2

Quality Protection Act (FQPA) of 1996. The overall goal of this SAP is to review various methods 

and models that will inform the Agency’s anticipated cumulative risk assessment (CRA) for 

pyrethroids in addition to future cumulative risk assessments on other pesticide groups. The 

SAP session will review individual and linked state-of-the-science exposure and dose 

assessment tools in the context of an example case study (permethrin), including proposed 

methodologies using linked SHEDS and PBPK models. In August 2007, the SAP reviewed an 

earlier version of SHEDS and also performed a peer consult on development of PBPK 

approaches (see http://www.epa.gov/scipoly/sap/meetings/2007/081407_mtg.htm and 

http://www.epa.gov/scipoly/sap/meetings/2007/081607_mtg.htm). The upcoming July 2010 

SAP will focus on work conducted by ORD and OPP scientists since the SHEDS 2007 review on 

these models, and will consist of:

 (i) A formal review of SHEDS-Multimedia version 4 which consists of 2 modules: 

SHEDS-Dietary v.1 and SHEDS-Residential v. 4. SHEDS-Dietary v.1 is a probabilistic, 

population-based dietary exposure assessment model that can simulate individual 

exposures to chemicals in food and drinking water over different time periods (e.g., 

daily, yearly). SHEDS-Residential v. 4 is a probabilistic, population-based residential 

exposure assessment model that can simulate cumulative (multiple chemicals) or 

aggregate (single chemical) residential exposures over time via multiple routes of 

exposure for different types of chemicals and scenarios. 

 (ii) A peer consult on refinements to ORD’s PBPK models and how SHEDS outputs are 

introduced into and used by PBPK models; and

 (iii) Demonstration of the application of linked SHEDS-PBPK models with a permethrin 

case study.

The Agency is requesting specific input from the SAP on this updated version of the SHEDS 

models and related software, and the Panel is being asked to review: 

 (i) The dietary module of SHEDS-Multimedia (SHEDS-Dietary v. 1), including 

algorithms, inputs, and results illustrated with a permethrin case study;

 (ii) The residential module of SHEDS-Multimedia (SHEDS-Residential v. 4), including 

algorithms, inputs, and results illustrated with a permethrin case study;

 (iii) The SHEDS-Multimedia version 4 aggregate (dietary and residential modules 

combined) permethrin case study, including algorithms, inputs, and results;

 (iv) Update on PBPK modeling since the August 2007 SAP, and approaches for and 

results of linking SHEDS-Multimedia with ORD PBPK models, illustrated with a 

permethrin case study; and
3

 (v) Current Agency plans and ideas for extending the permethrin case study to several 

(2-3) pyrethroid pesticides. 

To assist the July 20-22, 2010 FIFRA SAP in their review of the SHEDS-model, the PBPK and the 

SHEDS-PBPK linkage, and the permethrin case study, each FIFRA SAP member is being provided 

CD-ROMs containing a relevant material for this review as described in the Table below. 

List of SHEDS SAP Deliverables

CD-ROM Deliverable Title/Description/Comments

SAP Package #1 Materials

CD-ROM

1

OF

3

Installation Instructions: 

SHEDS-Residential v.4 

& SHEDS-Dietary v. 1 

(pdf)

INSTALLATION INSTRUCTIONS FOR SHEDS-MULTIMEDIA VERSION 4 

(both SHEDS-Dietary and SHEDS-Residential modules)

June 10, 2010

SAS code and GUIs: 

SHEDS-Residential v.4 

& SHEDS-Dietary v.1 

(exe) 

SHEDS_Multimedia_Setup_4.00.exe (for SHEDS-Residential)

SHEDS_Dietary_Setup_1.0.exe (for SHEDS-Dietary)

User Guide: SHEDSResidential v.4 (pdf) 

The Stochastic Human Exposure and Dose Simulation Model

for Multimedia, Multipathway Chemicals (SHEDS-Multimedia): Residential 

Module

SHEDS-Residential version 4

Draft User Guide

June 16, 2010

User Guide for SHEDSDietary v.1 (pdf)

The Stochastic Human Exposure and Dose Simulation Model

for Multimedia, Multipathway Chemicals (SHEDS-Multimedia): Dietary Module 

SHEDS-Dietary version 1

Draft User Guide

June 16, 2010

CD-ROM

2

OF

3

Technical Manual –

SHEDS Residential v.4 

(pdf)

The Stochastic Human Exposure and Dose Simulation Model

for Multimedia, Multipathway Chemicals (SHEDS-Multimedia):

Residential Module 

SHEDS-Residential version 4

Draft Technical Manual

June 16, 2010

Technical Manual –

SHEDS Dietary v.1 (pdf)

2 files; main and 

appendices

The Stochastic Human Exposure and Dose Simulation Model

for Multimedia, Multipathway Chemicals

(SHEDS-Multimedia): Dietary Module

SHEDS-Dietary version 1

Draft Technical Manual

June 16, 2010
4

CD-ROM Deliverable Title/Description/Comments

SAP Package #1 Materials

Response to 2007 SAP 

comments (dietary and 

residential) (pdf) 

AUGUST 2007 FIFRA SCIENTIFIC ADVISORY PANEL RECOMMENDATIONS FOR 

SHEDS-DIETARY AND SHEDS-RESIDENTIAL MODULES

(SUMMARIZED)

AND EPA RESPONSES

Meeting Minutes from 

2007 SAP on v.3 (pdf)

Available as PDF in SAP Package as well as on 2007 SAP website at 

http://www.epa.gov/scipoly/sap/meetings/2007/august/sap_minutes_aug_14_15_2007.pdf

Charge Questions for 

Issues 1 and 2 

(Contained in this letter)

Relate to SHEDS-Dietary and SHEDS-Residential software, algorithms, 

models, and written documentation (User Guide and Technical Manual).

ORD SHEDS website 

with background on v.3

Available at 

http://www.epa.gov/heasd/products/sheds_multimedia/sheds_mm.html

SAP Package #2 Materials

(To be sent the following week)

CD-ROM

3

OF

3

Charge Questions for 

Issues 3 through 5

To be provided. These relate to SHEDS-PBPK, Model linkage, and and 

model comparisons. 

Background paper for 

PBPK aspects

To be provided

SHEDS permethrin 

case study input 

spreadsheets (.xls)

To be provided

ACS/ISEA ModelModel Comparison 

(pdf)

To be provided

SHEDS Arsenic 

Evaluation Paper (EHP)

Xue, J. et al. Probabilistic Modeling of Dietary Arsenic Exposure and 

Dose and Evaluation with 2003-2004 NHANES Data. 2010. 

Environmental Health Perspectives 118(3): 345-350. 

Available at: http://www.ehponline.org

As can be seen, the material is being provided in two packages – an early SAP package which 

contains the dietary and residential SHEDS executable files, the User Manuals and Technical 

Guides for the dietary and residential SHEDS models, the Agency’s responses to the 2007 Panel 

report on SHEDS, as well as background material from the August 2007 SAP meeting where 

SHEDS was first discussed and reviewed. We anticipate the second package will be sent out on 

or about June 23. This second package will focus on material pertaining to the SHEDS- PBPK 

linkage issues and model comparisons. 

Below are the charge questions relating to items contained in the “Early Package” that pertain 

to the first two issues that we are asking the Panel to consider. Separate materials and charge 

questions will be provided subsequently to the SAP for the remaining issues.

_____________________________________________________
5

Issue 1: Usability aspects of the SHEDS Dietary Module (SHEDS-Dietary v.1.0) and the SHEDS 

Residential Module (SHEDS-Residential v.4.0)

A. SHEDS DIETARY

Question 1-1: What, if any, difficulties were encountered in loading or running the 

SHEDS –Dietary software?

Question 1-2: Please comment on the organization, clarity, completeness, and usefulness 

of the SHEDS-Dietary Technical Manual and the User Guide. Please provide any 

suggestions for improvement.

Question 1-3: Please comment on the organization and usability of the SHEDS-Dietary 

GUI (Graphical User Interface), and whether additional changes would be helpful for this 

model.

B. SHEDS RESIDENTIAL 

Question 1-4: What, if any, difficulties were encountered in loading or running the 

software for the SHEDS-Residential software?

Question 1-5: Please comment on the organization, clarity, completeness, and 

usefulness of the SHEDS-Residential Technical Manual and the User Guide. Please 

provide any suggestions for improvement.

Question 1-6: Please comment on the organization and usability of the SHEDSResidential GUI (Graphic User Interface), and whether additional changes would be 

helpful for this model.

Issue 2: Documentation, completeness, and clarity of technical aspects of SHEDS-Dietary v. 1.0 and 

SHEDS-Residential v. 4.0 

Question 2-1:

BACKGROUND: In August 2007, the FIFRA SAP reviewed the model and 

documentation for the SHEDS Residential module (then termed “SHEDS-Multimedia 

version 3”), plans for the dietary module, and plans for extending the model to aggregate 

the dietary and residential modules. The 2007 SAP report, EPA responses to the 2007 

SAP comments, and specific changes from version 3 to version 4 of the SHEDSResidential module have been provided to this SAP in the materials and background 

documents. 

QUESTION 2-1: Please comment on whether the exposure algorithms and model 

components as described in the Technical Manuals are science based and technically 

correct for a) the Dietary module and b) the Residential module. 
6

Question 2-2(a) and 2-2(b): 

BACKGROUND: The 2007 FIFRA SAP, which reviewed the aggregate SHEDSResidential model and code (version 3), was provided with the SAS code and asked to 

comment on whether the code was consistent with the descriptions provided in the 

SHEDS-Residential version 3 Technical Manual, and whether the code was clear and was 

adequately described and annotated such that the algorithms could be followed and 

understood. At that time, the Panel was not provided with code for the SHEDS-Dietary 

module and there was no graphical user interface for the SHEDS-Dietary module. The 

2007 SAP review of the dietary module of SHEDS was limited to reviewing several 

conceptual issues associated with dietary exposure and covered both data issues and 

algorithms. 

In the intervening three years, the Agency has updated the SHEDS-Residential model to 

include cumulative (multiple chemical) as well as aggregate (single chemical) algorithms, 

applicator exposures (the 2007 version was limited to post application exposures only) 

and a number of additional changes as per the 2007 Panel review comments. Additional 

changes were made based on considerations that arose during review of the model and 

the desire to simplify the code and reduce the number of user-specified inputs. The 

specific changes that were made are listed and detailed in Section 1.6 of the SHEDSResidential version 4 Technical Manual entitled “Changes from SHEDS-Residential 

version 3 to version 4”.

The SHEDS-Dietary module has also been developed further during this time. Advances 

include: (i) the development of a GUI through which users can more easily develop and 

produce dietary exposure estimates, (ii) the ability to read residue input files from another 

aggregate model (*.rdf), (iii) the option to use the NHANES\WWEIA food consumption 

data (FCID recipes will be incorporated following public release), (iv) the ability to 

conduct Eating Occasions Analyses, (v) the ability to select among different Food 

Residue Options, (vi) the simultaneous use of multi-chemical residue inputs for 

cumulative exposure assessment (i.e., pre-simulation adjustments using RPFs not 

required), and (vii) options for generating longitudinal (multi-day) consumption patterns. 

The Agency also prepared a draft User Guide and a Technical Manual for the SHEDSDietary module and we anticipate future work on both of these documents as SHEDSDietary advances. 

 

A. SHEDS RESIDENTIAL 

QUESTION 2-2(a): Version 4 of SHEDS-Residential provides a number of additional 

capabilities compared to the SHEDS-Multimedia v.3 model reviewed in August, 2007. A 

summary of the main changes from SHEDS-Residential version 3 to version 4 is provided in 

Section 1.6 of the Residential Technical Manual to which the Panel may wish to refer. The 

changes include: the ability to perform multichemical runs; the ability to reproduce (pseudo-) 

random number seeds; the capability of evaluating applicator (handler) exposures (and not 

just post application exposures); a new longitudinal diary assembly method based on the 
7

D&A (diversity and autocorrelation) statistics, which supplements the 8-diary method from 

version 3; a new option for evaluating uncertainty using bootstrap methods; and the 

implementation of Sobol’s method for sensitivity analysis, among numerous others. 

Please comment on (i) whether the annotated code for the SHEDS-Residential version 4 

model is sufficiently clear such that the algorithms can be followed and understood; and (ii) 

whether the algorithms defined in the SHEDS-Residential version 4 Technical Manual are 

consistent with those present in the code. In what ways might the code, its annotations, or the 

description in the Technical Manual be improved? Please consider in particular the new 

components of the code (i.e., added or modified since the 2007 SAP) as detailed and 

described in Section 1.6 of the SHEDS-Residential version 4 Technical Manual. 

B. SHEDS DIETARY 

QUESTION 2-2(b): SHEDS-Dietary version 1 provides the user with a graphical “point and 

click” user interface and other capabilities such as the ability to read residue input files from 

other dietary models (*.rdf), the option to use the NHANES\WWEIA food consumption data, 

and Eating Occasions Analyses options. These are detailed in the SHEDS-Dietary version 1 

User Guide and SHEDS-Dietary version 1 Technical Manual. While the underlying SAS 

code has not at this time been fully annotated and/or is not as “reader-friendly” as the 

SHEDS-Residential code, does the Panel have any comments or suggestions at this time on 

the structure or form of the code or ways in which the code may be improved? Can the Panel 

identify any apparent discrepancies between the calculations described in the SHEDS-Dietary 

version 1 Technical Manual and the algorithms operating in and described by the SAS code? 

_____________________________________________________