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The Reproductive Assessment by Continuous Breeding (RACB) design has been used by the National Toxicology Program for approximately 15 years. This article details the evolutions in the thinking behind the design and the end points used in the identification of hazards to reproduction. Means of nominating chemicals are provided, and both early and current designs are described as well as some proposed changes for the future. This introduction is followed by a text and tabular summary of each study performed to date. We hope that this will not only be an explicit presentation of the findings of this testing program to date, but will help stimulate thinking about new ways to detect and measure reproductive toxicity in rodents, and help identify new relationships among the end points that are measured in such studies.

Birth defects cause a myriad of societal problems and place tremendous anguish on the affected individual and his or her family. Current estimates categorize about 3% of all newborn infants as having some form of birth defect or congenital anomaly. As more precise means of detecting subtle anomalies become available this estimate, no doubt, will increase. Even though birth defects have been observed in newborns throughout history, our knowledge about the causes and mechanisms through which these defects are manifested is limited. For example, it has been estimated that around 20% of all birth defects are due to gene mutations, 5-10% to chromosomal abnormalities, and another 5-l0% to exposure to a known x Resource for Clinicians TERIS , The John Hopkins University Press, Baltimore, 1994 , the mutagenic activity of environmental agents and drugs as a factor in teratogenesis has been given very little attention. Epigenetic activity has also been given only limited consideration as a mechanism for teratogenesis. As new molecular methods are developed for assessing processes associated with teratogenesis, especially those with a genetic or an epigenetic basis, additional environmental factors may be identified. These are especially important because they are potentially preventable. This paper Ž . examines the relationships between chemicals identified as human teratogens agents that cause birth defects and their mutagenic activity as evaluated in one or more of the established short-term bioassays currently used to measure such damage. Those agents lacking mutagenic activity but with published evidence that they may otherwise alter the expressions or regulate interactions of the genetic material, i.e. exhibit epigenetic activity, have likewise been identified. The information used in making these comparisons comes from the published literature as well as from unpublished data of the U.S. National Ž . Toxicology Program NTP . q 1997 Elsevier Science B.V.) Corresponding author. Tel.: q1-919-541-187; Fax: q1-919-541-4634; E-mail: bishop@niehs.nih.gov 0027-5107r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved.Ž . PII S 0 0 2 7 -5 1 0 7 9 7 0 0 1 7 3 -5 ( ) J. B. Bishop et al.r Mutation Research 396 1997 9-43 10

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