摘要：Preventing adverse health effects of environmental chemical exposure is fundamental to protecting individual and public health. When done efficiently and properly, chemical risk assessment enables risk management actions that minimize the incidence and effects of environmentally induced diseases related to chemical exposure. However, traditional chemical risk assessment is faced with multiple challenges with respect to predicting and preventing disease in human populations, and epidemiological studies increasingly report observations of adverse health effects at exposure levels predicted from animal studies to be safe for humans. This discordance reinforces concerns about the adequacy of contemporary risk assessment practices for protecting public health. It is becoming clear that to protect public health more effectively, future risk assessments will need to use the full range of available data, draw on innovative methods to integrate diverse data streams, and consider health endpoints that also reflect the range of subtle effects and morbidities observed in human populations. Considering these factors, there is a need to reframe chemical risk assessment to be more clearly aligned with the public health goal of minimizing environmental exposures associated with disease. For the past several decades, human health risk assessment has been a pillar of environmental health protection. In general, the products of risk assessment have been numerical risk values derived from animal toxicology studies of observable effects at high doses of individual chemicals. Although this approach has contributed to our understanding of overt health outcomes from chemical exposures, it does not always match our understanding from epidemiology studies of the consequences of real-world exposures in human populations, which are characterized by exposure to multiple pollutants, often chronically, at concentrations that can fluctuate over wide ranges; susceptible populations and life stages; potential interactions between chemicals and nonchemical stressors and background disease states; and lifestyle factors that modify exposures (e.g., airtight houses). 1 These and other issues are particularly important when determining risk of complex diseases, such as cardiovascular disease. Ten years ago, the National Research Council offered a new paradigm for evaluating the safety of chemicals on the basis of chemical characterization, testing using a toxicity pathway approach, and modeling and extrapolating the dose–response relationship from in vitro testing, all embedded in a risk context and considering population-based data and exposure. 2 Efforts such as the Tox21 Consortium 3,4 and ToxCast program 5 have helped us better understand the biological interactions of large numbers of chemicals using high-throughput assay systems, and we are witnessing early adoption of new technologies and approaches for screening chemicals for integrated testing. 6 Several other factors are also changing the way environmental health professionals think about chemical risks and how to most effectively protect public health, especially for complex diseases like cardiovascular disease. It is estimated that intrinsic factors (e.g., those that result in mutations stemming from random errors in DNA replication) account for only 10% to 30% of many common cancers. 7 Similarly, only 30% to 40% of birth defects can be attributed to known causes such as genetics, fetal alcohol syndrome, maternal smoking, and folate insufficiency. 8 Other studies have concluded that nongenetic environmental factors and gene by environment interactions are the primary causes of chronic diseases. 9 The ability to evaluate and quantify the role of environmental factors on public health is a clear opportunity, but it is limited by the lack of readily available models for prominent clinical outcomes.
