to Inform EPA's Upcoming IRIS

Toxicological Review
of Inorganic Arsenic

INTRODUCTION

Tuesday, January 8 &
Wednesday, January 9
RTP, North Carolina

Hosted by EPA's National Center
for Environmental Assessment


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oEPA

United States
Environmental Protection

Public Stakeholder Workshop -

Development of Toxicological Review of
Inorganic Arsenic

USEPA / ORD / NCEA
Presented by: Reeder Sams II

Office of Research and Development
National Center for Environmental Assessment

oERA

United States
Environmental Protection
Agency

Welcome
Public Stakeholder
Workshop

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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Q EDA

NCEA Contacts

United States
Environmental Protection
Agency

Chemical Managers for iAs Assessment

•	John Cowden: Cowden.John@epa.gov
Phone: (919)541-3667

•	Janice Lee: Lee.JaniceS@epa.gov

Phone: (919)541-9458
Director for NCEA-IRIS - Acting

•	Vincent Cogliano: Cogliano.Vincent@epa.gov
Phone: (703)-347-0220

Deputy Director for NCEA-RTP - Acting

•	ReederSams: Sams.Reeder@epa.gov
Phone:(919)541-0661

Why is EPA holding

Environmental Protection	~

this workshop?

Human health

Most recent IRIS assessment completed in 1988
Support and use in EPA's program / regional risk
assessments and state / local government risk
assessments

Past human health assessment efforts for inorganic
arsenic

Stakeholder comments and requests
Congressional Request (HR2055; HR 112-151)
¦ Review by National Academy of Sciences (NAS)
Recommendations from the NAS

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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Selected NAS Recommendations

From "Science and Decisions" (NAS 2009)

•	Expand agency and interagency collaboration

•	Implement scoping and problem formulation

•	Consider feasibility/benefits of options in the design stages

•	Uncertainty and variability into dose response analysis

•	Incorporation of probabilistic and distributional methods into
dose-response analysis

•	Evaluate chemicals in terms of mode of action, background
exposure, disease processes, and vulnerable populations

•	Criteria to justify alternative assumptions in place of default
assumptions

Environmental Protection Selected NAS Recommendations

Agency

From Formaldehyde review (NAS 2011)

•	Literature search strategy and literature evaluation criteria
(e.g., systematic review)

•	Weight of evidence evaluation for non-cancer endpoints

•	Use HERO database to capture study information and data

•	Sensitivity analyses for reference values and effect of
uncertainty factors

•	Harmonize characterization of uncertainty and variability

•	Unify outcome consideration around common modes of
action

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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Common Themes

Environmental Protection

(NAS 2011. 2009: EPA. 2005. 2000)

Transparency- Explicitness in the health assessment process

Clarity- Health assessment is free from obscure language and is
easy to understand

Consistency- Conclusions of the health assessment are
characterized in harmony w/ other EPA actions

Reasonableness- Health assessment is based on sound
judgment

SEPA

Workshop Goals

United States
Environmental Protection
Agency

Ensure that EPA provides the public an opportunity to
inform the Toxicological Review.

-	Gather scientific information and public dialogue

-	Many opportunities beyond this workshop

>	Submit information to the docket

>	Future public meetings

>	Webinar series

Transparently communicate how EPA will produce an
assessment that meets the needs of the Agency and the
public.

-	Presentations during this workshop

-	NCEA website

¦ Other tools (e.g., IRIS List-serve, blogs, etc.)

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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SEPA

Workshop Logistics

United States
Environmental Protection

•	Workshop is organized into 5 sessions

1)	Applying Systematic Review to the iAs Toxicological Review

2)	Hazard Identification for iAs

3)	Dose Response

4)	Roundtable Discussion on Planning and Scoping

5)	Opportunity for Additional Public Comment and Workshop
Summary

•	General format for each session

-	Panel Discussion (State of the Science)

-	Opportunity for Public Comment (Webinar & In
Person)

•	Webinar Participants

-	Please submit comments or questions at any time
during the workshop. Comments or questions from
webinar participants will be during the Discussion
section for each session as indicated on the agenda.

-	If you experience technical difficulties, please type
this in as a comment on the webinar or email:
EPA_arsenic@icfi.com

•	RTP Facility (in-person participants)

-	Comments and question from in-person participants
will alternate with comments from the webinar

SEPA

Workshop Logistics

United States
Environmental Protectior
Agency

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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oEPA

United States
Environmental Protection
Agency

Thank You...

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oEPA

United States
Environmental Protection
Agency





EXTRA SLIDES

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^EPA past Efforts for the Toxicological

Environmental Protection

Review of Inorganic Arsenic

0 First arsenic assessment posted to IRIS database in 1988

0 National Research Council (NRC)/National Academy of Sciences (NAS) review
of scientific information: 1999

0 Science Advisory Board completes review of EPA Arsenic Rule: 2001

0 EPA establishes Primary Drinking Water Standard for Arsenic: 2001

0 NRC assessment and review of EPA Drinking Water Standard: 2001

0 EPA implements NRC 2001 recommendations in draft arsenic IRIS assessment
and submits for Science Advisory Board review: 2005

0 Science Advisory Board completes review of EPA 2005 draft: 2007

0 Science Advisory Board completes review of EPA 2010 draft: 2011

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oEPA

United States
Environmental Protection
Agency

Common Themes

(NAS 2011. 2009: EPA. 2005. 2000)

Transparency

Explicitness in the risk
assessment process

Clarity

Assessment is free from
obscure language and is easy
to understand

-Describe assessment
approaches, assumptions,
extrapolations and model use
-Describe plausible alternative
assumptions
-Identify data gaps
-Distinguish science from policy
-Describe uncertainty
-Describe relative strength of
assessment

-Employ brevity
-Use plain English
-Avoid technical terms
-Use simple tables, graphics,
equations

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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SEPA

United States
Environmental Protection
Agency

Common Themes Continued

(NAS 2011. 2009; EPA. 2005. 2000)

Consistency

Reasonableness

Conclusion of the risk
assessment are
characterized in harmony w/
other EPA actions

Risk assessment is based
on sound judgment

-Follow statutes
-Follow Agency Guidance
-Use Agency information
systems

-Define level of effort
-Use review by peers

-Use review by peers

-Use best available scientific

information

-Use good judgment

-Use plausible alternatives

United States iAs Human Health Assessment

Environmental Protection
Agency

-Considerations

•	NAS recommendations for human health
assessments (2011; 2009)

•	Common themes with guidance documents (EPA,
2005; EPA, 2000)

•	Social, behavioral, and physical impacts
(epigenome)

•	Useful reviews and documents: SAB (2011, 2007,
2001) NAS (2001, 1999)

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SEPA

United States
Environmental Protection
Aaencv

Decision-Making Framework

(NAS 2009)

FIGURE S-l A framework tor risk-based decision-making that maximizes the utility of risk assessment,

SEPA

United States
Environmental Protection
Agency

Environmental
Exposures

Intrinsic
Susceptibility

Human
Health/
Disease

Behavior/Age/Lifestage

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oEPA

EP4™ Useful Reviews and Documents:

•	SAB (2011; 2007) were reviews of existing EPA iAs cancer
assessments

•	NAS (2001) was a human health assessment; NAS (1999)
was a review of the state of the science

•	Recommendations should be utilized as appropriate
throughout the development of a new integrated assessment
(e.g., criteria categories for evaluating epi literature)

•	Some recommendations may not be as informative for
developing a new assessment compared to revising an
existing assessment

•	State of the science and human health assessment
approaches are evolving

Office of Research and Development

Mfltinnfll rpntor fnr Fnvirnnmpntal flccoccmont

&EPA

Workshop Goals

United States
Environmental Protection
Agency

Communication (throughout the development of the
assessment)

¦	Efficient and effective means

•	iAs human health assessment project page
(internal and external)

•	Arsenic Communication Committee

¦	List-serve

¦	Ongoing dialogue

¦	Assessment schedule

Clear understanding of current regulatory practices
and challenges across the Agency

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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Workshop Goals

United States
Environmental Protection
Agency

Based upon the current regulatory practices and
challenges, what are the needs of the Agency with
respect to a new iAs human health assessment?
Problem formulation / Scoping
Provide input as to how the Agency can effectively
engage outside stakeholders specifically for iAs
Address how Agency partners can collaborate to
develop an integrated assessment for iAs

SEPA

United States
Environmental Protection
Agency

EXTRA SLIDES

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Selected SAB Recommendations

SAB Review of 2010 iAs Cancer Assessment (SAB 2011)

•	Recommended EPA should more clearly state and utilize
criteria to evaluate epidemiological data

•	Improve the documentation of data sets utilized for sensitivity
analyses;

•	For complete EPA risk assessments provide context to the
cancer risk estimate should be interpreted w/ respect to
current cancer incidence in US populations

•	Improve the documentation for selection and use of exposure
assumptions for sensitivity analyses

•	Commented on the importance of conducting integrated
assessments (i.e., cancer and noncancer)

&EPA

Selected SAB Recommendations

SAB Review of 2005 iAs Cancer Assessment (SAB 2007)

•	Concluded that multiple modes of action are likely operable
for the effects due to iAs

•	Taiwanese dataset remains the most appropriate for dose-
response analysis

•	Epi studies of the US should be critically evaluated based
upon a uniform set of criteria

•	Information to determine a non-linear form of the dose-
response and the linear default is most appropriate

•	Recommendations regarding specific cancer modeling,
exposure assumptions, and corresponding sensitivity
analyses

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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SEPA

United States
Environmental Protection
Agency

Risk Assessment Design

(NAS 2009)

Issue
Problem
Concern
Objective

Is risk
assessment
the appropriate
decision support
tool?
(Manager)

Non-Risk
Considerations

PLANNING & SCOPING

Manage I. St»k«hc4dor,	DialoOJ^

Options Identification I

Hazard Identification



PROBLEM FORMULATION

Manager. Assessor, (stakeholder)

O3S09U0

Summary
Statement

Management
&

Risk Communication

XI

f "O
c Tl

OS J
1 o|

Conceptual





Model

Technical Analyas

p a S

-

(Exposure Analysis. Dos*-R«s pons*

o

Analysis

Analysis. Risk Characlemolion)



Plan





FIGURE 3-1 Schematic representation of the formative stages of risk-assessment design. Doited line in
figure denotes that decisions informed by risk assessment will be influenced by nonrisk considerations.
Source: Adapted from EPA 1998, 2003.

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DRAFT PLANNING
AND SCOPING
SUMMARY

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v>EPA

United States
Environmental Protection
Agency

Draft Planning and Scoping Summary for the
Inorganic Arsenic (iAs) IRIS Assessment

John Cowden
U.S. EPA/ORD/NCEA
Research Triangle Park, NC

Disclaimer: the views expressed in this presentation are those of the speaker
and do not necessarily represent the views or policies of the^.S. EPA.

xvEPA

United States
Environmental Protection
Agency

Key Terminology

IRIS Toxicological Review

Risk Assessment

• Hazard identification
•Dose-response assessment

Hazard identification
Dose-response assessment
Exposure assessment
Risk characterization





Planning and Scoping

Problem Formulation

• Establishes goals, breadth, depth,
and focus of the toxicological review

•Develops common understanding of
why assessment is being developed,
how assessment will be used, and
data needed to answer key questions

Describes specific technical details
for the toxicological review

Consists of conceptual model and
analysis plan

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SEPA

United States
Environmental Protection
Agency

NAS Guidance on
Planning and Scoping



Scoping Elements

Considerations





Partner and
Stakeholder needs

•Context and purpose
•Areas of interest





Exposure

•Spatial and temporal considerations

•Sources and source mitigation

•Environmental exposure and exposure mitigation

• Individual intake pathways and individual intake
mitigations





Hazard Identification

•	Direct and mitigation related hazards and
stressors

•	Direct and mitigation-related adverse health
outcomes

•At-risk populations and populations at mitigation-
related risk





Source: "Science and Decisions: Advancing Risk Assessment;"
National Research Council of the National Academies, 2009

Office of Research and Development
National Center for Environmental Assessment

&EPA

		 Draft Planning and Scoping Summary

Agency 1 ** *



Considered

Limited Consideration

Outside the Scope





•	Oral and inhalation
exposure

•	Chronic exposure and
exposure during
susceptible life stages
(e.g., in utero)

•	Cancer and non-cancer
effects

•	Susceptibility - stressors
and potential biomarkers
of at-risk populations

•	Impact of uncertainty

•	Exposure sources (e.g.,
environmental sources and
individual intake pathways) - as
related to dose-resoonse analysis

•Arsenic soeciation data - as data
inform hazard identification, mode
of action analyses, or dose
response analyses

•	Bioavailability - as related to
dose-resDonse analysis

•	Options for mitigating
exposure

•	Health effects related to
clinical or ecological
mitigation efforts

•	Dose-response analyses
for mitigation related health
effects

•	Cost benefit analysis on
human health effects of iAs
exposure or related
mitigation efforts





• Dose-response analysis
indicating risk at potential
exposure levels (including
background levels)







Office of Research and Development
National Center for Environmental Assessment



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SEPA

United States
Environmental Protection
Agency

Developing the Toxicological Review

PROPOSED PROCESS

PROPOSED DATE

Scoping and Problem Formulation Workshop

September 2012

Public Stakeholder Workshop

January 2013

NAS Public Workshops

January 24, 2013
April 4, 2013

Interim NAS Report

Fall 2013

Completed Draft iAs Toxicological Review

Spring 2014

Complete Internal Agency Review

Summer 2014

Complete Interagency Science Consultation

Summer 2014

Release draft to External Peer Review (NAS Review)

Fall 2014

Complete NAS Review of the iAs Toxicological Review

Winter 2015

Complete Internal Agency Review/lnteragency Science Discussion

Spring 2016

Post to IRIS Website

Summer 2016

Office of Research and Development
National Center for Environmental Assessment

oEPA

s;™rSl Pro,cc"on	Conclusions

>	Planning and Scoping Summary

•	DRAFT statement - discussion for Session 4

•	Context for discussions

>	Developing the IRIS Toxicological Review

•	Multiple opportunities for public engagement

•	Importance of utility to partners and stakeholders

>	Next steps

•	Meeting Report

•	Problem Formulation

•	NAS Public Meetings

Office of Research and Development

Natinnal Hpntpr fnr Fnuirnnmpntal SQtpcsmpnt

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SEPA

Additional Context: NAS
Recommendations

United States
Environmental Protection

From Formaldehyde review (NAS 2011)

•	Literature search strategy and evaluation criteria (e.g.,
systematic review)

• Use HERO database to capture study information and
data

•	Unify outcome consideration around common modes of
action

•	Weight of evidence evaluation for non-cancer endpoints

•	Sensitivity analyses for reference values and effect of
uncertainty factors

•	Harmonize characterization of uncertainty and variability

From "Science and Decisions" (NAS 2009)

•	Expand collaboration

•	Implement scoping and problem formulation

•	Criteria to justify alternative assumptions in place of default
assumptions

•	Consider feasibility/benefits of options in the design stages

•	Evaluate chemicals in terms of mode of action, background
exposure, disease processes, and vulnerable populations

•	Incorporation of probabilistic and distributional methods into
dose-response analysis

•	Develop process to communicate and incorporate
uncertainty and variability into analysis

SEPA

Additional context: NAS
Recommendations (con't)

United States
Environmental Protection
Agency

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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vvEPA

Protection

Outline

United States
Environmental Protection

>	Drafting the IRIS Toxicological Review

•	Draft planning and scoping summary

>	Developing the IRIS Toxicological Review

•	Proposed timeline

oEPA

0 con Draft Planning and Scoping Summary



Considered

Limited Consideration

le Scope

•	Oral and inhalation
exposure

•	Chronic exposure and
exposure during
susceptible life stages
(e.g., in utero)

•	Cancer and non-cancer
effects

•	Susceptibility - stressors
and potential biomarkers
of at-risk populations

•	Impact of uncertainty

•	Dose-response analysis
indicating risk at potential
exposure levels (including
background levels)

•	Exposure sources (e.g.,

environmental sources and HJJHHH
individual intake pathways) - as
related to dose-response analysis
•Arsenic speciation data - as data
inform hazard identification, mode

analyses, or dose ¦¦¦¦¦¦
response analyses

•	Bioavailability - as related to ______

dose-response ¦¦¦¦¦

exposure or re
mitigation effo

tigating

related to

logical

rts

e analyses
¦elated health

nalysis on
effects of iAs
:lated
rts







Office of Research and Development
National Center for Environmental Assessment

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<>EPA Selected NAS Recommendations

Environmental Protection
Agency

From Formaldehyde review (NAS 2011)

Literature search strategy and literature evaluation criteria (e.g., systematic
review)

Weight of evidence evaluation for non-cancer endpoints
Use HERO database to capture study information and data
Sensitivity analyses for reference values and effect of uncertainty factors
Harmonize characterization of uncertainty and variability
Unify outcome consideration around common modes of action

From "Science and Decisions" (NAS 2009)

Expand agency and interagency collaboration
Implement scoping and problem formulation
Consider feasibility/benefits of options in the design stages
Develop process to communicate and incorporate uncertainty and variability into
analysis

Incorporation of probabilistic and distributional methods into dose-response
analysis

Evaluate chemicals in terms of mode of action, background exposure, disease
processes, and vulnerable populations

Criteria to justify alternative assumptions in place of default assumptions

Office of Research and Development	39

National flpntpr fnr Fnvimnmpntal A««M«mpnt

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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c ERA

United States Draft Planning and Scoping Summary

Environmental Protection	w	I	w	J

Agency

Scoping
Elements

Considered

Limited
Consideration

Beyond the Scope

Exposure

•	Oral and inhalation
exposure

•	Chronic exposure

•	Exposure during
susceptible life stages
(e.g., in utero)

• Exposure sources
(e.g., environmental
sources and
individual intake
pathways) - as
related to dose-
response analysis

• Options for mitigating exposure

Hazard Identification

•	Cancer and non-
cancer effects

•	Susceptibility-
stressors and potential
bio markers of at-risk
populations

•	Impact of uncertainty

• Arsenic speciation
data - as data inform
hazard identification

• Health effects related to clinical or ecological
mitigation efforts

Dose-Response

•	Dose-response
analysis indicating risk
at potential exposure
levels (including
background levels)

•	Impact of uncertainty

•	Bioavailability- as
related to dose-
response analysis

•	Arsenic speciation -
as related to mode of
action/dose-response
analysis

•	Dose-response analyses for mitigation related
health effects

•	Cost benefit analysis on human health effects
of iAs exposure or related mitigation efforts

Office of Research and Development
National Center for Environmental Assessment

Public Stakeholder Workshop to Inform EPA's Upcoming IRIS Toxicological Review of Inorganic Arsenic

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