Smith Robert L, Cohen Samuel M, Doull John, Feron Victor J, Goodman Jay I, Marnett Lawrence J, Munro Ian C, Portoghese Philip S, Waddell William J, Wagner Bernard M, Adams Timothy B
Division of Biomedical Sciences Section of Molecular Toxicology, Imperial College School of Medicine, South Kensington, London SW7 2AZ, United Kingdom.
Food Chem Toxicol. 2005 Aug;43(8):1141-77. doi: 10.1016/j.fct.2004.11.012. Epub 2005 Apr 18.
The current status of the GRAS evaluation program of flavoring substances operated by the Expert Panel of FEMA is discussed. The Panel maintains a rigorous rotating 10-year program of continuous review of scientific data related to the safety evaluation of flavoring substances. The Panel concluded a comprehensive review of the GRAS (GRASa) status of flavors in 1985 and began a second comprehensive review of the same substances and any recently GRAS materials in 1994. This second re-evaluation program of chemical groups of flavor ingredients, recognized as the GRAS reaffirmation (GRASr) program, is scheduled to be completed in 2005. The evaluation criteria used by the Panel during the GRASr program reflects the significant impact of advances in biochemistry, molecular biology and toxicology that have allowed for a more complete understanding of the molecular events associated with toxicity. The interpretation of novel data on the relationship of dose to metabolic fate, formation of protein and DNA adducts, enzyme induction, and the cascade of cellular events leading to toxicity provides a more comprehensive basis upon which to evaluate the safety of the intake of flavor ingredients under conditions of intended use. The interpretation of genotoxicity data is evaluated in the context of other data such as in vivo animal metabolism and lifetime animal feeding studies that are more closely related to actual human experience. Data are not viewed in isolation, but comprise one component that is factored into the Panel's overall safety assessment. The convergence of different methodologies that assess intake of flavoring substances provides a greater degree of confidence in the estimated intake of flavor ingredients. When these intakes are compared to dose levels that in some cases result in related chemical and biological effects and the subsequent toxicity, it is clear that exposure to these substances through flavor use presents no significant human health risk.
讨论了由美国食品香料与提取物制造者协会（FEMA）专家小组开展的调味剂GRAS评估项目的现状。该小组维持着一个严格的、为期10年的循环项目，持续审查与调味剂安全评估相关的科学数据。该小组在1985年完成了对调味剂GRAS（GRASa）状态的全面审查，并于1994年开始对相同物质以及任何最近被认定为GRAS的材料进行第二次全面审查。这个被认为是GRAS再确认（GRASr）项目的调味成分化学组的第二次重新评估项目计划于2005年完成。在GRASr项目期间，该小组使用的评估标准反映了生物化学、分子生物学和毒理学进展的重大影响，这些进展使得人们能够更全面地理解与毒性相关的分子事件。对剂量与代谢命运关系、蛋白质和DNA加合物形成、酶诱导以及导致毒性的细胞事件级联等新数据的解读，为评估调味成分在预期使用条件下的摄入安全性提供了更全面的依据。遗传毒性数据的解读是在其他数据的背景下进行评估的，比如与实际人类经验更密切相关的体内动物代谢和终生动物喂养研究。数据并非孤立看待，而是构成了该小组整体安全评估所考虑的一个因素。评估调味剂摄入量的不同方法的趋同，为调味成分的估计摄入量提供了更高程度的可信度。当将这些摄入量与某些情况下会导致相关化学和生物学效应及后续毒性的剂量水平进行比较时，很明显，通过使用调味剂接触这些物质不会对人类健康造成重大风险。
