Exploring Potential Sources of Differential Vulnerability and Susceptibility in Risk From Environmental Hazards to Expand the Scope of Risk Assessment

摘要

Genetic factors, other exposures, individual disease states and allostatic load, psychosocial stress, and socioeconomic position all have the potential to modify the response to environmental exposures. Moreover, many of these modifiers covary with the exposure, leading to much higher risks in some subgroups. These are not theoretical concerns; rather, all these patterns have already been demonstrated in studies of the effects of lead and air pollution. However, recent regulatory impact assessments for these exposures have generally not incorporated these findings. Therefore, differential risk and vulnerability is a critically important but neglected area within risk assessment, and should be incorporated in the future. THIS ARTICLE EXPANDS ON the conceptual issues raised in our previous article in this issue, 1 illustrates them with empirical examples, and suggests strategies for incorporating the concepts in risk assessments. The central issue is the importance of capturing variation in the distribution of risk within a population as well as differences between populations in overall risk. This variation exists because of differential susceptibility of people to a single agent, interactions among multiple exposures, transgenerational propagation of risk, and because of differential exposure to other agents that affect the distribution of cumulative risk in the population. Finally, the distribution of exposures to such other agents, or to agents that convey susceptibility to the agent under study, and even to individual level factors that are risk modifiers (e.g., genes, chronic disease states, stress), are usually not independent. Capturing this lack of independence is critical to risk assessment. Finally, incorporating dose–response curves, as opposed to reference doses, is critical to accomplishing these tasks, and to understanding the actual magnitude of risk.