Caudill S P, Pirkle J L, Michalek J E
Division of Environmental Health Laboratory Sciences, Centers for Disease Control, Atlanta, GA 30333.
J Expo Anal Environ Epidemiol. 1992 Oct-Dec;2(4):463-76.
Direct computation of the observed biological half-life of a toxic compound in a person can lead to an undefined estimate when subsequent concentration measurements are greater than or equal to previous measurements. The likelihood of such an occurrence depends upon the length of time between measurements and the variance (intra-subject biological and inter-sample analytical) associated with the measurements. If the compound is lipophilic the subject's percentage of body fat at the times of measurement can also affect this likelihood. We present formulas for computing a model-predicted half-life estimate and its variance; and we derive expressions for the effect of sample size, measurement error, time between measurements, and any relevant covariates on the variability in model-predicted half-life estimates. We also use statistical modeling to estimate the probability of obtaining an undefined half-life estimate and to compute the expected number of undefined half-life estimates for a sample from a study population. Finally, we illustrate our methods using data from a study of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure among 36 members of Operation Ranch Hand, the Air Force unit responsible for the aerial spraying of Agent Orange in Vietnam.
当后续浓度测量值大于或等于先前测量值时，直接计算人体内有毒化合物的观察到的生物半衰期可能会得出无定义的估计值。这种情况发生的可能性取决于测量之间的时间长度以及与测量相关的方差（个体内部生物方差和样本间分析方差）。如果该化合物是亲脂性的，测量时受试者的体脂百分比也会影响这种可能性。我们给出了计算模型预测半衰期估计值及其方差的公式；并推导了样本量、测量误差、测量间隔时间以及任何相关协变量对模型预测半衰期估计值变异性的影响表达式。我们还使用统计建模来估计获得无定义半衰期估计值的概率，并计算来自研究人群的样本中无定义半衰期估计值的预期数量。最后，我们使用来自“牧场工行动”中36名成员的研究数据来说明我们的方法，“牧场工行动”是负责在越南空中喷洒橙剂的空军部队，该研究涉及2,3,7,8-四氯二苯并对二恶英（TCDD）暴露情况。
