National Toxicology Program

DEPARTMENT OF HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE

NATIONAL TOXICOLOGY PROGRAM

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) Announces the Future Evaluations of Fluoxetine Hydrochloride (Prozac®; Sarafen™, CAS RN 54910-89-3) and Acrylamide (CAS RN 79-06-1), Requests Public Comments on These Chemicals, and Solicits the Nominations of Scientists Qualified to Serve on Expert Panels Evaluating Fluoxetine Hydrochloride and Acrylamide.

Summary

The CERHR plans to conduct an expert panel evaluation of fluoxetine hydrochloride and a separate expert panel evaluation of acrylamide. The exact dates for these expert panel meetings are not yet set, but the meetings are tentatively planned for 2003 and early 2004. Fluoxetine hydrochloride will be evaluated first. Additional details about the meetings, including the dates and locations, will be published in future Federal Register notices and posted on the NTP website (http://ntp.niehs.nih.gov/ntp).

The CERHR will convene expert panels to evaluate the reproductive and developmental toxicities of fluoxetine hydrochloride and acrylamide. For each of these meetings, the expert panel will consist of approximately 12 scientists, selected for their scientific expertise in various aspects of reproductive and developmental toxicology and other relevant areas of science. The expert panel meetings will be open to the public with time scheduled for oral public comment.

Evaluation of Fluoxetine Hydrochloride

Fluoxetine hydrochloride (Prozac®; Sarafem™; CAS RN 54910-89-3), an antidepressant, is a widely prescribed drug in the United States. The CERHR selected fluoxetine hydrochloride for evaluation because of (1) numerous reproductive and developmental studies in laboratory animals and humans, (2) human exposure information, and (3) changing prescription patterns. Fluoxetine hydrochloride, under the name Sarafem™, is now being prescribed to treat premenstrual dysphoric disorder (PMDD), potentially increasing the number of exposures for women of childbearing age. Further, FDA recently approved Sarafem™ for use in 7-17 year-olds thereby increasing exposures of children. CERHR anticipates holding the expert panel evaluation in late 2003.

Evaluation of Acrylamide

Acrylamide (CAS RN 79-06-1) is used in the production of polyacrylamide, which is used in water treatment, pulp and paper production, and mineral processing. It is used in the synthesis of dyes, adhesives, contact lenses, soil conditioners, and permanent press fabrics and in molecular biology procedures such as electrophoresis. Acrylamide is a neurotoxicant and in animal studies has been shown to be a carcinogen, germ cell mutagen, and reproductive toxicant. The CERHR selected acrylamide for expert panel evaluation because of recent public concern for human exposures through its presence in starchy foods treated at high temperatures, e.g., french fries and potato chips. In addition, recent data are available on occupational exposure, bioavailability, and reproductive toxicity. It is anticipated that the expert panel evaluation on acrylamide will occur in 2004.

Request for Public Input

The CERHR invites input from the public and other interested parties on fluoxetine hydrochloride and acrylamide, including toxicology information from completed and ongoing studies, information on planned studies, and information about current production levels, human exposure, use patterns, and environmental occurrence. Information and comments should be forwarded to the CERHR at P.O. Box 12233, MD EC-32, Research Triangle Park, NC 27709 (mail), (919) 541-3455 (phone), (919) 316-4511 (fax), or shelby@niehs.nih.gov (e-mail). Information and comments received by July 17, 2003 will be made available to the CERHR staff and the expert panel for consideration in the evaluation and posted on the CERHR website.

The CERHR also invites nominations of qualified scientists to serve on the expert panel for the fluoxetine hydrochloride evaluation and the acrylamide evaluation. Panelists are primarily drawn from the CERHR Expert Registry and/or the nomination of other scientists who meet the criteria for listing in that registry that include: formal academic training and experience in a relevant scientific field, publications in peer-reviewed journals, membership in relevant professional societies, certification by an appropriate scientific board or other entities, and participation in similar committee activities. All panel members serve as individual experts in their specific areas of expertise and not as representatives of their employers or other organizations. Scientists on the expert panel will be selected to represent a wide range of expertise, including developmental toxicology, reproductive toxicology, epidemiology, general toxicology, pharmacokinetics, exposure assessment, and biostatistics. Nominations received by July 17, 2003 will be considered for the fluoxetine hydrochloride and acrylamide panels and for inclusion in the CERHR Expert Registry. Nominations should be forwarded to the CERHR at the address given above.

Background Information about the CERHR

The NTP established the NTP CERHR in June 1998 [Federal Register, December 14, 1998 (Volume 63, Number 239, page 68782)]. The CERHR is a publicly accessible resource for information about adverse reproductive and/or developmental health effects associated with exposure to environmental and/or occupational exposures. Expert panels conduct scientific evaluations of agents selected by the CERHR in public forums.

Information about CERHR and the its process for nominating agents for review or scientists for its expert registry can be obtained from its homepage (http://cerhr.niehs.nih.gov) or by contacting Dr. Shelby (contact information provided above). The CERHR selects chemicals for evaluation based upon several factors, including production volume, extent of human exposure, public concern, and published evidence of reproductive or developmental toxicity.

CERHR follows a formal, multi-step process for review and evaluation of selected chemicals. The formal evaluation process was published in the Federal Register notice July 16, 2001 (Volume 66, Number 136, pages 37047-37048) and is available on the CERHR website under "About CERHR" or in printed copy from the CERHR.

Dated: April 9, 2003

Samuel H. Wilson, M.D.
Deputy Director
National Institute of Environmental Health Sciences

[Billing Code 4140-01-P]