Hurtt M E, Mebus C A, Bogdanffy M S
Haskell Laboratory for Toxicology and Industrial Medicine, E. I. duPont de Nemours and Company, Newark, Delaware 19714.
Fundam Appl Toxicol. 1993 Aug;21(2):253-5. doi: 10.1006/faat.1993.1096.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
苯菌灵[甲基1-(丁基氨基甲酰基)-2-苯并咪唑氨基甲酸酯,化学物质登记号17804-35-2]是一种广泛使用的农用杀菌剂。此前,在吸入接触浓度为50和200毫克/立方米的苯菌灵45天后,出现了嗅觉上皮损伤。本研究作为一项两代繁殖研究的剂量探索研究的一部分,旨在确定先前报道的对鼻黏膜的影响是全身毒性的结果还是归因于吸入暴露途径。将10组7周龄雄性Crl:CD BR大鼠分为四组,分别喂食含0、5000、10000或15000 ppm苯菌灵的饲料,持续32天。每周以及在研究的最后一天测定个体体重和食物摄入量。在试验32天后,通过戊巴比妥麻醉和放血对大鼠实施安乐死,并检查大体变化。对鼻腔进行病理检查。在两个最高剂量水平下,治疗的第一周以及整个试验期(第0 - 32天),平均体重增加在统计学上显著降低。在试验第0 - 7天期间,两个最高剂量组的食物摄入量也显著减少。此外,与对照组相比,15000 ppm剂量组在第7 - 14天期间以及两个最高剂量组在第21 - 28天和第28 - 32天期间的食物摄入量在统计学上显著降低。在任何对照组或苯菌灵处理组的大鼠鼻上皮中均未发现组织病理学损伤。(摘要截短至250字)