AN OVERALL RISK PROBABILITY BASED METHOD FOR QUANTIFICATION OF SYNERGISIC AND ANTAGONISTIC EFFECTS IN HEALTH RISK ASSESSMENT FOR MIXTURES: THEORETICAL CONCEPTS
Health risk assessment of environmental chemicals is important in many aspects of environmental management. Examples include the assessment of health risks of organic contaminants in indoor air and endocrine disrupting chemicals in water recycling schemes. Risk assessment of environmental chemicals has a number of characteristics that need to be considered. These include long exposure time and chronic toxicity effects, large variations in exposure and/or dose response data, and mixture effects. In particular, the quantification of mixture effects is rarely studied, yet it is a very important aspect in the overall assessment of health risks of environmental chemicals. Currently, the only methods those are available for the quantification of mixture effects are the methods of "dose addition" or "independent action". The methods of dose addition can be used when the mixture components are assumed to act through a similar or common mode of action. In this case, it is assumed that one chemical can be replaced with an equivalent amount of another chemical. The chemicals do not exacerbate or diminish the effects of other components, and there are no synergistic or antagonistic effects present. The method of independent action assumes that the modes of action of each component are independent to each other and there are also no synergistic or antagonistic effects in the mixture. There is no method that can be used to quantify the synergistic and antagonistic effects. Probabilistic methods are relatively newer methods for the quantification of health risks of toxicants. Probabilistic risk assessment uses cumulative probability charts for the quantification of the adverse effects. Recently, we have developed a new concept of Overall Risk Probability (ORP) for the quantitative characterisation of health risks of environmental pollutants. The ORP is derived from integration of an exceedence curve that in turn is derived from the cumulative probability charts of exposure and effect. The ORP method represents a major improvement over the method of hazard quotient (eg HQ95/5) in which only single ratio values are used. The ORP method also has the advantage that it can be used for the quantification of mixture effects. In this paper, the theoretical concepts of ORP for mixtures were derived. For independent mixtures where there is no synergistic or antagonistic effect, a mixture ORP can be calculated. A synergistic and an antagonistic coefficient were defined to quantify the ORP for mixtures. This represents a first method that can be used to generally quantify the mixture effects of interacting toxicants.
15th International Symposium on Toxicity Assessment, Hong Kong, Jul.3-8, 2011
Environmental Sciences not elsewhere classified