Induction of cleft palate in mice by tranquilizers and barbiturates

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Abstract
Several barbiturates and tranquilizers, individually or in combination, were injected into pregnant mice of the A/J, CD1 and C3H strains in doses sufficient to induce sedation during the expected time of palate closure. Similar treatments were given during periods of fetal development 1 or more days prior to the time for normal palate closure. Among 2074 fetuses from treated pregnant females, 308 had isolated cleft palates. The most susceptible strains were A/J and CD1; the more teratogenic drugs were phenobarbital and hydroxyzine; the most critical treatment periods were at least 1 day prior to the time the palate would normally have closed. Thus, barbiturates and tranquilizers were shown to be significant cleft palate teratogens in mice although their mechanism of action was not investigated.