Science Inventory

NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea

Citation:

LIEBELT, E. L., S. J. BALK, W. FABER, J. W. FISHER, C. L. HUGHES, S. M. LANZKRON, K. M. LEWIS, F. MARCHETTI, H. M. MEHENDALE, J. M. ROGERS, A. T. SHAD, R. G. SKALKO, AND E. J. STANEK. NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea . BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY. John Wiley & Sons, Ltd., Indianapolis, IN, 80(4):259-366, (2007).

Impact/Purpose:

The findings and conclusions of this report are those of the expert panel and should not be construed to represent the views of the National Toxicology Program

Description:

The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed. Hydroxyurea was selected for evaluation by a CERHR expert panel because of (1) its increasing use in the treatment of sickle cell disease in children and adults, (2) knowledge that it inhibits DNA synthesis and is cytotoxic, and (3) published evidence of its reproductive and developmental toxicity in rodents. Hydroxyurea is FDA-approved for reducing the frequency of painful crises and the need for blood transfusions in adults with sickle cell anemia who experience recurrent moderate-to-severe crises. Hydroxyurea is used in the treatment of cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease aside from blood transfusion used in children. Hydroxyurea may be used in the treatment of children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea may be associated with cytotoxic and myelosuppressive effects, and hydroxyurea is mutagenic. To obtain information about hydroxyurea for the CERHR evaluation, the PubMed (Medline) and Toxline databases were searched through January 10, 2007 using ¿hydroxyurea¿ and its CAS RN (127¿07¿1). References were also identified from databases such as REPROTOX®, HSDB, IRIS, and DART and from the bibliographies of reports being reviewed. This evaluation results from the efforts of a 13-member panel of government and non-government scientists that culminated in a public expert panel meeting held January 24-26, 2007. This report is a product of the hydroxyurea expert panel and is intended to (1) interpret the strength of scientific evidence that hydroxyurea is a reproductive or developmental toxicant based on data from in vitro, animal, and/or human studies, (2) assess the extent of human exposures, especially for patients receiving hydroxyurea in the treatment of sickle cell disease and other health disorders, (3) provide objective and scientifically thorough assessments of the scientific evidence that adverse reproductive/developmental health effects may be associated with such exposures, and (4) identify knowledge gaps to help establish research and testing priorities to reduce uncertainties and increase confidence in future evaluations. This report has been reviewed by members of the hydroxyurea expert panel and by CERHR staff scientists. Copies have been provided to the CERHR Core Committee, which is made up of representatives of NTP-participating government agencies. This Expert Panel Report will be included in the subsequent NTP¿CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Hydroxyurea. That monograph will include the NTP-CERHR Brief, the Expert Panel Report, and all public comments on the Expert Panel Report. The NTP-CERHR Monograph will be made publicly available and transmitted to appropriate health and regulatory agencies.