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Pregnant Sprague\u2010Dawley rats, at 9 days 12 hours gestation (gastrulation stage), were partially immersed in a water bath until their core temperature, monitored by a rectal thermistor probe, was elevated to a nominated temperature. Seven temperatures were tested from 40.5\u00b0C to 43.5\u00b0C, elevations of 2.0\u20135.0\u00b0C in core temperature. Various durations at each of these temperatures were tested for potential teratogenicity. A single elevation of 5.0\u00b0C or 4.5\u00b0C needed only a \u201cspike\u201d in duration to be teratogenic, 4.0\u00b0C was teratogenic within 5 minutes, 3.5\u00b0C within 10 minutes, 3.0\u00b0C within 20 minutes, and 2.5\u00b0C within 1 hour. An elevation of 2.0\u00b0C for 8 hours was not teratogenic. Microphthalmia was the most common malformation at all teratogenic temperatures and was frequently the only malformation seen at the shortest time exposure for a particular temperature. Encephalocele, facial clefting, and maxillary hypoplasia were the other frequently seen malformations. Five control rats were placed in the water bath for 2 hours at 38\u00b0C so that their core temperature was not elevated. All the control fetuses were normal. An elevation of 2.5\u00b0C for 1 hour was the threshold combination for teratogenesis. As the temperature increased above a 2.5\u00b0C elevation the necessary duration of exposure for teratogenesis decreased.<\/jats:p>","DOI":"10.1002\/tera.1420310212","type":"journal-article","created":{"date-parts":[[2005,6,12]],"date-time":"2005-06-12T00:15:24Z","timestamp":1118535324000},"page":"265-272","source":"Crossref","is-referenced-by-count":116,"title":["Hyperthermia as a teratogen: Parameters determining hyperthermia\u2010induced head defects in the rat"],"prefix":"10.1002","volume":"31","author":[{"given":"Mary\u2010Ann","family":"Germain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Webster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall J.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,23]]},"reference":[{"key":"e_1_2_1_2_1","volume-title":"Heat shock\u2013from bacteria to man","author":"Brown I. 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