2 Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for the registration review of pr opoxur. The Final Work Plan in cludes the expected registration review timeline. The FWP also addresses public comments received on the Preliminary Work

Plan (PWP) in the Summary Document which was posted in the propoxur registration review docket (EPA-HQ-OPP-2009-0806). The Summary Document, dated December 14, 2009, provided information on what EPA knows about the pesticide and what additional risk analyses and data or information the Agency believes are n eeded to make a registration review decision.

The Agency’s implementation of the registrati on review program requi res review of each registered pesticide every 15 years to determin e whether it continues to meet the Federal Insecticide, Fungicide, and Rode nticide Act (FIFRA) standard for registration. Changes in science, public policy, and pestic ide use practices occur over time. The registration review program is intended to make sure that, as the ab ility to assess risk evolves and as policies and practices change, all registered pesticides contin ue to meet that statutory standard. The public phase of registration review begins when the ini tial docket is opened for e ach case. Information on this program is provided at http://www.epa.gov/oppsrrd1/registration_review/

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Propoxur is an N -methyl residual carbamate insecticide regi stered for use to control ticks, fleas, and a variety of insects including crickets, ants , wasps, cockroaches and silverfish in-and-around industrial, commercial (includi ng food handling establishments a nd food processing plants), and residential facilities. There are no labeled agri cultural uses, and residential indoor spray uses were previously cancelled. The Reregistra tion Eligibility Decisi on (RED) for Propoxur was completed in August 1997. Propoxur is a member of the N -methyl carbamate (NMC) class of

chemicals that share a common mechanism of to xicity and inhibit acetylcholinesterase. The

Revised N -Methyl Carbamate Cumulati ve Risk Assessment was completed in September 2007.

Updates Since the Summary Document:

As discussed in the “Recent Actions” secti on of the Propoxur Summary Document, EPA had received and was in the process of evaluati ng a Natural Resources Defense Council (NRDC) petition to cancel propoxur pet collar uses and the pub lic comments received during the April 8, 2009 to August 4, 2009 public comment period on that petition. (Federal Register notices, supporting documents, and additional informa tion are located in the docket EPA-HQ-OPP-2009- 0207.) Since the Summary Document, EPA has completed a conservative occupational and residential exposure (ORE) risk assessment, signed on April 7, 2010, specifically for the propoxur pet collar use utilizing the current standard operating pr ocedures for residential and incidental oral exposures. This assessment is available in the regist ration review and NRDC petition dockets. The ORE pet collar assessment identified risks above the Agency’s level of concern for dog and cat pet collars along with vari ous uncertainties and data needs. EPA is working to refine the risk assessment and will mi tigate where necessary to resolve risk concerns in advance of the preliminary risk assessments for registration review.

Also discussed in the “Recent Actions” sect ion of the Summary Document was the Ohio Department of Agriculture’s request for a one-y ear Section 18 Emergency Exemption for the use of propoxur to control bed bugs in residential single or multiple unit dwellings, apartments,3 hotels, motels, office buildings, modes of transp ortation, and commercial i ndustrial buildings in Ohio. In correspondence of June 2, 2010, EPA Ad ministrator Lisa Jackson informed Ohio's Governor Ted Strickland that the safety finding could not be made owing to projected risks to children from hand-to-mouth and inhalation exposur es. Therefore, EPA’s Office of Pesticide Programs will not be authorizi ng the emergency use request.

Comments Received on the Preliminary Work Plan:

The Agency received two comments during th e 60-day public comment period on the PWP, which began on December 16, 2009 and ended on February 16, 2010 (EPA-HQ-OPP-2009- 0806). Comments were submitted by NRDC and one of the propoxur technical registrants, McLaughlin Gormley King. The comments do not a ddress the timeline described in the PWP. However, the comments do address and could aff ect the planned data re quirements and risk

assessments. The submitted comments and EPA’s responses are presented in the “Summary of Comments and Agency Responses” section of this document.

In the PWP, EPA also solicited comment on the sp ecific topics of environmental justice, water body impairment, and trade irritants. No commen ts or information were received during the public comment period concerning these issues.

Risk Assessment and Data Needs:

The Agency intends to update and revise the ecological risk assessment for propoxur (including an endangered species risk assessment) and to update and revise th e human health risk assessment. Additional data that the Agency needs to complete these assessments are specified

below.

Ecological Risk:

• The most recent ecological risk assessment was completed in July 1996 in support of the 1997 Propoxur RED.

• The Agency has not conducted a risk asse ssment that supports a complete endangered species determination. The ecological risk assessment planned during registration review will allow the Agency to determine whether propoxur’s use has “no effect” or “may affect” federally listed threatened or e ndangered species (listed species) or their designated critical habitats. When an asse ssment concludes that a pesticide’s use “may affect” a listed species or its designated critic al habitat, the Agency will consult with the

U.S. Fish and Wildlife Service and/or Nationa l Marine Fisheries Service (the Services), as appropriate.

• One outdoor use pattern from currently regi stered propoxur labels, bait application, is planned to be assessed for ecological risk b ecause product labels have directions for use that may lead to environmental exposure. Th ese granular bait products are applied in a 2

to 3 foot band around structures. As is di scussed further in the “Summary of Comments and Agency Responses” section of this docum ent, the continued need for this risk assessment and certain data requirements may be subject to change based on the4 registrant’s intent to repack age the outdoor granular bait products into enclosed bait

stations.

• The Agency does not intend to conduct risk assessments for other outdoor use patterns, such as bait stations, aerosol sprays, or liq uid spot application, because they are not expected to lead to significant exposure in th e environment. These use patterns were not previously assessed for this same reason.

• Based on the limited terrestrial outdoor uses and the relatively low usage of propoxur, and because no current uses appear to be a significant route of aquatic exposure, EPA

does not intend to conduct an aquatic ecological risk a ssessment during registration

review.

• Data gaps exist in the environmental fate and toxicity databases for propoxur. EPA intends to require the following guideline studies in order to conduct a complete ecological risk assessment for the registra tion review of propoxur. As is discussed further in the “Summary of Comments and Ag ency Responses” section of this document, the continued need for certain data requireme nts may be subject to change based on the registrant’s intent to repack age the outdoor granular bait products into enclosed bait

stations.

835.6100 (Footnote 7) – Environmental chem istry analytical method in soil 850.2200 – Avian dietary toxicity (Bobwhite quail and mallard duck) 850.2300 – Avian reproduction (Bobwhite quail and mallard duck) 850.4100 – Terrestrial plant toxicity, Seedling emergence, Tier II 850.4150 – Terrestrial plant toxicity , Vegetative vi gor, Tier II

• Please refer to the October 16, 2009 document “Registration Review: Preliminary Problem Formulation for Ecological Risk, Environmental Fate, Endangered Species, and Drinking Water Assessments for Propoxur” in the registration review docket (EPA-HQOPP-2009-0806-0003) for a detailed discussi on of the risk assessment needs.

Human Health Risk:

• The most recent human health assessment was completed in July 1996 in support of the 1997 Propoxur RED. Propoxur was also included in the Revised N -methyl Carbamate

Cumulative Risk Assessme nt conducted in 2007.

• EPA plans to conduct an acute dietary exposur e and risk assessment during registration review to support the anticipa ted establishment of a tolera nce for use of propoxur in food handling establishments (FHE).

• Based on the limited terrestrial outdoor uses and the relatively low usage of propoxur, and because no current uses appear to be a significant route of aquatic exposure, EPA

does not intend to conduct a human hea lth drinking water assessment for propoxur.5 • Based on the current knowledge of the non- cancer mode of action for propoxur (i.e., rapid reactivation of the enzyme suppressed by exposure and then recovery), chronic dietary assessments are no longer appropriate for propoxur and are not intended to be conducted during registration review.

• A revised chronic cancer dietary assessment is also not intended to be conducted because the concentrations of exposure which elicited effects in the submitted studies are orders of magnitude greater than what would be e xpected based on registered use patterns of

propoxur.

• Revised residential and occupational handler and post-application risk assessments will be needed to support the re gistration review of propoxur. These assessments will incorporate the most recent points of departur e selected after a comp lete review of the toxicological database, including data from the requested toxicity studies, and incorporating any changes to policies and standard operating pro cedures within the Agency.

• Because propoxur is formulated into impregna ted pet collars, residential post-application dermal exposure and non-dietary ingestion will be considered for individuals coming into contact with (hugging, pe tting) treated pets.

• During registration review, EPA intends to conduct a new acute aggregate risk assessment combining the revised resi dential and dietary exposures.

• There are currently no esta blished tolerances for residues of propoxur on any raw agricultural commodities. However, the regi strant previously filed a food additive petition (9H5199, 10/16/78) and proposed a tole rance of 0.2 ppm. Sufficient data are available, and the tolerance petition to support the crack a nd crevice treatment of food areas of FHEs will be evaluated during registration review to determine if a safety finding

can be made.

• The toxicity database for pr opoxur is nearly complete. Ho wever, EPA plans to require the following studies in order to conduct a co mplete human health risk assessment for the registration review of propoxur:

870.7800 – Immunotoxicity study Special study – Comparative cholinesterase assay (CCA)

• Prior to a registration review decision for propoxur, the Agency will determine if there is any new information, such as new hazard or exposure data or information on changes to the use pattern, which could a ffect the results of the 2007 Revised NMC Cumulative Risk Assessment. If so, the Agency will re visit the cumulative risk assessment.

• Please refer to the November 17, 2009 document “Propoxur: Registration Review Scoping Document for Human Health Assessments” in the registration review docket (EPA-HQ-OPP-2009-0806-0004) for a detailed disc ussion of the risk assessment needs.6 Other Data Needs:

• A UV / Visible Light Absorption study (Gui deline 830.7050) 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 intends to require this study to obtain basic information about the compound’s iden tity, composition, and the wavelengths at which the compound may be suscepti ble to photochemical degradation.

Endocrine Disruptor Screening Program:

As required under FFDCA section 408(p), EP A has developed the Endocrine Disruptor Screening Program (EDSP) to determine whether certain substances (inc luding pesticide active and other ingredients) may have an effect in humans or wildlife si milar to an effect produced by a “naturally occurring estrogen, or other such endocrine effects as the Administrator may designate.” The EDSP employs a two-tiered ap proach to making the statutorily required

determinations. Tier 1 consists of a battery of 11 scr eening assays to identify the potential of a chemical substance to interact with the estrog en, androgen, or thyroid (E, A, or T) hormonal systems. Chemicals that go th rough Tier 1 screening and are found to have the potential to interact with E, A, or T hormonal systems will proceed to the next stag e of the EDSP where EPA will determine which, if any, of th e Tier 2 tests are necessary base d on the available data. Tier 2 testing is designed to identify a ny adverse endocrine related eff ects caused by the substance, and establish a quantitative relationship betw een the dose and the E, A, or T effect.

Between October 2009 and February 2010, EPA issued test orders / data call-ins for the first group of 67 chemicals, which contains 58 pesticid e active ingredients and 9 inert ingredients.

This list of chemicals was selected based on th e potential for human exposure through pathways such as food and drinking water, residential activity, and certain post- application agricultural

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

Propoxur is not among the group of 58 pesticide ac tive ingredients 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 issuin g future EDSP orders / data call-ins for all registration review cases, in cluding those for which EPA ha s already opened a registration review docket for a pesticide active ingredient.

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

Timeline:

EPA has created the following estimated timeline for the completion of the registration review for propoxur.7 Registration Review for Propoxur – Pr ojected Registration Review Timeline

Activities Estimated Date Opening the docket Open Docket and Public Comment Period Completed – Dec. 16, 2009

Close Public Comment Completed – Feb. 16, 2010 Case Development

Final Work Plan Completed – June 2010

Issue DCI 2011 – Jan. - March

Data Submission 2013 – Jan. - March Open Public Comment Period for Preliminar y Risk Assessments 2014 – July - Sept.

Close Public Comment Period 2014 – Oct. - Dec. Registration Review Decision Open Public Comment Period for Proposed Re gistration Review Decision 2015 – Jan. - March Close Public Comment Period 2015 – April - June Final Registration Review Decision and Begin Post-Decision Follow-up 2015 Total (years) 6

Summary of Comments and Agency Responses:

During the public comment period on the Propox ur Summary Document, the Agency received comments from one of the propoxur technical re gistrants, McLaughlin Gormley King Company, and from NRDC. The following is a summary of the comments and the Agency’s responses.

Comments submitted by McLaughlin Gorm ley King Company (MGK) in EPA-HQ-OPP2009-0806-0012.1 and -0013.

1. Comment: MGK’s submission dated February 15, 2010 st ated their belief that granular baits for outdoor use are no longer registered, and that MGK does not support their continued use. Furthermore, they stated that given th e other outdoor uses and low usage of propoxur, no significant environmental exposure would oc cur. For that reason, MGK believes that none of the environmental fate and ecological effects data listed in the PWP should be required.

Response: In subsequent communications with MGK, EPA identified two active product registrations for outdoor granul ar perimeter bait treatments (E PA Registration Nos. 499-518 and 655-802). MGK initiated conversation with the end-use registrants Whitmire Micro-Gen Research Laboratories Inc. and Prentiss Incorp orated, and jointly, th ey proposed to repackage the granular product in an enclos ed bait station to limit outdoor exposure.

In a follow-up submission from MGK to EPA, dated March 31, 2010 (available in the public

docket with confidential business informati on withheld), MGK provided further details indicating that the end-use regi strants intend to include empty bait stations with the loose granular product for outdoor applic ations and to revise the labe led Directions for Use to limit outdoor applications to encl osed bait stations only.8 Until revised product labels are submitted by e nd-use registrants and approved by EPA, the Agency will move forward w ith the environmental fate and ecological effects data requirements and outdoor ecological exposure asse ssments as previously described. Without specific details of the encl osed bait station design, EPA cannot determine whether environmental exposure and potential for outdoor movement are minimized or eliminated.

2. Comment: MGK invoked FIFRA Section 4(n) “Authoriz ation of funds to develop public

health data” and asked that EPA consult with the Secretary of Health and Human Services (HHS) for funds to conduct the Immunotoxic ity study (Guideline 870.7800) and Comparative Cholinesterase Assay (special study).

Response: MGK’s comment did not identify any reasons why the immunotoxicity and CCA studies are not necessary or appropriate to support registration of propoxur products. Discussing potential sources of funding for such studies is not germane to this stage of registration review.

3. Comment: MGK stated that they would submit use and usage information for propoxur to support their assertion that propoxur has limited and low usage.

Response: In MGK’s submission to EPA of March 31, 2010, a confidential appendix containing use and usage information was provi ded. The Agency thanks MGK for providing

this information and notes that it will he lp inform EPA during registration review.

Comments submitted by the Natural Reso urces Defense Council (NRDC) in EPA-HQOPP-2009-0806-0011.1.

4. Comment: “On November 26, 2007, NRDC submitted a pe tition to the USEPA to cancel the pet collar uses of propoxur and supplemented that petition on April 29, 2009. To date, EPA has not responded to NRDC’s petition. The re gistration review pro cess should not be a substitute to EPA making a final de termination on the petition to cancel all pet collar uses of propoxur... The registration review process is estimated to ta ke up to six years to finish, and EPA should not delay in can celing the pet collar uses.”

Response: The Agency published a Notice of Ava ilability announcing receipt of NRDC’s petition on April 8, 2009 (74 FR 15980), and public comments were accepted on this Notice until August 4, 2009. EPA has been in the proce ss of evaluating the petition and the public comments received during the comment period. As was noted in the “Updates Since the Summary Document” section of this documen t, EPA also recently completed an ORE assessment for the pet co llar use on April 7, 2010.

EPA is currently evaluating the information re garding pet collar expos ures and intends to respond to the petition when appropriate. The Agency agrees that the registration review process is not a substitute for EPA’s consider ation of NRDC’s petiti on to cancel propoxur pet collar uses. EPA anticipates re sponding to the petition prior to the completion of registration

review.9 5. Comment: “Given the toxicity and exposure data that already exist and that NRDC provided in its petition, EPA should act immediately to grant the petition and protect human health and the environment from this dangerous poison... As reported in NRDC’s ‘Poison on Pets II: Toxic Chemicals in Flea and Tick Collars,’ (Poison on Pets II) and noted in the petition, residues of propoxur on the pets’ fur are signi ficantly higher than EPA’s residue estimates.”

Response: As discussed in a series of letters between EPA and NRDC between May and August of 2009 (available in the public docke t EPA-HQ-OPP-2009-0207), some of the data submitted by NRDC, and specifically the informa tion and claims contained in NRDC’s issue paper Poison on Pets II cannot be relied upon by EPA. EPA believes that the research summarized in that paper is subject to 40 CF R part 26 “Protections for Subjects in Human Research.” EPA requested additional in formation from NRDC, including supporting

scientific data and documentation of the ethical conduct of the research, in order to determine whether the data may be relied upon in regulat ory actions under FIFRA. To date, EPA has

not received this addition al information from NRDC.

As indicated above, EPA recently completed a risk assessment for the propoxur pet collar use and is currently evaluating information for this use.

6. Comment: NRDC requests that EPA clar ify that both non-cancer and cancer endpoints will be considered for propoxur’s review.

Response: The November 17, 2009 document “Pr opoxur: Registration Review Scoping

Document for Human Health Assessments” notes that although the 1997 RED classified propoxur as a Group B2: Probabl e human carcinogen, this was based on feeding studies in rats and mice that were at extremely high doses . The concentrations of exposure that elicited effects in the submitted studies are orders of magnitude greater than what would be expected based on currently registered use patterns of propoxur. Given this information, and because propoxur involves maximal cholinesterase inhibi tion (typically within 15 minutes to an hour) followed by rapid reactivation of the enzyme and then recovery (minutes to hours), chronic cancer assessments are no longer appropriate a nd are not intended to be conducted during registration review. All appropriate non-can cer endpoints will be assessed by EPA during registration review.

7. Comment: “EPA’s registration review of propoxur should include the inhalation exposures from all indoor uses.”

Response: All appropriate exposure scenarios based on the registered uses of propoxur will be assessed during registration review.

8. Comment: NRDC made several comments regardi ng assumptions used to calculate exposures (non-dietary and dermal) from pet co llars in the N-methyl Carbamate Cumulative Risk Assessment. NRDC identified issues wi th some of EPA’s selected values for these parameters, including frequency of mouthing events, the amount of time children spend with pets per day, etc.10 Response: The probabilistic approach utilized in the NMC Cumulative Risk Assessment differs from the single chemical determinis tic approach. When responding to NRDC’s petition to cancel propoxur pe t collars and during the upcom ing registration review of propoxur, the Agency will be conducting a single chemical assessment to determine exposure and risk estimates using deterministic methods and parameters. The Agency will also be revising the NMC Cumulati ve Risk Assessment. Both the probabilistic and deterministic methods and parameters have been reviewed by the FIFRA Scientific Advisory Panel (SAP), but final implementation is still pending for asp ects of each. In future risk assessments, the Agency will incorporate any needed change s based upon the final implementation of these practices (e.g., updates to the Standard Oper ating Procedures for Residential Pesticide Exposure Assessment, as reviewed by the SAP in October 2009).

Next Steps:

As noted previously, the Agency plans to requ ire several ecological e ffects and human health studies through a data call-in, exp ected to be issued in early 2011. This new information will be used to conduct complete risk assessme nts for all registered uses of propoxur.