Syracuse Environmental Research Associates, Inc., 5100 Highbridge Street, 42C Fayetteville, New York, NY 13066-0950, USA.
Environ Toxicol Pharmacol. 2004 Mar;16(1-2):73-91. doi: 10.1016/j.etap.2003.09.003.
A PBPK model for 2,4-D was developed that involves flow-limited pH trapping modified to consider tissue binding, binding to plasma, and high-dose inhibition of urinary excretion. The PBPK model provides reasonable estimates of the kinetics of 2,4-D in rats as well as in humans, providing a common metric for expressing risk. The risk characterization for 2,4-D based on the PBPK model is consistent with that based on standard risk assessment methods, except that the apparent variability in the risk characterization is reduced. The model demonstrates that non-linear pharmacokinetics and inhibition of urinary excretion would not be expected in occupational exposures. This case study suggests that preliminary PBPK models could be developed for numerous pesticides based on commonly available data. If properly validated with well-designed worker exposure studies, such models may be useful in more complete assessments of risks to workers as well as members of the general public.
建立了 2,4-D 的 PBPK 模型，该模型涉及到有限流动 pH 捕获的改进，以考虑组织结合、与血浆结合以及大剂量抑制尿排泄。该 PBPK 模型为大鼠和人类的 2,4-D 动力学提供了合理的估计，为表达风险提供了共同的衡量标准。基于 PBPK 模型的 2,4-D 风险特征与基于标准风险评估方法的风险特征一致，只是风险特征的明显变异性降低了。该模型表明，在职业暴露中不会出现非线性药代动力学和尿排泄抑制。本案例研究表明，可以基于常用数据为许多农药建立初步的 PBPK 模型。如果通过精心设计的工人暴露研究进行适当验证，这些模型可能有助于更全面地评估工人和普通公众的风险。
