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Cancer Risk Assessment – Quantitative Approach
; Škola narodnog zdravlja "Andrija Štampar"
Puni tekst: pdf (351 KB),
Str. 31 - 42
This paper presents hazard identification and quantitative risk assessment as priority steps in risk control of environmental carcinogens. Without quantitative or at least semiquantitative risk assessment, no prognosis can be made of health effects of human exposure to a specific carcinogen. The main emphasis is on the relationship between the dose of a carcinogen and human health effect(s), or the exposure level and effect (dose-effect relationships). The paper describes the relationship between results obtained experimentally on animals and epidemiologically on humans. It considers the difficulties in applying animal results to humans and describes the most frequent methods of extrapolation, taking into account the variability of sensitivity within and between species. Particular attention is given to the questionable assumption that neoplastic processes have no exposure threshold. This assumption implies that any level of exposure to a carcinogen can cause a neoplastic process and that the only acceptable exposure level which would not induce neoplasms would be the zero level. By contrast, the author advocates a hypothesis that there is a threshold level for carcinogens acting through epigenetic mechanisms. This exposure level without carcinogenic effect is termed NOAEL – No-Observed- Adverse-Effect-Level. For genotoxic carcinogens and those which induce mutations in germ cells the »nothreshold- level« hypothesis has been accepted in spite of the fact that it has not been definitively proven. The paper exemplifies calculation of threshold levels of some epigenetic carcinogens which simultaneously cause toxic noncarcinogenic effects on some organs. Other examples show risk calculations of some genotoxic carcinogens by mathematical extrapolation from high (measured) to low (predicted) doses (low-dose extrapolation). The method is critically reviewed, as the exemplified mathematical extrapolation models yield risk calculations that vary by several orders of magnitude. The paper introduces to the reader a recent approach to defining risks which relies on referent doses and which avoids overextrapolation to low doses.
epigenetic mechanisms, genotoxic mechanisms, low-dose extrapolation, neoplastic process, referent doses, threshold level
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