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四周重复剂量经口给予Wistar大鼠木材防腐剂铬酸铜砷酸盐所诱导的病理及临床病理变化

Pathological and Clinical Pathological Changes Induced by Four-week, Repeated-dose, Oral Administration of the Wood Preservative Chromated Copper Arsenate in Wistar Rats.

作者信息

Takahashi Naofumi, Yoshida Toshinori, Kojima Sayuri, Yamaguchi Satoru, Ohtsuka Ryoichi, Takeda Makio, Kosaka Tadashi, Harada Takanori

机构信息

1 The Institute of Environmental Toxicology, Joso-shi, Ibaraki, Japan.

2 Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu-shi, Tokyo, Japan.

出版信息

Toxicol Pathol. 2018 Apr;46(3):312-323. doi: 10.1177/0192623318765392. Epub 2018 Mar 27.

Abstract

Chromated copper arsenate (CCA) is used as a wood preservative worldwide. Exposure to it may adversely affect human health. Some events have increased human exposure to CCA, including the Great East Japan Earthquake, which generated a large amount of lumber debris from CCA-treated woods. We elucidated the toxicity due to daily exposure to CCA over a 4-week period at doses of 0, 8, 40, and 80 mg/kg/day in Wistar Hannover rats. Chromium (Cr) and arsenic (As), but not copper, were detected in the plasma samples of rats treated with various doses of CCA. Males and females showed sedation, and males had poor body weight gain. The clinical pathologies observed in both sexes included hypochromic and microcytic anemia, hepatic and renal dysfunction, and changes in lipid and glucose levels. Histopathologically, males and females showed forestomach hyperkeratosis, mucosal epithelial hyperplasia in the small intestine, rectal goblet cell hypertrophy, and lipofuscin deposition in the proximal renal tubule. Females showed diffuse hepatocellular hypertrophy with increased 8-hydroxydeoxyguanosine levels. These results indicated that oral administration of CCA mainly affected hematopoietic, gastrointestinal, hepatic, and renal systems owing to the toxic effects of As and/or Cr. Major toxic effects were observed in both sexes receiving 40 and 80 mg/kg/day.

摘要

铬酸铜砷酸盐(CCA)在全球范围内用作木材防腐剂。接触它可能会对人体健康产生不利影响。一些事件增加了人类对CCA的接触,包括东日本大地震,该地震产生了大量来自经过CCA处理木材的木材碎片。我们在Wistar Hannover大鼠中,以0、8、40和80毫克/千克/天的剂量,对其进行了为期4周的每日接触CCA的毒性研究。在用不同剂量CCA处理的大鼠血浆样本中检测到了铬(Cr)和砷(As),但未检测到铜。雄性和雌性大鼠均出现镇静作用,且雄性大鼠体重增加不佳。在两性中观察到的临床病理包括低色素性和小细胞性贫血、肝肾功能障碍以及脂质和葡萄糖水平的变化。组织病理学上,雄性和雌性大鼠均出现前胃角化过度、小肠黏膜上皮增生、直肠杯状细胞肥大以及近端肾小管脂褐素沉积。雌性大鼠表现出弥漫性肝细胞肥大,8-羟基脱氧鸟苷水平升高。这些结果表明,口服CCA主要由于As和/或Cr的毒性作用而影响造血、胃肠、肝脏和肾脏系统。在接受40和80毫克/千克/天剂量的两性大鼠中均观察到主要的毒性作用。

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