Gaylor D W, Chen J J
Risk Anal. 1986 Sep;6(3):283-90. doi: 10.1111/j.1539-6924.1986.tb00220.x.
Extensive carcinogenesis data compiled by Gold et al. for 770 compounds tested in 2944 chronic bioassays in animals provided an opportunity to compare cancer rates across animal species for a wide variety of compounds administered by various routes of exposure. The comparisons in this paper are restricted to the most frequently tested species: rats, mice, and hamsters. When sufficient experimental data exist, Gold et al. provide estimates of the TD50 (the chronic dose rate expressed in mg/kg body weight/day which halves the actuarially adjusted percentage of tumor-free animals at the end of a standard lifetime experiment). Since the current practice generally is to base risk assessments upon the data set producing the highest cancer risk, the ratio of the minimum TD50's provides a measure of the relative potency between two species for each compound administered to animals by the same route. The geometric means of the ratios of minimum TD50's for rats:mice are 1/2.2 and 1/1.3 for diet and gavage, respectively. A mean ratio for rats: mice of 1/1.48 is obtained for compounds administered in the diet when the tumor site is the liver for both species. In general the minimum TD50 is lowest for the rat and highest for the hamster. Although limited data are available for inhalation studies, this route of administration resulted in the poorest agreement between rats and mice. In general, comparisons of minimum TD50's across the three rodent species are generally within a factor of 100 for a wide variety of compounds.
戈尔德等人针对在2944项动物慢性生物测定中测试的770种化合物汇编的大量致癌作用数据,提供了一个机会,可比较通过各种暴露途径给予的多种化合物在不同动物物种中的癌症发生率。本文中的比较仅限于测试最频繁的物种:大鼠、小鼠和仓鼠。当有足够的实验数据时,戈尔德等人会提供TD50的估计值(以毫克/千克体重/天表示的慢性剂量率,在标准寿命实验结束时,该剂量率会使经精算调整的无肿瘤动物百分比减半)。由于目前的做法通常是根据产生最高癌症风险的数据集进行风险评估,因此最小TD50的比值可衡量通过相同途径给予动物的每种化合物在两个物种之间的相对效力。大鼠与小鼠的最小TD50比值的几何平均值,经口摄入和灌胃分别为1/2.2和1/1.3。当肿瘤部位为两个物种的肝脏时,经口给予化合物的大鼠与小鼠的平均比值为1/1.48。一般来说,大鼠的最小TD50最低,仓鼠的最高。尽管吸入研究的数据有限,但这种给药途径导致大鼠和小鼠之间的一致性最差。一般而言,对于多种化合物,三种啮齿动物物种的最小TD50比较通常在100倍以内。