Teratogenicity of a commercial xylene mixture in the mouse

Pregnant outbred albino (CD-1) mice received (gavage, three times a day in cottonseed oil) a xylene mixture (60.2% m-xylene, 9.1% o-xylene, 13.6% p-xylene, and 17.0% ethyl benzene) on d 6-15 of gestation (d 1 being the day vaginal plugs were observed). The mice were killed on d 18, the general and reproductive health of the dams evaluated, and the fetuses examined and processed to characterize external, visceral, and skeletal malformation. At 3.6 ml/kg.d, xylene killed 12 of 38 dams and caused a significantly (p less than 0.05) smaller average weight gain during pregnancy than did the vehicle (cottonseed oil). Fetuses from dams treated with xylene at 2.4 ml/kg.d and higher doses had average fetal weights significantly lower than that of the control fetuses. However, the percent of resorptions for xylene was significantly greater than for the control only at 3.6 ml/kg-d. At 2.4, 3.0, and 3.6 ml/kg-d xylene produced a significantly (p less than 0.01) greater average percent of malformed fetuses than did the control. Cleft palate was the major malformation at all three doses. When bilateral (multiple) wavy ribs were counted as a malformation, the average percent of malformed fetuses increased from 7.8 to 10.5 at 3.0 ml/kg.d and from 9.1 to 13.4 at 3.6 ml/kg.d. It is concluded that xylene (mixed isomers) is teratogenic to the CD-1 mouse at 2.4 and 3.0 ml/kg.d, doses approaching lethal levels.