A 90-day inhalation toxicity study with benomyl in rats.
Benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate, CAS Registry No. 17804-35-2] is a fungicide and the possibility for inhalation exposure exists for field workers. To assess the toxicity of benomyl, groups of 20 male and 20 female CD rats were exposed nose-only 6 hr a day, 5 days a week, to concentrations of 0, 10, 50 or 200 mg/m3 of a benomyl atmosphere. At the midpoint (approximately 45 days on test) and at the end of the exposure period, blood and urine samples for clinical evaluation were collected from 10 rats/group/sex, and these animals were sacrificed for pathological examination. Similar evaluations were performed on all remaining rats at the end of the 90-day test period. After approximately 45 days on test, compound-related degeneration of the olfactory epithelium was observed in all males and in 8 of 10 female rats exposed to 200 mg/m3 benomyl. Two male rats exposed to 50 mg/m3 had similar, although less severe, areas of olfactory epithelial degeneration. After approximately 90 days of exposure, the remaining 10 rats/group/sex were sacrificed and examined. Of these rats, all of the males and females exposed to 200 mg/m3 had olfactory degeneration, along with 3 males exposed to 50 mg/m3 of benomyl. No other observed lesions were interpreted to have been caused by the benomyl exposure. In addition, male rats exposed to 200 mg/m3 benomyl had depressed mean body weights compared to controls and this finding correlated with a reduction in food consumption. Based on pathological observations, 10 mg/m3 represents the no-observable-effect level (NOEL) for the male rats, and 50 mg/m3 is the NOEL for the female rats.
Warheit
D B
DB
E. I. du Pont de Nemours and Company, Inc., Newark, Delaware 19714.
Kelly
D P
DP
Carakostas
M C
MC
Singer
A W
AW
D000280:Administration, Inhalation; D000818:Animals; D001273:Atmosphere Exposure Chambers; D001542:Benomyl / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002219:Carbamates / Q000633:toxicity*; D004435:Eating / Q000187:drug effects; D005123:Eye / Q000033:anatomy & histology; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012137:Respiratory System / Q000033:anatomy & histology; D012737:Sex Factors
D002219:Carbamates; D001542:Benomyl