Oral toxicity and metabolism of diuron (N-3,4-dichlorophenyl)-N[image],N[image]-dimethyrurea) in rats and dogs
Oral toxicity and metabolism of diuron (N-3,4-dichlorophenyl)-N[image],N[image]-dimethyrurea) in rats and dogs
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DOI：
10.1016/s0015-6264(67)83153-5
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发表时间：
1967-01-01
期刊：
影响因子：
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通讯作者：
MAYNARD, E. A.
中科院分区：
文献类型：
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作者：
HODGE, H. C;DOWNS, W. L.;MAYNARD, E. A.
敌草隆（N-（3,4-二氯苯基）-N[image],N[image]-二甲基脲）对大鼠具有相对较低的急性口服毒性。雄性的 LD50（14 天）为 3.4 g/kg。每天 10 次 1 g/kg 的剂量不会致死，但观察到生长抑制。在这两项研究中，组织学都表明红细胞生成增加。豚鼠皮肤刺激和致敏试验结果呈阴性。对大鼠进行的 90 天喂养研究显示，饮食水平为 400 ppm 或更低时，不会出现生长抑制；浓度为 2000 ppm 时，对雄性有轻微影响；男女的浓度均达到 2500 ppm 或更高。在 250 ppm 浓度下，女性以及在 2500 ppm 及以上浓度下，男女都会出现轻微贫血和红细胞生成增强。检测到一种异常的血液色素，被确定为硫血红蛋白，其浓度为 2000 ppm 或更高。对 2 只狗的喂养研究显示，1 个月内 160 ppm 没有任何影响，但从 400 ppm 开始到 2400 ppm 终止的 2 个月喂养增加饮食水平会引起轻微的生长迟缓和中度贫血。对大鼠和狗进行了为期两年的喂养研究，膳食浓度分别为 0、25、125、250 和 2500 ppm。在 25、125 或 250 ppm 浓度下，这两个物种均未发现任何影响，但在 125 或 250 ppm 敌草隆的作用下，一些动物体内出现了微量的异常血液色素，并且在 250 ppm 的敌草隆浓度下，狗的红细胞计数有减少的趋势。在最高浓度 2500 ppm 时，两个物种的主要症状是生长迟缓、轻微贫血、存在异常血色素、脾脏（偶尔在大鼠中）和肝脏（狗）肿大以及红细胞生成增加并伴有脾脏含铁血黄素沉着症。没有观察到任何水平的组织学变化，也没有致癌性的证据。在维持 0 或 125 ppm 敌草隆的大鼠的 3 代繁殖研究中，没有获得不良结果。在大鼠和狗饲喂 25-2500 ppm 敌草隆 9 个月至 2 年的代谢研究中，组织残留水平与敌草隆的膳食摄入量成正比，但没有发生组织储存。通过粪便和尿液排泄。 N-(3,4-二氯苯基)脲是尿液中的主要代谢物；还检测到少量的N-(3,4-二氯苯基)-N[图像]-甲基脲、3-4-二氯苯胺、3,4-二氯苯酚和未变化的敌草隆。 ——作者。
Diuron (N-(3,4-dichlorophenyl)-N[image],N[image]-dimethylurea) has a relatively low order of acute oral toxicity in the rat. The LD50 (14-day) for males was 3.4 g/kg. Ten daily doses of 1 g/kg were not lethal but growth depression was observed. In both studies, increased erythropoiesis was indicated histologically. Skin irritation and sensitization tests in guinea pigs proved negative. Ninety day feeding studies in rats disclosed no growth depression at a dietary level of 400 ppm or less; slight in males at 2000 ppm; marked in both sexes at 2500 ppm and higher. Slight anemia and enhanced erythropoiesis were observed at 250 ppm in females and in both sexes at 2500 ppm and above. An abnormal blood pigment, identified as sulphemoglobin was detected at 2000 ppm and higher. Feeding studies on 2 dogs revealed no effect at 160 ppm for 1 month but slight growth retardation and a moderate anemia were induced by 2-month feeding of increasing dietary levels commencing at 400 ppm and terminating at 2400 ppm. Two yr feeding studies were conducted on rats and dogs at dietary levels of 0, 25, 125, 250 and 2500 ppm. No effect was seen at the 25, 125 or 250 ppm levels in either species with the exception of a trace of abnormal blood pigment in some animals on 125 or 250 ppm diuron and of a trend towards reduced erythrocyte counts in dogs on 250 ppm. At the highest level of 2500 ppm the principal findings in both species were growth retardation, slight anemia, presence of abnormal blood pigment, enlargement of spleen (occasionally in rats) and of liver (dogs) and increased erythropoiesis with splenic hemosiderosis. No histological changes were seen at any level and there was no evidence of carcino-genicity. In a 3-generation reproduction study in rats maintained on 0 or 125 ppm diuron, no untoward findings were obtained. In metabolic studies in rats and dogs fed 25-2500 ppm diuron for 9 months-2 yr, tissue residue levels were proportional to the dietary intake of diuron but no tissue storage occurred. Excretion occurred in both feces and urine. N-(3,4-Dichlorophenyl)urea was the predominant metabolite in the urine; small amounts of N-(3,4-dichlorophenyl)-N[image]-methylurea, 3-4-dichloraniline, 3,4-dichlorophenol and unchanged diuron were also detected. - -Authors.