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This review compares the mechanisms regulating disposition of toxicants from the maternal circulation to the embryo during organogenesis in humans and the two species used predominantly in regulatory developmental toxicity testing, rats and rabbits. These three species utilize fundamentally different strategies for maternal\u2010embryonic exchange during early pregnancy. Early postimplantation rat embryos rely on the inverted visceral yolk sac placenta, which is in intimate contact with the uterine epithelium and is equipped with an extensive repertoire of transport mechanisms, such as pinocytosis, endocytosis, and specific transporter proteins. Also, the rat yolk sac completely surrounds the embryo, such that the fluid\u2010filled exocoelom survives through most of the period of organogenesis, and can concentrate compounds such as certain weak acids due to pH differences between maternal blood and exocelomic fluid. The early postimplantation rabbit conceptus differs from the rat in that the yolk sac is not closely apposed to the uterus during early organogenesis and does not completely enclose the embryo until relatively later in development (\u223cGD13). This suggests that the early rabbit yolk sac might be a relatively inefficient transporter, a conclusion supported by limited data with ethylene glycol and one of its predominant metabolites, glycolic acid, given to GD9 rabbits. In humans, maternal\u2010embryo exchange is thought to occur via the chorioallantoic placenta, although it has recently been conjectured that a supplemental route of transfer could occur via absorption into the yolk sac. Knowledge of the mechanisms underlying species\u2010specific embryonic disposition, factored together with other pharmacokinetic characteristics of the test compound and knowledge of critical periods of susceptibility, can be used on a case\u2010by\u2010case basis to make more accurate extrapolations of test animal data to the human. Birth Defects Research (Part C) 72:345\u2013360, 2005. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrc.20027","type":"journal-article","created":{"date-parts":[[2005,1,20]],"date-time":"2005-01-20T16:50:44Z","timestamp":1106239844000},"page":"345-360","source":"Crossref","is-referenced-by-count":96,"title":["Mechanisms regulating toxicant disposition to the embryo during early pregnancy: An interspecies comparison"],"prefix":"10.1002","volume":"72","author":[{"given":"Edward W.","family":"Carney","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony R.","family":"Scialli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca E.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"DeSesso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,1,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.157.3793.1180"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.76185"},{"key":"e_1_2_12_4_1","unstructured":"BenirschkeK.2004. 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