Conestoga-Rovers & Associates, Rochester, NY 14650-2136, USA.
J Toxicol Environ Health A. 2012;75(24):1484-516. doi: 10.1080/15287394.2012.722520.
The Fischer 344 (F344) rat has been the standard rat strain used in toxicology studies conducted by the National Cancer Institute (NCI) and the National Toxicology Program (NTP). However, the numerous reports published to date on growth, survival, and tumor incidence have not included an overall compilation of organ weight data. Notably, dose-related organ weight effects are endpoints used by regulatory agencies to develop toxicity reference values (TRVs) for use in human health risk assessments. In addition, physiologically-based pharmacokinetic (PBPK) models, which utilize relative organ weights, are increasingly being used to develop TRVs. Because a compilation of organ weights for F344 rats could prove beneficial for TRV development and PBPK modeling, all available absolute and relative organ weight data for untreated control F344 rats were collected from NCI/NTP feed, drinking-water, and inhalation studies in order to develop age-specific distributions. Results showed that organ weights were collected more frequently at 2-wk (59 studies), 3-mo (148 studies), and 15-mo (38 studies) intervals than at other intervals and more frequently from feeding and inhalation than from 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. Findings showed age-related increases in absolute weights and decreases in relative weights for brain, liver, right kidney, lung, heart, thyroid, and right testis. The results suggest a general variability trend in absolute organ weights of brain < right testis < heart < right kidney < liver < lung < thymus < thyroid.
费希尔 344(F344)大鼠一直是美国国立癌症研究所(NCI)和国家毒理学计划(NTP)进行毒理学研究的标准大鼠品系。然而,迄今为止发表的大量关于生长、存活和肿瘤发生率的报告并未包括器官重量数据的综合汇编。值得注意的是,剂量相关的器官重量效应是监管机构用来制定毒性参考值(TRV)的终点,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。由于 F344 大鼠的器官重量汇编可能有助于 TRV 的开发和 PBPK 模型的建立,因此从 NCI/NTP 饲料、饮用水和吸入研究中收集了所有未处理对照 F344 大鼠的可用绝对和相对器官重量数据,以制定特定年龄的分布。结果表明,器官重量在 2 周(59 项研究)、3 个月(148 项研究)和 15 个月(38 项研究)的间隔时间内比其他间隔时间更频繁地收集,并且从喂养和吸入研究中比从饮用水研究中更频繁地收集。肝脏、右肾、肺、心脏、胸腺和大脑的重量最常被收集。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。研究结果表明,大脑、肝脏、右肾、肺、心脏、甲状腺和右睾丸的绝对重量随着年龄的增长而增加,相对重量随着年龄的增长而降低。研究结果表明,大脑的绝对器官重量具有一般的变异性趋势<右侧睾丸<心脏<右侧肾脏<肝脏<肺<胸腺<甲状腺。