NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Styrene Ulrike Luderer, 1 Thomas F.X. Collins, 2 George P. Daston, 3 Lawrence J. Fischer, 4 Ronald H. Gray, 5 Franklin E. Mirer, 6 Andrew F. Olshan, 7 R. Woodrow Setzer, 8 Kimberley A. Treinen, 9 and Roel Vermeulen 10 1 University of California-Irvine, Irvine, CA 2 U.S. Food and Drug Administration, Laurel, MD 3 The Procter & Gamble Company, Cinncinati, OH 4 Michigan State University, East Lansing, MI 5 Johns Hopkins University, Baltimore, MD 6 International Union, United Auto Workers, Detroit, MI 7 University of North Carolina, Chapel Hill, CA 8 U.S. Environmental Protection Agency, Research Triangle Park, NC 9 Schering-Plough Research Institute, Lafayette, NJ 10 National Cancer Institute, Bethesda, MD PREFACE 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 the Center is to provide timely, unbiased, scientifically sound evaluations of human and experi- mental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed. Styrene was selected for expert panel evaluation because of public concern for the possible health effects of human exposures and exposure data available recently. Styrene (ethenylbenzene; CAS RN: 100-42-5) is a high production volume chemical used in the produc- tion of polystyrene resins and as a co-polymer with acrylonitrile and 1,3-butadiene. Styrene is found in items such as foam cups, dental fillings, matrices for ion exchange filters, construction materials, and boats. It is also used in protective coatings, reinforced glass fiber, agricultural products, and as a food additive. In addition to occupational exposures, the general public can be exposed to styrene by ingesting food or drink that has been in contact with styrene polymers or through inhalation of polluted air or cigarette smoke. To obtain information about styrene for the CERHR evaluation, the PubMed (Medline) and Toxline databases were searched through March, 2005, with CAS RNs for styrene (100-42-5), styrene oxide (96-09-3), and relevant keywords. References were also identified from data- bases such as REPROTOX s , HSDB, IRIS, and DART and from the bibliographies of reports being reviewed. This evaluation results from the effort of a 10-member panel of government and non-government scientists that culminated in a public Expert Panel meeting held June 1–3, 2005. This report is a product of the Expert Panel and is intended to (1) interpret the strength of scientific evidence that styrene is a reproductive or developmental toxicant based on data from in vitro, animal, or human studies, (2) assess the extent of human exposures to include the general public, occupational groups, and other sub-populations, (3) provide objective and scienti- fically 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 assessments of risk. This report has been reviewed by CERHR staff scientists and by members of the Styrene Expert Panel. Copies have been provided to the CERHR Core Committee, which is made up of representatives of NTP-participating agencies. This Expert Panel Report will be a central part of the subsequent NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Styrene. This monograph will include the NTP-CERHR Brief, the Expert Panel Report, and all public comments on the Expert Panel Report. The NTP-CERHR Mono- graph will be made publicly available and transmitted to appropriate health and regulatory agencies. The NTP-CERHR is headquartered at NIEHS, Re- search Triangle Park, NC and is staffed and administered by scientists and support personnel at NIEHS and at Sciences International, Inc., Alexandria, Virginia. Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/bdrb.20061 Correspondence to: Michael D. Shelby, PhD, NIEHS EC-32, PO Box 12233, Research Triangle Park, NC 27709. E-mail: shelby@niehs.nih.gov Birth Defects Research (Part B) 77:110–193 (2005) Published 2005 Wiley-Liss, Inc. w w This article is a U.S. Government work and, as such, is in the public domain in the United States of America.