Regulatory toxicology and pharmacology : RTP · 2007
Integration of time as a description parameter in risk characterisation: application to methyl mercury.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Verger Ph, Tressou J, Clémençon S
Аннотация
Within the food risk assessment procedure, the characterisation of the risk consists in the comparison of the dietary exposure with a health based guidance value established in a previous step. One of the identified weaknesses of this comparison is that the time is not considered in the description. The aim of this paper is to describe the dietary exposure as a dynamic process determined by the accumulation phenomenon due to successive dietary intakes and by the pharmacokinetics ruling the elimination process in between intakes. Such a process belong to the category of piecewise deterministic Markov processes, which are widely used in a large variety of applications in insurance risk or in operations research, ranging from queuing systems to inventory/storage models. The inputs of the Kinetic Dietary Exposure Model are the probability distributions governing intakes and inter-intake times, as well as the half-life of the contaminant in the human body. In this paper, an application to methyl mercury is considered, with exponential distributions for both the intakes and the inter-intake times, fitted from the French national consumption survey INCA, and a fixed half-life of 6 weeks for the elimination process. Within this framework, the process settles to a steady-state after approximately 5 years. A "Kinetic Tolerable Intake" (KTI), derived from the "Provisional Tolerable Weekly Intake" (PTWI) of 1.6 microg/kg bw, is set to 14.6 microg/kg and the probability of exceeding this threshold in the long run in the French adult female population is 1.22 E-15.