Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California 94612, USA.
Environ Health Perspect. 2013 Jan;121(1):23-31. doi: 10.1289/ehp.1205687. Epub 2012 Oct 19.
Characterizing variability in the extent and nature of responses to environmental exposures is a critical aspect of human health risk assessment.
Our goal was to explore how next-generation human health risk assessments may better characterize variability in the context of the conceptual framework for the source-to-outcome continuum.
This review was informed by a National Research Council workshop titled "Biological Factors that Underlie Individual Susceptibility to Environmental Stressors and Their Implications for Decision-Making." We considered current experimental and in silico approaches, and emerging data streams (such as genetically defined human cells lines, genetically diverse rodent models, human omic profiling, and genome-wide association studies) that are providing new types of information and models relevant for assessing interindividual variability for application to human health risk assessments of environmental chemicals.
One challenge for characterizing variability is the wide range of sources of inherent biological variability (e.g., genetic and epigenetic variants) among individuals. A second challenge is that each particular pair of health outcomes and chemical exposures involves combinations of these sources, which may be further compounded by extrinsic factors (e.g., diet, psychosocial stressors, other exogenous chemical exposures). A third challenge is that different decision contexts present distinct needs regarding the identification-and extent of characterization-of interindividual variability in the human population.
Despite these inherent challenges, opportunities exist to incorporate evidence from emerging data streams for addressing interindividual variability in a range of decision-making contexts.
描述人类对环境暴露的反应程度和性质的变异性是健康风险评估的一个关键方面。
我们的目标是探讨下一代人类健康风险评估如何在源-结果连续体概念框架的背景下更好地描述变异性。
本综述以美国国家研究理事会题为“潜在个体对环境应激源易感性的生物学因素及其对决策的影响”的研讨会为信息来源。我们考虑了当前的实验和计算方法，以及新兴的数据流（如基因定义的人类细胞系、遗传多样化的啮齿动物模型、人类组学分析和全基因组关联研究），这些数据流提供了评估个体间变异性的新类型信息和模型，可应用于环境化学物质的人类健康风险评估。
描述变异性的一个挑战是个体之间固有生物学变异性（如遗传和表观遗传变异）的来源范围广泛。第二个挑战是，每一对特定的健康结果和化学暴露都涉及这些来源的组合，这些组合可能会因外在因素（如饮食、心理社会应激源、其他外源性化学暴露）而进一步复杂化。第三个挑战是，不同的决策环境对人群中个体间变异性的识别和描述程度有不同的需求。
尽管存在这些内在的挑战，但仍有机会利用新兴数据流中的证据，在一系列决策背景下解决个体间变异性问题。
