{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T13:41:14Z","timestamp":1698327674981},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,9,9]],"date-time":"2005-09-09T00:00:00Z","timestamp":1126224000000},"content-version":"vor","delay-in-days":3904,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Teratog Carcinog Mutagen"],"published-print":{"date-parts":[[1995,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In previous studies the direct\u2010acting alkylating model compounds methylnitrosourea (MNU) and ethylmethanesulfonate (EMS) were investigated with regard to dose\u2010response of teratogenicity as well as DNA adduct formation in mice. In this study the teratogenic effects induced by combined treatment with these substances were analyzed using doses which, following single treatment with either substance, were around the threshold level, i.e., no adverse effect level (NOAEL) and lowest observed adverse effect level (LAOEL).<\/jats:p><jats:p>Combined treatment of LAOELs resulted in a threshold\u2010like response, while the combination of the NOAEL of one substance with the LAOEL of the other increased the response rate dramatically to nearly 100%.<\/jats:p><jats:p>This phenomenon was further evaluated using biometrical methods. The dose\u2010response surface as well as isobolograms were calculated in order to describe the combination effect. In addition, a dose\u2010response model was fitted to the data. In conclusion, the initially surprising high combination effect revealed to be not so extraordinary when considering the steepness of the dose\u2010response relationships of the single substances. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/tcm.1770150406","type":"journal-article","created":{"date-parts":[[2006,2,4]],"date-time":"2006-02-04T01:48:35Z","timestamp":1139017715000},"page":"201-214","source":"Crossref","is-referenced-by-count":3,"title":["Embryotoxicity induced by alkylating agents: 10. Analysis of the combined teratogenic effects of methylnitrosourea and ethylmethanesulfonate in mice"],"prefix":"10.1002","volume":"15","author":[{"given":"Thomas","family":"Platzek","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Bochert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,9,9]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"429","article-title":"Teratogenic interaction of chemical agents in the rat","volume":"144","author":"Wilson JG","year":"1964","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_3_2","first-page":"445","volume-title":"Handbook of Teratology","author":"Fraser 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