Guidance for Contaminated Sites

Practical Guidance for Contaminated Sites: Case Study: Trichloroethylene (TCE) Risk Assessment and Management

Latest TCE Publications & Presentations

 

 

Dourson, M. B. Gadagbui, R. Thompson, E. Pfau.  2016. Managing risks of noncancer health effects at hazardous waste sites: A case study using the Reference Concentration (RfC) of trichloroethylene (TCE).  Reg Tox Pharm. 80: 125-133.

 

 

 


ARA Contaminated Sites Webinar

Practical Guidance on a Non-cancer Hazard Range for Effective Risk Management of Contaminated Sites: A Case Study with Trichloroethylene and other Chemicals

Determining a Safety Range of the RfC for TCE: A Useful Tool in Addressing the Uncertainty Associated with Assessment of Non-cancer Health Effects at Vapor
Intrusion Sites

 ARA for Contaminated Sites to EPA

Estimates Of Risk Above/Around The RfC For TCE Using EPA (2011) And Alliance For Risk

Data from the Johnson Laboratory (University of Arizona) Should Not Be Used as Evidence of Cardiac Teratogenicity of TCE

 

Current Indoor Air Standards 

 

Monday, November 4, 2013
1:00 – 5:00 p.m. (Eastern)

If you have thought about one or more of the following questions, then this webcast and live videoconference at select locations nationally may be of interest to you:

  • What are the experiences of risk assessors and risk managers using the Reference Concentrations (RfCs) or Reference Doses (RfDs) from IRIS to evaluate contaminated sites over the past two years?
  • What is the nature of the uncertainty associated with RfC or RfD values?
  • What are the implications of this uncertainty on site remediation, vapor intrusion assessments, and stakeholder/community involvement?
  • How does US EPA incorporate this uncertainty into the derivation of RfCs specifically for TCE?
  • How are developmental toxicity endpoints incorporated into the derivation of RfCs, and how are these endpoints considered in risk management decisions?
  • How can good science and good judgment be applied to make informed risk management decisions based on the RfCs and RfDs?
  • How can regulators and stakeholders improve the risk assessment and risk management of sites with TCE?

These questions and more are the subject of a guidance document and a web-based and live videoconference presentation that are focused on the practical realities of assessing and regulating noncancer toxicity at contaminated sites. The guidance document was developed through the Alliance for Risk Assessment, a non-profit group committed to improving the clarity, consistency and transparency of the risk assessment process.

 

Project Overview

A coalition of interested parties set out to form a workgroup to develop practical application guidance for the use of USEPA Reference Concentration (TCE RfC) and Inhalation Unit Risk (IUR) values for trichloroethylene for the purpose of site cleanup and closure.

The goals of the coalition include:

1. Develop additional risk assessment guidance on how to interpret the non-cancer endpoint when it is used for deciding clean-up standards or acceptable exposure levels when closing sites.
2. Clarify the issues surrounding the potential developmental cardiac malformations for use in understanding clean-up standards and short term exposure levels.
3. Explore the margin of safety measures used to set the TCE RfC and evaluate if these measures are consistent with the baseline principles developed for determining the RfC.

The Steering Committee has voted to accept this project under the aegis of the Alliance for Risk Assessment.

Now seeking interested parties. For more information please contact Bernard Gadagbui (bernard.gadagbui@uc.edu).

Requested by: Alliance for Site Closure

Project Partners:

ACS


Gradient

Hull and Associates

TERA

 

If you have thought about one or more of the following questions, then this webcast and live videoconference at select locations nationally may be of interest to you:

  • What are the experiences of risk assessors and risk managers using the Reference Concentrations (RfCs) or Reference Doses (RfDs) from IRIS to evaluate contaminated sites over the past two years?
  • What is the nature of the uncertainty associated with RfC or RfD values?
  • What are the implications of this uncertainty on site remediation, vapor intrusion assessments, and stakeholder/community involvement?
  • How does US EPA incorporate this uncertainty into the derivation of RfCs specifically for TCE?
  • How are developmental toxicity endpoints incorporated into the derivation of RfCs, and how are these endpoints considered in risk management decisions?
  • How can good science and good judgment be applied to make informed risk management decisions based on the RfCs and RfDs?
  • How can regulators and stakeholders improve the risk assessment and risk management of sites with TCE?

These questions and more are the subject of a guidance document and a web-based and live videoconference presentation that are focused on the practical realities of assessing and regulating noncancer toxicity at contaminated sites. The guidance document was developed through the Alliance for Risk Assessment, a non-profit group committed to improving the clarity, consistency and transparency of the risk assessment process.

 

Project Overview

A coalition of interested parties set out to form a workgroup to develop practical application guidance for the use of USEPA Reference Concentration (TCE RfC) and Inhalation Unit Risk (IUR) values for trichloroethylene for the purpose of site cleanup and closure.

The goals of the coalition include:

  1. Develop additional risk assessment guidance on how to interpret the non-cancer endpoint when it is used for deciding clean-up standards or acceptable exposure levels when closing sites.
    2. Clarify the issues surrounding the potential developmental cardiac malformations for use in understanding clean-up standards and short term exposure levels.
    3. Explore the margin of safety measures used to set the TCE RfC and evaluate if these measures are consistent with the baseline principles developed for determining the RfC.

The Steering Committee has voted to accept this project under the aegis of the Alliance for Risk Assessment.

Now seeking interested parties. For more information please contact Bernard Gadagbui (gadagbui@tera.org).

 

Meeting Minutes

First Conference call on the TCE ARA Project: October 10, 2012

Present:

John Bell, Halogenated Solvents Industry Alliance
Michael Dourson, Alliance for Risk Assessment
Edward Pfau, Hull and Associates
Bernard Gadagbui, Toxicology Excellence for Risk Assessment
Lynne Haber, Society of Toxicology’s Ethical, Legal, and Social Issues Specialty Section
Oliver Kroner, Alliance for Risk Assessment
Sim Ooi, Parsons Brinkerhoff
David Reynolds, Inside Washington News (observer)
Lorenz Rhomberg, Gradient
Rod Thompson, Alliance for Site Closures

The meeting started with a discussion of ground rules for participation.  All parties agreed that discussion topics were completely open and reportable, but that attribution of a statement during discussion to either a person or his/her organization was not permitted.   Observers were allow to ask questions, but otherwise not participate in the discussion.  Afterwards, folks introduced themselves and gave reasons for participation.

A review of the work accomplished to date by TERA and the Alliance for Site Closures then followed, which is a blend of options 1 and 2 described below.  Bernard Gadagbui of TERA reported briefly about the risk assessment values of various organizations that could be brought into a risk management decision.  Discussion on these values included whether other groups had reviewed the latest developmental toxicology information when determining these values, or whether these groups analyzed this information subsequent to their determination.  Bernard stated that his group would look into this.  Rod Thompson of the Alliance for Site Closures reported briefly about risk management issues associate with site closures.  Discussion of these issues added several more; the ending list of these issues, included the meaning of an exceedance, precision of the risk value, the concept of bright line, the use of chronic values for 1 week exposure, the meaning of screening levels, and the level of confidence in risk values based on developmental endpoints.  After some additional discussion, the group requested written summaries of ongoing work prior to the next call.  During the discussion, Michael Dourson volunteered to send publications on precision of risk values and use of screening levels.  Lorenz Rhomberg volunteered to send a publication on acute inhalation dosimetry that would be particularly relevant for solvent exposures.

A discussion of building the coalition then followed.  As mentioned in a previous email, the Alliance for Site Closures and Toxicology Excellence for Risk Assessment have joined the coalition.  Other groups are welcome to join the coalition by either endorsement, sweat equity, or cash donation (or a combination of these) at any time.  Groups can also decide to drop out at any time.  If a sufficient number of groups has not joined to accomplish the work, the Steering Committee of the ARA(Steering Committee) will be asked for advice on how to proceed.

The next conference call will be held in 3 weeks time.

—–Related Notes—–
Options to accomplish the work:

  1. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and prepare tables for easy reference by a science panel.  The panel would then get together for a one or two day meeting to discuss these summarized data and models and to determine the appropriate RfDs.  The panel would be selected by the Advisory Committee, or perhaps the Steering Committee of the ARA.  A subsequent peer review of the panel’s work might be useful for this option.  This option would cost the most.
  2. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and determine the appropriate RfDs directly.  A subsequent peer review of the partner’s work would likely be useful for this option.  This would cost less than the option 1.
  3. The Advisory Committee would designate one individual from each group who would work with other designated members to look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and determine the appropriate RfDs directly.  A subsequent peer review of the group’s work would likely be useful for this option.  This would cost less than options 1 and 2.

Relationship among groups:

  • The Steering Committee of the Alliance for Risk Assessment (ARA) is like a board of directors for a nonprofit organization.  The Steering Committee set the direction of the ARA and agrees to all incoming projects, but the committee does not do any work, although some of its member might.  If the ARA was a separate nonprofit organization (it is not yet this), the Steering Committee would be considered its owners.  This is true of any nonprofit organization in the US.  For example, TERA is a nonprofit and its board of directors (http://www.tera.org/about/boardofdirectors.html) is considered to be the owner, even though none of the board members get paid and they do not own anything (if a nonprofit goes bankrupt, the board will distribute its assets to other nonprofit organizations).
  • The Advisory Committee is simply the committee that leads any particular project.  In contrast to the Steering Committee, all members of the Advisory Committee are active and supporting participants in the specific project.  For example, the ARA project “Beyond Science and Decisions: From Problem Formulation to Dose Response” has 55 sponsors, 4 of which form the Advisory Committee (ACC, EPA, TCEQ, and TERA).  The Advisory Committee has not yet formed for this project but this is getting closer; several members on the conference calls will likely be members of this committee.
  • A Science Panel for a project may or may not be needed depending on the judgment of its Advisory Committee.  Advise of the ARA Steering Committee is often helpful in this judgment and sometime it takes an active role in the panel’s selection.   For example, the Science Panel of the “Beyond Science and Decisions: From Problem Formulation to Dose Response” was chosen by the ARASteering Committee, because the project’s Advisory Committee wanted a neutral group making the selections.
  • A peer review committee might also be needed for any particular project.  This can be seen as a variation in the Science Panel, particularly when the project has a more limited time span.

In option one, the Science Panel does most of the technical work.  The project’s Advisory Committee would likely either choose this panel, or it could ask the ARA Steering Committee to do this.  If the latter, the Advisory Committee would be able to nominate folks to serve on this panel, including perhaps one or more members from its group.  The project Advisory Committee would then take the role of support, such as procuring resources for the project and it could certainly participate in the public parts of the project.  In option 2, one or more of the nonprofit partners do the technical work.  Afterwards, the project’s Advisory Committee could serve as a peer review, or it could select an independent group.  In option 3, the project’s Advisory Committee would do the technical work.  Afterward, it could have an independent panel review its work, or perhaps submit it to a journal for publication.

_______________________________________________________________________

2nd Conference call on the TCE ARA Project: September 19th, 2012

Present:

John Bell, Halogenated Solvents Industry Alliance
Shanna Clark, US Air Force
Michael Dourson, Toxicology Excellence for Risk Assessment & Alliance for Risk Assessment
Lynne Haber, Toxicology Excellence for Risk Assessment & Ethical, Legal, and Social Issues Specialty Section of the Society of Toxicology
Bernard Gadagbui, Toxicology Excellence for Risk Assessment
Anita Meyer, US Army Corps of Engineers (observer)
Dave Reynolds, Inside EPA (observer)
Rod Thompson, Alliance for Site Closures

Agenda

  • Introductions and individual group reasons for participation
  • Review of options to accomplish the work
  • Building the coalition
  • Rod’s webinar/SOT
  • Good and welfare

Folks again made statements regarding their interest in the project.  Afterwards Michael Dourson emphasized that the use of any scientific/management product was at the discretion of the risk managers of the individual sponsors.  That is, sponsorship does not necessitate the use or endorsement of any resulting scientific/management product.

Lynne Haber and Rod Thompson talked briefly about the ideas for an ELSI/SOT webinar.  Because part of the purpose of the webinar would be to draw attention to the work of this coalition, and issues related to the alliance’s work may be discussed, they suggested that the coalition be involved in the development of the webinar specifics and abstract.  The next deadline for SOT funding is in January.

Several of the proffered options were then discussed.  The prevailing feeling was that the preferred option would be one that is friendly to state regulators and be finished in a 3 to 6 month time frame.  After additional discussion, a preferred option emerged that is a blend of options 1 and 2, shown below.  This preferred option and tasking is for TERA, as the ARA nonprofit partner, and the Alliance for Site Closures to summarize studies, policies and choices of models or options for site closure, and prepare tables for easy reference.  As this work is being completed, the project’s advisory committee would then decide on either an independent science/management panel review of this summarized information and recommendation of policy choices, or that the committee or its designates would conduct the review and recommend policy choices for a separate peer review step.

Several members mentioned that this project might include both scientific and policy considerations for TCE at various sites.  It was again stated that a technical review of EPA’s TCE IRIS document was not the intent of the project, rather, the intent of the project was to address management issues at TCE and other solvent contaminated sites.  Furthermore, while individual members may choose to petition regulatory agencies, in part based on the work of the coalition, the coalition would remain independent.

In building the coalition, it was again noted that the coalition is open to all interested parties. Shanna Clark agreed to work with several of her colleagues to invite other federal scientists to the table.  Michael Dourson agreed to contact the 7 state agencies that are supporting another ARA task.  Rod Thompson volunteered to invite his list of state contacts.  John Bell stated that he would ask several other industry groups to consider joining and will forward a list of names to Michael Dourson.  Lynne Haber agreed to send Michael Dourson her contacts for scientific organizations.  In addition, several federal EPA staff are routinely being copied on all correspondence.

—–Additional Information—–
Several options have been briefly discussed on how the work might be done.  Options include:

  1. Staff of one of the ARA nonprofit partners and/or the Alliance for Site Closures would look at relevant scientific and policy data, summarize studies, policies and choices of models or options for site closure, and prepare tables for easy reference by a science panel.  The panel would then get together for a one or two day meeting (or perhaps several meetings) to discuss this summarized information to determine appropriate policy choices.  The panel would be selected by the project’s Advisory Committee, or perhaps the Steering Committee of the ARA.  A subsequent peer review of the panel’s work might be useful for this option.  This option would cost the most.
  2. Staff of one of the ARA nonprofit partners and/or the Alliance for Site Closures would look at relevant scientific and policy data, summarize studies, policies and choices of models or options for site closure, and determine the appropriate policies directly.  A subsequent peer review of the this work by this project’s Advisory Committee would likely be mandatory for this option.  This would cost less than the option 1.
  3. This project’s Advisory Committee would designate one individual from each group who would work with other designated members to look at relevant scientific and policy data, summarize studies, policies and choices of models or options for site closure.  A subsequent peer review of the group’s work would likely be useful for this option.  This would cost less than options 1 and 2.
  4. Other options are possible.

How do these various committees work?

  • The Steering Committee of the Alliance for Risk Assessment (ARA) is like a board of directors for a nonprofit organization.  The Steering Committee set the direction of the ARA and agrees to all incoming projects, but the committee does not do any work, although some of its member might.  If the ARA was a separate nonprofit organization (it is not yet this), the Steering Committee would be considered its owners.  This is true of any nonprofit organization in the US.  For example, TERA is a nonprofit organization and its board of directors (http://www.tera.org/about/boardofdirectors.html) is considered to be the owner, even though none of the board members gets paid and they do not own anything (if TERA goes bankrupt, the board will distribute its assets to other nonprofit organizations).
  • The Advisory Committee is simply the committee that leads any particular project.  In contrast to the Steering Committee, all members of the Advisory Committee are active and supporting participants in the specific project.  For example, the ARA project “Beyond Science and Decisions: From Problem Formulation to Dose Response” has 55 sponsors, 4 of which form the Advisory Committee (ACC, EPA, TCEQ, and TERA).  The Advisory Committee has not yet formed for the ARA/TCE project but this is likely to happen over the next several conference calls, and will likely include several members on our current phone calls.
  • A Science Panel for a project may or may not be needed depending on the judgment of its Advisory Committee.  Advise of the ARA Steering Committee is often helpful in this judgment and sometime it takes an active role in the panel’s selection.   For example, the Science Panel of the “Beyond Science and Decisions: From Problem Formulation to Dose Response” was chosen by the ARASteering Committee, because the project’s Advisory Committee wanted a neutral group making the selections.
  • A peer review committee might also be needed for any particular project.  This can be seen as a variation in the Science Panel, particularly when the project has a more limited time span.

In option 1, the Science Panel does most of the technical work.  The project’s Advisory Committee would likely either choose this panel, or would ask the ARA Steering Committee to do this.  If the latter, the Advisory Committee would be able to nominate folks to serve on this panel, including perhaps one or more members from its group.  The project Advisory Committee would then take the roll of support, such as procuring resources for the project and it could certainly participate in the public parts of the project, and remember, all aspects of this project are open.

In option 2, one or more of the nonprofit partners do the technical work.  Afterwards, the project’s Advisory Committee could serve as a peer review, or could select an independent group.

In option 3, the project’s Advisory Committee would do the technical work.  Afterward, it could have an independent panel review the work, or perhaps submit it to a journal for publication.

________________________________________________________________________

3rd Conference call on the TCE ARA Project: 10-10-12

Present:

John Bell, Halogenated Solvents Industry Alliance
Michael Dourson,Alliance for Risk Assessment
Edward Pfau, Hull and Associates
Bernard Gadagbui, Toxicology Excellence for Risk Assessment
Lynne Haber, Society of Toxicology’s Ethical, Legal, and Social Issues Specialty Section
Oliver Kroner, Alliance for Risk Assessment
Sim Ooi, Parsons Brinkerhoff
David Reynolds, Inside Washington News (observer)
Lorenz Rhomberg, Gradient
Rod Thompson, Alliance for Site Closures

The meeting started with a discussion of ground rules for participation.  All parties agreed that discussion topics were completely open and reportable, but that attribution of a statement during discussion to either a person or his/her organization was not permitted.   Observers were allow to ask questions, but otherwise not participate in the discussion.  Afterwards, folks introduced themselves and gave reasons for participation.

A review of the work accomplished to date by TERA and the Alliance for Site Closures then followed, which is a blend of options 1 and 2 described below.  Bernard Gadagbui of TERA reported briefly about the risk assessment values of various organizations that could be brought into a risk management decision.  Discussion on these values included whether other groups had reviewed the latest developmental toxicology information when determining these values, or whether these groups analyzed this information subsequent to their determination.  Bernard stated that his group would look into this.  Rod Thompson of the Alliance for Site Closures reported briefly about risk management issues associate with site closures.  Discussion of these issues added several more; the ending list of these issues, included the meaning of an exceedance, precision of the risk value, the concept of bright line, the use of chronic values for 1 week exposure, the meaning of screening levels, and the level of confidence in risk values based on developmental endpoints.  After some additional discussion, the group requested written summaries of ongoing work prior to the next call.  During the discussion, Michael Dourson volunteered to send publications on precision of risk values and use of screening levels.  Lorenz Rhomberg volunteered to send a publication on acute inhalation dosimetry that would be particularly relevant for solvent exposures.

A discussion of building the coalition then followed.  As mentioned in a previous email, the Alliance for Site Closures and Toxicology Excellence for Risk Assessment have joined the coalition.  Other groups are welcome to join the coalition by either endorsement, sweat equity, or cash donation (or a combination of these) at any time.  Groups can also decide to drop out at any time.  If a sufficient number of groups has not joined to accomplish the work, the Steering Committee of the ARA will be asked for advice on how to proceed.

The next conference call will be held in 3 weeks time.

—–Related Notes—–
Options to accomplish the work:

  1. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and prepare tables for easy reference by a science panel.  The panel would then get together for a one or two day meeting to discuss these summarized data and models and to determine the appropriate RfDs.  The panel would be selected by the Advisory Committee, or perhaps the Steering Committee of the ARA.  A subsequent peer review of the panel’s work might be useful for this option.  This option would cost the most.
  2. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and determine the appropriate RfDs directly.  A subsequent peer review of the partner’s work would likely be useful for this option.  This would cost less than the option 1.
  3. The Advisory Committee would designate one individual from each group who would work with other designated members to look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and determine the appropriate RfDs directly.  A subsequent peer review of the group’s work would likely be useful for this option.  This would cost less than options 1 and 2.

Relationship among groups:

  • The Steering Committee of the Alliance for Risk Assessment (ARA)  is like a board of directors for a nonprofit organization.  The Steering Committee set the direction of the ARA and agrees to all incoming projects, but the committee does not do any work, although some of its member might.  If the ARA was a separate nonprofit organization (it is not yet this), the Steering Committee would be considered its owners.  This is true of any nonprofit organization in the US.  For example, TERA is a nonprofit and its board of directors (http://www.tera.org/about/boardofdirectors.html) is considered to be the owner, even though none of the board members get paid and they do not own anything (if a nonprofit goes bankrupt, the board will distribute its assets to other nonprofit organizations).
  • The Advisory Committee is simply the committee that leads any particular project.  In contrast to the Steering Committee, all members of the Advisory Committee are active and supporting participants in the specific project.  For example, the ARA project “Beyond Science and Decisions: From Problem Formulation to Dose Response” has 55 sponsors, 4 of which form the Advisory Committee (ACC, EPA, TCEQ, and TERA).  The Advisory Committee has not yet formed for this project but this is getting closer; several members on the conference calls will likely be members of this committee.
  • A Science Panel for a project may or may not be needed depending on the judgment of its Advisory Committee.  Advise of the ARA Steering Committee is often helpful in this judgment and sometime it takes an active role in the panel’s selection.   For example, the Science Panel of the “Beyond Science and Decisions: From Problem Formulation to Dose Response” was chosen by the ARASteering Committee, because the project’s Advisory Committee wanted a neutral group making the selections.
  • A peer review committee might also be needed for any particular project.  This can be seen as a variation in the Science Panel, particularly when the project has a more limited time span.

In option one, the Science Panel does most of the technical work.  The project’s Advisory Committee would likely either choose this panel, or it could ask the ARA Steering Committee to do this.  If the latter, the Advisory Committee would be able to nominate folks to serve on this panel, including perhaps one or more members from its group.  The project Advisory Committee would then take the role of support, such as procuring resources for the project and it could certainly participate in the public parts of the project.  In option 2, one or more of the nonprofit partners do the technical work.  Afterwards, the project’s Advisory Committee could serve as a peer review, or it could select an independent group.  In option 3, the project’s Advisory Committee would do the technical work.  Afterward, it could have an independent panel review its work, or perhaps submit it to a journal for publication.

________________________________________________________________________

4th Conference call on the TCE ARA Project: 11-14-12

Present:
John Bell, Halogenated Solvents Industry Alliance (participant)
Tom Blackman, Lockheed Martin (observer)
Shanna Clark, USAF (observer)
Michael Dourson,Alliance for Risk Assessment (participant)
Bernard Gadagbui, Toxicology Excellence for Risk Assessment (participant)
Troy Kennedy, Honeywell (participant)
Jason Leuck, Lockheed Martin (observer)
John Lowe, CH2M Hill (observer)
Anita Meyer, Army Corps of Engineers (observer)
Edward Pfau, Hull and Associates (participant)
Rod Thompson, Alliance for Site Closures (participant)
Suzanne Yohannan, Inside Washington News (observer)
The meeting started with a discussion of ground rules for participation.  Discussion topics are completely open and reportable.  However, with the exception of expected reports attribution of a statement or question during discussion to either a person or his/her organization is not permitted.   Observers are allowed to ask questions, but otherwise not participate in the discussion.  Afterwards, folks introduced themselves and gave reasons for participation or observation.

A review of additional work since the time of the last conference call then followed.  Bernard Gadagbui of TERA reported briefly about the risk assessment values of various organizations that could be brought into a risk management decision.   As requested, Bernard also discussed whether these organizations included the latest developmental toxicology information, or whether such information was analyzed subsequently to the determination of the risk value.  Three of the 6 organizations have rejected the cardiac developmental toxicology information as the basis of the risk value, although one of these groups is now reconsidering.  Two of them have affirmed it.  The status of the RIVM information was unknown.  Bernard was asked to check the status of RIVM and he agreed to do so.

Rod Thompson of the Alliance for Site Closures then reported briefly about risk management issues associate with site closures, including imprecision of risk values in relationship to Hazard Quotient of 1, and potential risk managers’ interest in developing risk ranges for noncancer endpoints.  As to imprecision, one participant described EPA’s meaning in its definition of the RfD/C (“with uncertainty spanning perhaps an order of magnitude”) and gave an example of use for a range in an RfD by an EPA Region.  As to risk ranges, this participant described several tools that offer such ranges including categorical regression, benchmark dose, and probabilistic RfD/C.  All of these tools are EPA published methods and have been showcased in recent case studies, which have been vetted by a senior risk assessment science panel (http://www.allianceforrisk.org/Workshop/Panel.htm).  Another participant queried whether the uncertainty in the exposure information, such as averaging time, was a part of this effort.  Rod agreed that it uncertainty in exposure was very important and very much a part of this effort.

Mike Dourson then reported briefly on a meeting he attended with John Bell of HSIA, EPA scientists, and John DeSesso of Exponent, who is a well-known and erudite developmental toxicologist.  Mike reported that his presentation was well received and that Dr. DeSesso’s critique of the choice of cardiac effects as critical for the basis of the RfC was significant.  EPA staff was attentive and asked good questions.  Several participants and observers on this conference call asked questions about this HSIA, EPA andARA meeting.  John and Mike answered these questions as best possible in light of the fact that a member of EPA was not present on this call.

A discussion of building the coalition then followed.  Three additional groups joined the coalition.  These groups are: Halogenated Solvents Industry Alliance, Hull and Associates, and Honeywell.  This brings to a total of 5 participating organizations (the first two are Alliance for Site Closures and Toxicology Excellence for Risk Assessment), which is a sufficient number to constitute an advisory committee for this project.  During the next week, the Advisory Committee will select a final option on which to proceed with the outstanding work.

As mentioned in previous emails, other groups are welcome to join the coalition by either endorsement, sweat equity, or cash donation (or a combination of these) at any time.  Groups can also decide to drop out at any time.

The next conference call will be held in about 4 weeks time.

—–Related Notes—–
Options to accomplish the work:

  1. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and prepare tables for easy reference by a science panel.  The panel would then get together for a one or two day meeting to discuss these summarized data and models and to determine the appropriate RfDs.  The panel would be selected by the Advisory Committee, or perhaps the Steering Committee of the ARA.  A subsequent peer review of the panel’s work might be useful for this option.  This option would cost the most.
  2. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and determine the appropriate RfDs directly.  A subsequent peer review of the partner’s work would likely be useful for this option.  This would cost less than the option 1.
  3. The Advisory Committee would designate one individual from each group who would work with other designated members to look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and determine the appropriate RfDs directly.  A subsequent peer review of the group’s work would likely be useful for this option.  This would cost less than options 1 and 2.

Relationship among groups:

  • The Steering Committee of the Alliance for Risk Assessment (ARA) is like a board of directors for a nonprofit organization.  The Steering Committee set the direction of the ARA and agrees to all incoming projects, but the committee does not do any work, although some of its member might.  If the ARA was a separate nonprofit organization (it is not yet this), the Steering Committee would be considered its owners.  This is true of any nonprofit organization in the US.  For example, TERA is a nonprofit and its board of directors (http://www.tera.org/about/boardofdirectors.html) is considered to be the owner, even though none of the board members get paid and they do not own anything (if a nonprofit goes bankrupt, the board will distribute its assets to other nonprofit organizations).
  • The Advisory Committee is simply the committee that leads any particular project.  In contrast to the Steering Committee, all members of the Advisory Committee are active and supporting participants in the specific project.  For example, the ARA project “Beyond Science and Decisions: From Problem Formulation to Dose Response” has 55 sponsors, 4 of which form the Advisory Committee (ACC, EPA, TCEQ, and TERA).  The Advisory Committee has not yet formed for this project but this is getting closer; several members on the conference calls will likely be members of this committee.
  • A Science Panel for a project may or may not be needed depending on the judgment of its Advisory Committee.  Advise of the ARA Steering Committee is often helpful in this judgment and sometime it takes an active role in the panel’s selection.   For example, the Science Panel of the “Beyond Science and Decisions: From Problem Formulation to Dose Response” was chosen by the ARASteering Committee, because the project’s Advisory Committee wanted a neutral group making the selections.
  • A peer review committee might also be needed for any particular project.  This can be seen as a variation in the Science Panel, particularly when the project has a more limited time span.

In option one, the Science Panel does most of the technical work.  The project’s Advisory Committee would likely either choose this panel, or it could ask the ARA Steering Committee to do this.  If the latter, the Advisory Committee would be able to nominate folks to serve on this panel, including perhaps one or more members from its group.  The project Advisory Committee would then take the role of support, such as procuring resources for the project and it could certainly participate in the public parts of the project.  In option 2, one or more of the nonprofit partners do the technical work.  Afterwards, the project’s Advisory Committee could serve as a peer review, or it could select an independent group.  In option 3, the project’s Advisory Committee would do the technical work.  Afterward, it could have an independent panel review its work, or perhaps submit it to a journal for publication.

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Notes of the 5th Conference call on the TCE ARA Project: 1-8-13

Present:

  • John Bell, Halogenated Solvents Industry Alliance (observer)
  • Tom Blackman, Lockheed Martin (observer)
  • Shanna Clark, USAF (observer)
  • Michael Dourson,Alliance for Risk Assessment (participant)
  • Bernard Gadagbui, Toxicology Excellence for Risk Assessment (participant)
  • Lynne Haber, Society of Toxicology’s Ethical, Legal, and Social Issues Specialty Section (observer)
  • Kip Heaney, Texas Commission on Environmental Quality (observer)
  • Troy Kennedy, Honeywell (participant)
  • John Lowe, CH2M Hill (participant)
  • Charlene Lu, CDM Smith (observer)
  • Mary Morningstar, Lockheed Martin (observer)
  • Moiz Mumtaz, Agency for Toxic Substances and Disease Registry (observer)
  • Edward Pfau, Hull and Associates (participant)
  • Dave Reynolds, Inside Washington News (observer)
  • Lorenz Rhomberg, Gradient (participant)
  • Rod Thompson, Alliance for Site Closures (participant)

The meeting started with a discussion of ground rules for participation by Mike Dourson.  Discussion topics are completely open and reportable.  However, with the exception of expected reports, attribution of a statement or question during discussion to either a person or his/her organization is not permitted.   Observers are allowed to ask questions, but otherwise not participate in the discussion.  Afterwards, all folks introduced themselves and gave reasons for participation or observation.

A review of additional work since the time of the last conference call then followed.  Ed Pfau of Hull and Associates and Rod Thompson of the Alliance for Site Closures reported briefly about the imprecision of risk values in relationship to Hazard Quotient of 1, including the imprecision of RfCs (“with uncertainty spanning perhaps an order of magnitude”) based on the underlying toxicity data and choice of uncertainty factors, and the imprecision of multiple exposure measurements and different averaging times.  One participant brought up the idea of using the half life of a chemical as a way to choose an appropriate averaging time, for example, longer half lives would allow longer averaging times (and correspondingly smaller half lives would suggest smaller averaging times).  Another participant brought up the idea of using the length of window of cardiac development in humans as a way to judge the averaging time, based in part of a meeting with EPA/NCEA scientists where this topic came up in relationship to the cardiac effects in rat fetuses.  Ed Pfau and Rod Thompson agreed to work these considerations into their developing position.

Bernard Gadagbui of TERA then reported some progress on reviewing the risk assessment values of various organizations that could be brought into a risk management use (or not) of the critical effect of fetal heart malformations.  He stated that a draft report will be developed by the time of the next conference call.

Mike Dourson of the ARA then reported on the preliminary results of two methods for the development of ranges of risk around and EPA’s TCE RfCs.  These methods were adapted from two case studies on another ARA project entitled “Beyond Science and Decisions: From Problem Formulation to Dose Response,” both of these case studies were vetted by a senior risk assessment science panel (http://www.allianceforrisk.org/Workshop/Panel.htm).   The first case study entitled, “Use of biomarkers in the benchmark dose method,” has 4 approaches to estimating this risk.  Dourson reported on the first, and simplest of these four.   Preliminary results using EPA’s TCE BMD/L suggested that risks above EPA’s RfC for nephropathy were more severe than the results for fetal cardiac effects, but started at a higher dose.  One participant queried whether the response in this case study truly reflected the human risk to sensitive individuals or was it an alternate procedure to address exposures above the RfC.  Dourson responded that the risk is intended to represented sensitive individuals, but that this risk is preliminary, since the other 3 approaches are each expected to be more accurate (and complicated).  The purpose of exploring the first approach was to determine whether exploring these additional approaches would be fruitful.  Preliminary results suggested that this exploration would be fruitful and that nephropathy might become the sentinel effect.  Results from these additional approaches will be developed in the next several weeks.

The second case study was entitled “Estimating Risk Above the RfD Using Uncertainty Factor Distributions.”  The preliminary results of this study suggested that EPA’s RfCs for nephropathy and immunotoxicity were the same at a 95% confidence level, whereas RfCs for fetal cardiac effects and immunotoxicity were not similar at any confidence level.  Also, depending on a risk manager’s choice of confidence level, different RfCs would result, either higher or lower than what might be stated on EPA’s IRIS or elsewhere (http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?iter).

A brief discussion of building the coalition then followed.  Two additional groups joined the coalition.  These groups are: CH2M Hill with John Lowe as the contact, and Gradient Corporation with Lorenz Rhomberg as the contact.  Both CH2M Hill and Gradient will be asked to nominate a scientist to the working group.  Participating groups now include: Alliance for Site Closures, Alliance for Risk Assessment, CH2M Hill, Gradient, Honeywell, Hull and Associates, and Toxicology Excellence for Risk Assessment.  As mentioned in previous emails, other groups are welcome to join the coalition by either endorsement, sweat equity, or cash donation (or a combination of these) at any time.  Groups can also decide to drop out at any time.

Under good and welfare it was announced that Moiz Mumtaz of ATSDR is the Society of Toxicology’s Lehman award winner for 2013.  This annual and singular award is for for major contributions that improve the scientific basis of risk assessment.  Dr. Mumtaz is well known for his work on chemical mixtures risk assessment.

The next conference call will be held in about 4 weeks time.

—–Related Notes—–
Options to accomplish the work:

  1. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and prepare tables for easy reference by a science panel.  The panel would then get together for a one or two day meeting to discuss these summarized data and models and to determine the appropriate RfDs.  The panel would be selected by the Advisory Committee, or perhaps the Steering Committee of the ARA.  A subsequent peer review of the panel’s work might be useful for this option.  This option would cost the most.
  2. Staff of one of the ARA nonprofit partners would look at relevant scientific data, summarize critical studies and choices of dose response assessment models, and determine the appropriate RfDs directly.  A subsequent peer review of the partner’s work would likely be useful for this option.  This would cost less than the option 1.
  3. [This is the current option being used.] The Advisory Committee would designate one individual from each group who would work with other designated members to look at relevant scientific and management data, review critical studies and choices of dose response assessment models, and determine the appropriate risk management guidelines directly.  A subsequent peer review of the group’s work might be useful for this option.  This would cost less than options 1 and 2.

Relationship among groups:

  • The Steering Committee of the Alliance for Risk Assessment (ARA) is like a board of directors for a nonprofit organization.  The Steering Committee set the direction of the ARA and agrees to all incoming projects, but the committee does not do any work, although some of its member might.  If the ARA was a separate nonprofit organization (it is not yet this), the Steering Committee would be considered its owners.  This is true of any nonprofit organization in the US.  For example, TERA is a nonprofit and its board of directors (http://www.tera.org/about/boardofdirectors.html) is considered to be the owner, even though none of the board members get paid and they do not own anything (if a nonprofit goes bankrupt, the board will distribute its assets to other nonprofit organizations).
  • The Advisory Committee is simply the committee that leads any particular project.  In contrast to the Steering Committee, all members of the Advisory Committee are active and supporting participants in the specific project.  For example, the ARA project “Beyond Science and Decisions: From Problem Formulation to Dose Response” has 55 sponsors, 4 of which form the Advisory Committee (ACC, EPA, TCEQ, and TERA).  The Advisory Committee has not yet formed for this project but this is getting closer; several members on the conference calls will likely be members of this committee.
  • A Science Panel for a project may or may not be needed depending on the judgment of its Advisory Committee.  Advise of the ARA Steering Committee is often helpful in this judgment and sometime it takes an active role in the panel’s selection.   For example, the Science Panel of the “Beyond Science and Decisions: From Problem Formulation to Dose Response” was chosen by the ARASteering Committee, because the project’s Advisory Committee wanted a neutral group making the selections.
  • A peer review committee might also be needed for any particular project.  This can be seen as a variation in the Science Panel, particularly when the project has a more limited time span.

In option one, the Science Panel does most of the technical work.  The project’s Advisory Committee would likely either choose this panel, or it could ask the ARA Steering Committee to do this.  If the latter, the Advisory Committee would be able to nominate folks to serve on this panel, including perhaps one or more members from its group.  The project Advisory Committee would then take the role of support, such as procuring resources for the project and it could certainly participate in the public parts of the project.  In option 2, one or more of the nonprofit partners do the technical work.  Afterwards, the project’s Advisory Committee could serve as a peer review, or it could select an independent group.  In option 3, the project’s Advisory Committee would do the technical work.  Afterward, it could have an independent panel review its work, or perhaps submit it to a journal for publication.  

_________________________________________________________________________________

Notes of the 6th Conference call on the TCE ARA Project: 2-14-13

Present:

  • John Bell, Halogenated Solvents Industry Alliance (observer)
  • Shanna Clark, USAF (observer)
  • Michael Dourson,Alliance for Risk Assessment (participant)
  • Bernard Gadagbui, Toxicology Excellence for Risk Assessment (participant)
  • John Lowe, CH2M Hill (participant)
  • Marybeth Markowitz, Amy Public Health Command (observer)
  • Moiz Mumtaz, Agency for Toxic Substances and Disease Registry (ATSDR) (observer)
  • Edward Pfau, Hull and Associates (participant)
  • Dave Reynolds, Inside Washington News (observer)
  • Rod Thompson, Alliance for Site Closures (participant)

The meeting started with a discussion of ground rules for participation by Mike Dourson.  Discussion topics are completely open and reportable.  However, with the exception of expected reports, attribution of a statement or question during discussion to either a person or his/her organization is not permitted.   Observers are allowed to ask questions, but otherwise not participate in the discussion. All folks then introduced themselves and gave reasons for participation or observation.  Afterwards, a review of additional work since the time of the last conference call followed.

Bernard Gadagbui of Toxicology Excellence for Risk Assessment (TERA) described differences in cardiac development among species.  The length of cardiac development time differs between rats at 7 days and humans at 24 to 30 days.  The latter range was suggested as potentially being helpful in determining an averaging time for exposure estimates with which to compared health risk values, similar perhaps to Region X of EPA’s choice of 21 days.  After a brief discussion, Bernard was asked to contact Region X of EPA to explain their choice of 21 days for averaging time, and to work with members of the medical community to develop a choice of specific value for averaging based on the 24 to 30 day window of cardiac development in developing human fetuses.

Ed Pfau of Hull and Associates, John Lowe of CH2M Hill and Rod Thompson of the Alliance for Site Closures then reported on their work on uncertainties associated with the derivation of the RfC for TCE; with the hazard indexes based on the RfC for TCE; with the determination of the exposure concentrations, and with the determination of the exposure concentration with specific regard to the RfC for TCE.  A discussion ensued regarding the imprecision of risk values in relationship to Hazard Quotient of 1 and the imprecision of multiple exposure measurements and different averaging times.  Based on these multiple uncertainties and imprecisions, it would be very reasonable for a risk manager to make a safety decision at a concentration higher than the screening values determined by any one of EPA’s individual RfCs.  It was also considered very important by more than one participant for the biologists in the collective group to determine the length of time for cardiac development in humans, as possible exposure averaging time.

Bernard Gadagbui of TERA then reported on the judgments of various organizations on whether fetal heart malformations was used in their risk assessment.  It appears that several organizations have mixed judgments on this endpoint, with some supporting its use and others not.  This lead to discussion on the level of confidence with which a risk manager might place on any decision based on this endpoint; the general feeling of the group was that such confidence would be lower than with the other two endpoints.

Mike Dourson of the ARA then reported on the preliminary results of two methods for the development of hazard ranges around EPA’s TCE RfCs.  This first method used EPA’s TCE BMD/L and suggested that a hazard range for nephropathy was more severe than for fetal cardiac effects.  The second method used research by EPA’s National Center for Environmental Assessment.  It suggested that EPA’s RfCs for nephropathy and immunotoxicity were the same at a 95% confidence level, whereas RfCs for fetal cardiac effects and immunotoxicity were not as similar at any confidence level.  Moreover, depending on a risk manager’s choice of confidence level, different RfCs would result, either higher or lower than what might be stated on EPA’s IRIS or elsewhere.

A brief discussion of building the coalition then followed.  ATSDR has joined the effort, and along with the other coalition members (Alliance for Site Closures, Alliance for Risk Assessment, CH2M Hill, Gradient, Honeywell, Hull and Associates, and Toxicology Excellence for Risk Assessment) will work to develop draft guidance for discussion at the next open conference call.  As mentioned in previous emails, other groups are welcome to join the coalition by either endorsement, sweat equity, or cash donation (or a combination of these) at any time.  Groups can also decide to drop out at any time.

Project Contact:
Dr. Bernard Gadabui
bernard.gadagbui@uc.edu