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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 c umulative r isk a ssessment (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 dos e 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/s cipoly/sap/meetings/2007/081607_mtg.htm ) . T h e 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 cons ists 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 pe riods (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 ro utes 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 SHED S

- 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 (SH EDS

- 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 ca se 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

r esults 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 SH EDS 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: SHEDS

R esidential v.4 (pdf) The S tochastic H uman E xposure and D ose Si mulation Model for Multimedia, Multipathway Chemicals (SHEDS

- Multimedia): Residential Module

SHEDS

- Residential version 4 Draft User Guide June 1 6 , 2010

User Guide for SHEDS

Dietary v.1 (pdf ) The S tochastic H uman E xposure and D ose Si mulation Model for Multimedia, Multipathway Chemicals (SHEDS

- Multimedia): Dietary Module

SHEDS

- Dietary version 1 Draft User Guide June 1 6 , 2010

CD

- ROM

2

OF

3 Technical Manual

–

SHEDS Residential v.4 (pdf) The S tochastic H uman E xposure and D ose Si mulation Model for Multimedia, Multipathway Chemicals (SHEDS

- Multimedia):

Residential Module

SHEDS

- Residential version 4 Draft Technical Manual June 1 6 , 2010 Technical Manual

– SHEDS Dietary v.1 (pdf) 2 files; m ain and appendices The S tochastic H uman E xposure and D ose Si mulation Model for Multimedia, Multipathway Chemicals (SHEDS

- Multimedia): Dietary Module

SHEDS

- Dietary version 1 Draft Technical Manual June 1 6 , 2010

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CD

- ROM Deliverable Title/Description/Comments

SAP Package #1 Materials Response to 2007 SAP comments (dietary an d 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 P ackage as well as on 200 7 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 thi s 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 Model

Model 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.ehpo nline.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 A gency’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

. T his 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.

_____________________________________________________

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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 u sefulness 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, c ompleteness, 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 SHEDS

Residential 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 revie wed 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 respons es to the 2007 SAP comments, and specific changes from version 3 to version 4 of the SHEDS

Residential 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.

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Question 2

- 2(a) and 2

- 2(b):



### BACKGROUND: The 2007 FIFRA SAP, which reviewed the aggregate SHEDS

Residential 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 adequ ately 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 r eview 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 in clude 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. Additio nal 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 SHEDS

Residential 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

. A dvances includ e : (i) the development of a GUI through which users can mor e 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 r elease), (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 SHEDS

Dietary module and we anticipate future work on both of these docume nts as SHEDS

Dietary 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 s eeds; 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) statistic s, which supplements the 8

- diary method from

ver sion 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 anno tations, 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 t o 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 a nnotated 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 disc repancies between the calculations described in the SHEDS

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



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