Docket Number: EPA-HQ-OPP-2011-0662

www.regulations.gov

Propamocarb Hydrochloride Final Work Plan 

Registration Review

March 2012

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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-2011-0662). The 

Summary Document, dated September 21, 2011, 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. 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 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 interfering with the synthesis of fatty acids and phospholipids, thus affecting 

mycelia cell growth, spore production, and germination. Propamocarb hydrochloride is not an 

N-methyl carbamate and does not share a common mechanism of toxicity with the N-methyl 

carbamate group. Propamocarb hydrochloride was first registered in 1984, and a Reregistration 

Eligibility Decision (RED) was completed in 1995. The first food use, potatoes, was registered 

in 2000. Propamocarb 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 farms, 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 products. 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 beginning 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 concerning 

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 hydrochloride 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 Since 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 exposures from the 

registered use of propamocarb hydrochloride on ornamentals. The drinking water 

exposure estimates were based on default conservative assumptions because the 

propamocarb hydrochloride labels lacked clarity regarding application rates and other 

application parameters. To address these concerns, in January 2012, EPA sent a letter to 

propamocarb hydrochloride registrants with registered use ornamentals. This letter 

requested these 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

have 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 

concerns 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 PWP. 

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)
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Risk Assessment and Data Needs:

The Agency will require data for use in conducting a comprehensive ecological risk assessment, 

including an endangered species risk assessment, for all uses of propamocarb hydrochloride. 

The Agency also will require additional data for use in conducting a comprehensive human 

health risk assessment for all uses of propamocarb hydrochloride. A summary of the issues 

relevant to the registration 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 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, lettuce, peppers, and 

tomatoes. In addition, EPA conducted a drinking water assessment in 2009 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 propamocarb 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 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.

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 propamocarb

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 require the following data for propamocarb hydrochloride for use in 

conducting a comprehensive national ecological risk assessment, including an 

endangered species assessment:

GDLN 835.4300 – Aerobic Aquatic Metabolism1(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 data 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 Early Life Stage (estuarine/marine)3

EPA required a freshwater invertebrate life cycle study (GDLN 850.1300) in a Data CallIn (DCI) associated with the reregistration of propamocarb hydrochloride (GDCI119302-17708). Although one study (MRID 45894308) submitted to fulfill this 

requirement was determined to be invalid, another study (MRID 45727801) has been 

submitted and is currently in review. This will be considered 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, and the March 29,2012

document, EFED Response to Bayer 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 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 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 not established tolerances for propamocarb hydrochloride in/on 

lima beans. The 2009 risk assessment identified occupational (handler and postapplication) exposure and potential 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 through label amendments.

The Agency will require the following data for propamocarb hydrochloride for use in 

reevaluating toxicological endpoints (points of departure), safety/uncertainty factors and 

updating the human health toxicity profile:

 

2

The registrant may also conduct an acute freshwater daphnid study on the TGAI (GDLN 850.1010). 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 will require 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 the chronic 

fish study (GDLN 850.1400). However, if the TGAI shows greater toxicity than the formulated product in an acute 

study, EPA will require the chronic fish study (GDLN 850.1400).
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GDLN 870.7800 – Immunotoxicity

GDLN 870.3465 – Inhalation Toxicity 

During registration review, the Agency will revise the dietary risk assessment 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 occupational exposure databases for propamocarb hydrochloride are 

adequate; and therefore, EPA will not be requiring additional residential or occupational 

exposure data to support registration review. 

During registration review, the Agency anticipates revising 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 revise the aggregate assessment to incorporate changes to the dietary exposure 

estimates from food and/or drinking water (e.g., updated EDWCs). In addition, 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 exposure and/or risk assessment policies and procedures. 

EPA will reevaluate all occupational dermal and inhalation exposure assessments using 

standards and policies that are in place at the time of registration review. Revised 

occupational handler and post-application assessments will be needed in the event of 

changes to toxicological points of departure, receipt of new data, or changes to default 

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 and

maximum residue limits (MRLs), where possible, in key export markets during 

registration review. 

The 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 propamocarb hydrochloride use on potatoes, which are a livestock feed 

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

potatoes. 
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o GDLN 860.1360 - Multi-residue testing, 2-hydroxy and glucuronide metabolites

o GDLN 860.1380 - Storage stability for livestock commodities, glucuronide 

metabolite4

Please refer to Propamocarb Hydrochloride. Human Health Scoping Document in Support of

Registration Review, September 14, 2011, and Propamocarb Hydrochloride. Response to Public 

Comments. 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 assessment and data needs.

Endocrine Disruptor Screening Program

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic, and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, 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 effects 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 section 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 

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 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. Propamocarb

hydrochloride is not among the group of 58 pesticide active ingredients on the 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 

 

4 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. 
9

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/.

Timeline:

EPA has created the following 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 Docket

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 – 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

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 comments 

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 CropScience 

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 for 
10

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

on the assurance from EPA that other 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 terms. To this end, on January 11, 2012, EPA sent a letter to all propamocarb 

hydrochloride registrants requiring that 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)

Environmental 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 (Kd) is a more appropriate parameter for describing partitioning for propamocarbHCl, than the organic carbon-based adsorption coefficient (Koc). In addition, a positive 

relationship appeared to exist between Kd and both soil clay content and cation exchange 

capacity. Propamocarb-HCl is a typical strongly basic trialkylamine with a pKa 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 Kd values is due primarily to variations in the soil clay content and cation exchange 

capacity. The use of Koc 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 dataset for 

adsorption/desorption, EPA will use conservative assumptions for surface and groundwater 

modeling.

Comment 2: The Task Force conducted two aerobic aquatic metabolism studies (GDLN 

835.4300) with a total of four water/sediment systems to assess the aerobic degradation of 

propamocarb-HCl in aquatic systems. 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 fulfill 

the data requirements for GDLN 835.4300, aerobic aquatic metabolism. However, this guideline 
11

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 requirement for GDLN 850.1300, fresh water

invertebrate life cycle study, 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 fulfills 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-119302-17708, 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 

overall 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 also used mysid shrimp older than the age required by GDLN

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 requiring a chronic mysid life cycle study (GDLN 850.1350). Alternatively, the 

registrant has the option to conduct an acute freshwater daphnid study on the TGAI (GDLN

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, if 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 

demonstrating 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 HCl have seen effects only at high dose levels. Additional chronic fishing testing 

is not 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 in 
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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 

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

Alternatively, the registrant has the option of conducting an acute freshwater fish toxicity study 

with TGAI (GDLN 850.1075) rather than the chronic fish early life stage study. Although the 

registrant has already submitted an acute freshwater fish study (MRIDs 42083102 and 

42083103) this study was conducted with formulated products. 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 potentially waive the requirement for a chronic early life stage study with the 

sheepshead minnow. However, if the TGAI shows greater toxicity than the formulated product 

in an acute study, then EPA will 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 studies (MRIDs 42083102 and 42083103) and the same test exposure system 

(static or flow-through). 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 are sufficient to address the potential risk of 

propamocarb HCl to birds (GDLN 850.2100). Repeating a bobwhite quail LD50 study, or 

conducting a passerine LD50 study, are unlikely to have a significant impact on the overall 

assessment. No definitive LD50 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, the 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 terrestrial organisms than 

formulated product. Also, 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. 

Comment 7: EPA’s request that the bobwhite quail and mallard 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, but 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% propamocarb 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 livestock commodities. These data will support the use of 

propamocarb hydrochloride 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 food 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 commodities. 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 reviewed 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 addition, 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 2012. 

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 Requirements for Registration Review 

Test 

Material

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 Toxicity (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 Immunotoxicity10 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 toxicity 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 undergoing 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 prior 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.