Developmental toxicity of bromoxynil in mice and rats

Abstract

The developmental toxicity of the wide-spectrum herbicide bromoxynil (bromoxynil phenol; 3,5-dibromo-4-hydroxyphenyl cyanide) was evaluated in Sprague-Dawley rats and Swiss-Webster mice, and the developmental toxicity of its octanoate ester (2,6-dibromo-4-cyanophenyl octanoate) was evaluated in Sprague-Dawley rats. Animals were treated from Day 6 to Day 15 of gestation [presence of sperm or semen plug = 0 of gestation]. The doses administered were as follows: bromoxynil phenol in the mouse, 342, 114, and 38 μmol/kg/day; bromoxynil phenol and bromoxynil octanoate in the rat, 54, 18, and 6 μmol/kg/day. Some animals were killed on selected days during treatment for measurement of organ weights sensitive to stress. In mice treated with bromoxynil phenol, maternal mortality was noted at 114 and 342 μmol/kg/day, but surviving females gained weight normally. Liver to body weight ratios increased with increasing dose, but no consistent effect was seen on adrenal, thymus, or spleen weights. Fetuses of mice treated with the highest dose of bromoxynil phenol were of lower weight and had a higher incidence of supernumerary ribs than controls. In rats, bromoxynil phenol and its octanoate ester at the highest doses used caused no mortality but resulted in only transient decreases in maternal weight gain and significantly increased the liver to body weight ratio, but did not significantly alter adrenal, thymus, or spleen weight in the dams. No significant maternal effects were seen at lower doses. The highest doses of both compounds increased the incidence of supernumberary ribs in fetuses of treated rats, but did not induce other anomalies. Fetal weight was reduced in rats at the highest dose of bromoxynil octanoate, but no effects on fetal weight were seen with bromoxynil phenol. Bromoxynil exposure produced a high incidence of supernumerary ribs at maternally toxic doses in both rats and mice, although no evidence of maternal stress per se was found. The mechanism and significance of this effect require further study.