代谢
文献中普遍存在合成硝基麝香的实例。通过气相色谱-质谱法（使用选择离子监测，GC-SIM-MS）对麝香二甲苯（MX）和麝香酮（MK）-蛋白质加合物在大麻鱼肝脏中的活体分析已完成。描述了2-氨基-MX（2-AMX）、2-氨基-MK（2-AMK）和4-氨基-MX（4-AMX）代谢物通过酶促硝基还原MX和MK，与蛋白质中的半胱氨酸氨基酸共价结合的形成、生物转化、剂量-反应和毒物动力学研究。大麻鱼暴露于单一剂量的0.010、0.030、0.10和0.30 mg/g MX和/或MK。在暴露后1天、3天和7天的时间间隔内，从暴露组和对照组的大麻鱼中收集了42个鱼肝样本，并根据暴露计划和时间进行了组合。碱性水解释放了暴露肝复合材料中结合的代谢物，这些代谢物被提取到正己烷中，然后被浓缩并通过GC-SIM-MS进行分析。通过与大麻鱼标准的一致性确认了质谱特性和保留时间，从而证实了肝提取物中代谢物的存在。在剂量-反应研究中，2-AMX、2-AMK和4-AMX在肝中的最大加合形成分别为492.0 ng/g、505.5 ng/g和12588.5 ng/g，在1天后暴露于0.03 mg/g MX和MK鱼中。为了毒物动力学调查，发现目标代谢物的最高量与剂量-反应研究中1天后暴露于0.03 mg/g MX和MK鱼的观察到的浓度相同，根据一阶动力学的假设，代谢物的半衰期估计为2-9天。平均回收率超过95%，相对标准偏差（RSD）约为9%，根据信噪比10（S/N=10），代谢物的检测限范围为0.91至3.8 ng/g。在对照组和暴露的非水解肝提取物中没有检测到代谢物。这是关于鱼类肝脏中硝基麝香-半胱氨酸-蛋白质加合物的剂量-反应和毒物动力学的首次报告。
Ubiquitous occurrences of synthetic nitro musks are evident in the literature. The in vivo analysis of musk xylene (MX) and musk ketone (MK)-protein adducts in trout liver has been performed by gas chromatography-mass spectrometry using selected ion monitoring (GC-SIM-MS). Biotransformation, dose-response and toxicokinetics studies of 2-amino-MX (2-AMX), 2-amino-MK (2-AMK) and 4-amino-MX (4-AMX) metabolites, covalently bound to cysteine amino acids in proteins in fish liver, formed by enzymatic nitro-reduction of MX and MK, have been described. Trout were exposed to single exposures of 0.010, 0.030, 0.10, and 0.30 mg/g MX and/or MK. Forty-two fish liver samples were collected from exposed- and control-fish subsequent to exposure intervals of 1 day, 3 days, and 7 days and were composited as per exposure schedules and times. Alkaline hydrolysis released bound metabolites from exposed liver composites that were extracted into n-hexane and then concentrated and analyzed by GC-SIM-MS. The presence of the metabolites in liver extracts was confirmed based on agreement of similar mass spectral properties and retention times with standards. In the dose-response study, the maximum adduct formation was 492.0 ng/g for 2-AMX, 505.5 ng/g for 2-AMK and 12588.5 ng/g for 4-AMX in liver at 0.03 mg/g MX and MK fish in 1 day after exposure. For toxicokinetics investigation, the highest amount of the target metabolites was found to be the same concentration as observed in the dose-response study for 1 day after exposure with 0.03 mg/g MX and MK fish and the half-lives of the metabolites were estimated to be 2-9 days based on assumption of first-order kinetics. Average recoveries exceeded 95% with a relative standard deviation (RSD) around 9%, and the limit of detection (LOD) ranged from 0.91 to 3.8 ng/g based on a signal to noise ratio of 10 (S/N=10) could be achieved for the metabolites. No metabolites were detected in the controls and exposed non-hydrolyzed liver extracts. This is the first report on dose-response and toxicokinetics of nitro musk-cysteine-protein adducts in fish liver.
来源:Hazardous Substances Data Bank (HSDB)
