3,4,4'-Trichlorocarbanilide (triclocarban, TCC) is widely used as an antimicrobial agent in a variety of consumer and personal care products. TCC is considered a potential endocrine disruptor, but its potential toxic effects in humans are still largely unknown. Because of its widespread uses, the potential for human exposure to TCC is high. In order to identify adequate exposure biomarkers of TCC, we investigated the metabolic profile of TCC in adult female Sprague Dawley rats after administering TCC once (500 mg/kg body weight) by oral gavage. Urine was collected 0-24 h before dosing, and 0-24 h and 24-48 h after dosing. Serum was collected at necropsy 48 h after dosing. We identified several metabolites of TCC in urine and serum by on-line solid phase extraction-high performance liquid chromatography-mass spectrometry. We unambiguously identified two major oxidative metabolites of TCC, 3'-hydroxy-TCC and 2'-hydroxy-TCC, by comparing their chromatographic behavior and mass spectral fragmentation patterns with those of authentic standards. By contrast, compared to these oxidative metabolites, we detected very low levels of TCC in the urine or serum. Taken together these data suggest that in rats, oxidation of TCC is a major metabolic pathway. We also measured TCC and its oxidative metabolites in 50 urine and 16 serum samples collected from adults in the United States. The results suggest differences in the metabolic profile of TCC in rats and in humans; oxidation appears to be a minor metabolic pathway in humans. Total (free plus conjugated) TCC could serve as a potential biomarker for human exposure to TCC.

译文

3,4,4 '-三氯碳苯胺 (trilocarban,TCC) 被广泛用作各种消费和个人护理产品中的抗菌剂。TCC被认为是一种潜在的内分泌干扰物,但其对人类的潜在毒性作用仍在很大程度上未知。由于其广泛的用途,人类暴露于TCC的可能性很高。为了鉴定TCC的足够暴露生物标志物,我们研究了通过口服灌胃施用TCC一次 (500 mg/kg体重) 后成年雌性Sprague Dawley大鼠中TCC的代谢特征。给药前0-24小时收集尿液,给药后0-24小时和24-48小时收集尿液。给药后48小时尸检时收集血清。我们通过在线固相萃取-高效液相色谱-质谱法鉴定了尿液和血清中TCC的几种代谢产物。通过将TCC的色谱行为和质谱裂解模式与真实标准品进行比较,我们明确地确定了TCC的两种主要氧化代谢产物,即3 '-羟基-TCC和2'-羟基-TCC。相比之下,与这些氧化代谢物相比,我们在尿液或血清中检测到非常低的TCC水平。综合这些数据表明,在大鼠中,TCC的氧化是主要的代谢途径。我们还测量了从美国成年人收集的50个尿液和16个血清样本中的TCC及其氧化代谢产物。结果表明,大鼠和人类中TCC的代谢谱存在差异; 氧化似乎是人类次要的代谢途径。总 (游离加共轭) TCC可以作为人类暴露于TCC的潜在生物标志物。

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