National Toxicology Program

[Federal Register: November 19, 1999 (Volume 64, Number 223]
[Notices]
[Pages 63327 -63329]

DEPARTMENT OF HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE

National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), Center for the Evaluation of Risks to Human Reproduction, announces the second meeting of an expert panel to review phthalates, December 15-17, 1999. The meeting will be held at Hawthorn Suites Hotel, 300 Meredith Drive, Durham, NC (near the intersection of highways 54 and 55 in Research Triangle Park) and will begin at 8:30 a.m. each day.

Background

The NTP and the NIEHS established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) (63 FR 68782, No 239) in June 1998. The purpose of the Center is to provide timely and unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction, including development, which may be caused by agents to which humans are exposed. The evaluations produced through the Center will be published as monographs in Environmental Health Perspectives (EHP); a special effort will be made to summarize the reports in non-scientific terms for use by the general public. These documents will be available on the CERHR website (http://cerhr.niehs.nih.gov) or in hardcopy by contacting Ms. Peggy Sheren (contact information given below), and will also be transmitted to appropriate Federal and State Agencies. Public comments on the final documents will be welcome. The Center's first review is underway and covers the evaluation of the following seven phthalate esters (Chemical Abstracts Service registry numbers are in parentheses).

butyl benzyl phthalate (85-68-7)
di(2-ethylhexyl) phthalate (117-81-7)
di-isodecyl phthalate (26761-40-0, 68515-49-1)
di-isononyl phthalate (28553-12-0, 68515-48-0)
di-n-butyl phthalate (84-74-2)
di-n-hexyl phthalate (84-75-3)

First Meeting of the Expert Panel to Review Phthalates, August 17-19, 1999

An independent, expert panel began the phthalate review at the first Phthalate Expert Panel Meeting on August 17-19 in Alexandria, Virginia (64 FR 42707-42708). Prior to this meeting, panelists reviewed existing literature in their areas of expertise and provided other panel members with their summary evaluations. This effort involved the review of nearly 1,000 reports or publications covering general toxicity in animals and humans, developmental and reproductive toxicity, and information on human exposure. Integrated evaluation documents drafted at the Panel's meeting addressed the nature and consistency of the reviewed data, relevancy of experimental models to humans, and important papers in the areas of toxicity and human exposure.

Draft integrated evaluation documents were reviewed and discussed in plenary session by the Panel for the following phthalates: butyl benzyl phthalate, di(2-ethylhexyl)phthalate, and di-n-octyl phthalate. Further discussion of these draft documents and formulation of summary statements will take place at the second Phthalate Expert Panel Review. A summary of the first Phthalate Expert Panel meeting is available on the Center's website (http://cerhr.niehs.nih.gov) or can be obtained in hardcopy from Ms. Sheren (see below).

December 15-17, 1999 Phthalate Expert Panel Review

The integrated evaluations on the four remaining chemicals (di-isodecyl phthalate, di-isononyl phthalate, di-n-butyl phthalate, and di-n-hexyl phthalate) are being written and will be discussed at the Expert Panel meeting to be held December 15-17. The draft integrated evaluations will be publicly available after December 1, 1999 at the Center's website (see above) or can be obtained in hardcopy by contacting Ms. Peggy Sheren, (see below). Following review and agreement by the Panel on the integrated evaluations, the members will develop consensus summary statements for each of the seven phthalates. These narrative statements will reflect a consensus opinion of the Panel as to the developmental and reproductive toxicity of these chemicals in experimental models and will address the potential significance of these results to human reproduction and development. Following this meeting, integrated evaluations and the summary statements will be incorporated into a monograph on phthalates that is published in EHP and available for public comment.

Review Panel and Charge to Panel

A panel of 16 independent scientists selected for their expertise in various aspects of reproductive toxicology and other relevant areas are conducting this review. The roster of experts follows:

Phthalates Expert Panel

*Unable to attend the second Phthalate Expert Panel meeting
** Added to the Panel to assist in the evaluation of literature and identification of research and testing needs in epidemiology.

Charge to Expert Panel

Rigorously evaluate all relevant data and reach a conclusion regarding the strength of scientific evidence that exposure to a chemical may or may not present a risk to human reproduction or development.

1. Evaluate all reproductive and developmental toxicity studies - in humans and animals - for quality, completeness, and sufficiency. Determine consistency of reported effects within and among species. Briefly summarize relevant individual studies.

2. Review and summarize related studies paying particular attention to studies of general toxicity, pharmacokinetics, genetic toxicity, and mechanisms of toxicity within and across species. Both in vivo and in vitro studies will be included.

3. Determine, to the extent possible, patterns of use (such as timing, duration) and exposure (such as dose, route) to humans.

4. Integrate this information, using a weight of evidence approach. Determine how human, animal and other data can reasonably be used to predict reproductive or developmental effects in humans under particular exposure conditions.

5. Provide judgments, including qualitative statements of the certainty of the judgments, that an agent presents a potential risk to human reproduction and/or development. Describe the major factors that contributed to these judgments. State the exposure circumstances under which such risk might be expected to exist.

6. Identify specific areas of uncertainty (such as inadequate pharmacokinetic data in a given species) that would prevent a more definitive assessment of human risk.

7. Identify research and testing needs that, if met, would significantly reduce the uncertainty inherent in the stated judgments of risk.

Meeting Open to the Public

The meeting is open to the public and attendance is limited only by the availability of space. This review will take place from December 15-17 at Hawthorn Suites Hotel, 300 Meredith Drive, Durham, NC (near the intersection of highways 54 and 55 in Research Triangle Park). The meeting commences each day at 8:30 a.m.

Preliminary Agenda

December 15 (8:30 a.m.)

Opening remarks by Dr. George Lucier, Director, ETP, NIEHS; Dr. Michael Shelby, NIEHS and Director of the Center; Dr. John Moore, Sciences, International and CERHR; and Dr. Robert Kavlock, EPA and Chair of the Expert Panel on Phthalates.

Following opening remarks, the Panel will receive public comments (time seven minutes per speaker). Information for those wishing to register to give oral comments or to submit written comments is provided below. Following the comment period, draft integrated evaluations for each of the seven phthalates will be discussed in plenary session with the purpose of reaching consensus on each chemical. These draft documents will be available to the public electronically on the CERHR website (http://cerhr.niehs.nih.gov) after December 1 or in hardcopy by contacting Ms. Sheren at the address given below.

December 16 (8:30 a. m.)

Complete discussions of the integrated evaluations. Begin drafting summary statements for each of the chemicals. This will be accomplished through an iterative series of workgroup discussions and plenary sessions.

December 17 (8:30 a.m.)

Summary statements reflecting significant conclusions and judgements reached by the Panel Workgroups for each of the phthalates will be presented, discussed, and agreed upon by the entire expert panel in the final plenary session. Closing comments by Dr. Michael Shelby, NIEHS, and Dr. Lynn Goldman, Johns Hopkins University and NIEHS.

Solicitation of Oral and Written Public Comments

Following opening remarks on December 15, time is allotted for public comments (seven minutes per speaker on the chemicals being reviewed). In order to facilitate planning of this meeting, those wishing to make public comments are asked to notify Ms. Sheren, (CERHR, 1800 Diagonal Road, Suite 500, Alexandria, VA 22314-2808, Phone: (703) 838-9440) no later than December 10, 1999. When registering to comment orally, please provide your name, affiliation, mailing address, phone, fax, e-mail and sponsoring organization (if any). If possible, also send a copy of the statement or talking points to Ms. Sheren; this information will be provided to the Panel and will assist the Chair and Panel Members in identifying issues for discussion. Registration for public comments will also be available on-site (7:30 - 8:30 a.m.). Those registering on site are asked to bring 20 copies of their statement or talking points.

A written statement may be submitted in lieu of making an oral presentation. These written comments should be received by Ms. Sheren (address given above) no later than December 10 in order for them to be considered at the December 15-17 meeting. Persons sending written comments are asked to provide their name, affiliation, mailing address, phone, fax, e-mail and sponsoring organization (if any).

For other questions or additional information about the meeting, please contact Ms. Sheren.

Dated: November 10, 1999

Samuel H. Wilson, M.D.
Deputy Director, NIEHS and NTP

[Billing Code 4140-01-P]