a Division of Toxicology, College of Pharmacy , Sungkyunkwan University , Suwon , Gyeonggi-do , South Korea.
b Department of Biochemistry and Health Science, College of Natural Sciences , Changwon National University , Changwon , Gyeongnam , South Korea.
J Toxicol Environ Health A. 2018;81(12):465-480. doi: 10.1080/15287394.2018.1460782. Epub 2018 Apr 25.
N-nitrosamines and their precursors found in cosmetics may be carcinogenic in humans. Thus the aim of this study was to carry out risk assessment for N-nitrosamines (N-nitrosodiethanolamine [NDELA], N-nitrosodiethylamine [NDEA]) and amines (triethanolamine [TEA], diethanolamine [DEA]) levels in cosmetics determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) procedures. NDELA and NDEA concentrations were present at levels of "not detected" (N.D.) to 596.5 μg/kg and N.D. to 40.9 μg/kg, respectively. TEA and DEA concentrations ranged from N.D. to 860 μg/kg and N.D. to 26.22 μg/kg, respectively. The nitrite concentration (3-2250 mg/l), number of nitrosating agents to a maximum 5, and pH (3.93-10.09) were also assessed. The impact of N-nitrosamine formation on the levels of TEA, DEA, nitrite, and other nitrosating agents was also examined. N-nitrosamine concentrations correlated with the number of nitrosating agents and nitrite concentrations. Data demonstrated that higher nitrite concentrations and a greater number of nitrosating agents increased NDELA and NDEA yields. Further, the presence of TEA and DEA exerted a significant influence on N-nitrosamine formation. Risk assessments, including the margin of exposure (MOE) and lifetime cancer risk (LCR) for N-nitrosamines and margin of safety (MOS) for amines, were calculated using product type, use pattern, and concentrations. Exposure to maximum amounts of NDELA and NDEA resulted in MOE > 10,000 (based upon the benchmark dose lower confidence limit 10%) and LCR <1 × 10, respectively. In addition, TEA and DEA concentrations in cosmetic samples resulted in MOS values >100. Therefore, no apparent safety concerns were associated with cosmetic products containing NDELA, NDEA, TEA, and DEA in this study. However, since amines and nitrosating agents produce carcinogenic nitrosamines, their use in cosmetics needs to be minimized to levels as low as technically feasible.
在化妆品中发现的 N-亚硝胺及其前体可能对人类具有致癌性。因此，本研究的目的是使用经过验证的液相色谱-串联质谱（LC-MS/MS）程序，对化妆品中 N-亚硝胺（N-二乙醇胺[NDELA]、N-二乙胺[NDEA]）和胺（三乙醇胺[TEA]、二乙醇胺[DEA]）的水平进行风险评估。NDELA 和 NDEA 的浓度分别为“未检出”（N.D.）至 596.5μg/kg 和 N.D.至 40.9μg/kg。TEA 和 DEA 的浓度范围分别为 N.D.至 860μg/kg 和 N.D.至 26.22μg/kg。还评估了亚硝酸盐浓度（3-2250mg/l）、最大 5 个亚硝化剂数量和 pH 值（3.93-10.09）。还检查了 N-亚硝胺形成对 TEA、DEA、亚硝酸盐和其他亚硝化剂水平的影响。N-亚硝胺浓度与亚硝化剂数量和亚硝酸盐浓度相关。数据表明，较高的亚硝酸盐浓度和更多的亚硝化剂会增加 NDELA 和 NDEA 的产量。此外，TEA 和 DEA 的存在对 N-亚硝胺的形成有显著影响。使用产品类型、使用模式和浓度对 N-亚硝胺的暴露评估（MOE）和终生癌症风险（LCR）以及胺的安全边际（MOS）进行了计算。在化妆品中，最大量的 NDELA 和 NDEA 的暴露量导致 MOE>10000（基于基准剂量下限 10%）和 LCR<1×10，分别。此外，化妆品样品中 TEA 和 DEA 的浓度导致 MOS 值>100。因此，在本研究中，含有 NDELA、NDEA、TEA 和 DEA 的化妆品产品没有明显的安全问题。然而，由于胺和亚硝化剂会产生致癌的亚硝胺，因此需要将它们在化妆品中的使用量减少到技术上可行的最低水平。
