Sources and implications of variability in sensitivity to chemicals for ecotoxicological risk assessment.

Variability among individuals in their responses to toxic chemicals arises from several sources, the most important of which are genetic differences, environmental influences (including maternal effects and historical factors) and measurement error. Effective risk assessment requires that estimates of toxicant response (e.g., LD50, EC50, LOEC, NOEC) are precise--that is, have narrow confidence limits-, repeatable--that is, different laboratories must obtain the same or very similar result-, and accurate--that is, they must provide a reasonable approximation of the effects of toxicants on real ecological systems. Determining which of the above-mentioned sources of variability has the greatest influence on toxicant response has implications for both the design and interpretation of ecotoxicological tests. If, for example, genetic influences are of overriding importance, controlling genotype (by using clones or inbred strains) can lead to greater precision but at the expense of accuracy when the objective is to estimate toxicant response for the species as a whole. Likewise, if environmental influences are of primary importance in controlling the response to toxicants, performing experiments under a standard temperature, light, and food regime may provide highly repeatable test results that have little relevance to the responses of populations in nature. Although there is little doubt that the development of standard ecotoxicological test guidelines (e.g., by the OECD), that control genetic and environmental sources of variability, has led to improvements in the practice of risk assessment, further advances will require a more sophisticated approach for dealing with these sources of uncertainty. There is a need for more systematic approaches for quantifying the sources of variability in toxicant response and for formally combining the error associated with each source in key risk assessment endpoints.