional 

risk analyses and data or information it believes 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 develop and commit to a final work plan and 

schedule for the registration review of d-Limonene (“limonene” unless otherwise specified). 

Limonene has a lemon-like flavor and smell, and occurs naturally in citrus and certain fruits, 

vegetables, meats, and spices. Limonene is used as both an active and inert ingredient in 

pesticide products, and as an ingredient in food products, soaps, and perfumes. Pesticide 

products containing limonene as an active ingredient are registered for use as insecticides, 

herbicides, insect repellents, and animal (dog and cat) repellents. As a pesticide inert ingredient, 

it is used as a solvent or fragrance in antimicrobial products. The U.S. Food and Drug 

Administration (FDA) considers d-limonene to be Generally Recognized as Safe (GRAS) as a 

food additive when used as a synthetic flavoring substance and adjuvant (21 CFR §182.60). 

Limonene is registered for use in/on terrestrial food, feed crops, non-food crops, for residential 

uses, and as an inert ingredient. Non-pesticidal uses of limonene include use in solvents 

(substitute for chlorinated hydrocarbons, chlorofluorocarbons, and other solvents); use as a metal 

degreaser; use as a cleaning agent in the printing industry and household cleaning products; and, 

as a solvent for paint. Limonene was first registered as an insecticide in 1958 and as an 

antimicrobial in 1971. Currently, the only antimicrobial uses of limonene are as an inert 

ingredient and are not subject for registration review. The reregistration eligibility decision 

(RED) was issued in 1994 and the tolerance reassessment eligibility decision (TRED) was issued 

in 2005. 
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Anticipated Risk Assessment and Data Needs:

The Agency anticipates conducting a comprehensive ecological risk assessment, including an 

endangered species assessment, a new acute and chronic dietary assessment, an updated 

residential exposure and risk assessment, an aggregate risk assessment (residential and dietary 

water), and an updated occupational exposure and risk assessment for all uses of limonene. A 

drinking water exposure and risk assessment is also anticipated in order to support registration 

review. Below is a summary of the issues relevant to the registration review of limonene. 

Ecological Risk: 

• The most recent ecological risk assessment for limonene was completed in 1994 to 

support the RED. 

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

species determination for limonene. The ecological risk assessment planned during 

registration review will allow the Agency to determine whether limonene’s use has “no 

effect” or “may affect” federally listed threatened or endangered species (listed species) 

or their designated critical habitats. When an assessment concludes that a pesticide’s use 

“may affect” a listed species or its designated critical habitat, the Agency will consult 

with the U.S. Fish and Wildlife Service and/or National Marine Fisheries Service (the 

Services), as appropriate. 

• Based upon the use pattern and limonene’s current ecotoxicity and environmental fate 

database, the Agency anticipates requiring the following data in order to conduct a 

complete ecological risk assessment, including an endangered species assessment, for all 

uses: 

o GLN 850.4100 - Seedling emergence, Tier II (using TEP) 

o GLN 850.4150 - Vegetative vigor, Tier II (using TEP) 

o GLN 850.4400 - Aquatic plant toxicity test using Lemna spp., Tier II (using TEP) 

o GLN 850.5400 - Algal toxicity, Tier II (using TEP) 

• Please refer to the document, Registration Review – Problem Formulation for dLimonene dated June 30, 2010, located in the docket for a detailed discussion of the 

anticipated risk assessment and data needs. 

Human Health Risk:

• The most recent human health risk assessment for limonene was completed in 2004 to 

support the TRED. 

• The RED DCI required a developmental toxicity study and a 2-week dermal toxicity 

study. These studies have been received by the Agency and will be reviewed during 

registration review. The dietary endpoints established in 2004 risk assessment may be 

updated following Agency review of these studies. 
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• The human health toxicity database for limonene is adequate to support its current use 

patterns and the Agency does not anticipate requiring new data to support a human health 

risk assessment for registration review. 

• The Agency intends to conduct a new dietary risk assessment that incorporates potential 

drinking water residues and revised endpoints to support registration review. 

• Limonene is listed in 40 CFR §180.539 without numeric tolerances and is identified as 

being safe for use, as an insecticide, in tablecloths and repellant strips and in food or 

feed-handling establishments. The Agency does not anticipate the need to re-evaluate 

this tolerance expression during registration review. 

• The residential exposure assessment that was conducted to support the 2004 TRED only 

examined dermal exposure to pesticide products containing limonene as an active 

ingredient. The Agency intends to update the 2004 residential assessment using the 

revised Agency Standard Operating Procedures (SOPs) for residential exposure to 

incorporate potential changes in dermal and inhalation endpoints, and to include exposure 

from outdoor uses and pet product uses. 

• To support registration review, the Agency intends to conduct new and updated aggregate 

risk assessments once a dietary risk assessment incorporating drinking water residues and 

updated endpoints is available. 

• The most recent occupational exposure and risk assessments for limonene were 

conducted in 2008 to support proposed new uses. The Agency intends to update the 

occupational exposure and risk assessment to include the inhalation route of exposure and 

potential changes in the hazard endpoints. 

• Please refer to the document, d-Limonene: Human Health Assessment Scoping 

Document in Support of Registration Review dated August 13, 2010, located in the 

docket for a detailed discussion of the anticipated risk assessment and data needs for 

human health. 

Other Anticipated Data Needs: 

• GLN 830.7050 UV/Visible Light Absorption – this study is a new data requirement under 

40 CFR part 158 (Product Chemistry Data Requirements) for registration of a pesticide 

(food and non-food uses). The Agency anticipates requiring this study to obtain basic 

information about the compound’s identity/composition and the wavelengths at which the 

compound may be susceptible to photochemical degradation. 
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Endocrine Disruptor Screening Program:

As required under FFDCA section 408(p), EPA has developed the Endocrine Disruptor 

Screening Program (EDSP) to determine whether certain substances (including pesticide active 

and other ingredients) may have an effect in humans or wildlife similar to an effect produced by 

a “naturally occurring estrogen, or other such endocrine effects as the Administrator may 

designate.” The EDSP employs a two-tiered approach to making the statutorily required 

determinations. Tier 1 consists of a battery of 11 screening assays to identify the potential of a 

chemical substance to interact with the estrogen, androgen, or thyroid (E, A, or T) hormonal 

systems. Chemicals that go through Tier 1 screening and are found to have the potential to 

interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP where EPA 

will determine which, if any, of the 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 quantitative relationship between the dose and the E, A, or T effect. 

Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first 

group of 67 chemicals, which contains 58 pesticide active ingredients and 9 inert ingredients. 

This list of chemicals was selected based on the potential for human exposure through pathways 

such as food and water, residential activity, and certain post-application agricultural scenarios. 

This list should not be construed as a list of known or likely endocrine disruptors. 

Limonene was not among the group of 58 pesticide active ingredients or the 9 inerts 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 orders/data call-ins for 

all Registration Review cases, including those for which EPA has already opened a Registration 

Review docket for a pesticide active ingredient. 

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:

EPA has created the following estimated timeline for the completion of the limonene registration 

review. 

Registration Review for Limonene – Projected Registration Review Timeline

Activities Estimated Date 

Opening the Docket 

Open Docket and Public Comment Period 2010 – September 

Close Public Comment 2010 – November 

Case Development 

Final Work Plan 2011 – February 

Issue DCI 2011 – Oct – Dec 

Data Submission 2012 – Oct – Dec 

Open Public Comment Period for Preliminary Risk Assessments 2014 – April – June 

Close Public Comment Period 2014 – July – Sept 

Registration Review Decision 

Open Public Comment Period for Proposed Registration Review 

Decision 

 2014 – Oct – Dec. 

Close Public Comment Period 2015 – Jan. – March 

Final Registration Review Decision and Begin Post-Decision Follow-up 2015 

Total (years) 5 

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary registration review work plan and 

rationale. The Agency will carefully consider all comments as well as any additional 

information or data provided in a timely manner prior to issuing a final work plan for limonene. 

Trade Irritants:

Through the registration review process, the Agency intends to solicit information on trade 

irritants and, to the extent feasible, take steps toward facilitating irritant resolution. Growers and 

other stakeholders are asked to comment on any trade irritant issues resulting from lack of 

Maximum Residue Limits (MRLs) or disparities between U.S. tolerances and MRLs in key 

export markets, providing as much specificity as possible regarding the nature of the concern. 

There are currently no established Canadian, Codex, or Mexican MRLs for d-limonene, 

harmonization is thus not an issue. 

Water Quality:

Limonene is not identified as a cause of impairment 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 limonene, 
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based on information provided at 

http://iaspub.epa.gov/tmdl_waters10/attains_nation.tmdl_pollutant_detail?p_pollutant_group_id

=885&p_pollutant_group_name=PESTICIDES. More information on impaired water bodies and 

TMDLs can be found at http://www.epa.gov/owow/tmdl/. The Agency invites submission of 

water quality data for this pesticide. To the extent possible, data should conform to the quality 

standards in Appendix A of the OPP Standard Operating Procedure: Inclusion of Impaired 

Water Body and Other Water Quality Data in OPP’s Registration Review Risk Assessment and 

Management Process (see: 

http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm) in order to ensure they 

can be used quantitatively or qualitatively in pesticide risk assessments. 

Environmental Justice:

EPA seeks to achieve environmental justice, the fair treatment and meaningful involvement of all 

people, regardless of race, color, national origin, or income, in the development, 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 their location, cultural practices, or other factors, may have 

atypical, unusually high exposure to limonene, compared to the general population. Please 

comment if you are aware of any sub-populations that may have atypical, unusually high 

exposure compared to the general population. 

Other Information:

Stakeholders are also specifically asked to provide information and data that will assist the 

Agency in refining the ecological and human health risk assessments, including any speciesspecific ecological effects determinations. The Agency is interested in receiving the following 

information: 

1. suggestions from stakeholders on ways to reduce non-target organism exposures to 

limonene 

2. confirmation on the following label information: 

a. maximum application rates in units related to mass per unit area of treatment 

zone 

b. geographic limitations on use 

3. use or potential use distribution (e.g., acreage and geographical distribution of 

relevant crop) 

4. use history 

5. median and 90th percentile reported use rates (lbs. a.i./acre) from usage data – 

national, state, and county 

6. application timing (date of first application and application intervals) by crop – 

national, state, and county 

7. sub-county crop location data 

8. directly acquired county-level usage data (not derived from state level data) 

a. maximum reported use rate (lbs. a.i./acre) from usage data – county 
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b. percent crop treated – county 

c. median and 90th percentile number of applications – county 

d. total pounds per year – county 

e. the year the pesticide was last used in the county/sub-county area 

f. the years in which the pesticide was applied in the county/sub-county area 

9. state or local use restrictions 

10. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian, 

and mammalian mortalities) not already reported to the Agency 

11. monitoring data 

Next Steps:

After the 60-day comment period closes, the Agency will review and respond to any comments 

received in a timely manner, and then issue its Final Work Plan (FWP) for the limonene 

registration review.
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II. FACT SHEET 

Background Information:

• Limonene PC Code: 079701 CAS#: 5989-27-5 

• Technical registrants: 

o Wellmark International (EPA No. 2724) 

o Cutting Edge Formulations, Inc. (EPA No. 82052) 

o Florida Chemical Company, Inc. (EPA No. 82326) 

• First registered for use in 1958. 

• Reregistration Eligibility Decision issued in 1994 and the Tolerance Reassessment 

Eligibility Decision issued in 2005. 

• There are 22 FIFRA section 3 registrations and no FIFRA section 24 (c) registrations. 

• Pesticide Re-evaluation Division Chemical Review Manager (CRM): Rusty Wasem 

wasem.russell@epa.gov. 

• Registration Division Contact: Jim Tompkins tompkins.jim@epa.gov (for herbicide 

products) Rita Kumar kumar.rita@epa.gov (for insecticide products) and Venus Eagle 

eagle.venus@epa.gov (for insecticide products). 

Use & Usage Information: 

For additional details, please refer to the BEAD Appendix A document in the limonene docket. 

• Limonene is used as both an active and inert ingredient in pesticide products, and as a 

non-pesticidal ingredient in food products, soaps, and perfumes. 

• Limonene is formulated as an emulsifiable concentrate, granular, liquid, pressurized 

liquid, and a read-to-use liquid. 

• The Agency currently lacks data on the estimated nationwide use of limonene. 

Recent Actions:

• New uses for limonene on tree, nut, vine, berry crops, and non-crop areas were granted in 

March of 2008. An occupational risk assessment supporting this action can be found in 

the limonene docket under the title d-Limonene Occupational Exposure/Risk Assessment 

for Proposed New Uses of d-Limonene on Tree, Nut, Vine, Berry Crops and Non-Crop 

Areas, dated February 25, 2008. 

Ecological Risk Assessment Status: 

The following are key findings of the most recent ecological risk assessments for limonene. 

Please refer to the document, Registration Review – Problem Formulation for d-Limonene, 

located in the docket for a detailed discussion of the ecological risk assessment. 

• Limonene is classified as practically non-toxic to most test species (avian and mammals) 

and only slightly toxic to other test organisms (freshwater fish and invertebrates). 

• Previous risk assessments concluded that minimal risk is anticipated for birds, mammals, 

and aquatic animals for the pesticidal uses of limonene. At the time of the 1994 RED, the 
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Agency believed labeled applications of limonene did not pose risk to endangered 

species. 

• Risk to terrestrial plants has not been quantified in previous assessments, and no 

terrestrial plant seedling emergence or vegetative vigor toxicity data are currently 

available for limonene. Risk to aquatic plants has not been considered in previous 

assessments, and no aquatic vascular or non-vascular plant toxicity data are currently 

available for limonene. 

Human Health Risk Assessment Status:

The following are key findings of the most recent human health risk assessments for limonene. 

Please refer to the document, d-Limonene. Human-Health Assessment Scoping Document in 

Support of Registration Review, located in the docket for a detailed discussion of the human 

health risk assessment. 

Hazard Characterization: 

• Limonene has low acute oral and inhalation toxicity and moderate dermal toxicity. High 

doses (≥500 mg/kg/day) of limonene are needed to induce relevant toxicity in laboratory 

animals. It is a dermal irritant, a dermal sensitizer, and an eye irritant. 

• Laboratory studies show no clear evidence of limonene being a neurotoxin. 

• Limonene has been classified as negative for carcinogenicity in humans. 

Dietary (Food and Drinking Water): 

• Screening level dietary exposure assessments for limonene were conducted in 2004 to 

support the TRED. The assessments examined the potential dietary exposure (food only) 

to limonene as an inert ingredient in pesticide products. The exposure assessment, for 

limonene as an inert ingredient, incorporated extremely conservative assumptions, but did 

not include drinking water. Estimated dietary risks from this assessment were not of 

concern. 

Residential: 

• The limonene TRED assessed residential dermal risks from exposure to products 

containing limonene as an active ingredient for use scenarios registered at the time of the 

TRED. The only scenario that exceeded the Agency’s level of concern was the 

application of pet dips. The Agency considered this assessment to be an over-estimate of 

potential risk due to the conservative nature of the hazard and exposure assessment.

Aggregate: 

• The most recent aggregate risk assessments were performed for short- and long-term 

exposures to limonene in 2004 to support the TRED. The 2004 aggregate risk 

assessment found short-term risks of concern, but these were considered to be an overestimate of potential risk due to the conservative nature of the hazard and exposure 

assessment. 

Occupational: 
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• An occupational handler exposure/risk assessment was last conducted for proposed new 

uses of limonene on tree, nut, vine, berry crops, and non-crop areas in 2008. All of the 

occupational scenarios assessed were not of concern provided registrants adopted label 

language requiring handlers wear protective gloves. 

• Past limonene risk assessments rely in part on data from studies in which adult human 

subjects were intentionally exposed to a pesticide to determine their dermal and 

inhalation exposure. Many such studies, involving exposure to many different pesticides, 

comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure 

Database (PHED), the Outdoor Residential Exposure Task Force (ORETF) Database, and 

the Agricultural Reentry Task Force (ARTF) Database. EPA has reviewed all the studies 

supporting these multi-pesticide generic exposure databases, and has found no clear and 

convincing evidence that the conduct of any of them was either fundamentally unethical 

or significantly deficient relative to the ethical standards prevailing at the time the 

research was conducted. All applicable requirements of EPA’s Rule for the Protection of 

Human Subjects of Research (40 CFR Part 26) have been satisfied, and there is no 

regulatory barrier to continued reliance on these studies. 

Cumulative: 

• The Agency has not determined whether limonene shares a common mechanism of 

toxicity with other chemical substances. If, in the future, the Agency determines that new 

information on limonene is available that could potentially impact a cumulative risk 

assessment and result in a risk of concern, the Agency will revisit the need for a 

cumulative risk assessment. 

Incidents:

• The Office of Pesticide Programs Incident Data System (IDS) was reviewed for reports 

of limonene human incidents. Thirty-nine human incidents have been reported from 

2002 to the present associated with the use of limonene. Of these cases, five involved 

limonene as a single chemical. The Center for Disease Control/National Institute for 

Occupational Safety and Health Sentinel Event Notification System for Occupational 

Risk-Pesticides (NIOSH) identified four human incidents involving the active ingredient 

limonene. Of these cases, one involved limonene as a single chemical (i.e. the product 

did not contain additional active ingredients). Based on the low frequency and severity 

classification of the incident cases, there does not appear to be a concern at this time that 

would warrant further investigation. 

• No ecological incidents involving limonene were found in the Agency’s Ecological 

Incident Information System (EIIS) database. 

Data Call-In (DCI) Status:

• DCIs were issued for limonene as part of the reregistration process, and all previous data 

requirements have been satisfied. 
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Tolerances and International Harmonization: 

• Limonene is listed in 40 CFR §180.539 without numeric tolerances and is identified as 

being safe for use, as an insecticide, in tablecloths and repellant strips and in food or 

feed-handling establishments. Limonene is also listed among the inert ingredients for use 

in/on food commodities (40 CFR §180.910), and among the inert ingredient applied to 

animals (40 CFR §180.930), which are exempt from tolerances. 

• Limonene is considered by U.S. Food and Drug Administration to be Generally 

Recognized as Safe (GRAS) (21 CFR §182.60) as a food additive. 

• There are currently no established Canadian, Codex, or Mexican MRLs for d-limonene. 

Harmonization is thus not an issue. 

Labels: 

• The labels for limonene can be obtained from the Pesticide Product Label System (PPLS) 

website: http://oaspub.epa.gov/pestlabl/ppls.home.