The Reference Dose (RfD) and Reference Concentration (RfC) are human health reference values (RfVs) representing exposure concentrations at or below which there is presumed to be little risk of adverse effects in the general human population. The 2009 National Research Council report Science and Decisions recommended redefining RfVs as “a risk-specific dose (for example, the dose associated with a 1 in 100,000 risk of a particular end point).” Distributions representing variability in human response to environmental contaminant exposures are critical for deriving risk-specific doses. Existing distributions estimating the extent of human toxicokinetic and toxicodynamic variability are based largely on controlled human exposure studies of pharmaceuticals. New data and methods have been developed that are designed to improve estimation of the quantitative variability in human response to environmental chemical exposures. Categories of research with potential to provide new data useful for developing updated human variability distributions include controlled human experiments, human epidemiology, animal models of genetic variability, in vitro estimates of toxicodynamic variability, and in vitro-based models of toxicokinetic variability. In vitro approaches, with further development including studies of different cell types and endpoints, and approaches to incorporate non-genetic sources of variability, appear to provide the greatest opportunity for substantial near-term advances.

参考剂量（RfD）和参考浓度（RfC）是人类健康参考值（RfVs），表示在此浓度或低于该浓度时，一般人群中几乎没有不良反应风险的暴露浓度。2009年国家研究委员会报告《科学与决策》建议将RfV重新定义为“特定于风险的剂量（例如，与特定终点风险的100,000分之一相关的剂量）。” 代表人类对环境污染物暴露的响应变化的分布对于得出特定于风险的剂量至关重要。现有的估计人类毒物代谢动力学和毒物动力学变异性程度的分布主要基于对药物的人类暴露控制研究。已经开发出新的数据和方法，旨在改善对人类对环境化学暴露的反应中的定量变异性的估计。有可能为开发更新的人类变异性分布提供有用新数据的研究类别包括受控人类实验，人类流行病学，遗传变异性动物模型，体外估计toxicodynamic变异，并在vitro-毒代动力学变化的基础模型。体外方法的进一步发展包括对不同细胞类型和终点的研究，以及纳入非遗传变异性来源的方法，似乎为近期取得实质性进展提供了最大的机会。