During and after fabrication of polymeric food contact articles (FCA), polymers undergo oxidation by thermal decomposition processes initiated by oxygen, heat, light, shear, and catalyst residues. To reduce degradation of the polymer, a commonly used secondary antioxidant (AO), Irgafos 168 (I-168), may be included. Use of I-168 in polymeric FCAs presents a potential concern for neurotoxicity due to its phosphate-containing degradation species, I-168ate. As a result, we evaluated dietary exposure and oral toxicity data for I-168 and its degradants when used as an AO in FCAs. Our exposure assessment included extensive review of the U.S. food-contact regulatory history of I-168 resulting in a combined cumulative estimated daily intake (CEDI) of 0.09 mg/kg bw/day for I-168 and I-168ate when used as an AO in FCAs. Our comprehensive literature review of toxicological data and supporting structure activity relationship (SAR) analysis of I-168 reactivity against acetylcholinesterase diminished concern for potential neurotoxic effects of I-168 and its degradants. An acceptable daily intake (ADI) value of 1 mg/kg bw/day for I-168 was derived from a two-year rodent combined chronic toxicity/carcinogenicity study, which is higher than the CEDI and supports the safety of current authorized food contact use levels of I-168.

在制造聚合物食品接触制品 (FCA) 期间和之后，聚合物会通过由氧气、热、光、剪切和催化剂残留物引发的热分解过程进行氧化。为了减少聚合物的降解，可以加入常用的辅助抗氧化剂 (AO) Irgafos 168 (I-168)。在聚合物 FCA 中使用 I-168 由于其含磷酸盐的降解物质 I-168ate 存在潜在的神经毒性问题。因此，我们评估了 I-168 及其降解物在 FCA 中用作 AO 时的膳食暴露和口服毒性数据。我们的暴露评估包括对美国 I-168 食品接触监管历史的广泛审查，得出 I-168 和 I-168ate 用作 AO 时的累计估计每日摄入量 (CEDI) 为 0.09 mg/kg bw/day在 FCA 中。我们对毒理学数据的综合文献综述和 I-168 对乙酰胆碱酯酶反应性的支持结构活性关系 (SAR) 分析减少了对 I-168 及其降解物潜在神经毒性作用的担忧。I-168 的可接受每日摄入量 (ADI) 值为 1 mg/kg bw/天，来自一项为期两年的啮齿动物慢性毒性/致癌性综合研究，该值高于 CEDI 并支持当前授权食品接触的安全性使用 I-168 级别。