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Background: A new derived (i.e., calculated) endpoint of developmental toxicology has appeared in a very few studies since 1990. This endpoint is adjusted mean live fetal weight per litter or adjusted fetal weight. Given our lack of familiarity with the endpoint, we evaluated the basis, prevalence, methods, and usefulness in embryo‐fetal developmental toxicity (EFDT) studies in rats. Methods: Literature searches were performed with key terms using PubMed and Google Scholar. Major textbooks were consulted but lack of any mention of the endpoint. Unpublished EFDT data, which are readily available online, were utilized to test adjustment methods. Results: Pertinent information on factors that influence fetal weight goes back a century. Four papers utilizing rats were found in which fetal weights were adjusted using either statistical or formula‐based methods to adjust fetal weights. Only one study showed a clear benefit to the endpoint when there was a marked decrease in live litter size; this pointed to situations in which the new endpoint might be useful. The lone formula‐based adjustment method was found to be lacking adequate testing and justifications. A new experimental alternative formula‐based adjustment is shown to produce results very similar to statistical methods. Conclusions: From this assessment, we recommend that adjusted fetal weight should not be a routine endpoint at this time. However, there are likely cases where this derived endpoint could aid interpretation. We encourage other investigators to examine previous EFDT study data to establish guidance on the use of adjusted mean live fetal weights. [ABSTRACT FROM AUTHOR]

Rodriguez et al. recently reported that the adult female offspring of pregnant CD-1 mice exposed to 10 ppb or 42.5 ppm arsenic (As) exhibited reproductive and metabolic effects. These findings [...]

Embryos and tumors share several characteristics, but embryos differ from tumors in their coordination of cellular‐ and tissue‐level processes, including organized differentiation, remodeling of tissues through apoptosis, and disciplined migrations of cells. Embryonic cellular events are kept on track through orderly cell–cell communication via signal transduction pathways. If the pathways are disrupted, development is perturbed, and malformation may result. Despite profound differences between embryos and tumors, the study of one has benefited our understanding of the other. Using cyclopia as an example, the history of humans' beliefs concerning and reactions to this horrific malformation are explored. During the latter half of the 20th century, interest in cyclopic sheep from high pastures in western Idaho led to the discovery that cyclopia occurred after pregnant ewes foraged in fields containing corn lily (Veratrum californicum). Eventually, the proximate teratogen was identified as cyclopamine (a steroidal alkaloid). The teratogenic mechanism was identified as inhibition of the sonic hedgehog (Shh) signal transduction pathway. Alert cancer researchers noted that a prominent form of medulloblastoma (a devasting childhood brain tumor) overexpressed Shh. Cyclopamine effectively inhibited the tumor in mice and killed human medulloblastoma cells in vitro. Thus, over a 60‐year period, a molecule causing hideous malformations and much emotional pain was discovered and then found capable of restraining a destructive tumor, potentially saving children's lives and sparing emotional devastation of their families. The success of identifying cyclopamine as a cause of cyclopia and a potential cure for medulloblastoma emerged from mechanistic research shared by multiple disciplines. [ABSTRACT FROM AUTHOR]

While the discipline of Teratology has existed for about 60 years, there has been a deep interest in the causes of human malformations for millennia. Absent the scientific method and acting on fervent beliefs that made sense to ancient/medieval populations, "mechanisms" were described and prognostications of future events were assigned to terata resulting in tragic (and unwarranted) sequelae. This article examines the collective beliefs and thinking within various eras in the hope of providing lessons to inform future behavior. The eugenics movement is an informative, recent example. Science of the 19th century had unraveled some of the mysteries of development and the role of genetics in determining birth outcomes. There was, however, a deep misunderstanding about the enormous amount of information that had yet to be uncovered. Based on immature science and faulty assumptions, it was suggested that "unfit" individuals be euthanized and their parents sterilized. Such "solutions" would be considered deplorable today. Surprisingly, such a reprehensible program was supported (at least in part) by many intelligent and highly regarded individuals. Today, it is imperative that we enter into the era of molecular biology and gene editing cautiously and perspicaciously. The history of teratology has elucidated our inability to understand where our new technologies and actions might take us and how unintended consequences could disrupt even our most carefully thought‐out plans. [ABSTRACT FROM AUTHOR]