Bioassay of N,N'-diethylthiourea for possible carcinogenicity.

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Abstract

A bioassay for the possible carcinogenicity of N,N'-diethylthiourea was conducted using Fischer 344 rats and B6C3F1 mice. N,N'-Diethylthiourea was administered in the feed, at either of two concentrations, to groups of 50 males and 50 females of each species. Twenty animals of each sex and species, except for 19 male mice, were placed on test as controls. The high and low dietary concentrations of N,N'-diethylthiourea were, respectively, 250 and 125 ppm for rats and 500 and 250 ppm for mice. The compound was administered in the diet for 103 weeks, followed by an observation period of 1 week for all dosed groups. There were no significant positive associations between the dosages of N,N'-diethylthiourea administered and mortality in rats or mice of either sex. Adequate numbers of animals in all dose groups survived sufficiently long to be at risk from late-developing tumors. Compound-related mean body weight depression was apparent among dosed male and female mice when compared to their respective controls,indicating that the concentrations of N,N'-diethylthiourea administered to mice may have approximated the maximum tolerated dosages. There were statistically significant elevated incidences of follicular-cell carcinomas of the thyroid in high dose male rats. In addition, there were statistically significant elevated incidences of a combination of thyroid follicular-cell carcinomas and follicular-cell adenomas in high dose male and female rats. Under the conditions of this bioassay, N,N'-diethylthiourea was carcinogenic to Fischer 344 rats, causing follicular-cell carcinomas of the thyroid in males and follicular-cell neoplasms of the thyroid in females. There was no evidence for the carcinogenicity of the compound in B6C3F1 mice.

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N,N'-二乙基硫脲可能致癌性的生物测定。
采用Fischer 344大鼠和B6C3F1小鼠进行了N,N'-二乙基硫脲可能致癌性的生物测定。将N,N'-二乙基硫脲以两种浓度中的任意一种添加到饲料中,每组50只雄性和50只雌性。除19只雄性小鼠外,各性别、各物种各20只作为对照。大鼠饲粮N,N′-二乙基硫脲高、低浓度分别为250、125 ppm,小鼠饲粮N,N′-二乙基硫脲500、250 ppm。给药103周,各给药组观察1周。N,N'-二乙基硫脲给药剂量与大鼠或小鼠的死亡率无显著正相关。所有剂量组中都有足够数量的动物存活足够长的时间,从而有患晚期肿瘤的风险。与对照组相比,给药的雄性和雌性小鼠的平均体重明显下降,表明给药小鼠的N,N'-二乙基硫脲浓度可能接近最大耐受剂量。高剂量雄性大鼠甲状腺滤泡细胞癌的发生率有统计学意义。此外,在高剂量雄性和雌性大鼠中,甲状腺滤泡细胞癌和滤泡细胞腺瘤合并的发病率有统计学意义的显著升高。在本实验条件下,N,N'-二乙基硫脲对Fischer 344大鼠具有致癌性,可引起雄性甲状腺滤泡细胞癌和雌性甲状腺滤泡细胞瘤。没有证据表明该化合物在B6C3F1小鼠中具有致癌性。
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