Walton K, Walker R, van de Sandt J J, Castell J V, Knapp A G, Kozianowski G, Roberfroid M, Schilter B
Clinical Pharmacology Group, University of Southampton, UK.
Food Chem Toxicol. 1999 Dec;37(12):1175-97. doi: 10.1016/s0278-6915(99)00107-6.
The acceptable daily intake (ADI) for food additives is commonly derived from the NOAEL (no-observed-adverse-effect level) in long-term animal in vivo studies. To derive an ADI a safety or uncertainty factor (commonly 100) is applied to the NOAEL in the most sensitive test species. The 100-fold safety factor is considered to be the product of both species and inter-individual differences in toxicokinetics and toxicodynamics. Although in vitro data have previously been considered during the risk assessment of food additives, they have generally had no direct influence on the calculation of ADI values. In this review 18 food additives are evaluated for the availability of in vitro toxicity data which might be used for the derivation of a specific data-derived uncertainty factor. For the majority of the food additives reviewed, additional in vitro tests have been conducted which supplement and support the short- and long-term in vivo toxicity studies. However, it was recognized that these in vitro studies could not be used in isolation to derive an ADI; only when sufficient in vivo mechanistic data are available can such information be used in a regulatory context. Additional short-term studies are proposed for the food additives which, if conducted, would provide data that could then be used for the calculation of data-derived uncertainty factors.
食品添加剂的每日允许摄入量（ADI）通常源自长期动物体内研究中的未观察到有害作用水平（NOAEL）。为了得出ADI，会在最敏感的试验物种中将安全系数或不确定系数（通常为100）应用于NOAEL。100倍的安全系数被认为是毒代动力学和毒效动力学中物种差异和个体间差异的乘积。尽管体外数据此前在食品添加剂的风险评估中已被考虑，但它们通常对ADI值的计算没有直接影响。在本综述中，对18种食品添加剂的体外毒性数据可用性进行了评估，这些数据可能用于推导特定的数据衍生不确定系数。对于大多数所综述的食品添加剂，已经进行了额外的体外试验，这些试验补充并支持了短期和长期的体内毒性研究。然而，人们认识到，这些体外研究不能孤立地用于推导ADI；只有当有足够的体内机制数据时，此类信息才能在监管环境中使用。针对食品添加剂提出了额外的短期研究，如果进行这些研究，将提供可用于计算数据衍生不确定系数的数据。
