Docket Number EPA-HQ-OPP-20 14-0616 

W\VW.regulations.gov 

4-( or 5) Chloro-2-Methylcyclohexanecarboxlic Acid, I ,1-Dimethyl Ester 

(Trimedlure) 

Combined Work Plan, Summary Document, and Proposed Interim 

Registration Review Decision 

Case Number 6045 

December, 2015 

Date: ___ r_2---r{_l_o-+-(_r _s-__ _ 
Table of Contents 

Introduction 3 

Statutory and Regulatory Authority 3 

Trimedlure Chemical Facts 4 

Use and Usage Information 4 

Recent Actions 5 

Scientific Assessments 5 

Combined Work Plan, Summary Document, and Proposed Interim Registration 

Review Decision 9 

Next Steps and Timeline 9 

References 10 

Appendix A- Additional Areas Considered in the Trimedlure Registration Review 11 

2 
INTRODUCTION 

The docket for 4-(or 5) chloro-2-methylcyclohexanecarboxlic acid, l, !-dimethyl ester 

(trimedlure) is now open (EPA-HQ-OPP-2015-06 16), initiating the first public comment period 

for this registration review. This document is the Environmental Protection Agency's (EPA or 

the Agency) combined Work Plan, Summary Document, and Proposed Interim Registration 

Review Decision for trimedlure. It is being issued pursuant to 40 CFR Sections 155.50, 155.56, 

and 155.58. This document explains what EPA·s Office of Pesticide Programs knows about 

trimedlure, highlighting anticipated data and assessment needs and providing an anticipated 

timeline for completing trimedlure registration review. It also includes the Agency's Proposed 

Interim Registration Review Decision for trimedlure. In addition to general areas on which the 

public may wish to comment, the Appendix highlights topics of special interest to the Agency 

where additional information could be of particular use. 

A registration review decision is the Agency's determination of whether a pesticide 

meets, or does not meet, the standard for registration under the Federal Insecticide, Fungicide, 

and Rodenticide Act (FIFRA). The Agency may issue, when it determines it to be appropriate, an 

interim registration review decision before completing registration review. The interim 

registration review decision may require new risk mitigation measures, impose interim risk 

mitigation measures, identify data or information required to complete the review, and include 

schedules for submitting the required data, conducting a new risk assessment and completing 

registration review. 

The active ingredient trimedlure is a synthetic arthropod pheromone that is registered for 

use in manufacturing of end-use pheromone products intended for agricultural use for the control 

of the insect pest. Mediten·anean Fruit Fly. Currently. there are no registered end-use products 

containing trimedlure. The pheromone is intended for use in traps and lures to attract fruit flies in 

infested fruits and nuts orchards and vegetable crops. The EPA-approved manufacturing-use 

product label restricts the product to being formulated only into end-use products that are 

polymeric-matrix removable dispensers. If these dispensers are contained in traps and lures, and 

contain trimedlure as their sole active ingredient, these end-use products are exempt from 

registration per 40 CFR part 152.25(b). 

The Biopesticide Reregistration Action Document (BRAD) for trimedlure was completed on 

July 26, 2001 , and is available at: 

http://\\ww3 .epa.gov/pesticides/chem search/reg actions/registration/decision PC -112603 26-

Jul-0 !.pdf# ga= 1.136704888.95198873 1.1440526185. 

STATUTORY AND REGULATORY AUTHORITY 

The Food Quality Protection Act (FQPA) of 1996 mandated a registration review 

program. All pesticides distributed or sold in the U.S. generally must be registered by EPA, 

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 

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change, all registered pesticides continue to meet the statutory standard of no unreasonable 

adverse effects to hwnan health or the environment. Changes in science, public policy, and 

pesticide use practices will occur over time. Through the registration review program, the 

Agency periodical ly reevaluates pesticides to make sure that as change occurs, products in the 

marketplace are safe to use. Information on this program is provided at 

W\.vw.epa.gov/oppsrrd 1 /registration review/. 

The Agency is implementing the registration review program pursuant to Section 3(g) of 

FIFRA, and will review each registered pesticide every 15 years to determine whether it 

continues to meet the FIFRA standard for registration. The regulations governing registration 

review begin at 40 CFR § 155.40. 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 beli eves are needed to 

make a registration review decision. 

Trimedlure CHEMICAL FACTS 

PC code 112603 

Case Nwnber 6045 

CAS Number 12002-53-8 

Year first registered 2001 

Pesticide Type Biopesticide Chemical 

Chemical class Pheromone 

Biopesticide July 26, 2001 

Reregistration Action 

Document (BRAD) 

Cumulative Group EPA has not made a common mechanism of toxicity finding as to 

trimedlure and any other substances, and trimedlure does not 

appear to produce a toxic metabolite produced by other 

substances. 

40 CFR Citation 40 CFR § 180.1124 Arthropod pheromones, exemption from the 

requirement of a tolerance 

Dual-use Biochemical pesticidal uses only. 

Non-pesticidal uses No non-pesticidal uses of trimedlure. 

Regulatory Action Leader Gina Burnett, burnett.gina@epa.gov, 703-605-0513 

Biopesticide and Andy Bryceland, bryceland.andy@epa.gov, 703-305-6928 

Pollution Prevention 

Division, Team Leader 

USE AND USAGE INFORMATION 

Trimedlure is registered for use in the manufacturing and formulating of end-use 

pheromone products intended for agricultural use for the control of the insect pest, 

Mediten·anean Fruit Fly. Below is a summary of the use/usage oftrimedlure. 

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Summary ofUse The pesticide trimedlure is a synthetic arthropod pheromone 

registered for use in the manufacturing of end-use pheromone 

products intended for agri cultural use for the control of the insect 

pest. Mediterranean Fruit Fly. The pheromone is intended for use in 

traps and lures to attract fruit flies in infested fruit and nut orchards 

and vegetable crops. Per the EPA approved product label, the 

registered manufacturing-use product may only be formulated into 

end-use products that are removable dispensers. The dispensers must 

be comprised of polymer that is impregnated with the active 

ingredient, trimedlurc. fn accordance with 40 CFR § 180.1124, 

arthropod pheromones, when used in retrievably sized polymeric 

matrix dispensers, are exempt from the requirement of a tolerance in 

or on all raw agricultural commodities when applied to growing 

crops at a rate not to exceed 150 grams active ingredient/acre/year in 

accordance with good agricultural practices. 

Use Sites Commercial and residential fruit and nut orchards and vegetable 

crops. 

Summary of Usage No annual usage data has been reported for trimedlure. 

Formulation Type(s) Polymeric-matrix removable dispensers. 

Technical Registrant(s) lSP Fine Chemicals Inc. 

No. ofRegistrations One manufacturing-use product. 

Restricted Use No 

RECENT ACTIONS 

There are no recent actions for trimedlure. 

SCIENTIFIC ASSESSMENTS 

A summary of the Agency's human health, environmental fate and ecological risk 

assessments, 4-(or 5) chloro-2-methylcyclohexanecarboxlic acid, 1,1-dimethyl ester (trimedlure) 

Biopesticide Reregistration Action Document (BRAD) (July 26, 2001 ) is presented below. For 

the detailed risk assessmenrs, see the trimedlure public docket (EPA-HQ-OPP-20 15-0616) at 

www.regulations.gov. 

Human Health Assessment 

Hazard Characterization and Risk 

The toxicological database is considered complete for characterizing hazard and 

assessing risk from trimedlure. No additional studies are anticipated to be needed for registration 

review. 

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The mode of action for pheromones is target specific. Pheromones act by modifying 

behavior of the target pest species, are applied at low concentrations close to those found in 

nature and dissipate rapidly (OECD, 2002). The toxicological database for trimedlure is 

considered complete. The data requirements for acute toxicity studies for trimedlure were 

fulfilled by data presented in a technical journal article which indicate low toxicity via the oral, 

dermal and inhalation routes of exposure (Toxicity Category III for oral and dermal, Toxicity 

Category IV for inhalation). It is not irritating to the skin or eyes (Toxicity Category IV) (U.S. 

EPA, 2001). The Agency waived the requirements for subchronic studies (90-day oral, dermal 

and inhalation, mutagenicity, and developmental toxicity) studies for trimedlure. The studies 

were waived based on the results of two subchronic toxicity studies (90-day oral and 

developmental) used as bridging data for the safety assessment of other structurally similar 

pheromone products (OECD 2002), and on the demonstrated low acute toxicity oftrimedlure. 

The findings of the bridged data indicated that there were no significant health effects from 

subchronic exposure to this group of compounds. 

Dietary Exposure and Risk Assessment 

A dietary (food and drinking water) exposure and risk assessment was not conducted 

since the product is impregnated into a polymeric matrix dispenser that is contained within the 

trap and slowly emitted over time to control fruit flies. The product is not applied directly to the 

agricultural commodities and is therefore limited. Based on this limited exposure, residues of 

trimedlure are expected to be below the Agency's level of concern for the general population and 

all population subgroups. No new registration applications have been submitted since the initial 

registration of trimedlure, and no new risks have been identified. Further, due to the known low 

mammalian toxicity of arthropod pheromones and the low application rate of end-use products, 

EPA has determined that dietary exposure and risk are not of concern for trimedlure. Therefore, 

EPA's conclusions as reported in the 2001 BRAD are still current: any potential pesticidal 

residues of trimedlure in food and drinking water are anticipated to be negligible and the 

continued use of trimedlure as a pesticide does not present any concern to the Agency. 

Food Tolerances 

In accordance with CFR § 180.1124, arthropod pheromones, when used in retrievable 

sized polymeric matrix dispensers (within traps) are exempt from the requirement of a tolerance 

in or on all raw agricultural commodities when applied to growing crops only at a rate not to 

exceed 150 grams active ingredient (a.i.)/acre/year in accordance with good agricultural 

practices. Therefore, all existing polymeric matrix dispensers products which contain the a.i., 

trimedlure, and are applied at a rate equal to or below 150 grams a.i./acre /year, are exempt from 

the requirement of a tolerance on raw agricultural commodities. 

Residential and Occupational Exposure and Risk 

The potential for exposure during application and handling of dispensers containing 

trimedlure is anticipated to be minimal (U.S. EPA, 2001). The end-use products may only be 

formulated into polymeric-matrix removable dispensers and applied at a low rate not to exceed 

150 grams active ingredient (a.i.)/acre/year in accordance with good agricultural practices. 

Dispensers typically consist of polymeric adhesive panels, which contain the olfactory attractant, 

trimedlure, enclosed within a paperboard trap. Traps and dispensers are commercially available 

as ready to use items thereby significantly limiting the potential for applicator dermal and 

inhalation exposure. 

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The potential for post-application dennal and inhalation exposure resulting from entry 

into treated areas is anticipated to be negligible (U.S. EPA, 2001). The polymeric matrix 

dispensers (within traps) are for use outdoors in orchards and gardens and require no additional 

post-application treatment or handling other than to remove them for disposal or replacement 

approximately every 3 to 6 weeks.

1 At this time, it is highJy likely that all of the active ingredient 

will have completely dissipated. Although there is a remote potential for incidental non-dietary 

exposure to young children, the likelihood of an adverse effect is anticipated to be very low. The 

extent to which young children will be engaged with the enclosed dispenser in home gardens for 

prolonged periods of time is low, and significant non dietary ingestion exposure is not expected. 

Furthermore, the Agency has received no incident reports resulting from the use of pesticidal 

products containing the active ingredient trimedlure. Therefore, EPA has concluded that 

occupational and residential exposures and risks are not of concern. 

Environmental Assessment 

At the time of the first trimedlure registration, EPA conducted a qualitative 

environmental fate and effects assessment for trimedlure and determined that effects to nontarget species are unlikely (U.S. EPA, 2001). Trimedlure is registered for usc in retrievably sized 

polymeric matrix dispensers enclosed within traps, which will significantly limit potential 

exposure to birds, fish, non-target insects and aquatic organisms. Furthermore, its low 

application rate will limit the possibility of adverse ecological effects. As a result, environmental 

effects data requirements were waived; however. the registrant submitted a technical journal 

article2 which tested for freshwater fish toxicity, generally in accordance with Subdivision M 

Guideline 154-8. The study was accepted and reviewed by the Agency, which concluded that 

trimedlure was slightly toxic to fish . Furthermore, the Agency has reviewed and evaluated 

publically available ecotoxicity data for a number of chemicall y similar arthropod pheromones, 

and published ecotoxicity findings for pheromones in the Federal Register (59 FR 3681; January 

26, 1994) which conclude that pheromones are highly toxic to aquatic invertebrates and 

moderately toxic to fish. but practically non-toxic to birds (low toxicity to bobwhite quaiL with 

an acute oral LDso of>2,000 mg/kg of body weight and dietary LCso of>5.000 mg/kg). 

However, as noted above. because exposure is expected to be negligible, EPA had detem1ined 

that effects to non-target species are unlikely. 

The following end-use label language has been required since the product was first 

registered to mitigate any potential risk to aquatic organisms: "Do not discharge effluent 

containing this product into lakes, streams, ponds, estuaries, oceans or other waters unless in 

accordance with the requirements of a National Pollutant Discharge Elimination System 

(NPDES) permit and the pcrmit1ing authority has been notified in writing prior to discharge. Do 

not discharge effluent containing this product to sewer systems without previously notifying the 

sewage treatment plant authority. For guidance contact your State Water Board or Regional 

Office of the EPA. Do not contaminate water by cleaning of equipment or disposal of waste. " 

1 Trapping Guidelines for Area-Wide Fruit Fly Programs. International Atomic Energy Agency. November, 2003. 2 Acute Toxicity Studies with Insect Auractants. M. Bereza, et al. 1975. Toxicology and Applied Phannacology 

31:421-429; MRID449063-04. 

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Threatened and Endangered Species 

There have been no reports of adverse effects or incidents in nontarget organisms 

exposed to trimedlure during its 14 years of pesticidal use (EPA Ecological Incident Information 

System version 2. 1.1 12/08/20 15). Furthermore, based on the type and extent of use, the low 

expected toxicity and low exposure predicted by the highly diffuse nature of the use coupled 

with the target-species specificity and extremely low annual usage, the Agency believes that 

effects on the environment are not reasonably expected to occur from the registered use of 

trimedlure. Therefore, the EPA anticipates making a "No Effect" determination under the 

Endangered Species Act (ESA) for direct and indirect effects to listed species and their habitats. 

Endocrine Disruptor Screening Program 

As required by the Administrator under the Federal Food, Drug, and Cosmetic Act 

(FFDCA) section 408(p), the EPA has developed the Endocrine Disrupter Screening Program 

(EDSP) and has begun to implement the screening program that is to be used to test all pesticides 

in order 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 

"naturall y occurring estrogen, or other such endocrine effects as the Administrator may 

designate." 

FFDCA section 408(p)(4) authorizes the Administrator, by order, to exempt from the 

requirements of the Estrogenic Substances Screening Program a biologic substance or other 

substance if a determination is made that the substance is not anticipated to produce any effect in 

humans similar to an effect produced by a naturally occurring estrogenic substance. 

Bet ween October 2009 and February 20 I 0, the EPA issued test orders/data call-ins for 

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

ingredients. A second list of chemicals identified for EDSP screening was published on June 14, 

2013,3 and includes some pesticides scheduled for registration review and chemicals found in 

water. Trimedlure is not an1ong the group of pesticide active ingredients on the lists to be 

screened under the EDSP. 

The EPA, as part of this Combined Work Plan, Summary Document, and Proposed 

Interim Registration Review Decision, believes that trimedlure is a substance that would not 

likely produce any effect in humans similar to an effect produced by a naturally occurring 

estrogenic substance. As such, pursuant to Section 408(p)(4), the EPA will determine in the 

future whether it can exempt Trimedlure from the requirements of the Section 408(p) EDSP. ln 

the event the EPA does determine to exempt this substance from the EDSP, an order will be 

issued. 

For further information on the status of the EDSP, the policies and procedures, the lists of 

chemicals, future lists, the test guidelines and the Tier 1 screening battery, please visit our 

website at hllp://ww\1'. epa.govl endol . 

3 See http; I/''"" .rc.:gu lations.gO\ /#!documcntDetaii:D- EPA-110-0PPT-2009-0.J 77-007-l for the second list of chemicals. 

8 
COMBINED WORK PLAN, SUMMARY DOCUMENT, AND PROPOSED INTERIM 

REGISTRATION REVIEW DECISION 

In accordance with 40 CFR Sections 155.50, 155.56, and 155.58, the Agency is issuing 

this combined Work Plan, Summary Document, and Proposed Interim Registration Review 

Decision. Except for the ESA and EDSP components of the trimedlure registration review case, 

the Agency has made the following proposed interim decisions: (1) no additional data are 

required at this time: and (2) no changes to the affected registrations or their labeling are needed 

at this time. EPA has not identified any risks of concern to human health. Currently registered 

uses oftrimedlure are not expected to result in adverse effects to listed or non-listed species, or 

critical habitat. As such, EPA anticipates makjng a "No Effect" determination under the ESA for 

direct and indirect effects to listed species and their habitats. 

NEXT STEPS AND TIMELINE 

A Federal Register Notice will announce the availability of this combined Work Plan and 

Summary Document and Proposed Interim Registration Review Decision for trimedlure and 

allow a 60-day comment period. If there are no significant comments or additional information 

submitted to the docket during the comment period that leads the Agency to change its proposed 

decision, EPA may issue an Interim Registration Review Decision for trimedlure (case 6045), in 

accordance with 40 CFR Sections 155.56 and 155.58. A final decision on the trimedlure 

registration review case will also occur after an EDSP FFDCA section 408(p) determination has 

been made and an ESA determination has been made. 

EPA has created the following estimated timeline for the completion of trimedlure 

registration review: 

Registration Review for Trimedlure - Projected Registration Review Timeline 

Activities Estimated Date 

Opening the Docket and Combined Work Plan, Summary Document, and Interim 

Registration Review Decision 

Open Public Docket and Public Comment Period for Combined Work December 2015 

Plan, Summary Document, and Proposed Interim Registration Review 

Decision 

Close Public Comment Period February 2016 

Interim and Final Registration Review Decisions 

Interim Registration Review Decision June 2016 

Final Decision (estimated)4 December 20 16 

Total (years) 1 year, 0 months 

4 A final decision on the trimedlure registration review case, in accordance with 40 CFR Section 155.158, will occur 

after an EDSP FFDCA section 408(p) determination has been made and an ESA determination has been made. 

9 
References: 

This document summarizes the Environmental Protection Agency's current position based on the 

following documents: 

1. U.S. EPA, 2001. 4-(or 5) Chloro-2-Methylcyclohexanecarboxlic Acid, I, !-Dimethyl Ester 

(Trimedlure) Biopesticides Registration Action Document. U.S. Environmental Protection 

Agency. July 26, 2001. Available at: 

http:/ /www3 .epa.gov/pesticides/chem _search/reg_ actions/registration/decision_ PC112603 _26-Jul-0 l.pdf# _ga=1.136704888.95198873 1.1440526185 

2. IAEA, 2003. Trapping Guidelines for Area-Wide Fruit Fly Programmes, International 

Atomic Energy Agency. November, 2003. Available at: http://wwwpub.iaca.org/MTCD/publications/PDf/TG-FFP wcb.pdf 

3. OECD, 2002. Organization for Economic Co-operation and Development (OECD) 

Guidance for Registration Requirements for Pheromones and Other Semiochemicals Used 

for Arthropod Pest Control. February 26. 2002. Available at: 

hnp://wW\v.oecd.org/officialdocuments/publicdisplavdocumentpdfl?cote=env/jrn/mono(20 

0 1 ) 12&doclanguage=cn 

10 
Appendix - Additional Areas Considered in the Trimedlure Registration Review 

PUBLIC COMMENTS AND FEEDBACK: 

Guidance for Commenters: The areas below highlight topics of special interest to the Agency 

where your comments, data submissions, or reference to sources of additional information could 

be of particular use. 

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. The 

Agency will work to harmonize tolerances and international maximum residue limits (MRLs) 

and may modify tolerance levels to do so, when possible. Growers and other stakeholders are 

asked to comment on any trade irritant issues resulting from lack of 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. 

Although its registered pesticidal uses are non-food, should trimedlure inadvertently 

occur in food or feed commodities (e.g. through spray drift to crops grown adjacent to treated 

fields), this active ingredient is exempt from the requirement of a tolerance for arthropod 

pheromones when applied in a retrievable device per 40 CFR part 180.1124. Moreover, there are 

no known MRLs for trimedlure. Therefore, the EPA does not anticipate that current uses of 

trimedlure will pose concerns as trade irritants. 

Water Quality: 

Trimedlure is not identified as a cause of impairment for any water bodies listed as 

impaired under section 303(d) of the Clean Water Act.5 In addition, no Total Maximum Daily 

Loads (TMDL) have been developed for trimedlure.6 More infonnation on impaired water 

bodies and TMDLs can be found at the Agency's website.7 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 Process8 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. 

5 hnp://iaspub.epa.gov/tmdl waters I 0/attains nation cv.cause detail JOJd?p cause group id=885 6hnp://iaspub.epa.gov/tmdl waters I 0/attains nation.tmdl pollutant detail?p pollutant group id=885&p pollutant 

!!roup name=PESTICIDES 7 http://www.epa.gov/owow/tmdl/ 8 http://www.epa.gov/oppsrrd !/registration review/water quality sop.htm 

11 
To help address potential environmental justice issues, the Agency seeks infonnation 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 trimedlure 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. 

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