Metabolic rate parameters estimation using in vitro data is necessary due to numbers of chemicals for which data are needed, trend towards minimizing laboratory animal use, and limited opportunity to collect data in human subjects. We evaluated how well metabolic rate parameters derived from in vitro data predict overall in vivo metabolism for a set of environmental chemicals for which well validated and established methods exist. We compared values of VmaxC derived from in vivo vapor uptake studies with estimates of VmaxC scaled up from in vitro hepatic microsomal metabolism studies for VOCs for which data were available in male F344 rats. For 6 of 7 VOCs, differences between the in vivo and scaled up in vitro VmaxC estimates were less than 2.6-fold. For bromodichloromethane (BDCM), the in vivo derived VmaxC was approximately 4.4-fold higher than the in vitro derived and scaled up VmaxC. The more rapid rate of BDCM metabolism estimated based in vivo studies suggests other factors such as extrahepatic metabolism, binding or other non-specific losses making a significant contribution to overall clearance. Systematic and reliable utilization of scaled up in vitro biotransformation rate parameters in PBPK models will require development of methods to predict cases in which extrahepatic metabolism and binding as well as other factors are likely to be significant contributors.

由于需要数据的化学品数量、尽量减少实验室动物使用的趋势以及在人类受试者中收集数据的机会有限，使用体外数据估计代谢率参数是必要的。我们评估了来自体外数据的代谢率参数如何预测一组环境化学物质的整体体内代谢，这些环境化学物质存在经过充分验证和建立的方法。我们比较了来自体内蒸气吸收研究的 VmaxC 值与从体外肝微粒体代谢研究中按比例放大的 VmaxC 估计值，这些研究的数据可用于雄性 F344 大鼠。对于 7 种 VOC 中的 6 种，体内并且按比例放大的体外VmaxC 估计值不到 2.6 倍。对于溴二氯甲烷 ( BDCM )，体内衍生的 VmaxC 比体外衍生和放大的 VmaxC高约 4.4 倍。基于体内研究估计的 BDCM 代谢的更快速率表明其他因素，如肝外代谢、结合或其他非特异性损失，对整体清除做出了重大贡献。在 PBPK 模型中系统和可靠地利用放大的体外生物转化率参数将需要开发方法来预测肝外代谢和结合以及其他因素可能是重要贡献者的情况。