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NZW rabbits were used because of sensitivity to thalidomide's teratogenicity. <jats:bold>METHODS:<\/jats:bold> Range\u2010finding and pulse\u2010dosing studies preceded a full developmental toxicity study in New Zealand white (NZW) rabbits (25\/group) given lenalidomide (0, 3, 10, or 20\u2009mg\/kg\/day) or thalidomide (180\u2009mg\/kg\/day) by stomach tube on gestation days (GD) 7\u201319. Clinical signs, body weights, and feed consumption were recorded daily from GD 7. On GD 29, standard maternal necropsy, uterine content, and fetal evaluations were carried out. <jats:bold>RESULTS:<\/jats:bold> In all studies, thalidomide was selectively toxic to development. In the pulse\u2010dosing study, lenalidomide did not affect development at 100\u2009mg\/kg\/day. Increases in C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u201324\u2009hr<\/jats:sub> values for lenalidomide were slightly less than dose\u2010proportional; lenalidomide occurred in the fetuses. At 10 and 20\u2009mg\/kg\/day, lenalidomide was maternally toxic (reduced body weight gain and feed consumption; at 20\u2009mg\/kg\/day, weight loss and one abortion). Developmental toxicity at 10 and 20\u2009mg\/kg\/day included reduced fetal body weights and increased postimplantation losses and fetal variations (morbidity\/purple\u2010discolored skin, undeveloped intermediate lung lobe, irregular nasal\u2010frontal suture, and delayed metacarpal ossification). Thalidomide selectively reduced fetal body weight, increased postimplantation loss and caused characteristic limb and other dysmorphology. <jats:bold>CONCLUSIONS:<\/jats:bold> The maternal and developmental NOAELs for lenalidomide are 3\u2009mg\/kg\/day. Unlike thalidomide, lenalidomide affected embryo\u2013fetal development only at maternally toxic dosages, confirming that structure\u2010activity relationships may not predict maternal or developmental effects. No fetal malformations were attributable to lenalidomide. <jats:italic>Birth Defects Res (Part B)<\/jats:italic>, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdrb.20115","type":"journal-article","created":{"date-parts":[[2007,6,14]],"date-time":"2007-06-14T17:16:46Z","timestamp":1181841406000},"page":"188-207","source":"Crossref","is-referenced-by-count":42,"title":["Evaluation of the developmental toxicity of lenalidomide in rabbits"],"prefix":"10.1002","volume":"80","author":[{"given":"Mildred S.","family":"Christian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar L.","family":"Laskin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Sharper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Hoberman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David I.","family":"Stirling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Latriano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,6,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1323"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602774"},{"key":"e_1_2_6_4_1","first-page":"45","article-title":"Zur quantitativen Bestimmung und zum qualitativen Nachweis von N\u2010phthalyl\u2010glutaminsaureimid (thalidomide)","volume":"11","author":"Beckmann R","year":"1961","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420380308"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-10-4184"},{"key":"e_1_2_6_7_1","first-page":"1301","volume-title":"Principles and methods of toxicology","author":"Christian MS","year":"2001"},{"key":"e_1_2_6_8_1","article-title":"Recent increases in the incidence of skull, lung and rib alterations in vehicle control New Zealand white rabbits [Abstract 126]","volume":"6","author":"Christian MS","year":"1987","journal-title":"J Am Coll Toxicol"},{"key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.4049\/jimmunol.163.1.380","article-title":"Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF\u2010a","volume":"163","author":"Corral LG","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.1.210"},{"key":"e_1_2_6_11_1","first-page":"759a","article-title":"Lenalidomide and novel immunomodulatory drugs (IMiDs\u00ae): a new approach to the regulation of erythropoiesis and hemoglobin synthesis in anemia [abstract 2702]","volume":"106","author":"DeParseval LM","year":"2005","journal-title":"ASH Annual Meeting Proceedings. 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