1 Njo, Heather

From: Schaeffer, John
Sent: Friday, January 24, 2014 11:12 AM
To: Lickfeldt, Darin (DW)
Cc: Mattheisen, Mike; Lewis, Paul; Njo, Heather; Juberg , Daland (DR); Racke, Kenneth (D); Brooks, David; Lin, Chuantung; Boethling, Bob; Town send, Mark; Sadowsky, Don Subject: RE: HPV TSCA Testing Complications for DEPCT (CAS 2 524-04-1)
Attachments: 2524-04-1_HPV2_Response to Dow AgroSciences Comment s dated 01142014FINAL.docx

Darin,

I have attached EPA’s review of Dow AgroScience’s comments that were provided in your email below. T he comments in the attachment provide additional details, espec ially concerning the conduct of the aquatic and mam malian toxicity tests required under the test rule for DEPCT.

I have also inserted in the body of Dow AgroScience ’s comments, some additional comments that I receiv ed from our reviewers (red text).

Please look these over. If necessary, please feel f ree to provide additional comments from Dow AgroSciences or reques t
additional clarification from EPA.

Also, understanding the difficulties inherent in te sting this chemical, if Dow AgroSciences needs to r equest additional time to provide study plans and submit final report s, do not hesitate to request an extension.

Best regards,

John

John Schaeffer Senior Biologist
USEPA/OPPT/CCD/CITB 1201 Constitution Ave, NW Washington, DC 20460
Mail Code: 7405M
Phone: 202-564-8173

From: Lickfeldt, Darin (DW) [mailto:DWLickfeldt@dow.com]
Sent: Tuesday, January 14, 2014 9:33 AM

To: Schaeffer, John
Cc: Mattheisen, Mike; Lewis, Paul; Njo, Heather; Juber g, Daland (DR); Racke, Kenneth (D); Lickfeldt, Dari n (DW) Subject: HPV TSCA Testing Complications for DEPCT (CAS 2524 -04-1)

John:

Dow AgroSciences agreed in our Letter of Intent dat ed 18 October, 2013 to conduct the battery of tests on DEPCT (CAS No. 2524-04-1; O,O-diethyl chlorothiopho sphate or O,O-diethyl phosphorochloridothioate) as published in the Federal Register on 7 January 2011 (V. 76, No. 5, pg 1067). We thank you once again f or the recent granting of our extension request for submis sion of the study plan (now due 28 February 2014) a nd the final study reports (now due 31 December 2014).

In our initial protocol development over the last t wo months, we have discovered how unstable DEPCT is under the requested testing conditions and we will have e xtreme challenges completing some of the studies as2 requested. We respectfully ask USEPA to reconsider whether all of this testing is needed upon consider ation of the chemical instability of the DEPCT molecule in a queous and nonaqueous media.

DEPCT is highly reactive (hydrolyzes) in water, and the determination of a true water solubility limit is not likely possible (or meaningful). Phosphorylchlorid ate esters such as DEPCT have reactivity similar to that of carboxylic acid chlorides. The reactivity will have a significant influence on how testing is done - i f it can be done at all. The substance will react with water, proteins, alcohols, etc. (any nucleophilic substanc e), thus making it unstable and difficult to verify exposure concentrations in ecological and mammalian toxicit y tests. [EPA agrees with this statement as concerns testing for the water solubility endpoint. However, EPA n otes that the results from the hydrolysis study that is cited by Dow AgroSciences (from the REACH registration, available on the ECHA website) does not appear to provide enough details to determine if the data are reliable. For the hydrolysis endpoint, EPA needs the complete study, not just details or a summary of the study. Furthermore, if this study is unreliable -- as it a ppears, EPA recommends that Dow AgroSciences repeat the hydrolysis test to determine a reliable and accurat e hydrolysis half- life for this chemical. EPA also recommends that all products of hydrolysis be quantified.]

We recently found that a REACH registration has bee n submitted as an “intermediate use only” substance in

EU.

http://apps.echa.europa.eu/registered/data/dossiers /DISS-9ea6e71a-f3c6-6f79-e044-
00144f67d031/AGGR-bbbf528e-5536-47d6-ae3e-1fbe63232 a4a_DISS-9ea6e71a-f3c6-6f79-e044-
00144f67d031.html#AGGR-bbbf528e-5536-47d6-ae3e-1fbe 63232a4a

The EU submission also mentions reports that indica te the following:

Hydrolysis half-life is 14 min. at room temp in dis tilled water Water solubility testing was waived, as testing is technically infeasible Octanol-water partition was waived, as testing is t echnically infeasible. We do have a calculated (QSAR) value of log Pow = 2 .37 [EPA notes that for the Boiling Point (BP) & Vapor Pressure (VP) endpoints, the cited EU's submission has provided the measured values (at the reduced pressu res) for BP and VP, the sponsor could also cite the se values to fulfill the HPV 2 Test Rule requirement for thes e two endpoints.]

There is also an OECD 301F test of ready biodegrada bility, showing 9% BOD after 28 days. I suspect this test result is impacted by toxicity/inhibition of the inoculum by the test substance. As far as w e can tell, this study is not publically available. [EPA notes that there exists a negative result in a 301F test which the sponsor suggests could reflect toxicity (to the microbes). If true, ready testing at a lower s tarting concentration (usually, 301D is used in thi s case) could be helpful. EPA suggests doing a ready biodegradati on test, but with 301D.]

Due to chemical instability of DEPCT, especially in , but not limited to aqueous media, we will not be able to follow the required testing guidelines for the foll owing studies:

Water Solubility

Kow Biodegradation

Fish tox Daphnia tox Algae tox [EPA is in general agreement with the sponsor's arg ument on the reactivity of DEPCT in aqueous conditi ons. However, the sponsor indicated that DEPCT is highly reactive (hydrolyzes) in water and the cited EU's3 submission for DEPCT has indicated a hydrolysis hal f-life of 14 min. at room temp in distilled water. Results from a (reliable) hydrolysis test could be cited fo r the Water Solubility endpoint, instead to fulfill the HPV 2 test rule requirement for this endpoint. Therefore, the testing on Water Solubility and Log Kow endpoints a re not necessary. In addition, the EU's submission data al so included a calculated (QSAR) value of 2.37 for L og Kow and the sponsor could cite this calculated value fo r Log Kow endpoint to fulfill the HPV 2 Test Rule requirement for this endpoint.]

There are also challenges with conducting the mamma lian tox studies due to instability but maybe there are other options for testing media? [EPA’s review is attached. EPA maintains that aqua tic and mammalian toxicity testing should be conduc ted and provides recommendations for conducting this te sting in the attached document]

The melting point, boiling point, and vapor pressur e ought to be determined as requested since we don’ t think stability will be an issue for those tests. . [EPA agrees that a Melting (or Freezing) point de termination ought to be determined, however, as not ed above, for the Boiling Point (BP) & Vapor Pressure (VP) endpoints, the cited EU's submission has provi ded the measured values (at the reduced pressures) for BP a nd VP, EPA finds that the sponsor could cite thes e values to fulfill the HPV 2 Test Rule requirement for these t wo endpoints.]

The FR notice of 7 January 2011, mentions that modi fications to testing guidelines will be considered by EPA and in some instances testing was even waived when it was deemed irrelevant for given molecules (Secti on 7, page 1080). The FR Notice also states that EPA foun d a “low potential for adverse economic impact for the majority of the chemical substances” (p 1081), but a battery of 13 studies with a highly unstable mole cule such as DEPCT will likely require extensive stability te sting even before valid protocols could be written. Degradation studies and probe work will be infeasib le by February 28 for such a quickly degrading mole cule. After stability testing in various media, the testi ng conditions may then be unrealistic for any poten tial route of exposure (i.e. ecotox and mammalian testing in nona queous media? 30-day tox testing when the half-life is 14 minutes? etc...).

We look forward to EPA dialogue regarding the conce rns expressed for testing of DEPCT as described abo ve.

Respectfully,

Darin Lickfeldt, Ph.D. Dow AgroSciences LLC
9330 Zionsville Rd. Indianapolis, IN 46268

Office: 317-337-3774

dwlickfeldt@dow.com

From: Schaeffer, John [ mailto:Schaeffer.John@epa.gov ]
Sent: Thursday, January 09, 2014 12:18 PM

To: Juberg, Daland (DR)
Cc: Lickfeldt, Darin (DW); Mattheisen, Mike; Lewis, Pa ul; Njo, Heather Subject: RE: Call

Daland,4 In regards to your request, the response I got was a request that you write up your testing concerns and send them to us (an email or an attachment in an email is fine) -- that a call at this stage would [only]result in the same request. I also got a promise that your written concerns would be p rocessed quickly.

Best regards,

John

John Schaeffer Senior Biologist
USEPA/OPPT/CCD/CITB 1201 Constitution Ave, NW Washington, DC 20460
Mail Code: 7405M
Phone: 202-564-8173

From: Juberg, Daland (DR) [ mailto:DRJuberg@dow.com ]
Sent: Wednesday, January 08, 2014 3:59 PM

To: Schaeffer, John
Cc: Lickfeldt, Darin (DW) Subject: Call

Hi John – Would it be possible to have a call with the Agency related to some technical questions/conc erns we have on the DEPCT testing owing to some significant challenges we’ll have in conducting some of the st udies owing to the rapid aqueous degradation (hydrolysis) that is associated with the material? Even prior to submitting a study plan, it would be very helpful t o gain th e insight (or at least have us present our concerns and then let you react to them subsequently) of the Age ncy, notably including a chemist, ecotoxicologist, and mammalian toxicologist.

I can set up the call if you are willing and can in clude from your end a couple of the suggested techn ical scientists noted above. I am looking to get this i n the week of January 20.

Many thanks,

Daland

**Daland R. Juberg, Ph.D.**

, **Fellow**

, **ATS N.A. Leader, Human Health Assessment**  **Regulatory Sciences & Government Affairs Dow AgroSciences LLC** 
**9330 Zionsville Road Indianapolis, IN 46268** 

**317-337-3787 317-919-3157 (mobile)**  **drjuberg@dow.com**