Developmental Toxicity of Bromoxynil in Mice and Rats

Developmental Toxicity of Bromoxynil in Mice and Rats. ROGERS,J. M., FRANCIS, B. M., BARBEE B. D., AND CHERNOFF, N. (1991).Fundam. Appl. Toxicol 17, 442–447. The developmental toxicityof the wide-spectrum herbicide bromoxynil (bromoxynil phenol;3,5-dibromo-4-hydroxyphenyl cyanide) was evaluated in Sprague-Dawleyrats and Swiss-Webster mice, and the developmental toxicityof its octanoate ester (2,6-dibromo-4-cyanophenyl octanoate)was evaluated in Sprague-Dawley rats. Animals were treated fromDay 6 to Day 15 of gestation [presence of sperm or semen plug= 0 of gestation]. The doses administered were as follows: bromoxynilphenol in the mouse, 342, 114, and 38 µmol/kg/day; bromoxynilphenol and bromoxynil octanoate in the rat, 54, 18, and 6 µmol/kg/day.Some animals were killed on selected days during treatment formeasurement of organ weights sensitive to stress. In mice treatedwith bromoxynil phenol, maternal mortality was noted at 114and 342 µmol/kg/day, but surviving females gained weightnormally. Liver to body weight ratios increased with increasingdose, but no consistent effect was seen on adrenal, thymus,or spleen weights. Fetuses of mice treated with the highestdose of bromoxynil phenol were of lower weight and had a higherincidence of supernumerary ribs than controls. In rats, bromoxynilphenol and its octanoate ester at the highest doses used causedno mortality but resulted in only transient decreases in maternalweight gain and significantly increased the liver to body weightratio, but did not significantly alter adrenal, thymus, or spleenweight in the dams. No significant maternal effects were seenat lower doses. The highest doses of both compounds increasedthe incidence of supernumerary ribs in fetuses of treated rats,but did not induce other anomalies. Fetal weight was reducedin rats at the highest dose of bromoxynil octanoate, but noeffects on fetal weight were seen with bromoxynil phenol. Bromoxynilexposure produced a high incidence of supernumerary ribs atmaternally toxic doses in both rats and mice, although no evidenceof maternal stress per se was found. The mechanism and significanceof this effect require further study.