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Longitudinal assessment of mycotoxin co-exposures in exclusively breastfed infants
bioRxiv - Pharmacology and Toxicology Pub Date : 2020-05-25 , DOI: 10.1101/2020.03.27.011072
Dominik Braun , Eva Schernhammer , Doris Marko , Benedikt Warth

Early-life development of infants may be critically affected by man-made or natural contaminants including mycotoxins. However, data on the occurrence of food contaminants in breast milk is scarce and prohibits a comprehensive exposure and risk assessment for mothers and their infants. Here, we present a longitudinal exposure assessment over the first 211 days of a single newborn girl (study A) by measuring multiple mycotoxins in milk. Eighty-seven consecutive breast milk samples were obtained from the newborns mother living in Austria and following a regular mixed diet. Mycotoxins were analyzed by utilizing a highly sensitive LC-MS/MS approach covering 29 mycotoxins and key metabolites. In addition to this longitudinal study, three mothers provided breast milk samples each on five consecutive days, for a preliminary comparison of inter-day and inter-individual variation in exposures (study B). Study A revealed that mycotoxin occurrence in breast milk was limited to the emerging mycotoxins alternariol monomethyl ether (AME), beauvericin (BEA), enniatins (A, A1, B, B1) and to ochratoxin A (OTA), which is regulated in commercial infant food. These mycotoxins were, if present, mostly detected at very low concentrations (<10 ng/L), except AME which exceeded this concentration on two distinct days by a factor of 3x and 5x. Overall, longitudinal results indicated chronic low-dose exposure to the detected mycotoxins. Other regulated mycotoxins including the carcinogenic aflatoxins or the estrogenic zearalenone and their biotransformation products were absent in all tested samples. Study B confirmed the results of study A, with minimal inter-day and inter-individual variation. In addition, a preliminary correlation of OTA levels occurring in breast milk and matched urine samples was found (r=0.64, p=0.034) in study B. Based on the data set obtained in study A, exposure of the infant was estimated. Exposure estimates of individual mycotoxins were on average below 1 ng/kg body weight per day. Our preliminary findings suggest that recommended maximum daily intake levels might not be exceeded in the Austrian population. However, exposure is likely to be higher in populations with lower food safety standards. In the light of co-occurrence of several emerging mycotoxins in breast milk, future studies should address low-dose mixture effects. This also includes other environmental contaminants which may be present in this bio-fluid and should involve an exposome-scale risk assessment. All these efforts must be intended to minimize exposure of mothers and infants in a window of high susceptibility

中文翻译:

母乳喂养婴儿中真菌毒素共同暴露的纵向评估

人为或天然污染物(包括霉菌毒素)可能会严重影响婴儿的早期发育。但是,关于母乳中食物污染物的发生的数据很少,因此无法对母亲及其婴儿进行全面的接触和风险评估。在这里,我们通过测量牛奶中的多种霉菌毒素,对一个新生女婴的前211天(研究A)进行纵向暴露评估。连续八十七次母乳样本来自居住在奥地利并遵循常规混合饮食的新生儿母亲。通过使用涵盖29种真菌毒素和关键代谢物的高灵敏度LC-MS / MS方法分析了真菌毒素。除了这项纵向研究之外,三名母亲连续五天分别提供了母乳样本,初步比较日间和个体间的暴露差异(研究B)。研究A表明,母乳中的霉菌毒素仅限于新兴的霉菌毒素互作蛋白单甲醚(AME),博韦霉素(BEA),烯尿素(A,A1,B,B1)和曲霉毒素A(OTA),后者在商业上受到监管婴儿食品。这些霉菌毒素(如果存在)大多以非常低的浓度(<10 ng / L)检测到,除了AME在两个不同的天超过该浓度3倍和5倍。总体而言,纵向结果表明长期低剂量暴露于检测到的霉菌毒素。在所有测试样品中都没有其他受调节的真菌毒素,包括致癌性黄曲霉毒素或雌激素性玉米赤霉烯酮及其生物转化产物。研究B确认研究A的结果,日间差异和个体差异最小。此外,在研究B中发现了母乳和相匹配的尿液样品中OTA水平的初步相关性(r = 0.64,p = 0.034)。根据研究A中获得的数据集,可以估算婴儿的暴露水平。个别真菌毒素的暴露估计平均每天低于1 ng / kg体重。我们的初步发现表明,奥地利人口中可能不会超过建议的最大每日摄入量。但是,食品安全标准较低的人群中的暴露水平可能会更高。鉴于母乳中几种新兴霉菌毒素的共同存在,未来的研究应解决低剂量混合效应。这还包括可能存在于该生物流体中的其他环境污染物,并且应涉及暴露级别的风险评估。所有这些努力必须旨在最大程度地降低在高度易感性窗口内母婴的接触
更新日期:2020-05-25
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