Effect of food deprivation, phenobarbital, and SKF‐525a on teratogenicity induced by 2‐sec‐butyl‐4,6‐dinitrophenol (dinoseb) and on disposition of [14c] dinoseb in mice

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Abstract
Swiss‐Webster mice were treated ip with 2‐sec‐butyl‐4,6‐dinitrophenol (dinoseb) at doses of 0–18.8 mg/kg/day on days 10, 11, and/or 12 of gestation. These treatments were preceded by 24‐ or 48‐hr food deprivation or by pretreatment with phenobarbital or 2‐diethylaminoethyl‐2,2‐dlphenylvalerate hydrochloride (SKF‐525A). Resorption rate and fetal body weight were determined and external, soft tissue, and skeletal examinations were made on fetuses removed by Caesarean section on the 19th day of gestation. SKF‐525A potentiated and phenobarbital inhibited resorptions and reductions in fetal body weight induced by dinoseb. Dinoseb‐induced external, soft tissue, and skeletal anomalies were increased by 24‐hr food deprivation and SKF‐525A pretreatment, while 48‐hr food deprivation had no effect. In general, the effect of phenobarbital was to protect against dinoseb teratogenicity. Disposition of [14C] dinoseb was also examined in adult female mice following each of the pretreatments. Food deprivation for 24 hr slowed and phenobarbital hastened disappearance of dinoseb from plasma. Food deprivation for 48 hr and SKF‐525A pretreatment did not affect disappearance of dinoseb from plasma, but they, respectively, increased and decreased the rate of disappearance from liver. It was suggested that the alterations in dinoseb‐induced embryotoxicity and teratogenicity by the pretreatments could have been related to an alteration in the rate of disappearance of dinoseb from the mother.