Abstract

This report describes the development of a human physiologically based toxicokinetic model for nitrate and nitrite and its application in setting dietary standards (Acceptable Daily Intake). On the basis of a literature survey a concept of human PBPK-model was defined. This model contains the following processes: 1) The toxicokinetics of nitrate (oral absorption, uptake of absorbed nitrate in the blood followed by metabolic and renal clearance) 2) The duodeno-salivary circulation of nitrate (excretion of nitrate from the blood in the saliva) 3) The conversion of nitrate of nitrite by the oral microflora and the stability of formed nitrite in the stomach 4) The absorption kinetics of nitrite 5) The elimination of the absorbed nitrite in the blood. A calibrated model containing the processes mentioned under 1) is yet available. Using available literature data this model will be extended with the processes mentioned under 2) and 3). In order to include the processes mentioned under 4 and 5) additional experimental work will be carried out. The fully calibrated model will be validated in a reserach program involving human volunteers. This project will take place at the National Poison Control Centre of the National Institute of Public Health and Environmental Protection and will be carried out in 1993.