Mann S, Droz P O, Vahter M
Institute of Occupational Health Sciences, Lausanne University, Switzerland.
Toxicol Appl Pharmacol. 1996 Oct;140(2):471-86. doi: 10.1006/taap.1996.0244.
A physiologically based pharmacokinetic model (PB-PK) for inorganic arsenic exposure in humans has been developed. This model is an extension of a PB-PK model for hamsters and rabbits, with adjustments for body weight, metabolic rates, and absorption rates. It describes the absorption, distribution, metabolism, and excretion of arsenate, arsenite (As(III)), methyl arsonate, and dimethyl arsinate, the four major metabolites of inorganic arsenic. The routes of intake considered are inhalation of arsenic dust and fumes and oral intake of arsenic via drinking water and food. The PB-PK model for the oral exposure route is validated using data on urinary excretion after repeated oral exposure to As(III) as well as after exposure to inorganic As via drinking water. Absorption by inhalation is validated using data on urinary excretion after occupational exposure to arsenic trioxide dust and fumes. In both cases, the model gives satisfactory results for urinary excretion of the four As metabolites. The PB-PK model is also used in the description of the effects on the kinetics of exposure via different routes and for the simulation of various realistic exposure scenarios.
已经开发出一种用于人体无机砷暴露的基于生理的药代动力学模型（PB-PK）。该模型是仓鼠和兔子PB-PK模型的扩展，对体重、代谢率和吸收率进行了调整。它描述了无机砷的四种主要代谢产物砷酸盐、亚砷酸盐（As(III)）、甲基砷酸盐和二甲基砷酸盐的吸收、分布、代谢和排泄。考虑的摄入途径是吸入砷尘和烟雾以及通过饮用水和食物口服摄入砷。通过重复口服As(III)以及通过饮用水暴露于无机砷后尿排泄的数据，对口服暴露途径的PB-PK模型进行了验证。通过职业暴露于三氧化二砷粉尘和烟雾后尿排泄的数据，对吸入吸收进行了验证。在这两种情况下，该模型对四种砷代谢产物的尿排泄都给出了令人满意的结果。PB-PK模型还用于描述不同途径暴露对动力学的影响以及模拟各种实际暴露场景。
