Teratogenicity of a commercial xylene mixture in the mouse

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Abstract
Pregnant outbred albino (CD-1) mice received (by gavage, 3 times per 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 day 6-15 of gestation (day 1 being the day vaginal plugs were observed). The mice were killed on day 18, the general and reproductive health of the dams evaluated and the fetuses examined and processed to characterize external, visceral and skeletal malformations. At 3.6 ml/kg per day, xylene killed 12 of 38 dams and caused a significantly (P < 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 per day and higher doses had average fetal weights significantly lower than that of the control fetuses. The percent of resorptions for xylene was significantly greater than for the control only at 3.6 ml/kg per day. At 2.4, 3.0 and 3.6 ml/kg per day, xylene produced a significantly (P < 0.01) greater average percent of malformed fetuses than did the control. Cleft palate was the major malformation at all 3 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 per day, and from 9.1 to 13.4 at 3.6 ml/kg per day. Xylene (mixed isomers) is teratogenic to the CD-1 mouse at 2.4 and 3.0 ml/kg per day, doses approaching lethal levels.