### 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 t o Public Comment s o n the Propargite Registration Review Problem

Formulation

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## I It> 

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· 1/l"' Freeborn 

### G. Jewett, Biologist ,.,A

### Stephen Wente

, Ph.D.

, Fate •e ntist

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Environmenta l 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 Effect s Division (7507P)
Office of Pesticide Programs

Wilhelmena Livingston, Chemical Rev i ew Manager

· Kevin Costello, Branch Chief

Risk Management and Implementation Branch 4
Pesticide Re-Evaluation Division (750 8P)
Office of Pe s ticide Programs

In response to the "R

· egistration Review Problem Form u lation 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 Re s ponsible Medicine
has submitted comments and sugges tions about relevant studies. The purpose of this memorandum is to
address the se 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 locat e why it previou s l y updated the study to 'acceptable' and requested that if the Registrant can prov i de EFED such, the study would again be deemed acceptable.

Note the Registrant provided a previous reque s ted upgrade to the s tudy 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

up gr ade MRJD 42908402 to acceptable.

1

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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 Pr oblem 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 . P rotocol 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 Wa i ver Request if they feel th e requirement should be
waived

.

Comment: “MRID study 48557301 was previously submitted to the Agency for review. Guideline
850.1790 notes that eith er 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.,

r eview of t his stud y has not been initiated , but i t 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 stud ies 850.1010 and 850.4500 with the propargite metabolite, TBPC, these 2 studies will demonstrate ~10 x less toxicity than predicted by modelin g. 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 addressi ng 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.
Pro pargite Label Updates Proposed During EPA NMFS Salmonid Consultation Discussion... ) to voluntarily amend formulation labels by the end of 201 4. 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. Pr opargite 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 Condi t ions.
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). Photoly sis of [ 14 C]

- 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 C

TBPC 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 [ 14 C]

- 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). 14 C

- Propargite Route and Rate of Degradation in Aerobic Aquatic Systems.
48545817 835.1230 Walsh, K. (January 8, 2009). Adsorption/Desorption of [ 14 C] Propargite in Five
Soils.
48545818 850.1730 Suprenant, D.C. (January 26, 1988). Bioconcentration and Elimination of 14 C

Residues 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

14 C]

- 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

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- 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 [ 14 C] 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 promel as ) for Propargite.
49001501 850.1075 Knight, B. and K Ferguson (May 10, 2002). Omite 570 EW: Determination of Acute Toxicity (LC 50 ) 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 Lab oratory 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 : T he Agency has received all of the above listed studies and the r eview s are ongoing

. While this list of studies will not change the D ata C all I n (DCI) document

, t wo of the studies, 48557302 and 48557303 directly address data gaps identified in the problem formulation
document for the degradate TBPC

. I f these studies are approved

, t hey could be used to address missing data in the Data Call In (DCI) document . When the DER s are completed, MacDermi d Agricultural Solutions, Inc./ Chemtura Compan y 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 de termine 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 furthe r 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
shee pshead 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 bluegi ll and channel catfish.”

EPA response: T he Agency appreciates suggestions for relevant studies from the public. We
strive to incorpo rate all relevant data

, while upholding a high standard for validating good laboratory practice. T hese studies are part of our database of relevant toxicity literature and can help characterize the risk p icture of propargite.

Comment: If these data are not sufficient then we recommend the registrant c onsider 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 (F ET) (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 LC 5 0 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 concentrat ion (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 s ome 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 : 

### Recogni zing 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 Integrate d 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) re port, Toxicity Testing in the 21 st 

### 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) o f 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, relevan ce, and reliability.