[Probability of Causation (PC): historical motivations and legal transposition]. / PC: motivazioni storiche e recepimento giuridico.

OBJECTIVES: The Probability of Causation (PC) was introduced to compensate objectively and more possible legally the U.S. diseased subjects involved in the nuclear armament activities. METHODS: The methodology is related to the attributable risk concept, but it is widely different from it, since it doesn't evaluate the "attributablity" from a collective point of view, but from a "personalistic" point, that is from the particular exposure condition, from the specific physical parameters and from the biological individual features of the single exposed subject. So the PC become an evaluation of the harm probability "tailored" for "that" specific exposed person, on the basis of the epidemiological indications coming from an exposed group with very similar characteristics of the under investigation individual. This is clearly possible owing to the large and exhaustive amount of epidemiological studies in the specific field of radiation exposure. The process to reach the PC adoption took a long time, was plodding and politically thwarted and various reexaminations and bills during time were necessary to extended the laws to the different exposure categories. RESULTS: Now in the U.S. three departments (Health, Energy and Labour) are involved in the evaluation processes; they gather the personal, dosimetric and clinical data and with a computer program (usable on line also) based on the updated knowledge, evaluate the eligibility for compensation on the basis of the "more likely than not" criterion. CONCLUSIONS: The method meets the interest and the favor at international level and organizations in prominent positions in the pacific use of nuclear energy and in the radiation protection fields, like: NCRP, IAEA, WHO, ILO,... fight for it use. Now many institutional organism and the more enlightened justice courts utilize the PC to settle cases (increasing in frequency) in work and health activities, for which more often compensation claims are dealing with.

Intra- and inter-laboratory variation in the scoring of micronuclei and nucleoplasmic bridges in binucleated human lymphocytes. Results of an international slide-scoring exercise by the HUMN project.

One of the objectives of the HUman MicroNucleus (HUMN) project is to identify the methodological variables that have an important impact on micronucleus (MN) or micronucleated (MNed) cell frequencies measured in human lymphocytes using the cytokinesis-block micronucleus assay. In a previous study we had shown that the scoring criteria used were likely to be an important variable. To determine the extent of residual variation when laboratories scored cells from the same cultures using the same set of standard scoring criteria, an inter-laboratory slide-scoring exercise was performed among 34 laboratories from 21 countries with a total of 51 slide scorers involved. The results of this study show that even under these optimized conditions there is a great variation in the MN frequency or MNed cell frequency obtained by individual laboratories and scorers. All laboratories ranked correctly the MNed cell frequency in cells from cultures that were unirradiated, or exposed to 1 or 2Gy of gamma rays. The study also estimated that the intra-scorer median coefficient of variation for duplicate MNed cell frequency scores is 29% for unexposed cultures and 14 and 11% for cells exposed to 1 and 2Gy, respectively. These values can be used as a standard for quality or acceptability of data in future studies. Using a Poisson regression model it was estimated that radiation dose explained 67% of the variance, while staining method, cell sample, laboratory, and covariance explained 0.6, 0.3, 6.5, and 25.6% of the variance, respectively, leaving only 3.1% of the variance unexplained. As part of this exercise, nucleoplasmic bridges were also estimated by the laboratories; however, inexperience in the use of this biomarker of chromosome rearrangement was reflected in the much greater heterogeneity in the data and the unexplained variation estimated by the Poisson model. The results of these studies indicate clearly that even after standardizing culture and scoring conditions it will be necessary to calibrate scorers and laboratories if MN, MNed cell and nucleoplasmic bridge frequencies are to be reliably compared among laboratories and among populations.