Schlenker R A
Biological and Medical Research Division, Argonne National Laboratory, IL 60439.
Health Phys. 1988 Apr;54(4):383-96. doi: 10.1097/00004032-198804000-00001.
Two methods of interspecies extrapolation, one based on a correlation of skeletal 212Pb/224Ra with body weight, the other based on the mechanistic relationship between skeletal 212Pb/224Ra and reciprocal bone surface-to-volume ratio, lead to the conclusion that the retention of 212Pb in the adult human skeleton is approximately complete a few days after injection. The correlation-based method gives most probable values for 212Pb/224Ra of 1.0 and 1.1 at 2 d and 7 d after injection, compared with values of 1.05 and 1.27 expected at these same times if the retention of 212Pb were complete from the time of injection and if no 212Pb were in the injection solution. The range of values corresponding to one geometric standard error on either side of the most probable value is 0.87 to 1.21 at 2 d post-injection. With the method based on the reciprocal bone surface-to-volume ratio, the best estimate of 212Pb/224Ra at 2 d after injection is 0.88, equal to the value observed in young adult beagles. An alternative interpretation of the results of this latter method leads to the conclusion that retention is complete, with 212Pb/224Ra equal to 1.0 for a 212Pb-free injection solution and 1.1 for a solution containing 212Pb in secular equilibrium with 224Ra. This work, which uses 224Ra daughter product retention data from mice, rats and dogs following 224Ra injection, provides a scientific foundation for retention assumptions made in the calculation of mean skeletal dose for adult humans. There now appear to be few uncertainties in these latter dose values, stemming from inaccurate retention assumptions; but substantial uncertainties remain in the mean skeletal dose values for juveniles and in the endosteal tissue doses regardless of age. Risk coefficients such as those in the BEIR III report that give the lifetime probability of bone tumor induction per unit mean skeletal dose may be correct for adult humans but are probably too low for juveniles due to overestimation of juvenile dose. BEIR III risk coefficients that give tumor induction probability per unit endosteal tissue dose may be substantially too small, regardless of age, due to overestimation of endosteal dose.
两种种间外推方法，一种基于骨骼中212Pb/224Ra与体重的相关性，另一种基于骨骼中212Pb/224Ra与骨表面积与体积比的倒数之间的机制关系，得出的结论是，注射后几天内，212Pb在成年人体骨骼中的滞留基本完成。基于相关性的方法得出，注射后2天和7天212Pb/224Ra的最可能值分别为1.0和1.1，而如果212Pb从注射时起就完全滞留且注射溶液中不含212Pb，那么在相同时间预期的值分别为1.05和1.27。注射后2天，最可能值两侧对应一个几何标准误差的取值范围是0.87至1.21。对于基于骨表面积与体积比倒数的方法，注射后2天212Pb/224Ra的最佳估计值为0.88，与年轻成年比格犬中观察到的值相等。对后一种方法的结果的另一种解释得出的结论是，滞留是完全的，对于不含212Pb的注射溶液，212Pb/224Ra等于1.0，对于含有与224Ra处于长期平衡状态的212Pb的溶液，212Pb/224Ra等于1.1。这项工作利用了224Ra注射后小鼠、大鼠和犬的224Ra子体产物滞留数据，为计算成年人体平均骨骼剂量时所采用的滞留假设提供了科学依据。目前，这些后期剂量值因滞留假设不准确而产生的不确定性似乎很小；但青少年的平均骨骼剂量值以及无论年龄大小的骨内膜组织剂量值仍存在很大的不确定性。诸如BEIR III报告中的那些风险系数，即给出每单位平均骨骼剂量诱发骨肿瘤的终生概率，对于成年人可能是正确的，但由于高估了青少年剂量，对于青少年可能过低。BEIR III中给出每单位骨内膜组织剂量诱发肿瘤概率的风险系数，无论年龄大小，可能都因高估了骨内膜剂量而大幅偏小。
