04-8269. National Toxicology Program

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) announces plans for future evaluations of Methylphenidate and Adderall ®, Magnesium Sulfate, and Genistein and Soy Formula; Requests public comments on these substances; and solicits the nominations of scientists qualified to serve on expert panels evaluating these compounds.

Summary

The CERHR plans to convene 3 expert panels to evaluate potential reproductive and developmental toxicities of (1) methylphenidate (Ritalin ®) and Adderall ®, (2) magnesium sulfate, and (3) genistein and soy formula. For each evaluation, 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 CERHR invites the submission of public comments on any of these substances and the nomination of scientists to serve on the expert panels for their evaluation (see below). These meetings are tentatively scheduled for 2004 and 2005 although the exact dates and locations are not yet established. As plans are finalized, they will be announced in the Federal Register and posted on the NTP Web site (http://ntp-server.niehs.nih.gov). These expert panel meetings will be open to the public with time scheduled for oral public comment.

Evaluation of Methylphenidate and Adderall ®

Methylphenidate (Ritalin ®, CAS RN: 113-45-1) and Adderall ® (amphetamine, CASRN: 300-62-9 and dextraamphetamine, CASRN: 51-64-9) are stimulants used to treat attention deficit disorder with hyperactivity and narcolepsy in children and adults. Methylphenidate is also used off-label to treat depression. CERHR selected these chemicals for expert panel evaluation because of: (1) The increasing use of these drugs in children, (2) public concern for long-term effects of these drugs on child development and behavior, (3) the availability of human exposure data, and (4) findings from developmental studies in humans and experimental animals.

Evaluation of Magnesium Sulfate

Magnesium sulfate (CASRN: 7487-88-9) is the most common magnesium salt used for seizure prophylaxis in preeclampsia or seizure control in eclampsia, and for inhibition of uterine contractions during preterm labor. CERHR selected this chemical for expert panel evaluation because of: (1) The existence of an adequate exposure database, (2) concern for the survival and development of the infant after maternal treatment, and (3) the availability of developmental toxicity data.

Evaluation of Genistein and Soy Formula

Genistein (CASRN: 446-72-0) is found in some legumes, such as soybeans and clover, or in products obtained from animals ingesting genistein-containing feed. Genistein is a phytoestrogen, defined as a non-steroidal, estrogenic, naturally occurring plant product. It is found in food, in over-the-counter dietary supplements, and is the primary phytoestrogen in soy formula. Soy formula is administered to infants as a supplement or replacement for maternal breast milk or cow's milk. CERHR selected these substances for expert panel evaluation because of: (1) The availability of numerous reproductive and developmental studies in laboratory animals and humans, (2) exposure information in infants and women of reproductive age, and (3) public concern for effects on infant or child development.

Request for Public Comment on Substances To Be Evaluated

The CERHR invites input from the public and other interested parties on these substances, 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), [phone] (phone), [phone] (fax), or [e-mail] (e-mail). Information and comments received by 60 days from the publication date of this notice will be made available to the CERHR staff and the appropriate expert panel for consideration in the evaluation and posted on the CERHR Web site.

Request for the Nomination of Scientists for the Expert Panels

The CERHR invites nominations of qualified scientists to serve on the individual expert panels for: (1) Methylphenidate and Adderall ®, (2) magnesium sulfate, and (3) genistein and soy formula. 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, but not limited to, developmental toxicology, reproductive toxicology, neonatology and child development, epidemiology, general toxicology, pharmacokinetics, exposure assessment, and biostatistics. Nominations received by 60 days from the publication date of this notice will be considered for these panels and for inclusion in the CERHR Expert Registry. Nominations, including contact information and a current curriculum vitae (if possible) should be forwarded to the CERHR at the address given above.

Background Information About the CERHR

The NTP established the 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 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 (July 16, 2001: Volume 66, Number 136, pages 37047-37048) and is available on the CERHR Web site under “About CERHR” or in printed copy from the CERHR.

Dated: April 1, 2004.

Kenneth Olden,

Director, National Institute of Environmental Health Sciences.