The effects on rat pups when nitrofen (4-(2,4-dichlorophenoxy)nitrobenzene) was applied dermally to the dam during organogenesis

Abstract Nitrofen (4-(2,4-dichlorophenoxy)nitrobenzene; TOK® herbicide) was administered dermally as an aqueous dilution of an emulsifiable concentrate on Day 6–15 of gestation to pregnant Sprague-Dawley rats at dose levels of 0, 0.3, 0.6, 1.2 and 12.0 mg/kg/day. No maternal toxicity occured. At 12 mg/kg neonatal survival was reduced and the animals that died had a high incidence of diaphragmatic hernias. Survivors showed increased incidences of diaphragmatic hernias and of missing or reduced Harderian glands, chromodarcryorrhea (a clear red exudate around the eyes), and a high frequency of slight to severe dilation of the renal pelvis. Thyroid and Harderian gland weights were significantly depressed in Day 42 survivors of both sexes at 12.0 mg/kg; liver and lung weights were decreased, and renal weight was increased in the females. At 12.0 mg/kg thyroid weights of males and females were significantly depressed at 146 days postnatal. The incidence of dilated kidneys was increased at 0.3 mg/kg and higher. No effect was observed at any dose level on time to eye opening, time to vaginal opening, mitotic index of the liver, or T3 levels in the dams or the offspring, and no gross behavioral effects were recorded. The no observable effect level was estimated to be 0.28 mg/kg in males and 0.17 mg/kg in females using a mathematical extrapolation.