A biokinetic model to describe the distribution and excretion of arsenic by man following acute and chronic intakes of arsenite/arsenate compounds by ingestion

Abstract

An empirical mathematical model, comprising 17 compartments, has been produced to describe the biokinetics of ingested inorganic arsenic (As) in man — required to interpret bioassay data and to predict As tissue concentrations resulting from acute and chronic intakes of inorganic As. The rate constants used to describe the bi-directional transfer of As between compartments were chosen to result in model outcomes that match published data on the distribution of As in tissues and on the retention and excretion of radioisotopes of As administered to human subjects. The model was deployed in acute and chronic intake modes to produce predictions of tissue concentrations and excretion levels. Under conditions of chronic daily intake (1 μg d-1) for 50 years predicted final tissue concentrations vary by a factor of ∼2. Highest concentrations are predicted to occur in skin and bone (∼230ng kg-1). Tissue concentrations in all tissues other than bone are predicted to reach equilibrium after ∼100 days, and at this time, the amount of As excreted in urine has also reached approximate equilibrium at 79% of the daily dietary intake. This level then remains relatively constant unless intake ceases when tissue levels of As fall rapidly. Data on organic and inorganic As concentrations in urine were used to predict inorganic As intake and average tissue content for the USA population. Predicted tissue concentrations ranged from 2.3 μg kg -1 in skin to 1.1 μg kg-1 in muscle for an average inorganic As intake of 9.3 μg d-1.