OFFICE OF CHEMICAL SAFETY

AND POLLUTION PREVENTION

UNITED STATES ENVIRONMENTAL PROTECTION AGENCY

WASHINGTON, D.C. 20460

RE: Teleconference between Dow AgroSciences (DAS) and EPA to Discuss EPA’s 

Feedback on the Oxon Portion of the March 19, 2013 PBPK Meeting

List of Documents

1. Meeting Summary Page 1

2. Meeting Attendees Page 1

3. DAS Talking Points for the Meeting Page 2

1. Meeting Summary

On Thursday, May 2, 2013, EPA’s Office of Pesticide Programs met with Dow AgroSciences 

(DAS) via teleconference to discuss the feedback EPA had given DAS concerning the oxon 

portion of the March 19, 2013 meeting that EPA and DAS had.

2. Meeting Attendees

DAS attendees

Darin Lickfeldt, Dow

Mike Bartells, Dow

Daland Juberg, Dow

Ian vanWesenbeeck, Dow

Sue Marty, Dow

Jon Hotchkiss, Dow

EPA attendees

Jeff Dawson, HED

Wade Britton, HED

Rochelle Bohaty, EFED

Charles (Chuck) Peck, EFED

Tom Myers, PRD

Joel Wolf, PRD
PBPK MODEL 

DISCUSSION

Michael Bartels

May 2, 2013
| 2

• With regards to the PBPK modeling

• Using the model, what doses of both the oxon and chlorpyrifos would 

be predicted to produce 10% inhibition in brain? In RBC? In 

diaphragm? 

• The model (Timchalk et al 2002) does include diaphragm as a 

separate compartment with ChE inhibition, does Dow’s current model 

still include that?

• Concerning model outputs, it seems like a table of predictions for 

differing levels of ChE inhibition, from both chlorpyrifos and oxon, in 

brain, RBC, and diaphragm would be very helpful?

EPA Questions of May 2, 2013
| 3

• With regards to the PBPK modeling

• Using the model, what doses of both the oxon and chlorpyrifos would 

be predicted to produce 10% inhibition in brain? In RBC? In 

diaphragm? - Values have been calculated for chlorpyrifos. Also for 

for oxon, up to maximum predicted levels in drinking water. Oxon 

doses predicted to cause 10% inhibition can be calculated within 2 

weeks. 

• The model (Timchalk et al 2002) does include diaphragm as a 

separate compartment with ChE inhibition, does Dow’s current model 

still include that?

• Concerning model outputs, it seems like a table of predictions for 

differing levels of ChE inhibition, from both chlorpyrifos and oxon, in 

brain, RBC, and diaphragm would be very helpful?

Questions
| 4

CPF

CPO

RBC Brain

• Predictions of blood metabolites from a single oral dose of CPF

(3.5 ng/g)

(3.5 pg/g)

DAS Presentation at April 2012 SAP
| 5

• With regards to the PBPK modeling

• Using the model, what doses of both the oxon and chlorpyrifos would 

be predicted to produce 10% inhibition in brain? In RBC? In 

diaphragm? 

• The model (Timchalk et al 2002) does include diaphragm as a 

separate compartment with ChE inhibition, does Dow’s current model 

still include that? - Yes

• Concerning model outputs, it seems like a table of predictions for 

differing levels of ChE inhibition, from both chlorpyrifos and oxon, in 

brain, RBC, and diaphragm would be very helpful?

Questions
| 6 Poet 2013 (MRID 49074901)

• Current PBPK/PD model design
| 7

• With regards to the PBPK modeling

• Using the model, what doses of both the oxon and chlorpyrifos would 

be predicted to produce 10% inhibition in brain? In RBC? In 

diaphragm? 

• The model (Timchalk et al 2002) does include diaphragm as a 

separate compartment with ChE inhibition, does Dow’s current model 

still include that? 

• Concerning model outputs, it seems like a table of predictions for 

differing levels of ChE inhibition, from both chlorpyrifos and oxon, in 

brain, RBC, and diaphragm would be very helpful?

Questions
| 8

• With regards to the PBPK modeling

• Using the model, what doses of both the oxon and chlorpyrifos would 

be predicted to produce 10% inhibition in brain? In RBC? In 

diaphragm? 

• The model (Timchalk et al 2002) does include diaphragm as a 

separate compartment with ChE inhibition, does Dow’s current model 

still include that? 

• Concerning model outputs, it seems like a table of predictions for 

differing levels of ChE inhibition, from both chlorpyrifos and oxon, in 

brain, RBC, and diaphragm would be very helpful? - DAS agrees. 

Predictions of ChE inhibition in RBC and brain, from both chlorpyrifos 

and oxon in drinking water have been included in the recent Oxon 

PBPK model report (MRID 49047701). 

Questions
| 9 Poet 2013 (MRID 49047701)

• Predictions of ChE inhibition, as percent of control values, in human 

RBC and Brain tissue following repeated oral exposures to Oxon or 

Chlorpyrifos for 21 days. Doses are administered 3x/day.
Lessire, ToxApplPharm 138: 201-210, 1996 | 10

• Relationship between the guinea pig lung cholinesterase activity measured after 

18 min of perfusion with paraoxon (A), parathion (B), parathion plus piperonyl

butoxide. Data are expressed as percentage of the initial cholinesterase activity 

measured at zero time.

Paraoxon

Parathion

Parathion + CYP inhibitor

Data show comparable response in lung tissue 

from Parent OP and Oxon metabolite
Hotchkiss 2013 (MRID pending) | 11

• Summary of blood levels of chlorpyrifos and oxon and maximum % ChE 

inhibition (relative to the individual time-matched point control levels) in RBC, 

plasma, lung and brain tissues of rats nose-only exposed 6 hours to a near 

saturated chlorpyrifos vapors (0.254 mg/m3) or to solid particulate aerosolized 

chlorpyrifos aerosols (3.7, 12.9, 22.1, or 53.5 mg/m3).