2-YEAR TOXICITY AND CARCINOGENICITY STUDY OF ACROLEIN IN RATS

2-YEAR TOXICITY AND CARCINOGENICITY STUDY OF ACROLEIN IN RATS
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DOI:
10.1002/jat.2550120210
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发表时间:
1992-04-01
影响因子:
3.3
通讯作者:
LONG, JE
LONG, JE
中科院分区:
医学4区
文献类型:
--
作者:
PARENT, RA;CARAVELLO, HE;LONG, JE

文献摘要

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将 560 只 Sprague-Dawley 大鼠随机分为一个对照组和三个治疗组(每组每种性别 70 只)。每天给动物灌胃0.0、0.05、0.5和2.5 mg kg-1丙烯醛水溶液(10 ml kg-1)。这些剂量水平是经过 6 周范围探索研究的结果而选择的。每组各性别各 10 只大鼠在 1 岁时处死,其余动物接受 102 周的治疗。进行每日观察,并在治疗3、6、12和18个月后以及终止前立即测量各种临床、血液学和尿液参数。所有动物,无论是被发现死亡还是被处死,都接受尸检并记录绝对和相对器官重量。对所有试验动物的大量组织进行了显微镜检查。治疗组大鼠与对照组在统计学上存在差异的唯一影响是肌酸酐磷酸激酶水平持续下降(这很难解释),以及雄性和雌性早期累积死亡率的持续增加。在治疗的大鼠中,无论是肿瘤性的还是非肿瘤性的,显微病变的发生率没有显着增加。这项研究清楚地表明,通过强饲法接受丙烯醛治疗后,Sprague-Dawley 大鼠缺乏肿瘤反应。
Five-hundred and sixty Sprague-Dawley rats were randomized into one control and three treatment groups (70 of each sex per group). Animals were treated by daily gavage with 0.0, 0.05, 0.5 and 2.5 mg kg-1 acrolein in water (10 ml kg-1). These dosing levels were selected as a result of a 6-week range-finding study. Ten rats of each sex per group were sacrificed at 1 year, and the remainder of the animals were treated for 102 weeks. Daily observations were made, and various clinical, hematological and urine parameters were measured after 3, 6, 12 and 18 months of treatment and immediately prior to termination. All animals, whether found dead or sacrificed, were subject to necropsy and both absolute and relative organ weights were recorded. An extensive array of tissues were examined microscopically for all test animals.The only effects noted for treated rats that were statistically different from controls were consistent depression of creatinine phosphokinase levels, which was difficult to explain, and consistent increases in early cumulative mortalities in both males and females. There was no significantly increased incidence of microscopic lesions in treated rats, whether neoplastic or non-neoplastic. This study clearly demonstrates the lack of neoplastic response in Sprague-Dawley rats as a result of being treated with acrolein by gavage.