UNITED STATES ENVIRONMENTAL PROTECTION AGENCY 

WASHINGTON D.C., 20460 

PC Code: 09760 l 

DP Barcode: 423024 

Date: October 23,2014 

MEMORANDUM 

SUBJECT: 

FROM: 

THROUGH: 

TO: 

Response to Public Comments on the Propargite Registration Review Problem 

Formulation ~ I 

It> tt..·1/l"' Freeborn G. Jewett, Biologist ,.,AStephen Wente, Ph.D., Fate •entist ~ IP/27/-9' 

Environmental Risk Branch I 

Environmental Fate and Effects Division (7507P) 

Office of Pesticide Programs 

Meghan Radtke, Ph.D., Acting RAPL 

Sujatha Sankula, Ph.D., Branch Chief 

Environmental Risk Branch I 

Environmental Fate and Effects Division (7507P) 

Office of Pesticide Programs 

Wilhelmena Livingston, Chemical Review Manager 

· Kevin Costello, Branch Chief 

Risk Management and Implementation Branch 4 

Pesticide Re-Evaluation Division (7508P) 

Office of Pesticide Programs 

In response to the "R·egistration Review Problem Formulation for Propargite" (0415245), MacDermid 

Agricultural Solutions, Inc. I Chemtura Company submitted comments on the "Anticipated Data Needs 

for the Propargite Registration Review." In addition, the Physicians Committee for Responsible Medicine 

has submitted comments and suggestions about relevant studies. The purpose of this memorandum is to 

address these comments and data submissions. 

Comments from MacDermid Agricultural Solutions, Inc./ Chemtura Company 

Comment: "A footnote on page 23 in May 5, 2014. Propargite Problem Formulation to 'Upgradable' 

MRID 42908402 notes the Agency cannot locate why it previously updated the study to 'acceptable' and 

requested that if the Registrant can provide EFED such, the study would again be deemed acceptable. 

Note the Registrant provided a previous requested upgrade to the study that was assigned MRID 

4369710 I. This upgrade correspondence is likely what EFED has misplaced." 

EPA response: The Agency agrees that MRID 4369710 I provides sufficient information to 

upgrade MRJD 42908402 to acceptable. 

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Comment: “A study conducted with Chironomus riparius was previously submitted (Guideline 850-

1735, 850.1790) (MRID 48557301) at the request of the Agency as part of the on-going salmonid BiOps. 

Discussion on Page 27 of Table II-3 (Aquatic Ecological Effects data for Propargite) in May 5, 2014. 

Propargite Problem Formulation notes that just one chronic sediment test across Hyalella, Chironomus

and/or Leptocheirus is needed to fulfill the study requirement.”

EPA response: The Agency appreciates the submission of the study conducted with Chironomus 

riparius. Protocol dictates that all three species Hyalella, Chironomus and Leptocheirus must be 

evaluated. This requirement can be waived if there is sufficient evidence of low toxicity. The 

Registrant is welcome to submit a formal Waiver Request if they feel the requirement should be 

waived.

Comment: “MRID study 48557301 was previously submitted to the Agency for review. Guideline

850.1790 notes that either midge Chironomus tentans or C. riparius can be used in the trial.”

EPA response: The problem formulation will be altered to correct this error. In the meantime., 

review of this study has not been initiated, but it will be sent out for review by the Agency. When 

the DER is completed, the Registrant will receive notification and a copy.

Comment: “Upon review of guideline studies 850.1010 and 850.4500 with the propargite metabolite, 

TBPC, these 2 studies will demonstrate ~10x less toxicity than predicted by modeling. Thus this third 

study with a marine diatom is not needed.”

EPA response: Review of these studies has not been initiated, but these will be sent out for 

review by the Agency. When the DER is completed, the Registrant will receive notification and a 

copy.

Comment: “EPA was notified on June 4, 2014 that the Registrant had requested reassessment of the

'invalid' study (MRID 44086801) on June 16, 1997 with information addressing all concerns. However it 

appears it has never reviewed during the last RED/DCI process for propargite. EFED was requested to 

provide this related DER/address this supplemental information in that correspondence.”

EPA response: The Agency is unable to locate the supplemental information previously 

submitted by the registrant. The Agency requests that the supplemental data are resubmitted for 

review.

Comment: “The Registrant submitted a commitment letter to the Agency in March 2014 (March 6, 2014. 

Propargite Label Updates Proposed During EPA NMFS Salmonid Consultation Discussion...) to 

voluntarily amend formulation labels by the end of 2014. Such were recently submitted and received by 

the Agency on July 16. Changes include lessening total application number to ≤2 across formulations and 

crops, limiting a single application to ≤3.2 lbs. a.i./acre, and limiting the total aerial application volume to 

≥ 10 gallons/acre in the salmonid states (CA, ID, OR, WA). These same changes will be made to FIFRA 

24(c) I SLN state labels. Thus these inputs will need to be used in any subsequent risk assessments by the 

Agency.”

EPA response: The Agency will use updated label information at the time of the risk assessment.

Comment: “The Agency asked for any/all additional studies that were not part of the propargite data 

matrix for the on-going salmonid BiOps/NMFS Consultation (Docket EPA-HQ-OPP-2008-0654). These 
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trials have not been included in the discussion/cited studies of the Agency's May 5, 2014. Propargite 

Problem Formulation. The Registrant requests that the Agency upgrade this section with the following 

references and provide the Registrant with the associated DERs. The following table captures studies 

submitted to date.”

MRID Guideline Citation

48545806 835.4100 Galicia, H. (October 25, 1990). Degradation of 14C-Propargite Technical in Soil 

Speyer 2.2 Incubated under Aerobic Conditions.

48545807 835.4100 Nag, J.K. (March 31, 2004). Degradation of 14C-TBPC in Three Soils under 

Aerobic Conditions.

48545808 835.2240 Concha, B.S. (April 17, 2003). Photolysis of [14C]-Propargite in Buffered Aqueous 

Solution.

48545809 835.4100 Schocken, M.J. (March 19, 2001). Analysis of Degradation Kinetics from a 

Propargite Aerobic Soil Metabolism Study (UCC 9416).

48545810 835.2240 Wanner, U. (October 1, 2004). Isolation of Photodegradates from a Propargite 

Aqueous Photolysis Study (2002-030).

48545811 835.4100 Dzialo, D.G., M. Schocken and U. Wanner (January 21, 2003). Propargite Soil 

Degradation in Two Soils.

48545812 835.4100 Charlton, R.R. and J.K. Nag (September 26, 2007). Degradation Kinetics of 14 CTBPC and its Degradation Products (PBPC-Acid and TBPC-Sulfate) using KinGUI, 

Version 1.1.

48545813 835.2110

835.2130

van der Gaauw, A. (September 10, 2002). 14C-Propargite: Hydrolysis at Three 

Different pH Values.

48545814 835.2240 McCorquodale, G. and K. Paterson (April 10, 2003). Artificial Sunlight 

Photodegradation of [14C]-Propargite in Buffered Aqueous Solution.

48545815 835.6100 Greig, Ian (May 22, 2003). Propargite: Dissipation of Propargite Residues in Soil 

Resulting from a Single Application of OMITE 570 EW in Northern France, 

Germany, Italy and Southern Spain.

48545816 835.4300 Voekel, W. (January 16, 2001). 14C-Propargite Route and Rate of Degradation in 

Aerobic Aquatic Systems.

48545817 835.1230 Walsh, K. (January 8, 2009). Adsorption/Desorption of [14C] Propargite in Five 

Soils.

48545818 850.1730 Suprenant, D.C. (January 26, 1988). Bioconcentration and Elimination of 14CResidues by Bluegill (Lepomis macrochirus) Exposed to OMITE.

48545819 835.1410 Pierce, J.B. (March 23, 1995). Henry's Law Constant - Propargite. Report No. 9522.

48545820 835.1410 White, C.K. (July 17, 2002). Calculation of Henry's Law Constant for Propargite.

48545821 830.7950 Riggs, A.S. (February 27, 2001). Vapour Pressure of 98+% Omite.

48557301 850.1735

850.1790

Kelly, C.R. and J. Allan (April 12, 2002). Propargite Determination of Effects of

14C]-Propargite on Chironomus riparius (28 Day, Static) in a Sediment Water 

System.

48557302 850.1075 Knight, B. and J. Allan (May 10, 2002). TBPC: Determination of Acute Toxicity 

(LC50) of TBPC to Rainbow Trout (96 h, Semi-Static).

48557303 850.1010 Knight, B. and J. Allan (May 10, 2002). TBPC: Determination of Acute Toxicity 

(EC50) to Daphnia magna (48 h, Static).

48567401 70-1-SS Weiland, R.T. (July 29, 2011). Propargite Exposure and Potential Effects on 

Threatened and Endangered Pacific Salmonids.

48567402 835.1230 Walsh, K. (January 8, 2009). Adsorption/Desorption of [14C] Propargite in Five Soils 

- Amended Report to MRID# 48545017

48618906 890.1350 York, D.O. (October 27, 2011). Endocrine Disrupter Screening Program Short-Term 

Reproduction Assay with Fathead Minnow (Pimephales promelas) for Propargite.

49001501 850.1075 Knight, B. and K Ferguson (May 10, 2002). Omite 570 EW: Determination of Acute 

Toxicity (LC50) of Omite 570 EW, a 570 g/1 EW Formulation of Propargite to 

Rainbow Trout (96 h, Continuous Flow).
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MRID Guideline Citation

49001502 850.1010 Knight, B. (May 10, 2002). Omite 570 EW: Determination of Acute Toxicity (LC50) 

of Omite 570 EW, a 570 g/1 EW Formulation of Propargite to Daphnia magna (48 

h, Continuous-Flow).

49001503 850.1075

850.1925

Hargreaves, T.L. (May 8, 2003). Omite 570EW: A Laboratory Microcosm Study to 

Evaluate the Acute Toxicity of Omite 570EW to Rainbow Trout Oncorynchus 

mykiss Walbaum (Teleostel: Salmonidae) when Applied as Simulated Agricultural 

Spray Drift onto a Body of Static Water Containing a Natural Sediment Substrate.

49001504 850.1010

850.1925

Hargreaves, T.L. (May 8, 2003). Omite 570EW: A Laboratory Microcosm Study to 

Evaluate the Acute Toxicity of Omite 570EW to Daphnia magna Straus. (Cladocera: 

Crustacea) when Applied as Simulated Agricultural Spray Drift onto a Body of 

Static Water Containing a Natural Sediment Substrate.

EPA response: The Agency has received all of the above listed studies and the reviews are 

ongoing. While this list of studies will not change the Data Call In (DCI) document, two of the 

studies, 48557302 and 48557303 directly address data gaps identified in the problem formulation 

document for the degradate TBPC. If these studies are approved, they could be used to address 

missing data in the Data Call In (DCI) document. When the DERs are completed, MacDermid 

Agricultural Solutions, Inc./ Chemtura Company will receive notification and copies.

Comments from the Physicians Committee for Responsible Medicine

Comment: “We recommend that OECD Test Guideline 223, Avian Acute Oral Toxicity Test, be used as 

the protocol instead of EPA Guideline 850.2100 in the interest of reducing the numbers of animals used 

by up to 61%.; We also refer the registrant to the "Guidance for Classifying Studies Conducted Using the 

OECD Test Guideline 223 (TG223) (Acute Avian Oral Sequential Dose Study)" available on the 

Agency's website.”

EPA Response: The OECD adopted the TG 223 guideline and issued a validation report. The 

EPA evaluated the results of the OECD validation report to determine if the TG 223 effects 

endpoints and whether the dose/response information adequately address the purposes of the 

avian acute oral data requirement as described in 40 CFR Part 158 and 40 CFR Part 161. This 

evaluation has been completed and guidance was issued on November 9, 2011 regarding

classification of studies conducted using the TG 223.

The following conditions should be met if a TG223 study is going to be considered acceptable by 

the Agency (see the attached TG223 guidance document for further explanation):

 Background mortality data at the laboratory conducting the test should be submitted if the 

species used is different than the bobwhite quail. 

 The chemical being tested should not cause delayed effects.

 For the “LD50 – slope test,” the raw data and results are submitted electronically using 

the SEquential DEsign Calculator (SEDEC) (the Excel calculator that determines the 

placement of doses during testing and is used to estimate the LD50, slope, and confidence 

limits for TG223 studies).

 The study meets the same validity requirements as 850.2100 (e.g., no greater than 10% 

mortality in the control birds).

 Control birds are not added during the course of the study.

 No regurgitation in test birds.
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Comment: “We have found existing data in regard to the fish acute toxicity test in rainbow trout for 

Propargite. In this study, the minimum, median, and maximum LC50 values for Propargite in the rainbow 

trout were found to be 118, 143, and 455 ppb, respectively. This study also provides LC50 values in the 

sheepshead minnow and the bluegill.

Another publication has shown the LC50 of Propargite in the rainbow trout to be between 0.101 and 0.12 

ppm, placing it in the highly toxic category towards fish. This resource also provides LC50 values in the 

bluegill and channel catfish.”

EPA response: The Agency appreciates suggestions for relevant studies from the public. We 

strive to incorporate all relevant data, while upholding a high standard for validating good 

laboratory practice. These studies are part of our database of relevant toxicity literature and can 

help characterize the risk picture of propargite. 

Comment: If these data are not sufficient then we recommend the registrant consider an alternative 

strategy that can supplement otherwise unacceptable fish toxicity data or provide information on the 

concentrations likely to cause acute fish toxicity. Such a strategy includes the newly-adopted Fish 

Embyrotoxicity Test guideline (FET) (OECD TG 236), an acute threshold estimation approach, and 

QSAR or read-across methods. Together these methods may in some cases provide enough information to 

set safe exposure levels without conducting additional live fish testing.

The FET provides a calculation of the LC50 by exposing fertilized zebrafish embryo eggs for 96 hours. 

Apical indicators of acute toxicity are recorded every 24 hours and include: (i) coagulation of fertilized 

eggs, (ii) lack of somite formation, (iii) lack of detachment of the tail-bud from the yolk sac, and (iv) lack 

of heartbeat. This test performed well in a comparative validation study conducted under the auspices of 

the German Federal Environment Agency and European Committee for the Validation of Alternative 

Methods.

Registrants can also conduct an acute threshold or "limit test'' which can reduce the number of animals 

used. This approach was first pioneered on the observation that fish are rarely more sensitive than algae 

and daphnia. The fish median lethal concentration (LC50) test is replaced with an acute threshold test in 

which fish testing would be performed at one concentration only (the lowest ECSO concentration 

obtained with previous algae and daphnia testing). A version of this approach has been adopted by the

OECD as a guidance document. The FET could also provide this threshold level.

We also encourage the use of (Q)SAR data either in place of, or addition to, the fish experimental data. 

When correctly applied, (Q)SARs can feasibly replace in vivo data in some instances; the submission of 

(Q)SAR data in addition to in vivo data would increase Agency and registrant comfort and confidence 

with the use and evaluation of data from such methods, and so we encourage the registrant to do so.”

EPA Response: Recognizing the limitations of current testing approaches and the rapid 

development of new biochemical and cellular assay systems and computational predictive 

methods, pesticide and other regulatory agencies have initiated the long-term investigation of 

Integrated Approaches to Testing and Assessment (IATA). The development and application 

of IATA and (Q)SAR methods to pesticide assessments is consistent with the United States 

Environmental Protection Agency (US EPA) commissioned National Research Council 

(NRC) report, Toxicity Testing in the 21st Century: A Vision and a Strategy (NRC, 2007). 

Towards that end, the United States Environmental Protection Agency Office of Pesticide 

Programs (US EPA OPP) has partnered with the Pest Management Regulatory Agency 
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(PMRA) of Health Canada to develop common approaches to IATA for the human health 

and ecological risk assessment of pesticides.

Already, (Q)SAR methods are being utilized by the Agency to qualitatively assess the 

potential risks of chemical degradates. There is much progress being made in this area, but 

before (Q)SAR methods can become commonplace in the Agency’s risk assessment methods, 

the (Q)SAR tools must be evaluated for validity, acceptability, relevance, and reliability.