Bis(dicholroacetyl)diamine‐induced Craniofacial Anomalies in Jcl: ICR and A/J Mice

Craniofacial anomalies induced by bis(dichloroacetyl)diamine (bisdiamine) were studied in two strains of mice, Jcl:ICR and A/J. Bisdiamine was given by oral intubation at a dose of 3,200 mg/kg/day at days 7.5 and 8.5, 8.5 and 9.5, 9.5 and 10.5 or 10.5 and 11.5 of pregnancy (VP = day 0). A/J was more susceptible to embryolethal effects of bisdiamine and had a longer sensitive period to teratogenic effects of bisdiamine. The most susceptible period for craniofacial anomalies induced by bisdiamine in A/J was one day later than that in Jcl:ICR. In both strains, median facial anomalies, cleft palate, protuberance(s) on the forehead and open eyelids were commonly induced craniofacial anomalies. Median facial anomalies were more frequent and also more severe in Jcl:ICR, while lateral cleft lip was observed only in A/J. Strain differences for embryolethality and types and frequencies of craniofacial anomalies are discussed on the basis of genetic homozygosity, craniofacial development and embryonic face shape immediately before the fusion of the nasal prominences. Neural crest cells are thought to be the target of bisdiamine.