Investigation of the Effects of Benomyl on Rat Nasal Mucosa

Benomyl methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate,CAS Registry No. 17804-35-2] is a widely used agricultural fungicide.Previously, olfactory epithelial lesions were produced followinga 45-day inhalation exposure to 50 and 200 mg/m³ benomyl. Thepresent study, part of a range-finding study for a two-generationreproduction study, was conducted to determine if the previouslyreported effects on the nasal mucosa are the result of systemictoxicity or attributable to the inhalation route of exposure.Groups of 10 7-week-old male Crl:CD BR rats were fed diets containing0, 5000, 10000, or 15000 ppm benomyl for 32 days. Individualbody weights and food consumption were determined weekly andon the last day of the study. After 32 days on test, rats wereeuthanatized by pentobarbital anesthesia and exsanguinationand were examined for gross alterations. The nasal cavity wasprocessed for pathological examination. Mean body weight gainwas statistically significantly decreased during the first weekof treatment and the overall test period (Days 0–32) atthe two highest dose levels. A significant decrease in foodconsumption also was seen during test interval Days 0–7for the two highest dose groups. In addition, statisticallysignificant decreases in food consumption were observed at theDay 7–14 interval for the 15,000 ppm dose group and atthe 21–28 and 28–32 intervals for the two highestdose groups compared with controls. No histopathological lesionswere noted in the nasal epithelium of any of the control orbenomyl-treated rats. These results suggest that the nasal cavityis not a target following dietary administration of benomyland the olfactory epithelial damage reported following inhalationexposure is specific to the route of exposure.