Schoeffner D J, Warren D A, Muralidara S, Bruckner J V, Simmons J E
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, USA.
J Toxicol Environ Health A. 1999 Apr 9;56(7):449-62. doi: 10.1080/009841099157917.
The Fischer 344 (F344) rat and the Sprague-Dawley (SD) rat are used commonly to evaluate potential adverse health effects resulting from environmental exposure to chemicals. They are also the most common rat strain/stock used in physiologically based pharmacokinetic (PBPK) modeling. Accurate characterization of model input parameters will improve the usefulness of PBPK model predictions. Thus, organ (i.e., liver, kidneys, spleen, stomach, small intestine, large intestine, heart, lungs, brain) weights and body fat were measured in male SD rats of different ages (4 to 40 wk) and in young (9 to 10 wk) and old (22 to 23 mo) male F344 rats. Comparison of age-matched (9 to 10 wk) F344 and SD rats revealed that the SD rats weighed significantly more and had significantly higher absolute organ weights. These significant differences usually disappeared when organ weights were expressed as a percentage of body weight (relative organ weight). Percent body fat was significantly lower in the age-matched SD rats (6.48%) than in their F344 counterparts (8.67%). As expected, both body weight and absolute organ weights were significantly higher in old than in young F344 rats. However, these differences were largely reversed when relative organ weights were considered, with most relative organ weights significantly lower in the old F344 rats. Body fat as a percentage of body weight was 14.02% in the old F344 rats. When SD rats of various ages were examined, relative organ weights declined between the ages of 4 and 14 wk. In contrast, significant differences in percent body fat were not detected among the SD rats of different ages and weights examined in this study (4 to 40 wk, approximately 75 to approximately 450 g). In summary, values for physiological input parameters are provided that should prove useful in development and implementation of more accurate PBPK models.
Fischer 344（F344）大鼠和Sprague-Dawley（SD）大鼠常用于评估环境化学物质暴露对健康可能产生的不良影响。它们也是生理药代动力学（PBPK）模型中最常用的大鼠品系/种群。准确表征模型输入参数将提高PBPK模型预测的有用性。因此，对不同年龄（4至40周）的雄性SD大鼠以及年轻（9至10周）和老年（22至23月龄）的雄性F344大鼠测量了器官（即肝脏、肾脏、脾脏、胃、小肠、大肠、心脏、肺、脑）重量和体脂。年龄匹配（9至10周）的F344大鼠和SD大鼠的比较显示，SD大鼠体重显著更重，绝对器官重量也显著更高。当器官重量以体重百分比（相对器官重量）表示时，这些显著差异通常会消失。年龄匹配的SD大鼠的体脂百分比（6.48%）显著低于其F344对应组（8.67%）。正如预期的那样，老年F344大鼠的体重和绝对器官重量均显著高于年轻大鼠。然而，当考虑相对器官重量时，这些差异在很大程度上被逆转，老年F344大鼠的大多数相对器官重量显著更低。老年F344大鼠的体脂占体重的百分比为14.02%。检查不同年龄的SD大鼠时，相对器官重量在4至14周龄之间下降。相比之下，在本研究中检查的不同年龄和体重（4至40周，约75至约450克）的SD大鼠中，未检测到体脂百分比的显著差异。总之，提供了生理输入参数的值，这些值应有助于开发和实施更准确的PBPK模型。
