1 Njo, Heather

From: Lickfeldt, Darin (DW) [DWLickfeldt@dow.com] Sent: Tuesday, January 14, 2014 9:33 AM To: Schaeffer, John Cc: Mattheisen, Mike; Lewis, Paul; Njo, Heather; Juberg , Daland (DR); Racke, Kenneth (D); Lickfeldt, Darin (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 as 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.

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

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.

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
Kow2

Biodegradation
Fish tox Daphnia tox Algae tox

There are also challenges with conducting the mamma lian tox studies due to instability but maybe there are other options for testing media?

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.

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,

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,

John3 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 the 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**