Conestoga-Rovers & Associates, Rochester, New York 14650-2136, USA.
J Toxicol Environ Health A. 2012;75(2):76-99. doi: 10.1080/15287394.2011.625548.
The B6C3F1 mouse is the standard mouse strain used in toxicology studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). While numerous reports have been published on growth, survival, and tumor incidence, no overall compilation of organ weight data is available. Importantly, organ weight change is an endpoint used by regulatory agencies to develop toxicity reference values (TRVs) for use in human health risk assessments. Furthermore, physiologically based pharmacokinetic (PBPK) models, which utilize relative organ weights, are increasingly being used to develop TRVs. Therefore, all available absolute and relative organ weight data for untreated control B6C3F1 mice were collected from NCI/NTP studies in order to develop age-specific distributions. Results show that organ weights were collected more frequently in NCI/NTP studies at 2-wk (60 studies), 3-mo (147 studies), and 15-mo (40 studies) intervals than at other intervals, and more frequently from feeding and inhalation than drinking water studies. Liver, right kidney, lung, heart, thymus, and brain weights were most frequently collected. From the collected data, the mean and standard deviation for absolute and relative organ weights were calculated. Results show age-related increases in absolute liver, right kidney, lung, and heart weights and relatively stable brain and right testis weights. The results suggest a general variability trend in absolute organ weights of brain < right testis < right kidney < heart < liver < lung < spleen < thymus. This report describes the results of this effort.
B6C3F1 小鼠是美国国立癌症研究所(NCI)和国家毒理学计划(NTP)进行毒理学研究中使用的标准小鼠品系。虽然已经发表了许多关于生长、存活和肿瘤发生率的报告,但目前尚无器官重量数据的综合汇编。重要的是,器官重量变化是监管机构用来制定毒性参考值(TRV)的终点,以用于人类健康风险评估。此外,越来越多地使用基于生理学的药代动力学(PBPK)模型来开发 TRV,该模型利用相对器官重量。因此,为了制定特定年龄的分布情况,从 NCI/NTP 的研究中收集了所有未处理对照 B6C3F1 小鼠的可用绝对和相对器官重量数据。结果表明,与其他间隔时间相比,NCI/NTP 研究中更频繁地在 2 周(60 项研究)、3 个月(147 项研究)和 15 个月(40 项研究)的间隔时间收集器官重量,且更频繁地从饲料和吸入研究中收集,而不是从饮水研究中收集。肝脏、右肾、肺、心脏、胸腺和大脑的重量是最常收集的。从收集的数据中,计算了绝对和相对器官重量的平均值和标准差。结果表明,与年龄相关的绝对肝脏、右肾、肺和心脏重量增加,相对稳定的大脑和右睾丸重量。结果表明,大脑的绝对器官重量具有一般的变异性趋势,其变异性依次为右睾丸<右肾<心脏<肝脏<肺<脾脏<胸腺。本报告描述了这一工作的结果。