California’s Division of Occupational Safety and Health has initiated a process to update its standards for exposure to lead in workplaces. In support of this effort, the state’s Office of Environmental Health Hazard Assessment evaluated the age-specific, bio-kinetic model of lead metabolism in humans, originally published by R.W. Leggett in 1993. This model was ultimately chosen for its physiologic realism and practicality in characterizing the relationship between air lead concentrations and blood lead levels in chronically exposed worker and its practicality in making necessary adjustments. Leggett’s original model systematically under-predicts bone and blood levels in workers such that several adjustments to the parameters are needed to improve predictions for occupational exposure scenarios. The aim of this work is to incorporate new information about the bio-kinetics of lead in workers and to adjust the Leggett model to improve its predictions.

The Leggett model was evaluated by comparing its predictions with information on lead concentrations in bone, blood, and urine from workers and other chronically exposed adults. Key model parameters were identified based upon a review of the relevant exposure assessment and modeling literature. Adjustments to the model parameters were made based on empirical evidence. They included reducing the level of lead in blood (BLL) where the rate of decrease in red blood cell binding begins and ends, lead accumulation rate in cortical bone, the rate of lead elimination in trabecular bone, and rate of lead transferred from diffusible plasma to urine. Regression methods and visual inspection of plotted data were used to assess the effect of adjustments on model predictions. When compared with the original, the adjusted Leggett model more accurately predicted lead concentrations observed in active and retired workers. Also, the adjusted Leggett model required less lead uptake to reach the same BLLs for BLLs less than 25 µg/dL and more time for BLLs to decline than the original Leggett model. These findings are important for defining an adequately protective occupational standard for lead exposure.

加利福尼亚州职业安全与健康部已启动一项流程，以更新其工作场所铅暴露标准。为了支持这项工作，该州环境健康危害评估办公室评估了人类铅代谢的年龄特异性生物动力学模型，该模型最初由 RW Leggett 于 1993 年发表。该模型最终因其生理现实性和实用性而被选中。描述长期暴露工人的空气铅浓度和血铅水平之间的关系及其在进行必要调整时的实用性。Leggett 的原始模型系统地低估了工人的骨骼和血液水平，因此需要对参数进行多次调整以改进对职业暴露情景的预测。

Leggett 模型通过将其预测与工人和其他长期接触成年人的骨骼、血液和尿液中的铅浓度信息进行比较来评估。根据对相关暴露评估和建模文献的回顾，确定了关键模型参数。根据经验证据对模型参数进行了调整。它们包括降低血铅 (BLL) 的水平，其中红细胞结合开始和结束的下降速度、皮质骨中的铅积累率、骨小梁中铅的消除率以及从可扩散血浆中转移的铅率到尿液。回归方法和绘图数据的视觉检查用于评估调整对模型预测的影响。与原版相比，调整后的 Leggett 模型更准确地预测了在职和退休工人中观察到的铅浓度。此外，对于低于 25 µg/dL 的 BLL，调整后的 Leggett 模型需要更少的铅吸收才能达到相同的 BLL，并且与原始 Leggett 模型相比，BLL 下降的时间更长。这些发现对于定义一个充分保护铅暴露的职业标准非常重要。