Quantitative Risk Assessment for Acute Exposure to Carcinogens.* P. M. J. Bos and M. T. M. van Raaij, RIVM, The Netherlands
An important topic in assessing the risk of a single (one day) exposure to chemicals is how to evaluate the carcinogenic risk in case of a potential carcinogen. Questions that arise are whether a single exposure can give rise to tumor development and, if so, how the carcinogenic risk can be quantitatively estimated? Starting point is the assumption that a cumulative dose administered for life-time will induce the same risk when administered on a single day. Published data indicate that a single exposure to a carcinogen can induce tumors. Theoretical modeling and experimental data (e.g. stop-exposure experiments) have suggested that short-term exposures may induce a higher risk than expected from a cumulative dose administered for life-time. Hence, some attempts have been made to assess a Dose-Rate-Correction Factor (DRCF) to account for this higher risk after single exposure. An important aspect to be discussed is how to extrapolate a tumor incidence observed in a life-time animal experiment to a negligible incidence after single human exposure. This extrapolation requires two steps, one from high-to-low incidence, and one from life-time to single exposure. The first step implies a high-to-low dose extrapolation whereas the second step implies a reverse extrapolation: from low-to-high dose. Further important topics that have to be dealt with are the possibility of saturation of metabolic processes and of DNA-repair capacity and the occurrence of organotropism. In addition, since the individual risk may depend on the life-stage of a subject at exposure, it has to be considered whether risk assessment should concern the total population or specific susceptible subpopulations. The latter may be regarded to be a policy issue. Our main purpose is to develop a decision tree to assess the carcinogenic risk of a single exposure and to derive a preferably substance-specific DRCF.
*This project is financed by the Dutch Ministry of Public Health, Sports, and Well-being.
*International Travel Award.
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