Science Advisory Board; Notification of Public Advisory Committee Meeting

Pursuant to the Federal Advisory Committee Act, Public Law 92-463, notice is hereby given that a Committee of the US EPA Science Advisory Board (SAB) will meet on the dates and times noted below. All times noted are Eastern Standard Time. The meeting is open to the public, however, seating is limited and available on a first come basis. Important Notice: Documents that are the subject of SAB reviews are normally available from the originating EPA office and are not available from the SAB Office—information concerning availability of documents from the relevant Program Office is included below.

The Dioxin Reassessment Review Committee (DRRC) of the US EPA Science Advisory Board (SAB), will meet on November 1 and 2, 2000, at the Ramada Plaza Hotel Pentagon, 4641 Kenmore Avenue, Alexandria, VA. The hotel telephone number is (703) 751-4510. The meeting will begin at 8:45 a.m. on November 1 and adjourn no later than 5 p.m. on November 2.

Purpose of the Meeting

In April 1991, EPA announced that it would conduct a scientific reassessment of the potential health risks of exposure to dioxin and related compounds. The reassessment led to the publication of a multi-volume document titled “Exposure and Human Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds.” The draft of this document was published in 1994. In 1995, this draft was reviewed by EPA's Science Advisory Board (SAB), which issued a report (EPA-SAB-EC-95-021) with the following major findings: (a) There was no need for further SAB review of health and exposure sections (Chapters 1-7) as long as EPA updated these sections with any relevant new information before finalizing them; (b) EPA should develop a new chapter on toxicity equivalence factors (TEFs) to consolidate the discussion and scientific information on the use of TEFs for dioxin and related compounds; (c) the sections addressing Dose Response Modeling (Chapter 8) and the Risk Characterization document (Chapter 9) required revision and improvement; and (d) the revised chapters on Dose Response Modeling and Risk Characterization and the new chapter on TEFs should undergo external peer review and then be brought back to the SAB for another review.

EPA subsequently revised the document, and conducted an external peer review as recommended by the SAB (please see http://www.epa.gov/ncea/pdfs/dioxin/final.pdf for a copy of the peer review). The Agency has now requested that the SAB review the revised reassessment document.

Charge to the Committee

The Charge asks the DRRC to respond to specific questions in the following areas: (a) Cancer effects; (b) background and population exposures; (c) children's risk; (d) relative risks of breast feeding; (e) the risk characterization summary statement; and (f) dioxin sources. The complete set of 21 Charge Questions, sorted by category, follows:

Body Burdens

(Question 1) Did EPA adequately justify its use of body burden as a dose metric for inter-species scaling? Should the document present conclusions based on daily dose?

Use of Margin of Exposure Approach

There are two questions on EPA's proposed use of a margin of exposure (MOE) approach to evaluate dioxin-related health risks.

(Question 2) Has EPA's choice of the MOE approach to risk assessment adequately considered that background levels of the dioxins have dropped dramatically over the past decade, and are continuing to decline? How might the rationale be improved for EPA's decision not to calculate an RfD/RfC, and for the recommended MOE approach for conveying risk information? Is an MOE approach appropriate, as compared to the traditional RfD/RfC? Should the document present an RfD/RfC?”

(Question 3) The SAB commented that previous dose-response modeling was too limited to biochemical endpoints (CYPIA1, IA2, * * *). Are the calculations of a range of ED₀₁ body burden for noncancer effects in rodents responsive and clearly presented? Please comment on the weight of evidence interpretation of the body burden data associated with a 1% response rate for non-cancer effects that is presented in Chapter 8, Appendix I and Figure 8-1 (where EPA considers that the data best support a range estimate for ED₀₁ body burdens between 10 ng/kg to 50 ng/kg).

Mechanisms and Mode of Action

Two questions concern how the Integrated Summary addresses the mechanisms and mode of action of dioxin toxicity.

(Question 4) How might the discussion of mode of action of dioxin and related compounds be improved?

(Question 5) Despite the lack of congener-specific data, does the discussion in the Integrated Summary and Risk Characterization support EPA's inference that these effects may occur for all dioxin-like compounds, based on the concept of toxicity equivalence?

Toxicity Equivalence Factors

There are two questions that pertained specifically to the new TEF Chapter (i.e., Chapter 9) in the dioxin reassessment.

(Question 6) Is the history, rationale, and support for the TEQ concept, including its limitations and caveats, laid out by EPA in a clear and balanced way in Chapter 9? Did EPA clearly describe its rationale for recommending adoption of the 1998 WHO TEFs?

(Question 7) Does EPA establish clear procedures for using, calculating, and interpreting toxicity equivalence factors?

Non-Cancer Effects

There are two questions regarding how the Integrated Summary addresses non-cancer effects.

(Question 8) Have the available human data been adequately integrated with animal information in evaluating likely effect levels for the non-cancer endpoints discussed in the reassessment? Has EPA appropriately defined non-cancer adverse effects and the body burdens associated with them? Has EPA appropriately reviewed, characterized, and incorporated the recent epidemiological evidence for non-cancer risk assessment for human populations?

(Question 9) Do reviewers agree with the characterization of human developmental, reproductive, immunological, and endocrinological hazard? What, if any, additional assumptions and uncertainties should EPA embody in these characterizations to make them more explicit?

Cancer Effects

There are three questions regarding how EPA characterized cancer effects in the Integrated Summary.

(Question 10) Do you agree with the characterization in this document that dioxin and related compounds are carcinogenic hazards for humans? Does the weight-of-the-evidence support EPA's judgement concerning the listing of environmental dioxins as a likely human carcinogen?

(Question 11) Does the document clearly present the evolving approaches to estimating cancer risk (e.g., margin of exposure and the LED₀₁ as a point of departure), as described in the EPA “Proposed Guidelines for Carcinogenic Risk Assessment” (EPA/600/P-92/003C; April 1996)? Is this approach equally as valid for dioxin-like compounds? Has EPA appropriately reviewed, characterized, and incorporated the recent epidemiological evidence for cancer risk assessment for human populations?

(Question 12) Please comment on the presentation of the range of upper bound risks for the general population based on this reassessment. What alternative approaches should be explored to better characterize quantitative aspects of potential cancer risk? Is the range that is given sufficient, or should more weight be given to specific data sources?

Background and Population Exposures

There are three questions pertaining to background and population exposures to dioxin and related compounds.

(Question 13) Have the estimates of background exposures been clearly and reasonably characterized?

(Question 14) Has the relationship between estimating exposures from dietary intake and estimating exposure from body burden been clearly explained and adequately supported? Has EPA adequately considered available models for the low-dose exposure-response relationships (linear, threshold, “J” shaped)?

(Question 15) Have important “special populations” and age-specific exposures been identified and appropriately characterized?

Children's Risk

One question addresses the issue of children's risk of dioxin exposure.

(Question 16) Is the characterization of increased or decreased childhood sensitivity to possible cancer and non-cancer outcomes scientifically supported and reasonable? Is the weight of evidence approach appropriate?

Relative Risks of Breast Feeding

(Question 17) Has EPA adequately characterized how nursing affects short-term and long-term body burdens of dioxins and related compounds?

Risk Characterization Summary Statement

(Question 18) Does the summary and analysis support the conclusion that enzyme induction, changes in hormone levels, and indicators of altered cellular function seen in humans and laboratory animals, represent effects of unknown clinical significance, but they may be early indicators of toxic response?

(Question 19) Has the short summary statement in the risk and hazard characterization on page 107 adequately captured the important conclusions, and the areas where further evaluation is needed? What additional points should be made in this short statement?

Sources

(Question 20) Are these sources adequately described and are the relationships to exposure adequately explained?

General Comments

(Question 21) Please provide any other comments or suggestions relevant to the two review documents, as interest and time allow.

Availability of Review Materials

The principal review documents (Part III: Integrated Summary and Risk Characterization for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds; Chapter 8, Dose-Response Modeling for 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds; Chapter 9: Toxicity Equivalence Factors (TEFs) for Dioxin and Related Compounds; and Exposure and Health Reassessment of 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) and Related Compounds) were developed by the US EPA's Office of Research and Development, National Center for Environmental Assessment (ORD/NCEA) and are available on the Internet at the ORD/NCEA website ( http://www.epa.gov/ncea/dioxin.htm ), or by request to Ms. Linda Tuxen, phone (202) 564-3332, or by email to tuxen.linda@epa.gov.

FOR FURTHER INFORMATION CONTACT:

Any member of the public wishing further information concerning this meeting or wishing to submit brief oral comments (10 minutes or less) must contact Samuel Rondberg, Designated Federal Officer, Science Advisory Board (1400A), U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, Washington, DC 20460; telephone (301) 812-2560, FAX (410) 286-2689; or via e-mail at samuelr717@aol.com. Requests for oral comments must be in writing (e-mail, fax or mail) and received by Mr. Rondberg no later than noon (EDT) on Friday, October 20, 2000. The draft meeting Agenda will be available approximately three weeks prior to the meeting on the SAB website ( www.epa.gov/sab ) or from Ms. Wanda Fields, Management Assistant, USEPA Science Advisory Board (1400A), U.S. Environmental Protection Agency, 1200 Pennsylvania Avenue, NW, Washington, DC 20460; telephone (202) 564-4539, FAX (202) 501-0582; or via e-mail at fields.wanda@epa.gov.

Providing Oral or Written Comments at SAB Meetings

It is the policy of the Science Advisory Board to accept written public comments of any length, and to accommodate oral public comments whenever possible. The Science Advisory Board expects that public statements presented at its meetings will not be repetitive of previously submitted oral or written statements. Oral Comments: In general, each individual or group requesting an oral presentation at a face-to-face meeting will be limited to a total time of ten minutes. For teleconference meetings, opportunities for oral comment will usually be limited to no more than three minutes per speaker and no more than fifteen minutes total. Deadlines for getting on the public speaker list for a meeting are given above. Speakers should bring at least 35 copies of their comments and presentation slides for distribution to the reviewers and public at the meeting. Written Comments: Although the SAB accepts written comments until the date of the meeting (unless otherwise stated), written comments should be received in the SAB Staff Office at least one week prior to the meeting date so that the comments may be made available to the committee for their consideration. Comments should be supplied to the appropriate DFO at the address/contact information noted above in the following formats: one hard copy with original signature, and one electronic copy via e-mail (acceptable file formats: WordPerfect, Word, or Rich Text files (in IBM-PC/Windows 95/98 format). Those providing written comments and who attend the meeting are also asked to bring 25 copies of their comments for public distribution.

General Information

Additional information concerning the Science Advisory Board, its structure, function, and composition, may be found on the SAB Website ( http://www.epa.gov/sab ) and in The FY1999 Annual Report of the Staff Director which is available from the SAB Publications Staff at (202) 564-4533 or via fax at (202) 501-0256. Committee rosters, draft Agendas and meeting calendars are also located on our website.

Meeting Access

Individuals requiring special accommodation at this meeting, including wheelchair access to the conference room, should contact Mr. Rondberg at least five business days prior to the meeting so that appropriate arrangements can be made.