Docket Number: EPA

- HQ

- OPP

- 2 0 1 1

- 0 662

www.regulations.gov



## P ropamocarb Hydrochloride Final Work Plan

Registration Review

March 20 1 23 Propamocarb Hydrochloride Final Work Plan

Introduction:

This is the Environmental Protection Agency’s (EPA or the Agency) Final Work Plan (FWP) for the registration review of propamocarb hydrochloride . The FWP includes the expected registration review timeline. The FWP also addresses any public comments received on the Preliminary Work Plan (PWP) in the Summary Document

, which was posted in the propamocarb hydrochloride registration review docket (EPA

- HQ

- OPP

- 201 1

- 0 662 ). The Summary Document

, dated September 21, 2011

, provided information on wha t 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. This document is the work plan for the propamocarb hydrochloride registration review process.

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/

.

Propamocarb hydrochloride is a carbamate fungicide that targets several Oomycetes species, including Phytophthora

, Pythium , and dow n y mildew

, which cause foliar diseases and seedling, seed, root, foot, and stem rot in vari ous edible and ornamental crops. It disrupts formation of fungal cell walls by interfering with the synthesis of fatty acids and phospholipids , thus affecting mycelia cell growth, spore production, and germination

. Propamocarb hydrochloride is not an

N

- m ethyl carb a mate and does not share a common mechanism of toxicity with the N

- methyl

carbam a te group. Propamocarb hydrochloride was first registered in 1984, and a Reregistration Eligibility Decision (RED) was completed in 1995. The first food use , potato es, was registered

in 2000. Pro p amocarb hydrochloride is currently registered as emulsifiable concentrate ( EC)

formulations for use on potatoes, lettuce, cucurbit vegetables, and fruiting vegetables, as well as golf courses, ornamental turf/plants, sod fa rms, and in nurseries/greenhouses. It is formulated with other fungicides, including chlorothalonil and fluopicolide. There are nine FIFRA Section

3 product registrations for propamocarb hydrochloride, including two registrations for manufacturing use pr oducts. There are six FIFRA Section 24(c) Special Local Need registrations for propamocarb hydrochloride.

Comments Received on the Preliminary Work Plan:

The propamocarb hydrochloride registration review docket was open for a 60

- day comment period begi nning on September 30, 2011. EPA received comments until November 29, 2011. EPA solicited comments on three specific topics: environmental justice, water body impairment,

and trade irritants. However, EPA did not receive comments or other information co ncerning

these issues.4

EPA received two comments on the PWP from Bayer Crop Science (BCS) and the [Propamocarb] Regulatory Task Force

. BCS commented that they had revised the labels for all of their pesticide products containing propamocarb hydrochlorid e used on ornamentals. The Regulatory Task Force commented on the anticipated data requirements for the propamocarb hydrochloride registration review

.

The Agency believes that the comments received do not change the risk assessment needs or the

timeline provided in the Propamocarb Hydrochloride Summary Document

. However, the comments do change the data requirements for registration review, and these changes are summarized in this Final Work Plan (FWP). The comments and EPA’s response are

summarized in the Summary of Comments section of this document

.

Updates S ince the Summary Document:

Label Changes

. In 2009, EPA completed a drinking water assessment for propamocarb hydrochloride to support a petition for a new use in/on lima beans. This assessment

identified risk concerns for occupational and drinking water e x posures from the registered use of propamocarb hydrochloride on ornamentals

. The drinking water exposure estimates were based on default conservative assumptions because the propamocarb hydr ochloride labels lacked clarity regarding application rates and other application parameters

. To address these concerns, i n January 201 2 , EPA sent a letter to propamocarb hydrochloride registrants with registered use ornamental s. This letter requested th ese registrants to amend all pesticide product labels to clarify application
parameters for ornamentals

, such as the maximum seasonal application rate or maximum applications per crop cycle . To date, all three registrants with registered use ornamentals

h ave submitted amended product labels. EPA is currently reviewing these labels , in advance of the assessment and mitigation phases of registration review, to determine if the changes address potential occupational and drinking water human health risk

conce rns from use of propamocarb hydrochloride on ornamentals.

Data Requirements. EPA has revised the data requirements for propamocarb hydrochloride as a result of comments submitted on the Summary Document and P WP. The rationale for these changes may be found in the Summary of Comments section of

this document

. EPA no longer believes that the following guideline (GDLN) studies are needed to complete the risk assessment for registration review :

GDLN 835.1230

– Adsorption/Desorption

GDLN 850.2100

– Avian Oral Toxicity (bobwhite quail and passerine)

GDLN 850.2200

– Avian Dietary Toxicity (bobwhite quail and mallard duck)5

Risk Assessment and Data Needs:

The Agency will requir e data for use in conduct ing a comprehensive ecological risk assessment,

includi ng an endangered species risk assessment, for all uses of propamocarb hydrochloride

. The Agency also will requir e additional data for use in conduct ing a comprehensive human

health risk assessment for all uses of propam o carb hydrochloride

. A summary of t he issues relevant to the registration review of propamocarb hydrochloride is given below

.

E cological Risk :

The most recent comprehensive

, national

- level ecological risk assessment for propamocarb hydrochloride was completed in 1995 in support of the RED

. In addition,

l imited ecological risk assessments were completed in 2000 to support the registration of the first propamocarb hydrochloride food use on potatoes

, and

, in 2004

, to support the registration of propamocarb hydrochloride use on cucurbits, let tuce, peppers, and

tomatoes . In addition, EPA conducted a drinking water assessment in 20 09 to support a petition for use on lima beans

.

The Agency has not conducted a risk assessment that supports a complete endangered species determination for propam ocarb hydrochloride

. The ecological risk assessment planned during registration review will allow the Agency to determine whether propamocarb hydrochloride use has “no effect” or “may affect” federally listed threatened or endangered species (listed speci es) 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 Fisheri es Service (the Services), as appropriate.

On January 19, 2011, the Center for Biological Diversity and the Pesticide Action

Network North America filed a lawsuit in the United States District Court for the Northern District of California, against EPA for allegedly failing to undergo consultation

with the Services regarding the effects of over 350 pesticides, including p ropamocarb hydrochloride , on over 200 endangered and threatened species throughout the United

States (Center for Biological Diversity, et al. v. EPA, et al., No. C 11

- 00293 (N.D.Cal.) )

.

The Agency will requir e the following data for propamocarb hydrochloride for use in

conduct ing a comp rehensive national ecological risk assessment, including an endangered species assessment :

GDLN 835.4300

– Aerobic Aquatic Metabolism 1 (two additional water/sediment systems )

GDLN 835.4400

– Anaerobic Aquatic Metabolism ( one additional water/sediment system )

1 Aerobic aquatic metabolism data have been submitted and are undergoing Agency review. This GDLN will be

considered a da ta gap until the study has been reviewed and found to be acceptable.6 GDLN 850.1350

– Aquatic Invertebrate Life

- Cycle Toxicity (estuarine/marine) 2

GDLN 850.1400

– Fish E arly Life Stage (estuarine/marine) 3

EPA required a freshwater invertebrate life cycle study (GDLN 850.1300) in a Data Call

In ( DCI ) associated with the reregistration of propamocarb hydrochloride (GDCI

119302

- 17 708 ). Although one study (MRID 45894308) s ubmitted to fulfill this requirement was determined to be invalid, another study (MRID 45727801) has been

submitted and is currently in review. T his will be considered a data gap until the data have been reviewed and found to be acceptable.

Please refer t o the September 20 , 2011 document

, Registration Review

– Preliminary Problem Formulation for Ecological Risk and Environmental Fate, Endangered Species, and Drinking Water Assessments for Propamocarb

- HC l

, and the March 29, 2012 document, EFED Response to B ayer CropScience and Agriphar Comments to EFED Problem Formulation on the Registration Review of Propamocarb Hydrochloride

, located in docket EPA

- HQ

- OPP

- 2011

- 0662 for a detailed discussion of the risk

assessment and data needs and for a more detailed discu ssion of uncertainties on certain product labels

.

Human Health Risk :

The most recent comprehensive human health risk assessment for propamocarb hydrochloride w as compl eted 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 commodities. An occupational and residential risk assessment was completed on November 5, 2009 to support a proposed use on lima

beans. To date, EPA has n ot established tolerances for propamocarb hydrochloride in/on

lima beans. Th e 2009 risk assessment identified occupational (handler and post

application) exposure and potential drinking water exposure risk concerns associated with an existing use of propa mocarb hydrochloride on ornamentals. The Agency is currently working with the registrants to mitigate th e se risk concern s through label amendments

.

The Agency will requir e the following data for p ropamocarb hydrochloride for use in

reevaluat ing toxicolo gical endpoints (points of departure), safety/uncertainty factors and updat ing the human health toxicity profile :

2 The registrant may also conduct an acute freshwater daphnid study on the TGAI (G DLN 850.10 10 ). If the TGAI shows toxicity ≤ toxicity of formulated product, EPA may bridge toxicity data of available studies and waive the mysid chronic study (GDLN 850.1350). However, if the TGAI shows greater toxicity than the formulated product in an acute study, EPA w ill requ ire the chronic mysid study.

3 The registrant may also conduct an acute freshwater fish study on the TGAI (GDLN 850.1075). If the TGAI shows toxicity ≤ toxicity of formulated product , EPA may bridge the available toxicity data and waive th e chronic

fish s tudy (GDLN 850.1400). However, if the TGAI shows greater toxicity than the formulated product in an acute study, EPA w ill require the chronic fish study (GDLN 850.1400).7 GDLN 870.7800

– Immunotoxicity

GDLN 870. 3465

– Inhalation Toxicity

D uring registration review, the Agency will revis e the dietary risk asse ssment to incorporate refined estimated drinking water concentrations (EDWCs)

, updated
anticipated food residues and Pesticide Data Program (PDP) data

, and any changes to
toxicological points of departure or uncertainty factors

.

The residential and occu p ational exposure databases for propamocarb hydrochloride are adequate; and therefore, EPA will not be requiring additional residential or occupational exposure dat a to support registration review.

During registration review, the Agency anticipates revis ing the residential handler and bystander risk assessments if data are identified which may impact the points of departure or the FQPA safety factor; or if revisions are made to any of EPA’s exposure and/or risk assessment policies and procedures. EPA may also conduct a bystander risk assessment to address potential exposure via spray drift.

EPA will revis e the aggregate assessment to incorporate changes to the dietary exposure

estimates from food and/ or drinking water (e.g., updated EDWCs)

. In additio n, an aggregate assessment will be needed if data are identified which may impact the points of departure or the Food Quality Protection Act ( FQPA ) safety factor ; or if revisions are made to any of EPA’s e xposure and/or risk assessment policies and procedu res.

EPA 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

- application assessments will be needed i n the e vent of changes to toxicological points 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 cover s 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 and maximum residue limits (MRL s ), wher e possible, in key export markets during registration review.

T he following residue chemistry data are needed to establish tolerances for livestock

commodities

. These data were previously identified as being needed by the Agency in support of propamoca rb hydrochloride use on potatoes , which are a livestock feed commodity

. EPA granted a conditional registration for use of propamocarb chloride on potatoes

.8 o GDLN 860.1360

- Multi

- residue testing

, 2

- hydroxy and glucuronide metabolites

o GDLN 860.1380

- S torage stability for livestock commodities , glucuronide

metabolite 4

P lease refer to P ropamocarb Hydrochloride. Human Health Scoping Document in Support of Registration R eview

, September 14

, 2011

, and Propamocarb Hydrochloride. Response to Public

Commen ts. The Health Effects Division’s Response to Comments on Human

- Health Assessment Scoping Document in Support of Registration Review , February 8, 2012, located in the docket, for a detailed discussion of the anticipated risk a ssessment and data needs

.

En docrine Disru ptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potentia l ad v erse outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic

, and chronic toxicity, including assess ments of carcinogenicity, neurotoxicity, developmental,

repr oductive, and gener a l or systemic toxicity. These studies include endpoints which may be susceptible to endocrine influence, including effects on endocrine ta r get organ histopathology, organ weigh ts, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and chronic studies that assess growth, developmental and reproductive effect s in different taxonomic groups. As part of its most recent registration decision , EPA reviewed these data and selected the most sensitive endpoints for relevant risk assessment scenarios from the existing hazard database. However, as required by FFDCA s ection 408(p), propamocarb hydrochloride is subject to the endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). EPA has developed the 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

deter minations. 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 ad verse endocrine

- related effects 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 ingredients and 9 inert ingredients. P ro pamocarb hydrochloride is not among the group of 58 pesticide active ingredients on the initial lis t 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

4 This study has been submitted to EPA and is undergoing review. However, it will b e considered a data gap until the study has been reviewed and found to be acceptable.9

hydrochloride

. For further information on the status of the E DSP, 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/

.

Timeline:

EPA has created the foll owing estimated timeline for the completion of the propamocarb hydrochloride registration review

.

Table 1. Projected Registration Review Timeline for Propamocarb Hydrochloride

Activities Estimated Date Opening the D ocket Open Docket and Public Comment Period 2011

– September

Close Public Comment 2011

– November Case Development

Final Work Plan 2012

– March

Issue DCI 2012

– Oct.

– Dec.

Data Submission 2014

– Oct.

– Dec. Open Public Comment Period for Draft Risk Assessments 2016

– April

– Ju ne Close Public Comment Period 2016

– July

– Sept. Registration Review Decision Open Public Comment Period for Proposed Registration Review

D ecision 2016

– Oct.

– Dec.

Close Public C omment P eriod 2017

– Jan.

– March Registration Review D ecision a nd Begin P ost

- D ecision F ollow

- up 2017 Total ( years ) 6

Summary of Comments :

A summary of comments received on the Propamocarb Hydrochloride Summary Document and PWP and the Agency’s response is provided below. For a detailed description of the commen ts received and the Agency’s response, please refer to the February 8 , 2012 document, Propamocarb Hydrochloride. Response to Public Comments. The Health Effects Division’s Response to Comments on the Human

- Health Assessment Scoping Document in Support of Registration Review and the March 29 , 2012 document, EFED Response to Bayer C r opScience and Agriphar Comments to the EFED Problem Formulation on the Registration Review of Propamocarb Hydrochloride. Both of these documents are in the public docket.

(1) Bayer Crop Science (BCS)

Comment: BCS has revised the Banol product label to address EPA’s concerns about label clarity for the ornamental use. The amended label was submitted to EPA in 2010. EPA approved the amended label on July 7, 2011. BCS agreed to set single and maximum yearly use

rates for both the turf and ornamental uses, and to use a directed drench application for10

ornamentals to eliminate worker exposure from a foliar application. Bayer agreed to these terms

on the assurance from EPA that o ther registrants would comply with these same terms.

Response: EPA ’s concerns regarding label clarity for the ornamental use remain until all registrants have submitted, and EPA has approved

, amended labels. All registrants must comply

with the same te rms. To this end, on January 11, 2012, EPA sent a letter to all propamocarb hydrochloride registrants requiring t hat registrants amend all pesticide product labels to clarify application parameters such as the maximum seasonal application rate, or maximum applications per crop cycle

. All registrants have responded with amended labels, and these are currently under review. EPA expects to approve the amended labels in 2012.

(2) [Propamocarb Hydrochloride] Regulatory Task Force (BCS and Agriphar)

Environment al Fate and Effects

Comment 1 : BCS has conducted two additional adsorption/desorption studies to be submitted

to EPA. BCS conducted these studies to understand the differences in the mobility data in the studies reviewed by EPA. One study was conducted with soils from the same location but

different soil horizons with different organic carbon content, cation exchange capacity, and clay

content

. The other study was conducted with soils having a wide range of organic content, pH

, cation exchange capacity , and clay content. The results from these two studies showed no apparent relationship between the soil organic content and sorption; therefore

, the adsorption coefficient (K d ) is a more appropriate parameter for describing partitioning for propamocarb

HC l, than the organic carbon

- based adsorption coefficient (K

oc ). In addition, a positive relationship appeared to exist between K d and both soil clay content and cation exchange capacity

. Propamocarb

- HCl is a typical strongly basic trialkylamine with a pK

a ranging from 9.3

to 9.6 and can accept H + ions to be positively charged under most soil pH conditions. The protonated propamocarb is then bound to the negatively charged clays. In summary, the wide range of K d values is due primarily to variations in th e soil clay content and cation exchange capacity. The use of K

oc is not appropriate since no relationship exists between sorption and organic carbon.

Response 1 : EPA is aware of the analysis and conclusions for the studies referenced above and

will not be requiring any additional adsorption/desorption data (GDLN 835.1230) for registration review. Furthermore, EPA will review the two additional studies when they are submitted to determine if they fulfill GDLN 835.1230. In the absence of a complete data set for adsorption/desorption, EPA will use conservative assumptions for surface and groundwater modeling.

Comment 2 : The T ask F orce conducted t wo aerobic aquatic metabolism studies (GDLN 835.4300) with a total of four water/sediment systems to assess th e aerobic degradation of propamocarb

- HCl in aquatic system s

. BCS will submit these studies to EPA to fulfill the data requirement for aerobic aquatic metabolism.

Response 2 : EPA will review these studies when they are submitted and determine if they fu lfill the data requirements for G DLN 835.4300, a erobic a quatic m etabolism. However, this guideline11

will be considered a data gap until the study has been reviewed and the study is found to be acceptable.

Comment 3 : The Task Force wants to assess the re quirement for G DLN 850.1300, f resh w ater
i nvertebrate l ife c ycle s tudy, after EPA reviews the submitted study ( MRID 45727801 )

.

Response 3 : EPA will review the cited study and determine whether it is acceptable for use in

risk assessment and whether it fu lfills the guideline requirement. When the study review is complete, it will be sent to the registrant with a letter outlining the next steps. This invertebrate

life cycle study was required under a previous DCI, GDCI

- 119302

- 17 708 , and will be

considered a data gap until the data have been reviewed and found to be acceptable.

Comment 4 : Mysid shrimp are relatively insensitive to propamocarb HCl (Putt A 2001 and Schupner 1991) and additional chronic testing (GDLN 850.1350) is unlikely to change the

over all conclusion of the risk assessment.

Response 4 : EPA has reviewed the studies cited , but they were both conducted with a formulated product, rather than the technical grade active ingredient (TGAI) , and under static conditions. The Schupner study als o used mysid shrimp older than the age required by G DLN 850.1350. Both studies were classified as supplemental.

Formulated products contain inert ingredients that can affect the bioavailability of the pesticide active ingredient to aquatic organisms. For example, formulated products may contain certain solvents that might increase or decrease binding of the chemical to dissolved organic carbon in the water column, thereby affecting the level of chemical available for exposure to fish or

invertebrates. To better understand the comparative toxicity of the formulated product and TGAI, EPA is requ iring a chronic mysid life cycle study (GDLN 850.1350). Alternatively, the registrant has the option to conduct a n acute freshwater daphnid study on the TGAI (G D LN 850.1300)

. If the toxicity of the TGAI is less than or equal to that of the formulated product, EPA will bridge toxicity data of available studies and waive the requirement for a chronic mysid study (GDLN 850.1350)

. However, i f the TGAI shows greater toxicity than the formulated product in an acute study, then EPA would still require the chronic mysid life cycle study.

If the registrant chooses to conduct an acute daphnid study, the study should use the the same

nominal test concentrations used in the original acute freshwater invertebrate study (MRID 45894303), using the same test exposure system (i.e., static). Because the original studies were limit tests conducted at one nominal test concentration, EPA will also accept limit test data

demonstratin g that the TGAI is not toxic up to a similar concentration

.

Comment 5 : Existing chronic fish studies (Graves, W. and G.Peters, 1991; Gries, T. 2002) with propamocarb HC l have seen effects only at high dose levels. Additional chronic fishing testing

is n ot justified based on the compound ’ s toxicity profile.

Response 5 : EPA determined that the existing chronic fish study by Graves and Peters was invalid for a number of reasons, including problems with the water delivery system resulting in12

errors in the test concentration, number of replicates, and number of fish embryos per replicate. In addition, this study was conducted with a formulated product. Formulated products contain inert ingredients that can affect the bioavailability of the pesticide active ingredient to aquatic organisms. This study does not fulfill GDLN 850.1400.

To better understand the comparative toxicity of the formulated product and the TGAI, EPA is

requ iring an early life stage study with the sheepshead minnow (GDLN 850.1400).

Alt ernatively, the registrant has the option of conducting an acute freshwater fish toxicity study with TGAI ( G DLN 850. 1075) rather than the chronic fish early life stage study

. Although the registrant has already submitted an acute freshwater fish study (MRI Ds 42083102 and 42083103) th is stud y w as conducted with formulated product s . I f the toxicity of the TGAI is less than or equal to that of the formulated product, EPA will bridge toxicity data of available

studies and potentially waive the requirement for a chronic early life stage study with the sheepshead minnow. However, i f the TGAI shows greater toxicity than the formulated product in an acute study, then EPA w ill still require the fish early life stage study.

If the registrant chooses to conduct an acute freshwater fish study with the TGAI , then this study

should be conducted using the same nominal test concentrations as in the original acute

freshwater fish stud ies (MRIDs 42083102 and 42083103) and the same test exposure system (static or flow

- t hrough). Because the original studies were limit tests conducted at one nominal

test concentration

, EPA will also accept limit test data demonstrating that the TGAI is not toxic up to a similar concentration

.

Comment 6 : The existing avian oral studies a re sufficient to address the potential risk of propamocarb HC l to birds (GDLN 850.2100) . Repeating a bobwhite quail LD 50 study, or conducting a passerine LD 50 study, are unlikely to have a significant impact on the overall

assessment. No defin i t i ve LD 50 was reported in the submitted studies because insufficient toxicity was seen up to the standard maximum test concentration of 2000 mg/kg body weight. In addition, it appears that EPA has omitted a number of older avian studies from the current

assessment, including Hakin 1992, and two studies by Ross et al 1977.

Response 6 : The Hakin study , although classified as acceptable, was conducted on 71.7% ai (rather than the technical grade) and showed a nondefinitive endpoint and two mortalities. In addition, t he Ross studies had deficiencies that precluded their use by EPA. However, EPA is no longer requiring the avian acute oral toxicity studies on upland game bird or passerine species (GDLN 850.2100) because the TGAI is unlikely to be more toxic to terrestr ial organisms than formulated product

. Also, t he existing test data for the formulated product show relatively low toxicity to birds and additional data are not expected to be of significant value

.

Comment 7 : EPA’s request that the bobwhite quail and m allard duck studies (GDLN 850.2200) be repeated appears to be due to the use of a formulated product rather than the TGAI in the

studies. There is no reason to believe that the formulation had an undue influence on propamocarb’s toxicity, especially given the dietary study design. Also, as with the acute avian studies, EPA appears to have considered only the most recent studies, and ignored older studies (two by Hakin 1992, and two by Ross et al, 1977).13

Response 7 : The studies by Ross were considered, b ut both of these studies are invalid because of a number of reporting deficiencies and a discrepancy between food consumption and body weight data. The Hakin studies were missing the results of analytical analysis, and were also conducted on 72.2% propamo carb HCl , rather than the TGAI

. However, EPA is no longer requiring the avian acute dietary toxicity studies because the TGAI is unlikely to be more toxic to terrestrial organisms than formulated product

. The existing test data for the formulated product show relatively low toxicity to birds and additional data are not expected to be of significant value.

Human Health Effects

Comment 8 : EPA has requested multiresidue testing for the 2

- hydroxy and glucuronide

metabolites to establish tolerances for liv estock commodities. These data will support the use of propamocarb hydroc h loride on potatoes. Bayer has agreed to conduct this study following the

issuance of the DCI.

Response 8 : This study was required as a condition of registration for the first foo d use of propamocarb hydrochloride, but will also be included in the registration review DCI , which will

be issued late in 2012

.

Comment 9 : EPA has requested a storage stability study for the propamocarb glucuronide

metabolite in livestock commoditie s. Bayer submitted a storage stability study (MRID 46458801) for the glucuronide metabolite in livestock milk and tissues samples in 2005.

Response 9 : EPA is reviewing this study. However, it will be considered a data gap until the study has been rev iewed and the study is found to be acceptable.

Comment 10 : Bayer has completed an immunotoxicity study for propamocarb hydrochloride and is submitting this study to EPA.

Response 10 : The Agency will review this study when it is received. In additio n, the DCI for this study will be issued in late 2012.

Comment 11 : EPA has requested a 28

- day inhalation study to support the greenhouse use for propamocarb hydrochloride. The Propamocarb Regulatory Task Force will conduct a study to

fulfill this data requirement.

Response 11 : The Agency will review this study when it is received. In addition, the DCI for this study will be issued in late 2012.14

Next Steps:

EPA will require data through a DCI for propamocarb hydrochloride to be issued in late 2 012. The data generated will be reviewed by EPA and used to conduct risk assessments for the propamocarb hydrochloride registration review.15 Summary of Data Gaps

– Propamocarb Hydrochloride

EPA will require the following studies in order to conduct the planned ecological and human health risk assessments for the propamocarb hydrochloride registration review.

Table 2. Data Needs for the Propamocarb Hydrochloride Registration Review

Guideline

Number Data Requirement s for Registration Review Test

Ma terial Study

Duration
(months

from DCI receipt)

835.4300 Aerobic Aquatic Metabolism (two additional water/sediment

systems) 5 TGAI 24

835.4400 Anaerobic Aquatic Metabolism (one water/sediment system) TGAI 24

850.1350 Aquatic Invertebrate Life

- Cycle Toxic ity (estuarine/marine ) 6 TGAI 12

850.1400 Fish Early Life Stage (estuarine/marine ) 7 TGAI 12

860.1360 Multiresidue Testing (2

- hydroxy and glucuronide metabolites ) 8 Metab. 24

860.1380 Storage Stability in Livestock Commodities (glucuronide

metabolite) 8

, 9 Metab. 24

870.7800 Immunotoxicity 10 TGAI 12

870.3465 Inhalation Toxicity (28 day study) 11 TGAI 12

Outstanding Data Requirement from the Propamocarb Hydrochloride RED ( GDCI

- 119302

- 17708 )

850.1300 Invertebrate Life Cycle Toxicity ( Daphnia magna ) 5 TGAI 12

5 This study has been submitted to EPA and is undergoing review. However, it will be considered a data gap until the study has been reviewed and found to be acceptable.

6 EPA may waive this study if data from an acute freshwater invertebrate toxicity study (GDLN 850.1010) are submitted on the TGAI and if these data show toxicity ≤ toxicity of the formulated product.

7 EPA may waive this study if data from an acute toxic ity study on freshwater fish (GDLN 850.1075) are submitted on the TGAI and if these data show toxicity ≤ toxicity of the formulated product.

8 This study is required to establish livestock tolerances.

9 This study has been submitted to EPA and is underg oing review. However, it will be considered a data gap until the study has been reviewed and found to be acceptable.

10 The Data Call

- In (DCI) will require a study protocol to be submitted to EPA within 90 days of receipt of the DCI and approved by EPA pr ior to initiation of the study.

11 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.