硫代tepa可能致癌性的生物测定。

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引用次数: 0

摘要

通过对Sprague-Dawley大鼠和B6C3F1小鼠进行腹腔注射,对硫代tepa进行了可能致癌性的生物测定。每组31-39只雄性大鼠按三种剂量(0.7、1.4或2.8 mg/kg体重)中的一种,每周三次给药硫代tepa,最多52周,然后观察额外的时间。最长研究时间(给药和观察)为86周。低剂量组在中高剂量组69周后开始,因为高剂量组观察到高死亡率。配对对照组为每性别10只未治疗大鼠和10只对照大鼠。合并对照组也被使用。存活对照大鼠在82 ~ 87周处死;在81周或82周时杀死存活的老鼠。每组35只雌雄小鼠按1.15或2.3 mg/kg体重两种剂量中的一种给予硫代tepa,每周三次,最多持续52周,然后观察最多34周。配对的对照组包括各组15只未经治疗的小鼠和15只不同性别的对照小鼠。还使用了合并对照。存活的对照组和给药小鼠在86周或87周时被杀死。硫代tepa对大鼠和小鼠都有毒性,导致中、高剂量大鼠和高剂量小鼠的平均体重增加减少和早期死亡。由于早期死亡,统计分析仅基于经过时间调整的肿瘤发病率。由于所有高剂量雄性和雌性大鼠都在21周时死亡,因此仅对低剂量和中剂量的动物进行了组织的显微评估。在大鼠中,低剂量组(P=0.020)和中剂量组(P=0.001)中,雄性大鼠造血系统合并肿瘤(淋巴瘤、淋巴细胞白血病或粒细胞白血病)的发生率均显著高于对照组(混合对照组0/29,低剂量组6/34;混合对照组0/30,中剂量6/16)。低剂量组和中剂量组雄性大鼠皮肤或耳道鳞状细胞癌的发生率均显著高于对照组(P=0.009)。合并对照组0/30,中剂量组3/13)和中剂量组女性(P
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bioassay of thio-TEPA for possible carcinogenicity.

A bioassay of thio-TEPA for possible carcinogenicity was conducted by administering the test chemical by intraperitoneal injection to Sprague-Dawley rats and B6C3F1 mice. Groups of 31-39 rats of each sex were administered thio-TEPA in phosphate-buffered saline at one of three doses, either 0.7, 1.4, or 2.8 mg/kg body weight, three times per week for a maximum of 52 weeks, then observed for additional periods of time. The maximum time on study (administration of chemical and observation) was 86 weeks. The groups at the low dose were started 69 weeks after those at the mid and high doses, because of high mortalities observed in the groups at the higher doses. Matched controls consisted of groups of 10 untreated rats and 10 vehicle-control rats of each sex. Pooled-control groups also were used. Surviving control rats were killed at 82-87 weeks; surviving dosed rats were killed at 81 or 82 weeks. Groups of 35 mice of each sex were administered thio-TEPA at one of two doses, either 1.15 or 2.3 mg/kg body weight, three times per week for a maximum of 52 weeks, then observed for a maximum additional period of 34 weeks. Matched controls consisted of groups of 15 untreated mice and 15 vehicle-control mice of each sex. Pooled controls also were used. Surviving control and dosed mice were killed at 86 or 87 weeks. Thio-TEPA was toxic to both rats and mice, causing decreased mean body weight gains and early deaths in the mid- and high-dose rats and in the high-dose mice. Because of the early deaths, statistical analyses were based only on time-adjusted incidences of tumors. Since all high-dose male and female rats had died by 21 weeks, microscopic evaluation of tissues was performed only on the low- and mid-dose animals. In rats, the incidence of combined neoplasms of the hematopoietic system (lymphoma, lymphocytic leukemia, or granulocytic leukemia) was significant in the males in both the low-dose (P=0.020) and mid-dose (P=0.001) groups, using pooled controls (pooled controls 0/29, low-dose 6/34; pooled controls 0/30, mid-dose 6/16). Squamous-cell carcinoma of the skin or ear canal occurred at a significant incidence in the male rats in both the low-dose (P=0.009) and mid-dose (P=0.023) groups, using pooled controls (pooled controls 0/29, low-dose 7/33; pooled controls 0/30, mid-dose 3/13) and in the mid-dose females (P<0.001), using pooled controls (pooled controls 0/28, mid-dose 8/21); in addition, two low-dose females had such tumors, with none occurring in the corresponding low-dose controls. The incidence of adenocarcinoma of the uterus was significant in the mid-dose female rats (P=0.001), using pooled controls (pooled controls 0/28, mid-dose 7/21); in addition, two low-dose females had adenocarcinoma of the uterus, with no such tumor occurring in the corresponding low-dose controls. In rats, neuroepitheliomas (neuroblastomas) or nasal carcinomas occurred in three low-dose males, two low-dose females, and two mid-dose females. Although these are not statistically significant incidences, these tumors did not occur among control animals and no such tumors have occurred in 380 Sprague-Dawley control rats of each sex in other bioassays at the same laboratory. Thus, they may be associated with administration of the chemical. In the high-dose groups of both male and female mice, but not in the low-dose groups, the incidences of lymphoma or lymphocytic leukemia were significantly higher (P<0.001) for each sex than those of either the vehicle or pooled controls (males: vehicle controls 1/8, pooled controls 1/18, low-dose 2/24, high-dose 26/28; females: vehicle controls 0/14, pooled controls 0/29, low-dose 5/26, high-dose 32/32). In the low-dose male mice squamous-cell carcinoma was found in the skin of seven animals, in the preputial glands of six animals, and in the ear canal of two animals. A carcinoma of the preputial gland was also found in a high-dose male. When the incidences of the tumors at the different sites were combined, the incidence in the low-dose group was statistically significant using either the vehicle (P=0.004) or the pooled (P<0.001) controls (vehicle controls 0/8, pooled controls 0/18, low-dose 14/24, high-dose 1/2). It is concluded that under the conditions of this bioassay, thio-TEPA was carcinogenic in both Sprague-Dawley rats and B6C3F1 mice. In the rats, the chemical induced squamous-cell carcinoma of the skin or ear canal in both males and females, and hematopoietic neoplasms in the males; in the mice, it induced lymphoma or lymphocytic leukemia in both sexes and squamous-cell carcinoma in the skin and associated glands of males.

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