根据对邻苯二甲酸二丁酯进行化学案例研究的经验教训,开发了一种在化学风险评估中评估和整合基因组数据的方法。首先根据EPA的指导和科学界的建议开发了案例研究原型方法。选择邻苯二甲酸二丁酯(DBP)进行案例研究。邻苯二甲酸二丁酯病例研究的范围确定阶段是通过考虑可用的DBP基因组数据进行的,连同整个数据集,他们是否可以为各种风险评估方面提供信息,比如毒理学,毒物动力学,和剂量反应。对可用的邻苯二甲酸二丁酯数据集进行加权以用于风险评估的描述提供了考虑基因组数据用于未来化学评估的示例。作为进行范围界定过程的结果,两个问题--DBP毒理学数据是否告知1)作用机制或模式?,和2)毒理学的种间差异?-被选择作为案例研究的重点。一般方法的原则包括将基因组学数据与所有其他数据结合起来考虑,以确定它们为风险评估的各种定性和/或定量方面提供信息的能力,并评估可用的基因组和毒性结果数据之间关于研究可比性和表型锚定的关系。根据DBP案例研究的经验,我们提出了在化学评估中整合基因组数据的建议和一般方法,以推进在风险评估中利用21世纪数据的更广泛努力.
An approach for evaluating and integrating genomic data in chemical risk assessment was developed based on the lessons learned from performing a
case study for the chemical dibutyl phthalate. A
case study prototype approach was first developed in accordance with EPA guidance and recommendations of the scientific community. Dibutyl phthalate (DBP) was selected for the
case study exercise. The scoping phase of the dibutyl phthalate
case study was conducted by considering the available DBP genomic data, taken together with the entire data set, for whether they could inform various risk assessment aspects, such as toxicodynamics, toxicokinetics, and dose-response. A description of weighing the available dibutyl phthalate data set for utility in risk assessment provides an example for considering genomic data for future chemical assessments. As a result of conducting the scoping process, two questions--Do the DBP toxicogenomic data inform 1) the mechanisms or modes of action?, and 2) the interspecies differences in toxicodynamics?--were selected to focus the
case study exercise. Principles of the general approach include considering the genomics data in conjunction with all other data to determine their ability to inform the various qualitative and/or quantitative aspects of risk assessment, and evaluating the relationship between the available genomic and toxicity outcome data with respect to study comparability and phenotypic anchoring. Based on experience from the DBP case study, recommendations and a general approach for integrating genomic data in chemical assessment were developed to advance the broader effort to utilize 21st century data in risk assessment.