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烷基原儿茶酸酯作为对羟基苯甲酸酯(防腐剂)暴露的新型尿生物标志物。

Alkyl protocatechuates as novel urinary biomarkers of exposure to p-hydroxybenzoic acid esters (parabens).

机构信息

Wadsworth Center, New York State Department of Health, and Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Empire State Plaza, P.O. Box 509, Albany, New York 12210-0509, United States.

出版信息

Environ Int. 2013 Sep;59:27-32. doi: 10.1016/j.envint.2013.05.001. Epub 2013 Jun 7.

DOI:10.1016/j.envint.2013.05.001
PMID:23747757
Abstract

Human exposure to p-hydroxybenzoic acid esters (parabens) is a concern, owing to adverse health effects of these compounds. Parabens are metabolized and eliminated from the human bodies within a few hours of exposure. In this study, for the first time, methyl- and ethyl-protocatechuates (OH-MeP and OH-EtP) and their parent compounds, methyl- (MeP) and ethyl-parabens (EtP), were determined in urine samples collected from U.S. children and adults. Alkyl protocatechuates were found in almost all urine samples, with median concentrations of 11.8 (OH-MeP) and 2.90ng/mL (OH-EtP) in adults, and 5.43 (OH-MeP) and 0.85ng/mL (OH-EtP) in children. In adults, the concentrations of urinary OH-MeP and OH-EtP were higher than the corresponding concentrations of MeP and EtP. Significant correlation between OH-MeP/OH-EtP and MeP/EtP was observed. This is the first report to document hydroxylation of parabens in humans, and to propose hydroxylated metabolites (i.e., alkyl protocatechuates) as alternative biomarkers of exposure to parabens in human biomonitoring studies. The rates of transformation of parabens between children and adults appeared to be different, as evidenced from the slopes of regression between alkyl protocatechuates and parabens. In addition to alkyl protocatechuates, hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were found at considerable levels in the urine samples. The occurrence of a significant proportion of alkyl protocatechuates and 3,4-DHB suggests the need for inclusion of these derivatives in accurate estimation of human exposure to parabens and in epidemiological studies that associate paraben exposure to health outcomes in populations.

摘要

人体接触对羟基苯甲酸酯(parabens)是一个令人关注的问题,因为这些化合物会对健康产生不良影响。对羟基苯甲酸酯在暴露于人体后的几个小时内被代谢和消除。在这项研究中,首次在来自美国儿童和成年人的尿液样本中检测到甲基-和乙基-原儿茶酸酯(OH-MeP 和 OH-EtP)及其母体化合物,甲基-(MeP)和乙基-对羟基苯甲酸酯(EtP)。烷基原儿茶酸酯几乎存在于所有尿液样本中,成人中 OH-MeP 和 OH-EtP 的中位数浓度分别为 11.8ng/mL 和 2.90ng/mL,儿童中则分别为 5.43ng/mL 和 0.85ng/mL。在成人中,尿液中 OH-MeP 和 OH-EtP 的浓度高于相应的 MeP 和 EtP 浓度。观察到 OH-MeP/OH-EtP 和 MeP/EtP 之间存在显著相关性。这是首次报道人体对羟基苯甲酸酯的羟化作用,并提出羟化代谢物(即烷基原儿茶酸酯)作为人体生物监测研究中接触对羟基苯甲酸酯的替代生物标志物。儿童和成人之间对羟基苯甲酸酯的转化率似乎不同,这可以从烷基原儿茶酸酯和对羟基苯甲酸酯之间的回归斜率看出。除了烷基原儿茶酸酯外,尿液样本中还发现了相当水平的羟基苯甲酸(4-HB)和 3,4-二羟基苯甲酸(3,4-DHB)。烷基原儿茶酸酯和 3,4-DHB 的大量存在表明,在准确估计人体接触对羟基苯甲酸酯和进行将对羟基苯甲酸酯暴露与人群健康结果相关联的流行病学研究时,需要包括这些衍生物。

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