Evaluation of hepatic and renal effects of acute and subacute oral exposure to bromochloromethane in rats

IF 3.4 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Jane Ellen Simmons , TaCriasha L. Willoughby , Mikayla D. Armstrong , Maura J. Donohue , A. McDonald , Yusupha Mahtarr Sey
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引用次数: 0

Abstract

Bromochloromethane (BCM) is a disinfection byproduct (DBP) formed in drinking water when oxidizing disinfectants (i.e., chlorine) react with natural organic matter. BCM is structurally analogous to other DBPs, such as chloroform and bromodichloromethane, that have human health effects, specifically hepatic or renal toxicity. Given the lack of robust studies in rodents and the structural similarity of BCM to known liver and kidney toxicants, the current study was designed to examine the potential for hepatotoxicity or nephrotoxicity from either acute or subacute oral exposure to BCM in male and female Fischer 344 rats. Biomarkers of liver and kidney injury were evaluated in serum and urine samples. In the acute exposure study to 1000 mg/kg body weight BCM, there was little evidence of liver or kidney toxicity. In the subacute exposure studies to 1000 mg/kg body weight BCM, lethality occurred in both male and female rats following multiple oral doses. In the subacute exposure to 750 mg/kg/day BCM, there were only temporary changes to hepatic biomarkers in females, and there were no histological changes observed. These oral gavage studies indicate that BCM is less toxic to the liver and the kidney relative to their structural analogs.
大鼠急性和亚急性口服暴露于溴氯甲烷对肝脏和肾脏影响的评价。
溴氯甲烷(BCM)是饮用水中氧化性消毒剂(即氯)与天然有机物反应时产生的消毒副产物(DBP)。BCM在结构上类似于其他dbp,如氯仿和溴二氯甲烷,具有人体健康影响,特别是肝或肾毒性。鉴于缺乏对啮齿动物的有力研究,以及BCM与已知肝脏和肾脏毒物的结构相似性,本研究旨在检查雄性和雌性Fischer 344大鼠急性或亚急性口服暴露于BCM的肝毒性或肾毒性的可能性。在血清和尿液样本中评估肝脏和肾脏损伤的生物标志物。在急性暴露于1000 mg/kg体重BCM的研究中,几乎没有肝或肾毒性的证据。在亚急性暴露于1000 mg/kg体重BCM的研究中,多次口服剂量后,雄性和雌性大鼠均出现死亡。在亚急性暴露于750 mg/kg/天BCM时,女性的肝脏生物标志物只有暂时的变化,没有观察到组织学变化。这些口服灌胃研究表明,BCM相对于其结构类似物对肝脏和肾脏的毒性较小。
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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
309
审稿时长
32 days
期刊介绍: Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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