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© 1993 Oxford University Press

other

Investigation of the Effects of Benomyl on Rat Nasal Mucosa

MARK E. HURTT, CHARLES A. MEBUS2 and MATTHEW S. BOGDANFFY

Haskell Laboratory for Toxicology and Industrial Medicine E. I. duPont de Nemours and Company P.O. Box 50 Newark, Delaware 19714

Received November 5, 1992; accepted May 3, 1993

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


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