Docket Number: EPA-HQ-OPP-2011-0662 www.regulations.gov



## Propamocarb Hydrochloride Summary Document Registration Review: Initial Docket September 2011

### TABLE OF CONTENTS

Page

I. Preliminary Work Plan (PWP) 4

II. Fact Sheet 12

III. Summary of Data Gaps 19

______________________ __________________

Please Note

This Preliminary Work Plan and Fact Sheet summarize the Environmental Protection Agency's current position base d on the following documents:

1. Registration Review – Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Propamocarb-HCl. September 20, 2011.

2. Propamocarb Hydrochloride: Human-Health Assessment Scoping Document in Support of Registration Review. September 14, 2011.

3. Propamocarb hydrochloride: Review of Human Incidents. May 18, 2011.

4. Propamocarb HCl (119302) Screening Level Us age Analysis (SLUA). November 23,

2010.

5. BEAD Chemical Profile for Registration Review: Propamocarb-HCl (119302). April 7,

2011.

6. Appendix A: Food/Feed & Non-Food/Non-Feed Uses Considered in Registration Review Work Planning. March 3, 2011.

Additional supporting documents for propamocarb may be found in the registration review docket EPA-HQ-OPP-2011-0662 locat ed on the internet at www.regulations.gov

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3I. PRELIMINARY WORK PLAN – Propamocarb Hydrochloride

Introduction:

The Food Quality Protection Act (FQP A) of 1996 mandated a registration review program. All pesticides sold or distributed in the United States generally must be registered by the Environmental Protection Agency (EPA or the Ag ency), based on scientific data showing that they will not cause unreasonable ri sks 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 unreasonabl e 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 prog ram, the Agency periodically r eevaluates pesticides to make sure that as change occurs, products in the mark etplace can be used safely. Information on this program is provided at: http://www. epa.gov/oppsrrd1/registration_review/.

The Agency is implementing the registration revi ew program pursuant to Section 3(g) of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), a nd will review each registered pesticide every 15 years to determine whether it continues to meet th e 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 whatit knows about the pesticide and what additional risk analyses and data or information it belie ves 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 de velop and commit to a final work plan and schedule for the registration review of propamocarb hydrochloride.

Propamocarb hydrochloride is a carbamate fungic ide that targets seve ral Oomycetes species, including Phytophthora

, Pythium , and downy mildew, which cause foliar diseases and seedling, seed, root, foot, and stem rot in various edible and ornamental crops. It disrupts formation of fungal cell walls by in terfering with the synthesis of fatty acids and phospholipids, thus affecting mycelia cell growth, spore produc tion, and germination. Propam ocarb hydrochloride is not an

N

-methyl carbmate and does not share a co mmon mechanism of toxicity with the N -methyl carbamate group. Propamocarb hydrochloride was fi rst registered in 198 4, and a Reregistration Eligibility Decision (RED) was co mpleted in 1995. The first food use, potatoes, was registered in 2000. Promamocarb is currently registered as emulsifiable-concentrate (EC) formulations for use on potatoes, lettuce, cucurbit vegetables, a nd fruiting vegetables, as well as golf courses, ornamental turf/plants, sod farms, and in nurseri es/greenhouses. It is formulated with other fungicides, including chlorothalonil and fluopicoli de. There are nine FIFRA Section 3 product registrations for propamocarb hydrochloride, in cluding two registrations for manufacturing use products. There are six Section 24(c) Special Local Need registrations for propamocarb hydrochloride.

In 2009, EPA received a request for a new use of propamocarb hydrochloride on lima beans.
The risk assessments conducted to evaluate the re quested new use identified risks of concern for the existing use of propamocarb hydrochlorid e on ornamentals. Certain propamocarb

4hydrochloride labels are unclear with respect to application parameters (e.g., the maximum seasonal application rate, or maxi mum applications per crop cycle) and the Agency believes that
the identified risks of concern can be mitigated through label change s. In the absence of clear label information, EPA must employ conservative assumptions to complete risk assessments. The Agency encourages clear and consistent labe l language for the sake of all stakeholders and encourages the technical registra nts to review the product labels for clarity. EPA is currently working with registrants to mitigate these risk concerns.

Anticipated Risk Assessment and Data Needs:

The Agency anticipates requiring data for use in conducting a comprehensive ecological risk assessment, including an endangere d species risk assessment, for all uses of propamocarb hydrochloride. The Agency also anticipates re quiring additional data for use in conducting a comprehensive human health risk assessment fo r all uses of propamacarb. A summary of the issues relevant to the regi stration review of propamocarb hydrochloride is given below.

Ecological Risk:

• The most recent comprehensive, national-level ecological risk assessment for propamocarb hydrochloride was completed in 1995 in support of the RED. In addition, limited ecological risk assessments were comp leted in 2000 to support the registration of the first propamocarb food use on potatoes and, in 2004, to support the registration of propamocarb hydrochloride use on cucurbits, lettuce, peppers, and tomatoes.

• The Agency has not conducted a risk asse ssment that supports a complete endangered species determination for propamocarb hydrochl oride. The ecological risk assessment planned during registration review will a llow the Agency to determine whether propamocarb hydrochloride use has “no eff ect” or “may affect” federally listed threatened or endangered species (listed specie s) or their designated critical habitats. When an assessment concludes that a pesticid e’s use “may affect” a listed species or its designated critical habitat, the Agency w ill consult with the U.S. Fish and Wildlife
Service and/or National Marine Fisheries Se rvice (the Services), as appropriate.

• On January 19, 2011, the Center for Biologi cal Diversity and the Pesticide Action
Network North America filed a lawsuit in th e United States District Court for the Northern District of California, against EP A for allegedly failing to undergo consultation with the Services regarding the effects of over 350 pesticides, including propamocarb, on over 200 endangered and threatened sp ecies throughout the United States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11-00293 (N.D.Cal.))

.

• The Agency anticipates requiring the follo wing data for propamocarb hydrochloride for use in conducting a comprehensive national ecological risk assessment, including an endangered species assessment:

• GDLN 835.1230 – Adsorption/Desorption

5• GDLN 835.4300 – Aerobic Aquatic Meta bolism (two additional soils)

• GDLN 835.4400 – Anaerobic Aquatic Meta bolism (one additional soil)

• GDLN 850.1350 – Aquatic Invertebra te Life-Cycle Toxicity (estuarine/marine)

• GDLN 850.1400 – Fish Early Life Stage (estuarine/marine)

• GDLN 850.2100 – Avian Oral Toxicity (bobwhite quail and passerine)

• GDLN 850.2200 – Avian Dietary Toxicity (bobwhite quail and mallard duck)

• EPA required a freshwater i nvertebrate life cycle study (GDLN 850.1300) in a Data Call In (DCI) associated with the reregistration of propamocarb (GDCI-119302-17298). Although one study (MRID 45894308) submitted to fulfill this requirement was determined to be invalid, another stu dy (MRID 45727801) has been submitted and is currently in review. This will be considered as a data gap until the data have been reviewed and found to be acceptable.

• Please refer to the September 20, 2011 document, Registration Review – Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Propamocarb-HCl , located in docket EPA-HQOPP-2011-0662 for a detailed discussion of the anticipated risk assessment and data needs and for a more detailed discussion of uncertainties on certain product labels.

Human Health Risk:

• The most recent comprehensive human health risk assessment for propamocarb hydrochloride was completed in February 2004 in support of use on lettuce, fruiting vegetables, and cucurbits. These uses were granted on August 4, 2004 and tolerances
were established for the associated food co mmodities. An occupational and residential risk assessment was completed on November 5, 2009 to support a proposed use on lima beans. To date, EPA has not established to lerances for propamocarb hydrochloride in/on
lima beans. The 2009 risk assessment id entified occupational (handler and postapplication) exposure and potenti al drinking water exposure risk concerns associated with an existing use of propamocarb hydrochloride on ornamentals. The Agency is currently working with the registrants to mitigate these risk concerns.

• The Agency anticipates requiring the follo wing data for propamocarb hydrochloride for use in reevaluating toxicologi cal endpoints (points of depa rture), safety/uncertainty factors and updating the human health toxicity profile:

• GDLN 870.7800 – Immunotoxicity

• GDLN 870.3465 – Inhalation Toxicity

• During registration review, the Agency anticipa tes revising the dietary risk assessment to incorporate refined estimated drinking water concentrations (EDWCs), updated

6anticipated food residues and Pesticide Data Program (PDP) data, and any changes to toxicological points of departure, or uncertainty factors.

• The residential and occupational exposure databases for propamocarb hydrochloride are adequate; and therefore, at this time, EPA does not anticipate the need for additional residential or occupational exposure da ta to support regi stration review.

• During registration review, the Agency antici pates revising the resi dential handler and bystander risk assessments if data are identifi ed which may impact the points of departure or the FQPA safety factor; or if revisions ar e made to any of EPA’s exposure and/or risk assessment policies and procedures. EPA ma y also conduct a bystander risk assessment to address potential exposure via spray drift.

• EPA anticipates revising the aggregate assessm ent to incorporate changes to the dietary exposure estimates from food and/or drinki ng water (e.g., updated EDWCs). In addition, an aggregate assessment is anticipated as be ing needed if data are identified which may impact the points of departure or the FQPA safe ty factor; or if revisions are made to any of EPA’s exposure and/or risk asse ssment policies and procedures.

• EPA anticipates that it will reevaluate all occupational dermal and inhalation exposure

assessmen t s using standards and policies that are in place at the time of registration
review. Revised occ u pational handler and post-applica tion assessments may be needed in the event of changes to toxicological poi nts of departure, receipt of new data, or changes to d efault exposure assessment assumptions.

• The tolerance expression in 40 CFR §180.499 will be reviewed during registration review to ensure that it appropriately covers the metabolites and degradates of propamocarb hydrochloride and that it specifies the residues to be measured for each commodity. The Agency will modify tolerance levels as needed, and work to harmonize tolerances/ maximum residue limits (MRL), where possible, in key export markets during registration review.

• The following residue chemistry data are need ed to establish tolerances for livestock
commodities

. These data were previously identifie d as being needed by the Agency in support of propamocarb use on potatoes, whic h are a livestock feed commodity. EPA granted a conditional use of propamocarb on potatoes, which has been extended to March 31, 2012.

o GDLN 860.1360 - Multi-residue testing, 2-hydr oxy and glucuronide metabolites.

o GDLN 860.1380 - Storage stability for livestock commodities, glucuronide
metabolite.

7• P lease refer to Propamocarb Hydrochloride. Human Health Scoping Document in Support of Registration Review

, September 14, 2011, located in the docket, for a detailed discussion of the anticipated risk assessment and data needs.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews num erous studies to asse ss potential adverse outcomes from exposure to chemicals. Collectiv ely, these studies includ e acute, subchronic and chronic toxicity, including asse ssments of carcinogenicity, ne urotoxicity, developmental, reproductive, and general or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influe nce, including effects on endocri ne target organ histopathology, organ weights, estrus cyclicity, sexual maturatio n, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess gr owth, developmental and reprod uctive effects in different taxonomic groups. As part of its most recent re gistration decision, EPA re viewed these data and selected the most sensitive endpoi nts for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA section 408(p), propamocarb hydrochloride is subject to the endocrine screeni ng part of the Endocrine Disrup tor Screening Program (EDSP).

EPA has developed the EDSP to determine whet her 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 ot her such endocrine effect s as the Administrator may designate.” The EDSP employs a two-tiered approach to making th e 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 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 dose-response relationship between the dose and the E, A, or T effect.

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, which contains 58 pesticide active in gredients and 9 inert ingredients. Propamocarb hydrochloride is not among the group of 58 pesticide active ingredients on th e initial list to be screened under the EDSP. Accordingly, as part of registration review, EPA will issue future EDSP orders/data call-ins, requiring the submission of EDSP screening assays for propamocarb hydrochloride. For further information on the status of the EDSP, the policies and procedures, the list of 67 chemicals, future lists, the test guidelines and the Tier 1 screening battery, please
visit our website: http://www.epa.gov/endo/

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Timeline:

EPA has created the following estimated timeline for the completion of the propamocarb hydrochloride registration review.

8Projected Registration Review Time line for Propamocarb Hydrochloride

Activities Estimated Date Opening the Docket Open Docket and Public Comm ent Period 2011 – September

Close Public Comment 2011 – November Case Development

Final Work Plan 2012 – February

Issue DCI 2012 – Oct. – Dec.

Data Submission 2014 – Oct. – Dec. Open Public Comment Period for Draft Risk Assessments 2016 – April – June

Close Public Comment Period 2016 – July – Sept. Registration Review Decision Open Public Comment Period for Proposed Registration Review
Decision 2016 – Oct. – Dec.

Close Public Comment Period 2017 – Jan. – March Registration Review Decision and Begin Post-Decision Follow-up 2017 Total (years) 6

Guidance for Commenters:

The public is invited to comment on EPA’s preliminary work plan and rationale. The Agency will carefully consider all commen ts, as well as any additional information or data provided in a timely manner, prior to issuing a Final Work Plan for propamocarb hydrochloride.

Trade Irritants:

Through the registration review process, the Ag ency intends to solicit information on trade irritants and, to the extent feas ible, take steps toward facilitating irritant resolution. Growers and other stakeholders are asked to comment on any trad e irritant issues resul ting from lack of MRLs or disparities between U.S. tolerances and MR Ls in key export markets, providing as much specificity as possible regardi ng the nature of the concern.

Water Quality:

Propamocarb hydrochloride is not iden tified as a cause of impairment for any water bodies listed as impaired under section 303( d) of the Clean Water Act 1 . In addition, no To tal Maximum Daily Loads (TMDL) have been developed for propamocarb hydrochloride 2 . More information on impaired water bodies and TMDLs can be found on the Agency’s website 3 . 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 Proc edure: Inclusion of Impaired Water Body and Other Water Quality Data in OPP’ s Registration Review Risk

1 http://iaspub.epa.gov/tmdl_waters10/attains _nation_cy.cause_detail_30 3d?p_cause_group_id=885

2 http://iaspub.epa.gov/tmdl_waters10/attain s_nation.tmdl_pollutant_detail ?p_pollutant_group_id=885&p_ pollutant_group_name=PESTIC IDES

3 http://www.epa.gov/owow/tmdl/

9Assessment and Management Process 4 in order to ensure they can be used quantitatively or qualitatively in pesticide risk assessments.

Environmental Justice:

EPA seeks to achieve environmenta l justice, the fair tr eatment and meaningful involvement of all people, regardless of race, color, national origi n, or income, in the deve lopment, implementation, and enforcement of environmental laws, regulati ons, 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 thei r location, cultural practices, or other factors, may have atypical, unusually high exposure to propamo carb hydrochloride, compared to the general population. Please comment if you are aware of any sub-populati ons that may have atypical, unusually high exposure compared to the general population.

Additional Information:

Stakeholders are also specifically asked to prov ide information and data that will assist the Agency in refining its risk assessments, incl uding any species-specific ecological effects determinations. The Agency is interested in receiving the following information:

1. confirmation on the following label information

a. sites of application

b. formulations

c. application methods and equipment

d. maximum application rates

e. frequency of application, applicati on intervals, and maximum number of applications per season and per year

f. geographic limitations on use

2. use or potential use distribu tion (e.g., geographical distri bution of relevant uses)

3. use history and reason for changes in use

4. median and 90 th percentile reported use rates (lbs ai/1000 sq ft) from usage data – national, state, and county

5. application timing (date of first applicati on and application inte rvals) by use site – national, state, and county

6. sub-county use site location data

7. usage/use information for non-agricultural uses, especially tu rf and ornamentals

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

a. maximum reported use rate (lbs ai/1 000 sq ft) from usage data – county

b. percent use site treated – county

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

d. total pounds per year – county

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

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

4 http://www.epa.gov/oppsrrd1/registration_review/water_quality_sop.htm

109. typical application interval (days)

10. state or local use restrictions

11. information on plants resistant to this herbicide

12. ecological incidents (non-target plant damage and avian, fish, reptilian, amphibian and mammalian mortalities) not alr eady reported to the Agency

13. monitoring data

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Next Steps:

After the 60-day comment period closes, the Ag ency will review and respond to any comments received in a timely manner, and expects to issue a Final Work Plan for propamocarb hydrochloride.

11II. FACT SHEET

Background Information:

• Registration review case number: 3124

• PC code: 119302

• The first pesticide containing propamocarb hydroc hloride was registered in the U.S. in
1984.

• A Reregistration Eligibility Decision (RED) for propamocarb hydrochloride was completed in September 1995.

• Technical registrants: Bayer CropScience and Agriphar SA.

• There are nine FIFRA Section 3 product re gistrations for propamocarb hydrochloride, including two registrations fo r manufacturing use products. There are six Section 24(c) Special Local Need registrations for propamocarb hydrochloride.

• Tolerances for residues of propamocarb hydrochl oride in or on lettuce, leaf and head; potato; tomato, paste; vegetable, cucurb it, crop group 9; and vegetable, fruiting, crop group 8 are codified in 40 CFR §180.499.

• Pesticide Re-evaluation Di vision (PRD) Chemical Review Manager (CRM): Christina Scheltema, scheltema.christina@epa.gov.

• Registration Division (RD) Produc t Manager (PM): Mary Waller, waller.mary @ epa.gov.

Use & Usage Information:

• Propamocarb hydrochloride is a carbamate fungicide registered for use on potatoes, lettuce, cucurbit vegetables, and fruiting vegeta bles; as well as golf courses, ornamental turf/plants, sod farms, and in nurseries/g reenhouses. The first food use for propamocarb hydrochloride (on potatoes) was regist ered on September 29, 2000 (65 FR 58390). Additional food uses of propamocarb hydroc hloride on lettuce, cucurbits, fruiting vegetables, peppers, and eggplan ts (crop group 8); and tomato paste were registered on August 4, 2004 (69 FR 47013).

• Propamocarb hydrochloride is form ulated as an emulsifiable concentrate (EC). It is applied via chemigation, soil surface spray, foliar spray, band treatment, and drench treatment. It is also applied to potted or namentals by soil and foliar sprays, drenches, and dips.

• According to the most recent usage data, approximately 240,000 pounds of propamocarb hydrochloride active ingredient (a.i.) ar e used on approximately 220,000 acres (A) of agricultural crops. Propamocarb hydrochloride is typically applied at a rate of 0.7 to 1.4 lbs ai/A. The greatest amount of propamocar b hydrochloride was applied to lettuce (52% of lbs applied), cucumbers (37%), squash (3%), peppers (3%), and pumpkins (3%). The states with the greatest am ount of propamocarb hydrochloride applied were California, Michigan, Georgia, Florida, Texas, and Indiana.

• Lawn care operators used approximately 4,000 lbs of propamocarb hydrochloride in 2006, the only year for which data are availa ble. Nurseries and greenhouses also used approximately 4,000 lbs that year.

12• Although propamocarb hydrochloride is used on golf courses, use has been declining, from 85,000 lbs in 2002 to appr oximately 10,000 lbs in 2006.

• For additional details, please refer to the following documents: BEAD Chemical Profile for Registration Review: Propamocarb-HCl

, April 7, 2011; Propamocarb Screening Level Usage Analysis (SLUA)

, November 23, 2010; and Appendix A: Food/Feed & NonFood/Non-Feed Uses Considered in Registration Review Work Planning , March 3, 2011.

Recent and Ongoing Actions:

• The Agency received a petition to establis h tolerances for propamocarb hydrochloride
residues in/on lima beans from IR-4, Rutgers University in 2009. (See 74 FR16866.) To date, EPA has not established tolerances for propamocarb hydrochloride in/on lima
beans. For more information on the lima bean petition, please see docket EPA-HQ-OPP2008-0887 on www.regulations.gov

.

• The 2009 risk assessment conducted in support of the petition to establish tolerances in/on lima beans identified occupational handl er and post-application risks of concern for existing ornamental uses. In addition, potenti al drinking water risks of concern for the existing ornamental uses were identified. The Agency is currently working with the propamocarb hydrochloride registrants to mitigate these risk concerns.

Ecological Risk Assessment Status:

The key findings of the most recent ecological risk assessments for propamocarb hydrochloride
are summarized below. For a detailed di scussion of the eco logical risk assessm e nt status, please refer to the September 20, 2011 memo, Registration Review – Prelim inary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Propamocarb-HCl , in docket EPA-HQ-OPP-2011-0662.

• The most recent comprehensive, national ecological risk assessment for propamocarb hydrochloride was completed in Augus t 1995 in support of the propamocarb hydrochloride RED. This risk assessment wa s limited to registered uses at that time, including use on ornamental la wns and turf, ornamental sod farms (turf), and ornamental herbaceous plants, woody shrubs, and vine s. Propamocarb hydrochloride was not registered for use on agricultural crops until 2000. In the 1995 ecological risk assessment, use of propamocarb hydrochloride on turf and ornamentals was associated with risk quotients that exceeded the Agen cy’s Level of Concern (LOC) for birds and
mammals. No risk concerns were identifie d for fish, but acute risk concerns were identified for aquatic invertebrates. These risk concerns were mitigated in the propamocarb hydrochloride RED through required label changes.

• Limited ecological risk assessments were conducted in 2000 and 2004 to support uses of propamocarb hydrochloride on potatoes, tomato es, lettuce, peppers, and other fruiting vegetables. The June 2000 risk assessment fo r potatoes concluded that LOCs for avian endangered species were exceeded; however, no acute or chronic risk concerns for aquatic or non-endangered terrestrial or ganisms were identified. The 2004 risk

13assessment for lettuce showed potential chronic risk concerns for birds only; there were
no other acute or chronic risk concerns for terrestrial or aquatic organisms.

• Chronic risk to aquatic invertebrates has not been characterized in previous risk assessments, because EPA did not have suffi cient chronic toxicity data for aquatic invertebrates. However, a chronic daphnid study (MRID 45727801) has been submitted and is currently undergoing review.

• Many of the ecological effects studies (both terrestrial and aquatic) submitted for propamocarb hydrochloride were conducte d using formulated propamocarb hydrochloride pesticide products rather than th e technical grade activ e ingredient (TGAI). Although all but one of these studies were sc ientifically sound, there is uncertainty because a higher percent active ingredient formulation may cause increased toxicity than what was seen in the submitted studies. Therefore, uncertainty exists regarding all taxa for which a formulated product was tested.

Human Health Risk Assessment Status:

The key findings of the most recent human health risk assessment for propamocarb hydrochloride are summarized belo w. For a detailed discussion of the human health risk assessment status, please refer to the September 14, 2011 memo, Promamocarb Hydrochloride: Human-Health Assessment Scoping Docu ment in Support of Registration Review , in docket EPA-HQ-OPP-2011-0662.

• The most recent comprehensive human health risk assessment for propamocarb hydrochloride was completed in February 2004 in support of a FIFRA Section 3 petition for use of propamocarb hydrochloride on lettuce, fruiting vegetables, and cucurbits. An occupational and residential risk assessme nt was completed on November 5, 2009 to support a proposed use on lima beans (to date, this use has not been granted and this action is pending).

Hazard Characterization:

• Propamocarb hydrochloride has lo w acute toxicity via the or al, dermal, and inhalation routes of exposure. It is not a dermal ir ritant and does not cause skin sensitization; however, it is a slight eye irritant.

• In animal studies, propamocarb hydrochloride is associated with neurotoxic effects.
Subchronic and chronic rat studies showed d ecreased motor activity and brain lesions, and ocular effects. A dog st udy also showed ocular effects. In addition, subchronic and chronic dog studies showed toxici ty to the gastrointestinal tr act and lesions in the trachea and lungs following dietary exposure.

• Developmental toxicity studies with propamocarb hydrochlorid e in the rat and rabbit did not show any increased evidence of susceptibi lity in offspring at doses associated with maternal toxicity. However, qualitative eff ects were seen in offspring, postimplantation losses, minor skeletal abnormalities, and mi nor lesions in the ears, heart, and upper gastrointestinal tract.

14• In the 2004 human health risk assessment, EPA reduced the 10x FQPA safety factor to 1x because the toxicity database was adequate to characterize the potential for pre- and postnatal risk for infants and children, no devel opmental effects were observed in rats, and
there was a lack of evidence of increased su sceptibility. However, this FQPA safety factor decision preceded changes in EPA’s current science policy.

• Propamocarb hydrochloride is not c onsidered to be mutagenic, and it has been classified by EPA as “not likely to be carcinogenic in humans.”

Dietary:

• In support of the 2004 risk assessment, EPA conducted unrefined acute and chronic dietary (food) exposure assessmen ts for the general U.S. population and various subgroups. Drinking water exposure was not incorporated directly in the dietary assessment. Acute and chronic dietary exposure estimates were below EPA’s levels of concern for all population subgroups.

• In support of a petition for use of propamocarb hydrochloride in/on lima beans, a 2009 preliminary (Tier I) drinking water assessment was conducted, which indicated risks of concern for drinking water based on the ex isting ornamental use (highest labeled application rate). The Agency is currently working with the regist rants to mitigate the
identified risk concerns.

• For further details regarding the updated EDWC assessment, please see the August 7, 2009 memo, Propamocarb Hydrochloride: Ti er I Drinking Water Estimated Environmental Concentrations for Use in the Human Health Risk Assessment . This document may be found in docket EPA-HQ-OPP-2011-0662.

Residential:

• As previously mentioned, EPA conducted an occupational and residential risk assessment in 2009 to support a proposed use on lima bean s (this action is currently pending). The risk assessment considered exposure to resi dential handlers mixing, loading, and applying pesticide products containing propamocarb hydrochloride as well as post-application exposure to golfers. EPA’s risk estimates fo r residential handlers and post-application exposure to golfers did not exceed the Agency’s levels of concern.

• Post-application residential e xposure from the treatment of ornamentals was considered to be negligible.

Aggregate:

• The Agency’s most recent aggregate risk assessment for propamocarb hydrochloride can be found in the February 2004 human health risk assessment supporting food uses on cucurbits and fruiting vegetables. Alt hough exposure to drinking water was not incorporated directly in the dietary assessmen t, aggregate exposure to food and drinking water were estimated using EPA’s drinki ng water levels of comparison (DWLOCs) methodology. The 2004 risk assessment did not id entify any aggregate risks of concern.

15• However, the Agency’s preliminary 2009 eval uation of drinking water exposure indicates aggregate risks of concern due to drinking wa ter residues from the ornamental use. The Agency is currently working with the registra nts to mitigate the identified risk concerns.

Occupational:

• The Agency’s most recent occupational handl er and post-application risk assessment was conducted in 2009 to support a petition for a new use of propamocarb hydrochloride on lima beans (this action is currently pending).

• For most uses, handler risks were below the le vel of concern, provide d that handlers wore gloves, as specified on propamocarb hydrochlorid e product labels. However, for the turf and ornamental use, EPA identified risk concerns for (1) handlers mixing/loading propamocarb hydrochloride for chemigation and groundboom application at the highest assumed application rate (218 lbs ai/A ) and (2) handlers applying propamocarb hydrochloride by groundboom at the highest as sumed application ra te (218 lbs ai/A). EPA is working with registrants to mitigate identified risk concerns.

• Post-application risks of concern were identi fied for workers handling ornamental plants treated with propamocarb hydrochloride via foliar drenching. The highest assumed application rate of 218 lbs ai/A results in risk concerns for re-entry workers for several days after treatment, resulting in recommended restricted en try intervals (REIs) ranging from 12 to 53 days. As previously menti oned, EPA has identified issues with label clarity for propamocarb hydrochloride produc ts registered for use on turf and ornamentals. EPA is working with registrants to mitigate the identified risk concerns.

Human Studies:

• Past propamocarb hydrochloride risk assessments rely in part on da ta from studies in which adult human subjects were intentionally exposed to a pesticide to determine their dermal and inhalation exposure. Many such studies, involv ing exposure to many different pesticides, comprise generic pesticide exposure databases such as the Pesticide Handlers Exposure Database (PHED) and the Agricultural Reentry Task Force (ARTF)
Database. EPA has reviewed all the studi es supporting these multi-pesticide generic exposure databases, and has found no clear a nd convincing evidence that the conduct of any of them was either fundamentally unethic al or significantly defi cient relative to the ethical standards prevailing at the time th e research was conducted. All applicable requirements of EPA’s Rule for the Protecti on of Human Subjects of Research (40 CPR Part 26) have been satisfied, and there is no regulatory barrier to continued reliance on
these studies.

Cumulative:

• Although propamocarb hydrochloride is a carbamat e pesticide, it is not a cholinesterase
inhibitor and EPA has determined that it doe s not share a common mechanism of toxicity
with the N -methyl carbamate pesticides. Ther efore, it is not included in the N -methyl
carbamate cumulative risk assessment.

16• EPA has not yet determined whether or not propamocarb hydrochlor ide shares a common mechanism of toxicity with any other chemical substances. If the Agency determines that new information on propamocarb hydrochloride is available that could potentially affect
a cumulative risk assessment and result in a risk of concern, the Agency will revisit the
need for a cumulative assessment.

Incidents:

• The Office of Pesticide Programs (OPP) Incide nt Data System (IDS) was consulted for reports of human health incidents associated with propamocarb hydrochloride, but no incident cases were reported. EPA will continue to monitor incident information for propamocarb hydrochloride and conduct additional analyses if needed.

• The Agency has conducted a preliminary review of the Ecological Incident Information System (EIIS), which is maintained by O PP, and the Avian Monitoring Information System (AIMS), which is maintained by the American Bird Conservancy. In the EIIS, one ecological incident involving propamocarb hydrochloride was reported in Montana in July of 2002. In this inci dent, the product PREVICUR ® FLEX was applied to 500 acres of sugar beets resulting in damage to 200 acres . An adjuvant was determined to be the probable cause of the incident. No inci dents involving propamocarb were found in

AIMS.

Tolerances and International Harmonization:

• Tolerances for residues of propamocarb hydroc hloride in or on various food and feed crops are established under 40 CFR §180.499.

• Where possible, the Agency will work to harmonize U.S. tolerances for propamocarb hydrochloride with Codex, Canadian, and Mexican Maximum Residue Levels (MRLs) for propamocarb hydrochloride.

Data Call-In Status:

• The most recent data call-in (DCI) for pr opamocarb hydrochloride was issued on October 11, 1995, following completion of the propamocarb hydrochloride RED (GDCI-119302- 17708). All of the data requirements from this DCI have been fulfilled or waived, with the exception of GDLN 850.1300, Freshwater Invertebrate Life Cycle. A study has been submitted in support of this requirement and is currently undergoing Agency review. Although data have been submitted to EPA, this will be considered as a data gap until the data have been reviewed and found to be acceptable.

• Certain data were required as a condition of registration for the first food use of propamocarb hydrochloride on potatoes. EPA has yet to receive data to fulfill Guideline 860.1360, Storage Stability for Livestock Commoditi es (metabolites). During review of the livestock feeding study required as a condition of re gistration, EPA identified the need for Guideline 880.1380, Multiresidue testing (metabolites). These residue chemistry data are needed to establish livestock tolerances for propamocarb

17hydrochloride because potatoes are a livestock feed commodity and will be listed as a data gap.

Labels:

Propamocarb hydrochloride Section 3 product labels can be obtaine d from the Pesticide Product Label System (PPLS) website: http://oaspub.epa.gov/pestlabl/ppls.hom

1819 III. SUMMARY OF DATA GAPS – Propamocarb hydrochloride

The table below summarizes all anticipated data needs for propamocarb hydrochloride identified
in Section I of this document (Preliminary Work Plan), the Registration Review – Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Propamocarb-HCl

, dated September 20, 2011 and the Propamocarb Hydrochloride: Human-Health Assessment Scoping Document in Support of Registration Review , dated September 14, 2011. It also lists outstanding data requirements from the propamocarb RED and data required to estab lish livestock tolerances (associated with a conditional registra tion on potatoes).

Table 1. Summary of Current Data Gaps for Propamocarb Hydrochloride

Guideline

Number Anticipated Data Requirement Test
Material Study

Duration

Anticipated Data Needs for Propamocarb Registration Review

835.1230 Adsorption/Desorption TGAI 12

835.4300 Aerobic Aquatic Metabolism (two additional soils) TGAI 24

835.4400 Anaerobic Aquatic Metabolism (one additional soil) TGAI 24

850.1350 Aquatic Invertebrate Life Cycle (estuarine/marine, mysid) TGAI 12

850.1400 Fish Early Life Stage Estuarin e/marine (sheepshead minnow) TGAI 12

850.2100 Avian Oral Toxicity (passerine species) 5 TGAI 12

Avian Oral Toxicity (upland game bird) TGAI 12

850.2200 Avian Dietary Toxicity (waterfowl and upland game bird) TGAI 12

860.1360 Multiresidue Testing (2-hydroxy and glucuronide metabolites ) 6 Metab. 24

860.1380 Storage Stability in Livestock Commodities (glucuronide metabolite) 6 Metab. 24

870.7800 Immunotoxicity TGAI 12

870.3465 Inhalation Toxicity (28 day study) 7 TGAI 12

Outstanding Data Requirement from the Propamocarb RED (GDCI-119302-17708)

850.1300 Invertebrate Life Cycle Toxicity ( Daphnia magna ) TGAI 12

5 The anticipated DCI will require the submission of a study protocol for review and approval by the Agency prior to study initiation.

6 This study is required to establish livestock tolerances.

7 EPA previously waived this study because minimal inhalation exposure is associated with outdoor agricultural uses and the study was not needed to evaluate worker risk. However, the study is now needed to evaluate worker risks for use of propamocarb hydrochloride in greenhouses.