Bioassays in workers exposed to long time random intakes.

Workers who are occupationally exposed to radioactive aerosols are usually subjected to periodic controls of internal contamination by performing bioassays (whole body or partial body monitoring and measurement of excreta samples). The intakes are also estimated by using Static Air Samples (SAS). These measurements are used to estimate the radioactive intakes of the workers. A typical assumption is the workers are chronically (constant) exposed for long periods of time. However, the intakes are random and there are also periods without any exposure (weekends, holidays, etc.). The method presented here considers both facts. Simulations help to choose the most appropriate method of evaluation to minimize the statistical uncertainties in the intake. It has been applied to evaluate workers exposed to UO2 aerosols for a long time (30 years or more for most of them) in the same working area (sintering). Results of measurements of uranium in urine and daily intakes (from SAS) of these workers have been used. For this evaluation, the new Occupational Intakes of Radionuclides (OIR) biokinetic models of the International Commission on Radiological Protection (ICRP) for uranium have been solved. For some workers the evaluation gives a significative deviation between the intake estimated from urine samples and the intake estimated using the SAS values, supporting the idea that the physiological standard parameters of the reference worker are not always applicable. The computations have been implemented in the BIOKMOD code.

INTERNAL DOSIMETRY TOOL FOR THE IMPLEMENTATION AND USE OF NEW ICRP/OIR MODELS: A CAESIUM STUDY.

In case of accidental intake of radioactive material, the dose assessment requires information on the radionuclide distribution in the body. Measurements of retention or excretion are compared with model's predictions to estimate the intake. The reference models for internal dosimetry purposes are those proposed by ICRP and have been recently updated in the 'Occupational Intakes of Radionuclides (OIR)' series. This work focusses on the implementation of the new caesium model in a computer package, ICRP130Models (integrated in the toolbox BIOKMOD), together with new features aimed at estimating the intake and the dose from bioassay measurements. The software gives the best fitted intake and the committed effective dose, as well as the chi-squared test and the p-value as an indication of the goodness of the fit in the assessment process. The possibility to build the model as a function of a parameter allows the user to look for different options when fitting the bioassay measurements.

Design optimality for models defined by a system of ordinary differential equations.

Many scientific processes, specially in pharmacokinetics (PK) and pharmacodynamics (PD) studies, are defined by a system of ordinary differential equations (ODE). If there are unknown parameters that need to be estimated, the optimal experimental design approach offers quality estimators for the different objectives of the practitioners. When computing optimal designs the standard procedure uses the linearization of the analytical expression of the ODE solution, which is not feasible when this analytical form does not exist. In this work some methods to solve this problem are described and discussed. Optimal designs for two well-known example models, Iodine and Michaelis-Menten, have been computed using the proposed methods. A thorough study has been done for a specific two-parameter PK model, the biokinetic model of ciprofloxacin and ofloxacin, computing the best designs for different optimality criteria and numbers of points. The designs have been compared according to their efficiency, and the goodness of the designs for the estimation of each parameter has been checked. Although the objectives of the paper are focused on the optimal design field, the methodology can be used as well for a sensitivity analysis of ordinary differential equation systems.