Littlefield N A, Gaylor D W
J Toxicol Environ Health. 1985;15(5):545-50. doi: 10.1080/15287398509530684.
One element of the ED01 Study contained a group of animals that were dosed with 2-acetylaminofluorene for 9, 12, 15, 18, or 24 mo and then sacrificed at 18 or 24 mo. This provided data to compare the relative effects on carcinogenicity of dose rate versus total dose. The prevalence of liver and bladder tumors were used as the comparison. Animals receiving similar total doses but over a different length of time (different dose rates) were compared at the 18- and 24-mo sacrifices. When the total doses were similar, the higher dose rates for shorter time periods induced a higher prevalence of tumors. Results were more consistent for bladder tumors than for liver tumors, although the same trends were noted for both endpoints. Those groups dosed at higher rates but for fewer months had a generally higher prevalence than those receiving similar total doses but at lower rates for more months. This data from the ED01 Study illustrates the importance of experimental design, dosing regime, length of study time, and age of the animals at time of dosing in respect of calculation of risk.
ED01研究的一个部分包含一组动物，这些动物用2-乙酰氨基芴给药9、12、15、18或24个月，然后在18或24个月时处死。这提供了数据以比较剂量率与总剂量对致癌性的相对影响。以肝脏和膀胱肿瘤的发生率作为比较指标。在18个月和24个月处死时，对接受相似总剂量但给药时间长度不同（不同剂量率）的动物进行比较。当总剂量相似时，较短时间内较高的剂量率会导致肿瘤发生率更高。膀胱肿瘤的结果比肝脏肿瘤更一致，尽管两个终点都观察到相同的趋势。那些以较高剂量率给药但给药月数较少的组，其发生率通常高于接受相似总剂量但以较低剂量率给药且给药月数较多的组。ED01研究的这些数据说明了实验设计、给药方案、研究时间长度以及给药时动物年龄在风险计算方面的重要性。
