Empirical Determination of Sufficiently Similiar Complex Mixtures

足够相似的复杂混合物的经验测定

• 批准号: 7478317
• 负责人: Chris Gennings
• 金额: $ 13.14万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-03 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478317
• 关键词: Aromatic Hydrocarbons; Aromatic Polycyclic Hydrocarbons; Attention; Automobile Exhaust; Base Ratios; Biological; Chemicals; Chlorine; Class; Coke; Complex; Complex Mixtures; Daily; Data; Disinfection; Disruption; Doctor of Philosophy; Dose; Environment; Environmental Carcinogens; Enzymes; Evaluation; Fire - disasters; Flowers; Funding; Gasoline; General Population; Goals; Grant; Health; Heating; Human; Judgment; Location; Logic; Mammary Gland Parenchyma; Methodology; Methods; Modeling; Monitor; Numbers; Pesticides; Process; Production; Property; Public Health; Publications; Research; Research Personnel; Risk; Risk Assessment; Route; Seeds; Source; Specific qualifier value; Structure; Testing; Thyroid Function Tests; Thyroid Gland; Thyroid Hormones; Time; Tobacco smoke; Toxic effect; United States Environmental Protection Agency; Water; Xenobiotics; base; concept; cooking; drinking water; exposed human population; food consumption; food marketing; forest; interest; neurotoxicity; novel strategies; programs; pyrethroid; response; simulation; volcano; wasting

DESCRIPTION (provided by applicant): The U.S. EPA (Suppl Guidance for Conducting Health Risk Assessment of Chemical Mixtures, 2000) suggests that when toxicity data are not available for a mixture of concern, the risk assessment of the mixture can be based on data for a surrogate mixture which is considered "sufficiently similar" in terms of chemical composition and component proportions, and when available, considerations of similar biological disposition and toxicity. The objective of this research is to develop methodology to define sufficient similarity in dose-responsiveness for mixtures of many chemicals containing the same components, but whose component ratios vary. The method assumes that dose-response data on a fixed-ratio mixture are available. Statistical equivalence testing logic will be applied to define boundary ratios for mixtures with mean, dose-response relationships sufficiently similar to an observed mixture, based on a specified biologically meaningful region of insensitivity as defined by the investigator using expert judgment. Once the methodology is further developed as described herein, simulation studies will be conducted to elucidate the properties of the approach. The simulation study will be based on data from at least three dose-response curves of mixtures of chemicals including: (1) a mixture of 11 pesticides (pyrethroids) and the effect on neurotoxicity; (2) a mixture of 18 polyhalogenated aromatic hydrocarbons in a fixed ratio based on evaluation offish tissue, breast rnilk and other sources of human exposure and the effect on thyroid disruption; (3) a mixture of 5 organophosphorous pesticides in a relevant ratio based on dietary exposures and the effect on neurotoxicity. The result of this research will impact public health by adding new approaches to the risk assessment of chemical mixtures. In particular, all possible environmentally/industrially relevant chemical mixtures to which humans are exposed cannot each be evaluated for risk. The funded project will further develop/characterize a method of determining sufficient similarity in dose-responsiveness for mixtures with many components.

说明(由申请人提供)：美国环保局(2000年《进行化学混合物健康风险评估的补充指南》)建议，当没有令人担忧的混合物的毒性数据时，混合物的风险评估可以基于被认为在化学成分和成分比例方面“足够相似”的替代混合物的数据，以及当可用时，考虑类似的生物处置和毒性。这项研究的目的是开发方法学，为含有相同成分但成分比率不同的许多化学品的混合物定义足够的剂量-反应相似性。该方法假定固定比例混合物的剂量-反应数据是可用的。统计等价性检验逻辑将被应用于定义具有与观察到的混合物足够相似的平均剂量-反应关系的混合物的边界比率，基于调查者使用专家判断所定义的具有特定生物意义的不敏感区域。一旦如本文所述进一步开发了该方法，将进行模拟研究以阐明该方法的特性。模拟研究将以至少三种化学品混合物的数据为基础，这些化学品包括：(1)11种杀虫剂(拟除虫菊酯)的混合物及其对神经毒性的影响；(2)18种多卤代芳香烃按固定比例混合的混合物，其依据是对鱼类组织、乳汁和其他人类暴露来源的评估以及对甲状腺破坏的影响；(3)5种有机磷农药的混合物，其比例基于饮食暴露和对神经毒性的影响。这项研究的结果将通过为化学混合物的风险评估增加新的方法来影响公众健康。特别是，不能对人类接触到的所有可能的环境/工业相关的化学混合物进行风险评估。该资助项目将进一步开发/表征一种确定具有多种成分的混合物在剂量-响应性上的足够相似性的方法。