Early Liver and Kidney Dysfunction Associated with Occupational Exposure to Sub-Threshold Limit Value Levels of Benzene, Toluene, and Xylenes in Unleaded Petrol

Masoud Neghab; Kiamars Hosseinzadeh; Jafar Hassanzadeh

摘要

Abstract BackgroundUnleaded petrol contains significant amounts of monocyclic aromatic hydrocarbons such as benzene, toluene, and xylenes (BTX). Toxic responses following occupational exposure to unleaded petrol have been evaluated only in limited studies. The main purpose of this study was to ascertain whether (or not) exposure to unleaded petrol, under normal working conditions, is associated with any hepatotoxic or nephrotoxic response.MethodsThis was a cross-sectional study in which 200 employees of Shiraz petrol stations with current exposure to unleaded petrol, as well as 200 unexposed employees, were investigated. Atmospheric concentrations of BTX were measured using standard methods. Additionally, urine and fasting blood samples were taken from individuals for urinalysis and routine biochemical tests of kidney and liver function.ResultsThe geometric means of airborne concentrations of BTX were found to be 0.8?mg?m?3, 1.4?mg?m?3, and 2.8?mg?m?3, respectively. Additionally, means of direct bilirubin, alanine aminotransferase, aspartate aminotransferase, blood urea and plasma creatinine were significantly higher in exposed individuals than in unexposed employees. Conversely, serum albumin, total protein, and serum concentrations of calcium and sodium were significantly lower in petrol station workers than in their unexposed counterparts.ConclusionThe average exposure of petrol station workers to BTX did not exceed the current threshold limit values (TLVs) for these chemicals. However, evidence of subtle, subclinical and prepathologic early liver and kidney dysfunction was evident in exposed individuals. Keywords blood biochemical tests ; benzene, toluene, and xylenes ; hepatotoxicity ; nephrotoxicity ; unleaded petrol prs.rt("abs_end"); 1. Introduction Unleaded petrol contains significant amounts of aromatic hydrocarbons [1] . Among aromatic compounds, benzene, toluene, and xylenes (BTX) are the most dangerous elements of petrol [2] and [3] . The risk of acute or chronic toxicity in humans exists during production, distribution, and use of petrol [4] . Hepatotoxicity and nephrotoxicity have been reported following human and animal exposure to unleaded petrol [2] , [3] and [5] . For instance, kidney adenoma [5] , elevated serum activity of liver enzymes [6] and [7] , urea, creatinine, and potassium, and decreased chlorine and sodium have been reported in laboratory animals [8] . Similarly, proteinuria, elevated serum activity of liver enzymes (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase), and total bilirubin and fatty liver changes have been reported in drivers and workers following exposure to unleaded petrol [9] , [10] , [11] and [12] . Furthermore, xylene and toluene have been reported to cause renal and liver damage and toxicity in humans [13] , [14] and [15] . Kidney effects including renal tubular acidosis, hypokalemia, hypophosphatemia, azotemia, hematuria, proteinuria, and pyuria after exposure to toluene have also been reported [16] . Additionally, exposure to benzene and alkyl benzene has been associated with kidney and liver injury and kidney cancer [17] and [18] . Moreover, xylene has been reported to cause liver and kidney damage in laboratory animals [14] and [19] . Conversely, some studies have failed to demonstrate any renal and liver injuries following exposure to BTX [20] and [21] . Although the issue of nephrotoxic and hepatotoxic potentials of petrol components has been considered individually, these effects from petrol as a complex of hydrocarbons have not been thoroughly investigated, and little information exists in this regard. This study was, therefore, undertaken to address this issue and in response to the concerns raised by the public regarding the safety of newly introduced unleaded petrol. 2. Materials and methods This was a cross-sectional study in which the hepatotoxic and nephrotoxic potentials of occupational exposure to unleaded petrol were assessed in a group of workers employed in Shiraz private petrol stations. The criteria of workers' selection were: (1) a history of at least 1 year occupational exposure to unleaded petrol; and (2) lack of history of exposure to other known nephrotoxic and hepatotoxic agents and no job history of exposure to other chemical materials. A referent group was composed of healthy individuals without current or past exposure to agents known to cause any hepatotoxic or nephrotoxic response. Collectively, 400 individuals (200 referent individuals and 200 exposed workers) entered the study. Exposed participants were the employees of all (20 active) private petrol stations in Shiraz. They were shift workers who used to work in rotating 8-hour shift schedules, morning shifts (5:00 AM to 1:00 PM), mid-day shifts (1:00 PM to 9:00 PM) and overnight shifts (9:00 PM to 5:00 AM). All individuals signed an informed consent form before entering the study. The study was funded by the Vice

机译：抽象背景无铅汽油包含大量的单环芳烃，如苯，甲苯和二甲苯（BTX）。仅在有限的研究中评估了职业性接触无铅汽油后的毒性反应。这项研究的主要目的是确定在正常工作条件下暴露于无铅汽油是否与任何肝毒性或肾毒性反应有关。调查了无铅汽油的暴露情况以及200名未暴露的雇员。使用标准方法测量BTX的大气浓度。此外，还从个体中采集尿液和空腹血样，以进行尿液分析和肾和肝功能的常规生化检查。结果发现，空气中BTX浓度的几何平均值为0.8？mg？m ？3 ，分别为1.4？mg？m ？3 和2.8？mg？m ？3 。此外，接触者的直接胆红素，丙氨酸氨基转移酶，天冬氨酸氨基转移酶，血尿素和血浆肌酐的含量明显高于未接触者。相反，加油站工人的血清白蛋白，总蛋白以及钙和钠的血清浓度显着低于未暴露的工人。结论加油站工人的平均暴露于BTX的水平不超过当前阈值（TLV）化学药品。然而，在暴露的个体中，有明显的，亚临床的和病理前的早期肝肾功能不全的证据。关键词血液生化检验;苯，甲苯和二甲苯;肝毒性;肾毒性;无铅汽油prs.rt（“ abs_end”）; 1.简介无铅汽油包含大量的芳香烃[1]。在芳香族化合物中，苯，甲苯和二甲苯（BTX）是汽油中最危险的元素[2]和[3]。在汽油的生产，分配和使用过程中，存在人类急性或慢性毒性的风险[4]。人类和动物接触无铅汽油后，已经报道了肝毒性和肾毒性[2]，[3]和[5]。例如，在实验动物中已报道了肾腺瘤[5]，肝酶[6]和[7]，血清尿素，肌酐和钾的血清活性升高，以及氯和钠的降低[8]。同样，据报道，驾驶员和工人接触无铅汽油后蛋白尿，肝酶（天冬氨酸氨基转移酶，碱性磷酸酶，丙氨酸氨基转移酶）血清活性升高以及总胆红素和脂肪肝变化[9]，[10]，[11] ]和[12]。此外，已经报道二甲苯和甲苯在人类中引起肾脏和肝脏损害以及毒性[13]，[14]和[15]。肾脏的影响包括肾小管酸中毒，低血钾，低血磷症，氮质血症，血尿，蛋白尿和脓尿，均已暴露于甲苯后[16]。此外，接触苯和烷基苯与肾脏和肝损伤以及肾癌有关[17]和[18]。而且，已经报道二甲苯在实验动物中引起肝和肾损害[14]和[19]。相反，一些研究未能证明暴露于BTX后会造成肾脏和肝脏损伤[20]和[21]。尽管已单独考虑了汽油成分的肾毒性和肝毒性潜力问题，但尚未充分研究汽油作为碳氢化合物的复合物所产生的这些影响，在这方面几乎没有信息。因此，进行这项研究是为了解决这个问题，并回应了公众对新引入的无铅汽油安全性的关注。 2.材料和方法这是一项横断面研究，其中在设拉子私人加油站工作的一组工人中评估了职业性接触无铅汽油的肝毒性和肾毒性潜力。选择工人的标准是：（1）有至少一年无铅汽油职业暴露史; （2）没有接触其他已知肾毒性和肝毒性药物的病史，也没有接触其他化学物质的工作史。指称组由健康个体组成，他们没有或没有暴露于已知会引起任何肝毒性或肾毒性反应的药物。总共有400个人（200位推荐人和200位受雇的工人）进入了研究。暴露的参与者是设拉子所有（20个在用）私人加油站的员工。他们是轮班工作人员，过去通常轮班工作8小时，早上上班（凌晨5:00至1:00 PM），中班（凌晨1:00至9:00 PM）和过夜（9 ：00 PM到5:00 AM）。所有个人在进入研究之前均签署了知情同意书。该研究由副院长资助

Early Liver and Kidney Dysfunction Associated with Occupational Exposure to Sub-Threshold Limit Value Levels of Benzene, Toluene, and Xylenes in Unleaded Petrol

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