2

Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) 

for the registration review of propoxur. The Final Work Plan includes 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 needed to make a registration review decision. 

The Agency’s implementation of the registration review program requires review of each 

registered pesticide every 15 years to determine whether it continues to meet the Federal 

Insecticide, Fungicide, and Rodenticide Act (FIFRA) standard for registration. Changes in 

science, public policy, and pesticide use practices 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/ . 

Propoxur is an N-methyl residual carbamate insecticide registered for use to control ticks, fleas, 

and a variety of insects including crickets, ants, wasps, cockroaches and silverfish in-and-around 

industrial, commercial (including food handling establishments and food processing plants), and 

residential facilities. There are no labeled agricultural uses, and residential indoor spray uses 

were previously cancelled. The Reregistration Eligibility Decision (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 toxicity and inhibit acetylcholinesterase. The 

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

Updates Since the Summary Document:

As discussed in the “Recent Actions” section of the Propoxur Summary Document, EPA had 

received and was in the process of evaluating a Natural Resources Defense Council (NRDC) 

petition to cancel propoxur pet collar uses and the public comments received during the April 8, 

2009 to August 4, 2009 public comment period on that petition. (Federal Register notices, 

supporting documents, and additional information 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 procedures for residential and 

incidental oral exposures. This assessment is available in the registration 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 various uncertainties and data needs. EPA is 

working to refine the risk assessment and will mitigate where necessary to resolve risk concerns 

in advance of the preliminary risk assessments for registration review. 

Also discussed in the “Recent Actions” section of the Summary Document was the Ohio 

Department of Agriculture’s request for a one-year 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 transportation, and commercial industrial buildings in 

Ohio. In correspondence of June 2, 2010, EPA Administrator 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 exposures. Therefore, EPA’s Office of Pesticide 

Programs will not be authorizing the emergency use request. 

Comments Received on the Preliminary Work Plan:

The Agency received two comments during the 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 address the timeline described in the PWP. 

However, the comments do address and could affect the planned data requirements 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 specific topics of environmental justice, water 

body impairment, and trade irritants. No comments 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 the 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 assessment 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 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. 

• One outdoor use pattern from currently registered propoxur labels, bait application, is 

planned to be assessed for ecological risk because product labels have directions for use 

that may lead to environmental exposure. These granular bait products are applied in a 2 

to 3 foot band around structures. As is discussed further in the “Summary of Comments 

and Agency Responses” section of this document, the continued need for this risk 

assessment and certain data requirements may be subject to change based on the 
4

registrant’s intent to repackage 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 liquid spot application, because they are not 

expected to lead to significant exposure in the 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 assessment 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 registration review of propoxur. As is discussed 

further in the “Summary of Comments and Agency Responses” section of this document, 

the continued need for certain data requirements may be subject to change based on the 

registrant’s intent to repackage the outdoor granular bait products into enclosed bait 

stations. 

835.6100 (Footnote 7) – Environmental chemistry 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 vigor, 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 discussion 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 Assessment conducted in 2007. 

• EPA plans to conduct an acute dietary exposure and risk assessment during registration 

review to support the anticipated establishment of a tolerance 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 health 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 expected based on registered use patterns of 

propoxur. 

• Revised residential and occupational handler and post-application risk assessments will 

be needed to support the registration review of propoxur. These assessments will 

incorporate the most recent points of departure selected after a complete review of the 

toxicological database, including data from the requested toxicity studies, and 

incorporating any changes to policies and standard operating procedures within the 

Agency. 

• Because propoxur is formulated into impregnated pet collars, residential post-application 

dermal exposure and non-dietary ingestion will be considered for individuals coming into 

contact with (hugging, petting) treated pets. 

• During registration review, EPA intends to conduct a new acute aggregate risk 

assessment combining the revised residential and dietary exposures. 

• There are currently no established tolerances for residues of propoxur on any raw 

agricultural commodities. However, the registrant previously filed a food additive 

petition (9H5199, 10/16/78) and proposed a tolerance of 0.2 ppm. Sufficient data are 

available, and the tolerance petition to support the crack and 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 propoxur is nearly complete. However, EPA plans to require 

the following studies in order to conduct a complete 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 affect the results of the 2007 Revised NMC Cumulative Risk 

Assessment. If so, the Agency will revisit 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 discussion of the risk assessment needs. 
6

Other Data Needs: 

• A UV / Visible Light Absorption study (Guideline 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 identity, composition, and the wavelengths at 

which the compound may be susceptible to photochemical degradation. 

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 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 active 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 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 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 – Projected 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 Preliminary Risk Assessments 2014 – July - Sept. 

Close Public Comment Period 2014 – Oct. - Dec. 

Registration Review Decision 

Open Public Comment Period for Proposed Registration 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 Propoxur Summary Document, the Agency received 

comments from one of the propoxur technical registrants, McLaughlin Gormley King Company, 

and from NRDC. The following is a summary of the comments and the Agency’s responses. 

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

1. Comment: MGK’s submission dated February 15, 2010 stated 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 the other outdoor uses and low usage of propoxur, 

no significant environmental exposure would occur. 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 granular perimeter bait treatments (EPA Registration Nos. 499-518 

and 655-802). MGK initiated conversation with the end-use registrants Whitmire Micro-Gen 

Research Laboratories Inc. and Prentiss Incorporated, and jointly, they proposed to repackage the granular product in an enclosed 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 information withheld), MGK provided further details 

indicating that the end-use registrants intend to include empty bait stations with the loose 

granular product for outdoor applications and to revise the labeled Directions for Use to limit 

outdoor applications to enclosed bait stations only. 
8

Until revised product labels are submitted by end-use registrants and approved by EPA, the 

Agency will move forward with the environmental fate and ecological effects data 

requirements and outdoor ecological exposure assessments as previously described. Without 

specific details of the enclosed 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) “Authorization 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 Immunotoxicity 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 provided. The Agency thanks MGK for providing 

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

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

4. Comment: “On November 26, 2007, NRDC submitted a petition 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 registration review process should not be a 

substitute to EPA making a final determination on the petition to cancel all pet collar uses of 

propoxur... The registration review process is estimated to take up to six years to finish, and 

EPA should not delay in canceling the pet collar uses.”

Response: The Agency published a Notice of Availability 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 process 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 document, EPA also recently completed an ORE 

assessment for the pet collar use on April 7, 2010. 

EPA is currently evaluating the information regarding pet collar exposures and intends to 

respond to the petition when appropriate. The Agency agrees that the registration review 

process is not a substitute for EPA’s consideration of NRDC’s petition to cancel propoxur pet 

collar uses. EPA anticipates responding 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 significantly 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 docket EPA-HQ-OPP-2009-0207), some of the data 

submitted by NRDC, and specifically the information 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 CFR part 26 “Protections for Subjects in Human 

Research.” EPA requested additional information 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 regulatory actions under FIFRA. To date, EPA has 

not received this additional 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 clarify that both non-cancer and cancer endpoints will 

be considered for propoxur’s review.

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

Document for Human Health Assessments” notes that although the 1997 RED classified 

propoxur as a Group B2: Probable 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 inhibition (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 and are not intended to be conducted during 

registration review. All appropriate non-cancer 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 regarding assumptions used to calculate 

exposures (non-dietary and dermal) from pet collars in the N-methyl Carbamate Cumulative 

Risk Assessment. NRDC identified issues with 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 deterministic approach. When responding to NRDC’s 

petition to cancel propoxur pet collars and during the upcoming 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 Cumulative 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 aspects of each. In future risk assessments, the 

Agency will incorporate any needed changes based upon the final implementation of these 

practices (e.g., updates to the Standard Operating Procedures for Residential Pesticide 

Exposure Assessment, as reviewed by the SAP in October 2009). 

Next Steps:

As noted previously, the Agency plans to require several ecological effects and human health 

studies through a data call-in, expected to be issued in early 2011. This new information will be 

used to conduct complete risk assessments for all registered uses of propoxur.