American Chemistry
Council
June 19, 2018
Kristina Thayer, Ph D. Director, Integrated Risk Information System (IRIS) National Center for Environmental Assessment USEPA Headquarters Ariel Rios Building 1200 Pennsylvania Avenue, N.W. M ail Code: 8601P Washington, DC 20460
By email (thayer.kris@EPA.gov) and submission to EPA Docket Nos. EPA-HQ-ORD-20140313 and EPA-HQ-ORD-2010-0540
RE:
Draft IRIS Assessment of Hexavalent Chromium (Chromium VI)
Docket ID Nos. EPA-HQ-ORD-2014-0313 and EPA-HQ-ORD-2010-0540
Dear Dr. Thayer,
Following up on my correspondence from March 21, 2018 and April 30, 2018, the American Chemistry Council's (ACC) Hexavalent Chromium Panel (Panel) has concerns about how the IRIS program will incorporate the large toxicogenomics dataset sponsored by the Panel into the assessment of hexavalent chromium [Cr(VI)]. The mode of action (MOA) researchers communicated with Dr. Lyle Burgoon, formerly at EPA, from 2014 - 2016 concerning this Cr(VI) toxicogenomics dataset, and in my last correspondence I requested a meeting with EPA to discuss the following concerning use of the dataset to inform the MOA for tumors observed in a 2-year rodent cancer bioassay:
1. A timeline of events relevant to the Cr(VI) genomics data; 2. An explanation for the varying number o f microarrays available through different online
data repositories; and 3. A general findings comparison between published analyses.
Since the IRIS program has declined my request for a meeting, we are submitting this information into the docket for the Cr(VI) IRIS assessment.
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Timeline of events relevant to Cr(VI) genomics data
Table 1 summarizes the timeline of events surrounding the Cr(VI) genomics data and clarifies any potential discrepancies between data repositories over time and differences in analysis strategies used in different publications.
Table 1. Timeline summarizing events involved in the Cr(VI) genomics dataset.
DATE 2012
EVENT
RELEVANT WEBSITE*12
Two studies were published using:
dbZach
1. Mouse duodenum and jejunum data (Kopec et al. 2012a)
2. Mouse and rat duodenum and jejunum data (Kopec et al.
2012b).
Data from manuscripts were deposited in dbZach, an internal data
management system that is compliant with the Minimum
Information About a Microarray Experiment (MIAME) standard
(Burgoon et al. 2006).
2014
Data were provided online through Cr6study.info. Data included: Crstudy.info
1. qRT-PCR data used in the Kopec (2012a.b) publications
2, Raw genomics microarrav data used in the Kopec (2012a.b) publications
All raw microarray data (as .gpr files) for the mice and rat, oral palate, duodenum, and jejunum (day 8 and 91), alongside a metadata file
3. Genomics analysis code used in the Kopec (2012a.b) publications
Note that this analysis included data from both array dyes (Cy3 and Cy5) and data were processed using in-house code and algorithms, which are provided in Cr6study.info, and include: o SAS code used to analyze microarray data (note: input files with appropriate tags referred to in the code were not originally provided - see 2018 update) o R code to calculate Pl(t) statistics
4. Genomics analysis statistical results used in the Kopec (2012a.b) publications
Excel worksheets containing all array probe sets and their corresponding fold change values and Pl(t) statistical results for the rat and mouse, duodenum and jejunum, at day 8 and 91
APRIL 2016 A labeling error was identified in the raw genomics data for the Crstudy.info rat within the files in Cr6study.info.
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DATE
EVENT
RELEVANT WEBSITE1
Specifically, incorrect probeset identifiers were included
in the rat raw array data files (.gpr files). These identifiers
were corrected, and Dr. Burgoon was notified of this edit
via email on January' 8, 2016 and April 5, 2016 (see
ATTACHMENT A)
This labeling error had no effect on the analyses or
interpretation reported in Kopec et al. (2012b)
AUGUST 2016
ToxStrategies received a request from Stiven Foster at the US Cr6study.info EPA to access data from the Cr6study.info website. Access was granted on August 10, 2016 (see ATTACHMENT A).
SEPTEMBER All raw and processed array files were uploaded into the NCBFs GEO
2016
Gene Expression Omnibus (GEO) repository. These data
included:
All raw microarray files
Processed array data, consisting of quantile normalized
expression data derived from the Cy3 array signal. Note:
these processed array data were updated in 2016 and differ
from those used in the Kopec (2012a,b) publications.
Updated results from these data were published
(Thompson et al. 2016, Rager et al. 2017, described
below)
Data were uploaded alongside a reference to the Thompson et al. (2016) publication (final publication on November 2016, below)
NOVEMBER A study was published using the mouse and rat palate data
2016
(Thompson et al. 2016), using the updated array processing
strategy provided in GEO.
GEO
MAY 2017
A study was published using the mouse duodenum data (Rager et GEO al. 2017), using the updated array processing strategy provided in GEO.
FEBRUARY The GEO posting was updated to include additional citation
2018
information, referencing Rager et al. (2017).
GEO
FEBRUARY The link to the raw microarray files was temporarily not working Cr6study.info
2018
through Cr6study.info. This link was corrected.
FEBRUARY 2018
More data were provided to further support the analysis
Cr6study.info
conducted in the Kopec (2012a,b) publications.
To detail, the original SAS code used in the genomics
statistical analysis was originally provided in the 2014
data upload. This update added the specific input files that
were used to execute the SAS code.
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1website URLs are Cr6study.info (https://cr6st.udv.info). dbZach (http://dbzach.fst.rnsu.edu/). GEO (https://www.ncbi.nlm.nih.gov/geo/auerv/acc.cgi?acc=GSE87262).
Explanation for varying numbers of arrays on different websites
The number of array samples included at Cr6study.info, representing the analysis published in the Kopec et al. (2012a,b) publications, differs slightly from the number of array samples included in the GEO repository, representing the analyses published in the recent publications (Rager et al. 2017, Thompson et al. 2016). Specifically, the arrays in Table 2 were excluded from the GEO repository.
Table 2. Arrays that are included in Cr6study.info but excluded in the GEO repositories.
GPR file 4417.gpr
Species, Tissue,
and Duration
Array Components1
Group
Mouse
Cy3 signal: animal ID 3426, control
duodenum day Cy5 signal: animal ID 3401, exposed at 4 mg/L
91
dose
Note Duplicate
4418.gpr
Mouse duodenum day
Cy3 signal: animal ID 3401, exposed at 4 mg/L dose
91
Cy5 signal: animal ID 3426, control
Duplicate
4451.gpr
Mouse duodenum day
Cy3 signal: animal ID 3416, exposed at 14 mg/L dose
91
Cy5 signal: animal ID 3426, control
Technical replicate
4452.gpr 4453.gpr
Mouse Cy3 signal: animal ID 3421, exposed at 60 mg/L
duodenum day 91
Cy5 signal: animal ID 3426, control
Mouse duodenum day
Cy3 signal: animal ID 3409, exposed at 170 mg/L
91
Cy5 signal: animal ID 3425, control
Technical replicate Technical replicate
4454.gpr
Mouse
Cy3 signal: animal ID 3400, control
duodenum day Cy5 signal: animal ID 3404, exposed at 520
91
mg/L
Technical replicate
1Note that data from the Cy3 and Cy5 dye signals were used in the Kopec et al. (2012a,b) publications; while analyses only focused on data from the Cy3 dye signal in the Rager et al (2017) and Thompson et al. (2016) publications to minimize potential dye bias / interference issues.
These arrays in Table 2 were excluded from the GEO repository, reflective of the more recent Rager et al. (2017) publication, because these arrays represented duplicated data or technical replicates. Specifically, chip scan data in array IDs 4417 and 4418 were identified as duplicated data; thus both o f these arrays were removed from the analysis. Array IDs 4451, 4452, 4453, and 4454 represented technical replicate arrays used for internal quality purposes. These arrays measured gene expression profiles of samples from animals that were already accounted for by
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other arrays. Neither the Kopec et al. nor the Rager et al. analyses included technical replicate arrays.
The biological replicates were explained in the Rager et al. (2017) publication in the methods section:
"RNA samples were assessed in biological triplicate in all dose groups (0, 0.03, 4, 14, 60, 170, and 520 mg/l SDD at day 8 and day 91) exceptfor the 4 mg/l SDD exposure group from day 91, which was analyzed in biological duplicate due to potential microarray quality issues. "
The arrays that were removed due to duplicate issues or represented technical replicates were excluded from the data in the GEO repository, to be consistent with the Rager et al. (2017) publication. The number of biological replicates used in this analysis is detailed in Table 3. All array data, including duplicate data/technical replicates, are included in Cr6study.info.
Table 3. Biological replicate numbers in the GEO database, reflective of the array analysis in Rager et al. (2017).
Duration Group
Species, Tissue
Dose (mg/L sodium dichromate dihydrate)
0
0.3 4 14 60 170 520 Total
8 days
Mouse, duodenum
33
333
3
3
21
91 days
Mouse, duodenum
3
3
21 3 3
3
3
20
1Note that the analyses conducted by Kopec et al. (2012a,b) contained one more biological replicate in this dose
group.
General comparison between publication findings
Genomics data analysis methods and standards have evolved over time. Thus, the data processing and statistical methods differed between the original publications using the Cr(VI) genomics data in the mouse duodenum (Kopec et al. 2012a,b) and more recent, updated publication (Rager et al. 2017); however, overall general findings remained consistent despite these varying approaches. For example, Kopec et al. 2012a, which focused on the mouse intestinal responses, identified genes involved in oxidative stress and cytotoxicity with altered expression, representing early key events. Other pathways noted as enriched included those involved in cell cycle, lipid metabolism, and immune response. Pathways involved in DNA repair were also noted in the day 8 results, including the nucleotide excision repair pathway, which did not show enrichment at day 91 (Kopec et al. 2012a). Similarly, Kopec et al. (2012b) noted pathways relevant to oxidative stress, immune response, protein synthesis, cell cycle/cell growth and proliferation, and DNA damage and repair in the mouse and rat duodenum and jejunum.
Similar results were apparent in the Rager et al. (2017) analysis focusing on the mouse duodenum, with pathways involved in cell stress and injury, cell death, and cell growth, proliferation and
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development involved in early key events that were also sustained in the day 91 results. The nucleotide excision repair pathway was also identified as enriched in the day 8 results, but not the day 91 results; and it was noted that this pathway included eight genes showing increased expression associated with Cr(VI), all of which were involved in general DNA transcription and cell cycle signaling. Pathways involved in metabolism and immune response were also identified as enriched, similar to Kopec et al. (2012a). In summary, analysis strategies have evolved over time surrounding the use of the Cr(VI) genomics data; still, general findings have remained consistent despite varying approaches.
In conclusion, the raw and processed Cr(VI) genomics data are provided online, and the methods used to analyze these data have evolved over time to parallel ongoing advances in genomics-based assessments. This robust data set provides important information that can be used to further understand the MOA of Cr(VI). We have been fully transparent about the research conducted, including making the raw genomics data as well as other raw data available to EPA and other scientists.
If you have any questions, please contact me at eileen conneelv@americanchemistry.com or at 202-249-6711.
Sincerely,
S e rn (fa m e e ly Eileen Conneely, M.P.H., J.D. Director, Chemical Products & Technology Division American Chemistry Council
Attachment A: Email communication on updates to Crstudy.info genomics data
cc: C. Gibbons, gibbons.catherine@epa.gov A. Sasso, sasso.alan@epa.gov R. Yamada, yamada.richard@epa.gov J. Orme-Zavaleta, orme-zavaleta.jennifer@epa.gov T. Bahadori, bahadori.tina@epa.gov E. Ohanian, ohanian.edward@epa.gov
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ATTACHMENT A
Email communication on updates to Cr6study.info
genomics data
NDCA
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Friday, March 2, 2018 at 7:54:31 AM Central Standard Time
Subject: Cr(VI) raw microarray data
Date: Thursday, March 13, 2014 at 12:37:11 PM Central Daylight Time
From: Apple-Mail=_405249D0-D0F5-4909-96A9-35F59E23F6BE Mark Harris boundary=
To:
Burgoon.Lyle@epa.gov
CC: Rusty Thomas, Tim Zacharewski, Gibbons.Catherine@epa.gov, Chad Thompson, Deb Proctor
Lyle: as I mentioned in the meeting on Monday, the data will be posted to our new Cr(VI) MOA website before SOT. Once the site is live I will send you all a link to it. You will be able to download the genomics data at that time.
The approach and methods that were used to analyze the data are adequately described in the Kopec papers. Our use of the genomics data to support the Mode of Action can be found in our Critical Reviews in Toxicology paper. Links to these Open Access papers can be found at the web page below:
http://www.toxstrategies.com/publications/CRVI MOA studv.htm
mark
From: "Burgoon, Lyle" <Burgoon, Lvle@eoa.gov> Date: March 12, 2014 at 8:43:16 AM CDT To: "cthomoson@toxstrategies.com" <cthompsoniStoxstrategies.com> Cc: "tzachare@msu.edu" <tzachare@msu.edu>. "Gibbons, Catherine" <GibbQns.Catherine@epa.gov> Subject: Cr(VI) raw microarray data
Dr. Thompson,
It was nice seeing you and Dr. Harris (via video) at Monday's meeting @ NCEA HQ. I was quite pleased to hear Ms. Mason state that ACC expected the researchers would share their data and results with NCEA.
I'm following up on our discussion from Monday and am requesting access to all of your raw microarray data, as well as your analyzed data that supports the conclusions in your papers. In addition, it would be helpful if you could also supply us with the analysis code that was used, any protocols used for the analyses, and any other supporting documentation that may help us understand how the assays and analyses were performed.
For clarity, I am using the MIAME definition of 3raw data2, and my request for the additional information is in line and keeping with the MIAME standard, which can be found here: http://www.mged.org/Workgroups/MIAME/miame.html.
To facilitate data transfer, I can set-up an EPA-based FTP site where you can upload the data.
Thanks again for presenting your latest results to us, and I look forward to receiving the data.
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Cheers, Lyle
L y le D. Burgoori, Ph.D
N ational Center fo r Environm ental Assessment
C h ie f, Hazardous P o llu ta n t Assessment Group (A c tin g )
US Environm ental P ro te c tio n Agency
Phone: 919.541.7808
Fax: 919.685.3473
C ell
Ex. 6
Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherwise, please notify me immediately so that proper contract action can be initiated.
Note New Address T oxS trate g ies, Inc
Mark Harris, Ph.D. Principal Health Scientist
23123 Ciuco Ranch Bivci,, Suce 220 Katy, I X 77494
fax : Email: miiarri_s@toxstrategfes,cg
: http://www.toxstrateqies.com
; rns e-man, ano any armonroenrs m im ic,. :: inmnoeci only mr u s i oy cm aociresseeis: nanieci nerain ano may contain legally privileged and/or confidential Information, If you are not: the intended recipient: of this email, you are hereby notified that: any dissemination,, distribution or copying of this e-mail, and any artaenmerrm m e m o , is srneny prornonoo. rr yon rravo r'ecreivoa mis o-man m army irooase irnrnemaroiy ao'my ToxStrategies, Inc, at: (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout: thereof,
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Friday, March 2, 2018 at 7:55:20 AM Central Standard Time
Subject: Cr(VI) MOA Study Website
Date: Monday, March 24, 2014 at 8:34:03 AM Central Daylight Time
From: Apple-Mail=_B33E4A44-0724-416B-A519-ClB4A7F9AE29 Mark Harris boundary=
To:
Burgoon.Lyle@epa.gov
CC: Tim Zacharewski, Gibbons.Catherine@epa.gov, Chad Thompson, Rusty Thomas
Lyle: our Cr(VI) MOA study website is live. You can access is at www.cr6studv.info
Linder the Study Data tab you can register to download data. Once registered, you will receive a password to access the data download portion of the site.
Not all of the genomics data you requested has been posted. Things that are not posted yet are:
1. Analysis Code 2. QRT-PCR data
These items will be added in the next few weeks,
mark
Note New Address
T oxS trate g ies, Inc
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Chico Ranch Blvd; Suite 220 Katy, TX 77494
Direct Dial
Ex. 6
i
x. 6
i
fax:
Ext: Ex. 6
Email: m lw r i^ -t g x s t j^ q je s x o m : http://www.toxstrateqies.com
; on e~mam ano any arcocnmenrs cnerato., :: mcenoea may tor use oy cne aooressaeis: nanieu nerem anc: may contain legally privileged and/or confidential Information, If you are not the Intended recipient: of this emaii, you are hereby notified that any dissemination, distribution or copying of this e-mail, arid any attachments thereto, is strictly prohibited, If you have received this e-mail in error, please immediately notify ToxStrategles, Inc, at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof.
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Friday, March 2, 2018 at 7:57:26 AM Central Standard Time
Subject: Re: Cr(VI) MOA Study Website Date: Thursday, April 3, 2014 at 3:07:45 PM Central Daylight Time From: Mark Harris To: Burgoon, Lyle CC: Gibbons, Catherine, Vandenberg, John, Flowers, Lynn
I will have to talk to our legal folks about this.
Back in touch shortly.
mark
Note New Address
ToxS tralegiesf lee,
innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Bled, Suite 220 Katy, I X 77494
Ex. 6
i-k>ysrosi.Di0.ce ..2D1..Z12-2067 Ex. 6
Ext
Ex.
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fax: il: mharris@ttoxstrateaies.com
: http://www.toxstrateaies.com
: ssss sa-mam any any amwmmesxs cncrcuo, ss inccnuau oroy mr sjse oy cnc yuarcoyocio,} rmmsao ssamsu one: may contain legally privileged and/or confidential information. If you are not the intended recipient of this email, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any atcacnmencs enareno, ss sxsac'uy prosaanao. ir you navo: rocosvum mas a-mms in ccTop cnoace UTmiocaamiy uousy ToxSfrategles, lac, at (832) 868-7729 and permanently delete the anginal and any copy of any e-mail and any printout thereof.
On Apr 3, 2014, at 2:59 PM, Burgoon, Lyle <Burgoon.Lvle(5)eoa.gov> wrote:
Hi Mark,
We cannot access the data at this time due to our inability to agree to the Terms and Conditions associated with data access found here: http://cr6studv.info/studv-data/terms-and-conditions/
Specifically, we request that ToxStrategies delete the indemnification clause in the Terms and Conditions, As written, the Agency cannot agree to the terms as it would be a violation of the Anti-Deficiency Act (i.e,, making a commitment to an unknown future cost is a direct violation of the Anti-Deficiency Act),
Please let me know what action you are willing to take as soon as possible. As you are aware,
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time is of the essence with respect to the Cr(VS) IRiS Assessment, Your prompt attention to this matter is appreciated.
Thanks,
Lyle
L y le D. Burgeon., Ph.D C h ie f, Hazardous P o llu ta n t Assessm ent Group (A c tin g ) N atio n al Center fo r Environm ental Assessment US E n v iro n m e n ta l P r o t e c t io n Agency Phone: 919.541.7808 Fax: 919.685.3473
Cell: EX. 6
i_____________i Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherwise, please notify me immediately so that proper contract action can be initiated.
From: Mark Harris rmailto:mharns@toxstrateaies.coml Sent: Monday, March 24, 2014 9:34 AM To: Burgoon, Lyle Cc: Tim Zacharewski; Gibbons, Catherine; Chad Thompson; Thomas, Russell Subject: Cr(VI) MOA Study Website
Lyle: our Cr(VI) MOA study website is live. You can access is at www.crhstudv.info
Under the Study Data tab you can register to download data. Once registered, you will receive a password to access the data download portion of the site.
Not all of the genomics data you requested has been posted. Things that are not posted yet are:
1. Analysis Code 2. QRT-PCR data
These items will be added in the next few weeks,
mark
Note New Address ToxS trategies, Inc*
Innovative Solutions > Sound S
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Slvd, Suite 220 Katy, TX 77494
Direct: Di
Ex. 6
Houston Off: ci':"'728 f }"? 2 0 67 Ext: Ex. 6
Page 2 of 3
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Cell;
Ex. 6
tax: .............
Eniai h mharris@toxstrateaies.com
: http://www.toxstrateaies.com
This e-mail, and any attachments thereto, is intended only for use by the acidressee(s) named herein and may contain legally privileged and/or confidential Information. If you are not the mtenoeo: secmmm or o rs amiam you see nereny notmeo tests arm tsssenuneoon, srsttiDooon or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-mail in error please immediately notify ToxStrategies. Inc. at (832) 868-7729 ami permanermy aemte me enigma smo any copy tummy e~man ano any printout iiuereon
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Friday, March 2, 2018 at 7:57:58 AM Central Standard Time
Subject: Terms and Conditions Modified
Date: Monday, April 7, 2014 at 12:23:08 PM Central Daylight Time
From: Apple-M ail=_54682036-6E73-4A57-B537-DA70B702C164 Mark Harris boundary=
To:
Burgoon, Lyle
We modified the terms and conditions for the US Government for our website http://cr6studv.info. The additional text is: If you are a United States Government entity, the indemnification provision of the Terms and Conditions is hereby waived. Your liability for any breach of the Terms and Conditions, or any claim arising from the Terms and Conditions, shall be determined under the Federal Tort Claims Act, or other governing authority.
mark
Note New Address
ToxStrategies, lee,
Innovative Solutions > Sound S
Mark Harris, Ph.D. Principal Health Scientist
23123 G oto Ranch Bivd, Suite 330 Katy, TX 77494
Direct Dial: (
Ex. 6
r-------- -E--?---!----
Ex. 6
rax: (8321 218-2756
Email: mharris@toxstrateaies.com
: http://www.toxstrateaies.com
This e-mail, and any attachments thereto, Is intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information. If yon are not the Intended recipient: of this email, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any attachments thereto, Is strictly prohibited. It you have received this e-mail In error, pleese immediately notify ToxStrategles, Inc, at (832) 868-772S and permanently delete the original and any copy of any e-mail and anv printout memor.
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Friday, March 2, 2018 at 7:58:49 AM Central Standard Time
Subject: Website
Date: Monday, April 7, 2014 at 3:43:02 PM Central Daylight Time
From: Apple-Mail=_5CAFA6EE-E253-474E-8737-E357CC0E69C7 Mark Harris boundary=
To:
Burgoon, Lyle
We have also posted the genomics analysis code to the website today. Only thing remaining is the QRT-PCR info which is still being assembled.
mark
Note New Address ToxS tralegiesf lee.
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Blvch Suite 220 Katy I X 77494
Direct Dial: Houston Off
Ex. 6
Ext Ex. 6
Cali: i
Ex. 6
i
fax:
?56
Email : mharns@toxstrateqies.com
: http://www.toxstrateqies.com
: ms e-ma:u any any arsaemmeuts snerato, m msenuen coxy mr uaa oy see aaoraanncia,} narnnn narem ana may contain legally privileged and/or confidential Information, If you are net the intended recipient of tills email, you are hereby notified that any dissemination, distribution or copying of this e-mail, ami any artaenments oneraro, m sancey prommryo. ,u you cava recemeo rum amtau m arrant rvease mnnacaamiy nocry TPxSfrategies, Inc, at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof.
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Friday, March 2, 2018 at 7:59:19 AM Central Standard Time
Subject: T&C - how does this
Date:
Wednesday, April 23, 2014 at 2:09:01 PMCentral Daylight Time
From:
Apple-Mail=_1704D469-54A7-4A17-9C82-0F0AADD0DE20
To:
Burgoon, Lyle
Attachments: Revised Cr6 Website Terms.docx
Mark Harrisboundary=
Lyle: I got some revised T&C language from the attorneys today. See attached in Tracked Changes. If this works let me know and I will get the website updated.
Also, if these words donH work, can you ask the attorney reviewing this to suggest some words that would work for the US government?
thanks
mark
Note New Address
ToxS tralegiesf Irte,
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Bled, Sude 220 Katy, TX 77494
Diced: Dial:
Ex. 6
Cell: fax: Email:
Ex. 6
Ex. 6
mharris@toxstrateaies.com : http://www.toxstrateaies.com
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Subject: Re: T&C - how does this
Date: Tuesday, April 29, 2014 at 7:28:32 AM Central Daylight Time
From: Apple-M ail=_3480B4DA-5FF4-4C62-AE8C-422044ED03FF Mark Harris boundary=
To:
Burgoon, Lyle
Lyle: the website has been updated with this revised language. Also, we have added the QRT-PCR data that we received from Tim.
mark
Note New Address ToxS tralegiesf lee.
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinoo Ranch Bivd, Suite 220 Katy TX 77494
Direct Dial: 1
Ex. 6
>06:: Ex. 6
Ex. 6
Email: mhams@toxstrateaies.com : http ://www .toxstrateaies.com
i me e-mom any any ectacnmanm tnareto, m mtanuen may mr use ny tna aunrassaaiou nameo naram ano may contain legally privileged and/or confidential information. If you are net the Intended recipient of tills email, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any artaenmeots tnerero, m srncay pcommteo. n you nave cecemao rum a-maa in array yvaaoe CT-mamataiy notny TPxSfrategles,. Inc, at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof.
On Apr 28, 2014, at 10:08 AM, Burgoon, Lyle <Burgoon.Lvlefn)epa.gov> wrote:
Hi Mark, Thanks for working with us that language meets our needs. Sorry for the delay was out sick last week. Cheers,
Lyle
L y le D. Burgoon, Ph.D C h ie f, Hazardous P o llu ta n t Assessm ent Group (A c tin g ) N atio n al Center fo r Environm ental Assessment US E n v iro n m e n ta l P r o t e c t io n Agency Phone: 919.541.7888 Fax: 919.685.3473
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C ell: Ex. 6
Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherkdse, please notify me immediately so that proper contract action can be initiated.
From: Mark Harris fmailto:mharris@tGxstrategies.caml Sent: Wednesday, April 23, 2014 3:09 PM To: Burgoon, Lyle Subject: T&C - how does this
Lyle: I got some revised T&C language from the attorneys today. See attached in Tracked Changes. If this works let me know and I will get the website updated.
Also, if these words don't work, can you ask the attorney reviewing this to suggest some words that would work for the US government?
thanks
mark
Note New Address
ToxStrategies, Inc*
innovative Solutions > Sound S
Mark Harris, Ph.D. Principal Health Scientist
1_______x_._6______ :
i
Ex. 6
i
Ex. 6
i_______j
rnharris(Hoxsi:ral:eQies.t:om : http://www.toxstrateqies.com
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Friday, March 2, 2018 at 8:06:46 AM Central Standard Time
Subject: cr6study.info
Date: Friday, September 18, 2015 at 12:51:30 PM Central Daylight Time
From: Mark Harris
To:
lyle.d.burgoon@usace.army.mil
Lyle: you should have received an approval for access to the data via email. If you have any issues downloading data just let me know. I did not realize you had changed jobs. Good luck with the new position. Why is the Army interested in Cr(VI)?
mark
ToxS trategies# Inc*
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Qnco Ranch Bivd, Suite 220 Kety, I X 77494
Direct Dial:
Ex. 6
Houstem Otflce: .i28.1}.7j.2-2062 Ex. 6 j
Cell: j
Ex. 6
j
fax: '"1................... 756
ma11: mhams@toxstrateaies.com
: http ://www.toxstrateaies.com
Unkedln: http://www.linkedin.com/in/toxstrateQiesharris
This e-mail, and any attachments thereto, is intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information. If you are not the Intended recipient of this email, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any attachments thereto. Is strictly prohibited. If you have received this e-mail In error, please Immediately notify ToxStrategies, Inc. at (832) 868- 7729 and permanently delete the original and any copy of any e-mail and any printout: thereof.
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Friday, March 2, 2018 at 8:07:19 AM Central Standard Time
Subject: Re: [EXTERNAL] cr6study.info
Date: Friday, September 18, 2015 at 3:40:14 PM Central Daylight Time
From: Mark Harris
To:
Burgoon, Lyle D ERD-MS
Lyle: that is good to know about being able to collaborate on future projects. You never know when a client will ask for such analyses.
One question - is it is relatively straightforward to engage you all for a project? Meaning, if something came up, could the paperwork being done relatively quickly to get going?
mark
From: "Burgoon, Lyle D ERD-MS" Date: Friday, Septem ber 18, 2015 at 3:35 PM To: Mark Harris Subject: Re: [EXTERNAL] cr6study.info
Hey Mark,
Thanks. The Army has no interest in chromium (thankfully). However, ERA is in the process of contracting with the Army to reanalyze the data. So, in preparation for that, we requested the data.
On a side note, in my new federal job I'm soft money, and we operate like a consulting company. So if in the future you need CompTox or toxicogenomic support, let me know. We can accept funds from companies for collaborative work.
if you want to chat sometime, my number is Cheers,
Ex. 6
Lyle
Lyle D. Burgoon, PhD Environmental Laboratory US Army Engineer Research and Development Center Research Triangle Park, NC
Sent from my BiackBerry 10 smartphone on the Verizon Wireless 4G LIE network.
From: Mark Harris Sent: Friday, September 18, 2015 1:51 PM To: Burgoon, Lyle D ERD-MS Subject: [EXTERNAL] cr6study.info
Lyle: you should have received an approval for access to the data via email. If you have any issues downloading data just let me know. I did not realize you had changed jobs. Good luck with the new position. Why is the Army interested in Cr(VI)?
mark
ToxS tralegiesf Inc,
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Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
Bivd, Suite 220
Ex. 6
Ex. 6 t 8 3 2 ) 7 8 : 2?56'''
Ex. 6
rnharrjsMQxstrategiesx : Blockedhttp://www.toxstrateqies.com : Blockedhttp://www.linkedin.com/in/toxstrateaiesharris
This e-mail, and any attachments thereto, is intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information. If you are not the Intended recipient of this email, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-rnail In error, please immediately notify loxStrategles, Inc. at (832) 86S-2229 and permanently delete the original and any copy of any e-mail and any printout: thereof.
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Friday, March 2, 2018 at 8:08:37 AM Central Standard Time
Subject: Re: [EXTERNAL] cr6study.info
Date: Friday, January 8, 2016 at 5:04:08 PM Central Standard Time
From: Burgoon, Lyle D ERD-MS
To:
Mark Harris
Thanks for the heads up, Mark.
Have a nice weekend.
Lyle D. Burgoon, PhD Envi ronmenta! Laboratory US Army Engineer Research and Development Center Research Triangle Park, IMC
Sent from my BiaekBerry 10 smartphone on the Verizon Wireless 4G LIE network.
From: Mark Harris Sent: Friday, January 8, 2016 6:02 PM To: Burgoon, Lyle D ERD-MS Subject: Re: [EXTERNAL] cr6study.info
Lyle: we were doing some work on the Cr(VI) genomics data and noticed an error in the rat data (some probe ID's were mislabeled). The actual data is correct - just the labels are wrong. This doesn't impact our publications but does impact the data available for download from our Cr(VI) study website. MSU is fixing and I will alert you when we update the files.
mark
ToxStrategies^ Inc
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Ciuco Ranch Bivd, Suite 22 Katy, TX 77494
Direct Dial:
Ex. 6
fio usto .CM ioe Z28T! ZC2C 62 Ext Ex. 6
Cell:
Ex. 6
fax: (832) 218-2756
Email: m harrjsM Q xstrategj^
Website: BJockedhttp://www,toxstrate
Lsnkedin: MQckMhttpi/ / ^ ^ ^
This e-mail, and any attachments thereto, is Intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information. If you are not the intended recipient of this emall, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-mail in error; please immediately notify loxStrategies, Inc. at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof,
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From: "Burgoon, Lyle D ERD-MS" <Lvje.D.Burgoon@ysace.armv.mil> Date: Friday, Septem ber 18, 2015 at 3:50 PM To: Mark Harris <mharris@toxstfategies.com> Subject: Re: [EXTERNAL] cr6study.info
Army moves paperwork pretty quick. If I know it's coming, I can grease the skids, if you have a tight turnaround on paperwork approval needed my lab director can expedite and maybe l-2weeks we should be able to turn it around. Unless it's after July 31, then it might take longer be of the backlog at contracts.
Lyle D. Burgoon, PhD Environmental Laboratory US Army Engineer Research and Development Center Research Triangle Park, NC
Sent from my BlackBerry 10 smartphone on the Verizon Wireless 4G LIE network. From: Mark Harris Sent: Friday, September 18, 2015 4:40 PM To: Burgoon, Lyle D ERD-MS Subject: Re: [EXTERNAL] cr6study.info
Lyle: that is good to know about being able to collaborate on future projects. You never know when a client will ask for such analyses.
One question - is it is relatively straightforward to engage you all for a project? Meaning, if something came up, could the paperwork being done relatively quickly to get going?
mark
From: "Burgoon, Lyle D ERD-MS" Date: Friday, Septem ber 18, 2015 at 3:35 PM To: Mark Harris Subject: Re: [EXTERNAL] cr6study.info
Hey Mark,
Thanks. The Army has no interest in chromium (thankfully). However, ERA is in the process of contracting with the Army to reanalyze the data. So, in preparation for that, we requested the data.
On a side note, in my new federai job I'm soft money, and we operate like a consulting company. So if in the future you need Complex or toxicogenomic support, let me know. We can accept funds from companies for collaborative work.
If you want to chat sometime, my number is Ex. 6
Cheers,
Lyle
Lyle D. Burgoon, PhD Environmental Laboratory
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US Army Engineer Research and Development Center Research Triangle Park, NIC
Sent from my BiackBerry .1.0 smartphone on the Verizon Wireless 4G LIE network. From: Mark Harris Sent: Friday, September 18, 2015 1:51 PM To: Burgoon, Lyle D ERD-MS Subject: [EXTERNAL] cr6study.info
Lyle: you should have received an approval for access to the data via email. If you have any issues downloading data just let me know. I did not realize you had changed jobs. Good luck with the new position. Why is the Army interested in Cr(VI)?
mark
ToxS trategies#Inc*
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Ciuco Ranch Bivd, Suite 22 Katy, TX 77494
Direct: Dial
Ex. 6
Houston Offne lM I) T X O 6 2 Ext Ex. 6
Cell:
Ex. 6
fax: - ( E T Z r XI87775C
Ema11: mharris@toxstrateaies.com
We!::': BiockedBiockedhttp://www.toxstrateqies.com
Linked in: BiockedBiockedhttp://www.linkedin.com/in/toxstrategiesharris
This e-mail,, and any attachments thereto, is intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information. If you are not the intended recipient of this emall, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-mail in error please immediately notify ToxStrategles, Inc. at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof.
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Friday, March 2, 2018 at 8:08:56 AM Central Standard Time
Subject: Re: [EXTERNAL] cr6study.info
Date: Tuesday, April 5, 2016 at 2:42:13 PM Central Daylight Time
From: Burgoon, Lyle D ERD-MS
To:
Mark Harris
Hey Mark,
Not started yet, hut thanks for the update. Once I get cranking if i have questions I'll let ya know.
Cheers,
Lyle
Lyle D. Burgoon, PhD Environmental Laboratory US Army Engineer Research and Development Center Research Triangle Park, NC
Sent from my BlackBerry 10 smartphone on the Verizon Wireless 4G LIE network.
From: Mark Harris Sent: Tuesday, April 5, 2016 2:09 PM To: Burgoon, Lyle D ERD-MS Subject: Re: [EXTERNAL] cr6study.info
Lyle: just touching base. Have you done anything with the data - the labels are all fixed in the raw data.
Trust all is well.
mark
T o x S tra te g ie s # Ine
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Gnco Ranch Bivd, Suite 220 Katy, TX 77494
Direct Dial:
Ex. 6
Houston Office II1Z F 2062: Ext Ex. 6
Cell:
Ex. 6
fax: (fG 2 )''2 lB G 7 S6 `
Email:
.corn
VVebsiL Blockedhttp://www.toxstrateaies.com
Lsnkedin: Blockedhttp://www.linkedin.com/in/toxstrateaiesharris
This e-mail, and any attachments thereto, is Intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential Information, If you are not the Intended recipient of this e~ mail, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-mail in error; please immediately
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notify ToxStrategles, Inc, at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof.
From: "Burgoon, Lyle D ERD-MS" < Lyle.D.Burgoon@ usace.army.m il> Date: Friday, January 8, 2016 at 5:04 PM To: Mark Harris < m harns@ toxstrategies.com > Subject: Re: [EXTERNAL] cr6study.info
Thanks for the heads up, Mark.
Have a nice weekend.
Lyle D. Burgoon, PhD Environmental Laboratory LJS Army Engineer Research and Development Center Research Triangle Park, NC
Sent from my BlaekBerry 10 smartphone on the Verizon Wireless 4G LIE network. From: Mark Harris Sent: Friday, January 8, 2016 6:02 PM To: Burgoon, Lyle D ERD-MS Subject: Re: [EXTERNAL] cr6study.info
Lyle: we were doing some work on the Cr(VI) genomics data and noticed an error in the rat data (some probe ID's were mislabeled). The actual data is correct - just the labels are wrong. This doesn't impact our publications but does impact the data available for download from our Cr(VI) study website. MSU is fixing and I will alert you when we update the files.
mark
ToxS trategies# Inc*
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
Bivd, Suite 220
Ex. 6 E x ......
Ex. 6
;832) 218-2756 mharris@toxstrateqies.com : BlockedBlockedhttp://www.toxstrateqies.com
: BlockedBlockedhttp://www,nnkedin.com/in/toxstrateaiesharris
This e-mail, and any attachments thereto, is intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information. If you are not the Intended recipient of this ernaii, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any
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attachments thereto, is strictly prohibited. If you have received this e-mail in error please immediately notify ToxStrategles, Inc. at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof,
From: "Burgoon, Lyle D ERD-MS" <Lvle.D.Burgoon(Susace.armv.mil> Date: Friday, Septem ber 18, 2015 at 3:50 PM To: Mark Harris <mharnsfStoxstfafegies.com> Subject: Re: [EXTERNAL] cr6study.info
Army moves paperwork pretty quick. If ! know it's coming, I can grease the skids, if you have a tight turnaround on paperwork approve! needed my iah director can expedite and maybe l-2weeks we should be able to turn it around. Unless it's after July 31, then it might take longer be of the backlog at contracts.
Lyle D, Burgoon, PhD Envi ronmentaI Laboratory US Army Engineer Research and Development Center Research Triangle Park, IMC
Sent from my BiackBerry 10 smartphone on the Verizon Wireless 4G LIE network. From: Mark Harris Sent: Friday, September 18, 2015 4:40 PM To: Burgoon, Lyle D ERD-MS Subject: Re: [EXTERNAL] cr6study.info
Lyle: that is good to know about being able to collaborate on future projects. You never know when a client will ask for such analyses.
One question - is it is relatively straightforward to engage you all for a project? Meaning, if something came up, could the paperwork being done relatively quickly to get going?
mark
From: "Burgoon, Lyle D ERD-MS" Date: Friday, Septem ber 18, 2015 at 3:35 PM To: Mark Harris Subject: Re: [EXTERNAL] cr6study.info
Hey Mark,
Thanks, The Army has no interest in chromium (thankfully). However, ERA is in the process of contracting with the Army to reanalyze the data. So, in preparation for that, we requested the data.
On a side note, in my new federai job I'm soft money, and we operate like a consulting company. So if in the future you need Complex or toxicogenomic support, let me know. We can accept funds from companies for collaborative work.
Ex. 6 if you want to chat sometime, my number is
Cheers,
Lyle
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Lyle D, Burgeon, PhD Environmental Laboratory LJS Army Engineer Research and Development Center Research Triangle Park, MC
Sent from my BlaekBerry 10 smartphone on the Verizon Wireless 4G LIE network. From: Mark Harris Sent: Friday, September 18, 2015 1:51 PM To: Burgoon, Lyle D ERD-MS Subject: [EXTERNAL] cr6study.info
Lyle: you should have received an approval for access to the data via email. If you have any issues downloading data just let me know. I did not realize you had changed jobs. Good luck with the new position. Why is the Army interested in Cr(VI)?
mark
ToxStrategies^ In c .
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Bivd, Suite 22 Katy, TX 77494
Direct Dial:
Ex. 6
E x . 6 Houstor Of k i : i 2 i n : z n w 062
Cell:
Ex. 6
tax: (832) 218-2756
Email: m h a m s M t ^
Website: BlockedBlockedBlo^
Unkedin: BlockedBlockedBlockedhttp://www.linkedin.com/in/toxstrateaiesharris
This e-mail, and any attachments thereto, is Intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information. If you are not the intended recipient of this emall, you are hereby notified that: any dissemination, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-mail in error please immediately notify loxStrategies, Inc. at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof,
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Friday, March 2, 2018 at 8:02:15 AM Central Standard Time
Subject: Re: Cr(VI) raw microarray data
Date: Thursday, March 13, 2014 at 12:39:33 PM Central Daylight Time
From: Burgoon, Lyle
To:
Mark Harris
Thanks, Mark; looking forward to the data. If you're going to SOT, safe travels.
Cheers,
Lyle
From: Mark Harris <mharris@toxstrategies.com> Sent: Thursday, March 13, 2014 1:37:10 PM To: Burgoon, Lyle Cc: Thomas, Russell; Tim Zacharewski; Gibbons, Catherine; Chad Thompson; Deborah Proctor Subject: Cr(VI) raw microarray data
Lyle: as I mentioned in the meeting on Monday, the data will be posted to our new Cr(VI) MOA website before SOT. Once the site is live I will send you all a link to it. You will be able to download the genomics data at that time.
The approach and methods that were used to analyze the data are adequately described in the Kopec papers. Our use of the genomics data to support the Mode of Action can be found in our Critical Reviews in Toxicology paper. Links to these Open Access papers can be found at the web page below:
http://www.toxstrategies.com/publications/CRVI MOA studv.htm
mark
From: "Burgoon, Lyle" <Burgoon.Lvle@epa.gov> Date: March 12, 2014 at 8:43:16 AM CDT To: "cthQmpson@toxstrategies.cam" <cthompson@toxstrategies,com> Cc: "tzachare@msu.edu" <tzachare@msu.edu>. "Gibbons, Catherine" <Gibbons.Catherine@epa.gov> Subject: Cr(VI) raw microarray data
Dr. Thompson,
It was nice seeing you and Dr. Harris (via video) at Monday's meeting @ NCEA HQ. I was quite pleased to hear Ms. Mason state that ACC expected the researchers would share their data and results with NCEA.
I'm following up on our discussion from Monday and am requesting access to all of your raw microarray data, as well as your analyzed data that supports the conclusions in your papers. In addition, it would be helpful if you could also supply us with the analysis code that was used,
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any protocols used for the analyses, and any other supporting documentation that may help us understand how the assays and analyses were performed.
For clarity, I am using the MIAME definition of "raw data", and my request for the additional information is in line and keeping with the MIAME standard, which can be found here: http://www.mged.org/Workgroups/MIAME/miame.html.
To facilitate data transfer, I can set-up an EPA-based FTP site where you can upload the data.
Thanks again for presenting your latest results to us, and I look forward to receiving the data.
Cheers,
Lyle
L y le D. Burgoori, Ph.D N ational Center fo r Environm ental Assessment C h ie f, Hazardous P o llu ta n t Assessment Group (A c tin g ) US Environm ental P ro te c tio n Agency Phone: 919.541.7808 Fax: 9,19,.685,..34.73...,
C e l l : i Ex. 6 I
Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherwise, please notify me immediately so that proper contract action can be initiated.
Note New Address
ToxStrategies^ Inc.
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Chico Ranch Blvd, Suite 220 Kafy, IX 77494
Direct Dia
Ex. 6
Ex. 6
! Ex. 6 i
fax:
email: m jw i^tQ xstrateq jesxom : http://www.toxstrateqies.com
This e-mail; and any attachments thereto, is intended only ter use lay the addressee(s) named herein and may contain legally privileged and/or confidential Information, If you are not the Intended recipient of this emaii, you ar e hereby notified that: any dissemination, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited, If you have received fids e-mail in error-; please immediately notify iOxStrafegies, Inc, at (832) 868-7729 and permanently delete the original anti any copy of any e-mail
and any printout thereof.
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Friday, March 2, 2018 at 8:01:37 AM Central Standard Time
Subject: Re: Cr(VI) raw microarray data Date: Monday, March 17, 2014 at 9:40:37 AM Central Daylight Time From: Burgoon, Lyle To: mharris@toxstrategies.com CC: tzachare@msu.edu, Gibbons, Catherine, cthompson@toxstrategies.com
Hi Mark,
I have read the Kopec, et al papers again, at your suggestion. Reading them reaffirms that we absolutely need to have the analysis code in order to understand what exactly was done. Per the MIAME standard (Minimum Information About a Microarray Experiment: http://www.mged.org/Workgroups/MIAME/miame 2.0.html):
The essential laboratory and data processing protocols are usually described in the journal methods section. It is sufficient to simply reference the standard experimental or data processing protocols, such as MAS5 or RMA. However, if a protocol depends on parameters that can be varied, their values should be provided. If novel or non-standard data processing protocols are used, these should be described in sufficient detail to allow the user to understand what exactly has been done in the experiment and how the data have been analysed to reach the conclusions of the study.
In the case of the Kopec, et al papers, the analysis protocols used are non-standard data processing methods. As far as I can tell, these methods are commonly used in Dr. Zacharewski's laboratory; however, they are not commonly used elsewhere. The Eckel, et al 2005 and Eckel, et al 2004 papers describe analysis methods used in the Kopec, et al papers that require parameterization or changes to the code in order to work properly. Thus, it is critical for us to see the code in order to understand how the data were treated. Without the code we will be unable to understand how you came to draw the hypotheses you did in the Kopec, et al and subsequent papers. Without this understanding, we cannot interpret your results.
As MIAME is a community standard, first adopted several years ago by many prominent journals, you can see that this request is not unusual.
Likewise, we need to have the rawest form of the data possible for the QRT-PCR analyses, which Kopec, et al have used to support their microarray data. At a minimum, this would include any spreadsheets or text files of the data from the ABI machine, detailing all of the mathematical manipulations of the data from prior to standardization, through normalization, ratio calculation, and statistical analysis. Note: I couldn't find any details on how the statistical analysis of the QRT-PCR was performed, nor can I find a reference for how the standard errors of a ratio were calculated.
We may have additional data requirements and needs as we dig into the toxicogenomics data further, and we look forward to working with you in obtaining the information we need to better understand these studies.
Thanks,
Lyle
L y le D. Burgoon^ Ph.D C h ie fj Hazardous P o llu ta n t Assessment Group (A c tin g ) N ational Center fo r Environm ental Assessment US Environm ental P ro te c tio n Agency Phone: 919.541.7808
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Fax: 919.685.3473
Cell
Ex. 6
Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherwise, please notify me immediately so that proper contract action can be initiated.
From: Mark Harris <mharris(5)toxstrategies.com> Sent: Thursday, March 13, 2014 1:37:10 PM To: Burgoon, Lyle Cc: Thomas, Russell; Tim Zacharewski; Gibbons, Catherine; Chad Thompson; Deborah Proctor Subject: Cr(VI) raw microarray data
Lyle: as I mentioned in the meeting on Monday, the data will be posted to our new Cr(VI) MOA website before SOT. Once the site is live I will send you all a link to it. You will be able to download the genomics data at that time.
The approach and methods that were used to analyze the data are adequately described in the Kopec papers. Our use of the genomics data to support the Mode of Action can be found in our Critical Reviews in Toxicology paper. Links to these Open Access papers can be found at the web page below:
http://www.toxstrategies.com/publications/CRVI MOA studv.htm
mark
From: "Burgoon, Lyle" <Burgoon.Lvle@epa.gov> Date: March 12, 2014 at 8:43:16 AM CDT To: "cthompson(5itoxstrategies.com" <cthompson(5)toxstrategies.com> Cc: "tzacharef5imsu.edu" ctzachare(5)msu.edu>. "Gibbons, Catherine" <Gibbons.Catherine(5ie pa.gov> Subject: Cr(VI) raw microarray data
Dr. Thompson,
It was nice seeing you and Dr. Harris (via video) at Monday's meeting (5) NCEA HQ. I was quite pleased to hear Ms. Mason state that ACC expected the researchers would share their data and results with NCEA.
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I'm following up on our discussion from Monday and am requesting access to all of your raw microarray data, as well as your analyzed data that supports the conclusions in your papers. In addition, it would be helpful if you could also supply us with the analysis code that was used, any protocols used for the analyses, and any other supporting documentation that may help us understand how the assays and analyses were performed.
For clarity, I am using the MIAME definition of "raw data", and my request for the additional information is in line and keeping with the MIAME standard, which can be found here: http://www.mged.org/Workgroups/MIAME/miame.html.
To facilitate data transfer, I can set-up an EPA-based FTP site where you can upload the data.
Thanks again for presenting your latest results to us, and I look forward to receiving the data.
Cheers,
Lyle
L y le D. Burgoon, Ph.D
N ational Center fo r Environm ental Assessment
C h ie f, Hazardous P o llu ta n t Assessment Group (A c tin g )
US Environm ental P ro te c tio n Agency
Phone: 919.541.7808
Fax: 919.685.3473
C e ll:
Ex. 6
Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherwise, please notify me immediately so that proper contract action can be initiated.
Note New Address T ox8 tra te g ie s # Inc
Mark Harris, Ph.D. Principal Health Scientist
23123 Ciuco Ranch Bivd, Suite 220 Katy. IX 77494
Direct Dial;
Ex. 6
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13 X :
Email : mharris@toxstrateqies.com
: http://jwm Joxstratqjesxom
This e-mail; and any attachments thereto, is intended only for- use by the addressee(s) named herein and may contain iegaiiy privileged and/or confidential information. If you are not: the intended recipient of this emaii, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-rnaii in error, piease immediately notify "idxStrafegles, Inc, at (832) 868-7729 and permanently delete the original ami any copy of any e-mail
arid any printout thereof.
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Friday, March 2, 2018 at 8:02:43 AM Central Standard Time
Subject: RE: Cr(VI) MOA Study Website Date: Thursday, April 3, 2014 at 2:59:52 PM Central Daylight Time From: Burgoon, Lyle To: Mark Harris CC: Gibbons, Catherine, Vandenberg, John, Flowers, Lynn
Hi Mark,
We cannot access the data at this time due to our inability to agree to the Terms and Conditions associated with data access found here: http://cr6study.info/studv-data/terms-and-conditions/
Specifically, we request that ToxStrategies delete the indemnification clause in the Terms and Conditions. As written, the Agency cannot agree to the terms as it would be a violation of the Anti-Deficiency Act (i.e., making a commitment to an unknown future cost is a direct violation of the Anti-Deficiency Act).
Please let me know what action you are willing to take as soon as possible. As you are aware, time is of the essence with respect to the Cr(VI) IRIS Assessment. Your prompt attention to this matter is appreciated.
Thanks,
Lyle
L y le D. Burgoon, Ph.D
C h ie fj Hazardous P o llu ta n t Assessm ent Group (A c tin g )
N atio n al Center fo r Environm ental Assessment
US E n v iro n m e n ta l P r o t e c t io n Agency
Phone: I
Ex! 6
]
Fa x: 919768573473
C e ll:
Ex. 6
Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherwise, please notify me immediately so that proper contract action can be initiated.
From: Mark Harris [mailto:mharris@toxstrategies.com] Sent: Monday, March 24, 2014 9:34 AM To: Burgoon, Lyle Cc: Tim Zacharewski; Gibbons, Catherine; Chad Thompson; Thomas, Russell Subject: Cr(VI) MOA Study Website
Lyle: our Cr(VI) MOA study website is live. You can access is at www.cr6studv.info
Under the Study Data tab you can register to download data. Once registered, you will receive a password to access the data download portion of the site.
Not all of the genomics data you requested has been posted. Things that are not posted yet are:
1. Analysis Code 2. QRT-PCR data
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These items will be added in the next few weeks. mark
M o te M e w Address ToxStrategies^ Inc*
Innovative Solutions > Sound S
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Bivci, Suite 220 Katyn TX 77090
Diced: Dial:
Ex. 6
2 Ext x. 6
Cali
Ex. 6
fax: ......
750"
Email: mharris@toxstrateqies.com
: http://www.toxstrateqies.com
: ms e-nras, ano any arcecnmonrs cneraco,. mconoou com tor use ny cne aooressaets: namoo narem ana may contain legally privileged and/or confidential Information, If you ace not: the intended recipient of this emaib you are hereby notified that: any dissemination,, distribution or- copying of this e-mail, and any etcacnmenrs rnerero, :s snocuy pr'onmrreo, rr yorr rrave recemoo mss e-man in errors irsease u'orneomroiy notify TbxSfrategles,. Inc, at: (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof.
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Friday, March 2, 2018 at 8:03:12 AM Central Standard Time
Subject: RE: T&C - how does this
Date: Monday, April 28, 2014 at 10:08:36 AM Central Daylight Time
From: Burgoon, Lyle
To:
Mark Harris
Hi Mark, Thanks for working with us - that language meets our needs. Sorry for the delay - was out sick last week. Cheers, Lyle
L y le D. Burgoon, Ph.D C h ie fj Hazardous P o llu ta n t Assessm ent Group (A c tin g ) N atio n al Center fo r Environm ental Assessment US E n v iro n m e n ta l P r o t e c t io n Agency Phone: 919.541.7808 Fax: 919.685.3473
C e ll: Notice (If This Communication Regards a Contract): Nothing in this message shall be construed as a change to the price, schedule, or terms and conditions of the contract. If the receiver does construe it otherwise, please notify me immediately so that proper contract action can be initiated.
From: Mark Harris [mailto:mharris@toxstrategies.com] Sent: Wednesday, April 23, 2014 3:09 PM To: Burgoon, Lyle Subject: T&C - how does this
Lyle: I got some revised T&C language from the attorneys today. See attached in Tracked Changes. If this works let me know and I will get the website updated.
Also, if these words don't work, can you ask the attorney reviewing this to suggest some words that would work for the US government?
thanks
mark
Note Mew Address ToxStrategiesf lee,
Innovative Solutions > Sound S
Mark Harris, Ph.D. Principal Health Scientist
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Kaly, TX 778 M
Dired: Dia::
Ex. 6
Houston Office 281': 712-2062 Ext 2001
Ceii:
Ex. 6
fax:
Email: mharris@toxstrateqies.com
_______: http://www.toxstrateqies.com
.............................................................................................................................................................................. _____________________________________________________________________________________________ i _________________________________________________________________________________
............ .............................................................................................................................................................
________________________________________________________________________________________ and any printuiti: thereof.
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Friday, March 2, 2018 at 8:05:08 AM Central Standard Time
Subject: Re: [EXTERNAL] cr6study.info
Date: Friday, September 18, 2015 at 3:35:41 PM Central Daylight Time
From: Burgoon, Lyle D ERD-MS
To:
Mark Harris
Hey Mark,
Thanks, The Army has no interest in chromium (thankfully). However, ERA is in the process of contracting with the Army to reanalyze the data. So, in preparation for that, we requested the data.
On a side note, in my new federal job I'm soft money, and we operate like a consulting company. So if in the future you need CompTox or toxicogenomic support, let me know. We can accept funds from companies for collaborative work.
if you want to chat sometime, my number is
Ex. 6
Cheers,
Lyle
Lyle D. Burgoon, PhD Environmental Laboratory US Army Engineer Research and Development Center Research Triangle Park, NC
Sent from my BiackBerry 10 smartphone on the Verizon Wireless 4G LIE network.
From: Mark Harris Sent: Friday, September 18, 2015 1:51 PM To: Burgoon, Lyle D ERD-MS Subject: [EXTERNAL] cr6study.info
Lyle: you should have received an approval for access to the data via email. If you have any issues downloading data just let me know. I did not realize you had changed jobs. Good luck with the new position. Why is the Army interested in Cr(VI)?
mark
T o x S tra te g ie s # Ine
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Blvd, Suit: 220 Katy, TX 77494
Direct Dial:
Ex. 6
Houstor-.atiLiS2 E E I t l 362 Ext 2001
Cell:
Ex. 6
fax: (832) 218-2756
Email:
>.com
Webs! t e : Blockedhttp://www,toxstrateaies.com
Lsnkedin: Blockedhttp://www.linkedin.com/in/toxstrateaiesharris
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This e-mail. and any attachments thereto, is intended only for use by the addressee(s) named herein and may contain legally privileged and/or confidential information, If you are not: the intended recipient of this c mail, you are hereby notified that any dissemination,, distribution or copying of this e-mail, and any attachments thereto, is strictly prohibited. If you have received this e-mail in error, please immediately notify 'TdxStrafegies,- Inc, at: (832) 888-7729 and permanently delete the original end any copy of any e-mail and any printout thereof.
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Friday, March 2, 2018 at 8:06:04 AM Central Standard Time
Subject: Re: [EXTERNAL] cr6study.info
Date: Friday, September 18, 2015 at 3:50:25 PM Central Daylight Time
From: Burgoon, Lyle D ERD-MS
To:
Mark Harris
Army moves paperwork pretty quick. If I know it's coming, I can grease the skids, if you have a light turnaround on paperwork approval needed my lab director can expedite and maybe l~2weeks we should be able to turn it around. Unless it's after July 31, then it might take longer be of the backlog at contracts.
Lyle D. Burgoon, PhD Envi ronmenta! Laboratory US Army Engineer Research and Development Center Research Triangle Park, IMC
Sent from my BiaekBerry 10 smartphone on the Verizon Wireless 4G LIE network.
From: Mark Harris Sent: Friday, September 18, 2015 4:40 PM To: Burgoon, Lyle D ERD-MS Subject: Re: [EXTERNAL] cr6study.info
Lyle: that is good to know about being able to collaborate on future projects. You never know when a client will ask for such analyses.
One question - is it is relatively straightforward to engage you all for a project? Meaning, if something came up, could the paperwork being done relatively quickly to get going?
mark
From: "Burgoon, Lyle D ERD-MS" Date: Friday, September 18, 2015 at 3:35 PM To: Mark Harris Subject: Re: [EXTERNAL] cr6study.info
Hey Mark,
Thanks. The Army has no interest in chromium (thankfully). However, ERA is in the process of contracting with the Army to reanalyze the data. So, in preparation for that, we requested the data.
On a side note, in my new federal job I'm soft money, and we operate like a consulting company. So if in the future you need Complex or toxicogenomic support, let me know. We can accept funds from companies for collaborative work.
if you want to chat sometime, my number isjL_______E_x_. _6
Cheers,
Lyle
Lyle D, Burgoon, PhD Environmental Laboratory LJS Army Engineer Research and Development Center
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Sent from my BlackBerry 10 smartphone on the Verizon Wireless 4G LIE network. From: Mark Harris Sent: Friday, September 18, 2015 1:51 PM To: Burgoon, Lyle D ERD-MS Subject: [EXTERNAL] cr6study.info
Lyle: you should have received an approval for access to the data via email. If you have any issues downloading data just let me know. I did not realize you had changed jobs. Good luck with the new position. Why is the Army interested in Cr(VI)?
mark
ToxStrategies^ In c .
Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 u n co Ranch Bivd, Suite 22 Katy, TX 77494
Direct Dial: [ Ex. 6
Honsfon.-OiSx Z5M i:5I3T2062 Ext 2001
Cell:
EX. 6
fax: LC83Zj"'ZIS-275F'
Ema iI: mharris@toxstrateaies.com
: Blockedhttp://www.toxstrateqies.com
Llnkedin: Blockedhttp://www.linkedin.com/in/toxstrateaiesharris
This e-mail, and any attachments thereto, Is intended only for use by the addressee(s) named herein and may contain iegaily privileged and/or confidential information. If you are not the intended recipient of this email, you are hereby notified that any dissemination, distribution or copying of this e-mail, and any
attachments thereto, Is strictly prohibited. If you have received this e-mail in error; please immediately notify ToxStrategies, Inc. at (832) 868-7729 and permanently delete the original and any copy of any e-mail and any printout thereof,
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Friday, March 2, 2018 at 8:19:29 AM Central Standard Time
Subject: New user registration for Cr(VI) MOA Study
Date: Wednesday, August 10, 2016 at 1:16:17 PM Central Daylight Time
From: CrVI MOA Study
To:
mharris@toxstrategies.com
The following user registered for Cr(VI) MOA Study (and is pending approval)
username: sfoster email: foster.stivenfSeoa.gov
First Name: Stiven Last Name: Foster Company: USEPA Position: Toxicologist Address 1: 1200 Pennsylvania Ave, NW Address 2: MC-5103T City: Washington State: DC Zip: 20460 Country: USA Day Phone: 202-566-1911 Plans for Data Use: Evaluation of finding for consideration in EPA efforts. TOS: agree
This user registered here: http://cr6studv.info/register/
Ex. 6
This is an automated message from Cr(VI) MOA Study Please do not reply to this address
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Friday, March 2, 2018 at 8:11:20 AM Central Standard Time
Subject: (none)
Date: Wednesday, August 10, 2016 at 1:19:59 PM Central Daylight Time
From: Mark Harris
To:
foster.stiven@epa.gov
I have activated your access to the raw data. If you have any problems accessing the data let me know.
Mark
ToxStrategies, Inc. Innovative Solutions > Sound Science
Mark Harris, Ph.D. Principal Health Scientist
23123 Cinco Ranch Blvd, Suite 220 Katy, TX 77494
Direct Dial: ! Ex. 6 !
Houston Office:"(28lf712-2062 Ext 2001
Cells' Ex. 6 I fax: (832) 218-2756 " Email: mharris(5)toxstrategies.com Website: http://www.toxstrategies.com Linkedin: http://www.linkedin.com/in/toxstrategiesharris
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