Krausová Magdaléna, Ayeni Kolawole I, Gu Yunyun, Borutzki Yasmin, O'Bryan Jane, Perley Lauren, Silasi Michelle, Wisgrill Lukas, Johnson Caroline H, Warth Benedikt
Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090 Vienna, Austria.
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
Environ Int. 2024 Dec;194:109081. doi: 10.1016/j.envint.2024.109081. Epub 2024 Oct 19.
Mycotoxins are fungal toxins that may trigger adverse health effects in pregnant women and their unborn children. Yet, data is scarce on the dynamic exposure patterns of mycotoxins in pregnant women, especially in the United States. This study assessed mycotoxin exposure profiles in women (n = 50) from the Yale Pregnancy Outcome Prediction Study (YPOPS) cohort at four distinct time points. Multi-analyte human biomonitoring assays based on liquid chromatography tandem mass spectrometry (LC-MS/MS), were developed for human serum and plasma matrices. The serum method was applied, together with an established urine method, to quantify mycotoxin levels in longitudinally collected matched serum (n = 200) and spot urine (n = 200) samples throughout pregnancy. The serum samples were mostly contaminated by the potential carcinogen ochratoxin A (detection rate: 46 %; median: 0.09 ng/mL), the hepato- and nephrotoxic citrinin (detection rate: 32 %; median: 0.02 ng/mL) and two enniatins (EnnB; detection rate: 97 %; median: 0.01 ng/mL and EnnB; detection rate: 12 %; median: 0.003 ng/mL) which may act as immunotoxins. The most prevalent mycotoxins quantified in urine included deoxynivalenol (detection rate: 99 %; median: 23 ng/mL), alternariol monomethyl ether (detection rate: 69 %; median: 0.04 ng/mL), and zearalenone (detection rate: 63 %; median: 0.16 ng/mL). Seven other biomarkers of exposure including the highly estrogenic α-zearalenol and genotoxic Alternaria toxins, were also determined. Carcinogenic aflatoxins were not detected in any of the samples. Exposure assessment was based on the urinary data and performed by calculating probable daily intakes and comparing the human biomonitoring guidance value (HBM-GV) for deoxynivalenol. The results showed that the individuals exceeded the tolerable daily intake for deoxynivalenol and zearalenone on average at 28 % and 2 % over the different time points. Using the HBM-GV approach, the average exceedances for deoxynivalenol increased to 48 % indicating high exposure. For all the samples in which ochratoxin A was quantified, the estimated margin of exposure for neoplastic effects was below 10,000, indicating possible health concerns. Overall, this study showed that pregnant women were exposed to several regulated and emerging mycotoxins and that exposome-scale assessment should be a future priority in susceptible populations to better characterize xenobiotic exposure.
霉菌毒素是真菌毒素，可能会对孕妇及其未出生的胎儿产生不良健康影响。然而，关于孕妇霉菌毒素动态暴露模式的数据很少，尤其是在美国。本研究评估了耶鲁大学妊娠结局预测研究（YPOPS）队列中50名女性在四个不同时间点的霉菌毒素暴露情况。基于液相色谱串联质谱（LC-MS/MS）开发了针对人体血清和血浆基质的多分析物人体生物监测方法。血清方法与已建立的尿液方法一起应用，以量化整个孕期纵向收集的匹配血清（n = 200）和随机尿液（n = 200）样本中的霉菌毒素水平。血清样本大多受到潜在致癌物赭曲霉毒素A（检出率：46%；中位数：0.09 ng/mL）、肝毒性和肾毒性桔青霉素（检出率：32%；中位数：0.02 ng/mL）以及两种可能作为免疫毒素的恩镰孢菌素（EnnB；检出率：97%；中位数：0.01 ng/mL和EnnB；检出率：12%；中位数：0.003 ng/mL）的污染。尿液中定量的最普遍霉菌毒素包括脱氧雪腐镰刀菌烯醇（检出率：99%；中位数：23 ng/mL）、单甲基交替霉素（检出率：69%；中位数：0.04 ng/mL）和玉米赤霉烯酮（检出率：63%；中位数：0.16 ng/mL）。还测定了其他七种暴露生物标志物，包括高雌激素性α-玉米赤霉醇和具有遗传毒性的链格孢毒素。在任何样本中均未检测到致癌黄曲霉毒素。暴露评估基于尿液数据，通过计算可能的每日摄入量并比较脱氧雪腐镰刀菌烯醇的人体生物监测指导值（HBM-GV）来进行。结果表明，在不同时间点，个体平均超过脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮的每日耐受摄入量分别为28%和2%。使用HBM-GV方法，脱氧雪腐镰刀菌烯醇的平均超标率增至48%，表明暴露水平较高。对于所有定量了赭曲霉毒素A的样本，肿瘤效应的估计暴露边际低于10000，表明可能存在健康问题。总体而言，本研究表明孕妇暴露于多种受监管和新出现的霉菌毒素，暴露组规模评估应成为易感人群未来的优先事项，以更好地表征外源性物质暴露情况。
