Brodkin C A, Moon J D, Camp J, Echeverria D, Redlich C A, Willson R A, Checkoway H
Department of Medicine, University of Washington, Seattle, WA, USA.
Occup Environ Med. 2001 Feb;58(2):95-102. doi: 10.1136/oem.58.2.95.
To determine whether hepatic biochemical changes, as measured by routinely available tests indicative of hepatocellular necrosis, cholestasis, or altered hepatic clearance of bilirubin, occur in association with low to moderate exposure to styrene commonly experienced in industrial production.
Two independent cross sectional studies were performed comparing serum hepatic transaminases (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)), cholestatic enzymes (alkaline phosphatase (AP) and gamma glutamyl transpeptidase (GGT)), and bilirubin in (a) 47 workers of fibreglass reinforced plastics who were exposed to styrene and (b) 21 boat and tank fabricators, with separate referent groups of unexposed workers. Exposure to styrene was assessed in air by dosimetry, and in venous blood by headspace analysis. Hepatic biochemical variables were assessed across strata of exposure to styrene defined as 25 ppm in air, or 0.275 mg/l in blood, adjusting for age, sex, body mass index, and ethanol consumption.
A consistent and significant linear trend for increasing direct bilirubin and direct/total bilirubin ratio was found in association with increasing exposure to styrene, by both air and blood monitoring, in both studies. Mean direct bilirubin concentrations increased from 0.05-0.08 mg% in referents to 0.12-0.19 in workers exposed above 25 ppm, with a significant exposure-response trend (p<0.005). Significantly increased direct/total bilirubin ratios, ranging from 0.22 to 0.35 were associated with exposure to styrene (p<0.001), indicating diminished hepatic clearance of conjugated bilirubin. Also, a significant linear association between the hepatic transaminases ALT and AST and exposure to styrene was found in pooled regression analyses, with an increase in AP of about 10 IU/ml in workers exposed above 25 ppm air or 0.275 mg/l blood styrene in pooled analyses from both studies.
The consistent finding of increased direct bilirubin and AP concentrations in these two independent studies provides evidence for diminished hepatic clearance of conjugated bilirubin with associated cholestasis in workers exposed to styrene. The finding of a significant linear association between hepatic transaminase concentrations and exposure to styrene in pooled analyses is consistent with mild hepatic injury and associated metabolic dysfunction.
通过常规可用的检测方法来测定肝细胞坏死、胆汁淤积或胆红素肝清除率改变相关的肝脏生化变化是否与工业生产中常见的低至中度苯乙烯暴露有关。
进行了两项独立的横断面研究，比较了（a）47名接触苯乙烯的玻璃纤维增强塑料工人和（b）21名船舶及罐体制造者的血清肝转氨酶（丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST））、胆汁淤积酶（碱性磷酸酶（AP）和γ-谷氨酰转肽酶（GGT））以及胆红素，并分别设立未接触工人作为对照。通过剂量测定法评估空气中苯乙烯暴露情况，通过顶空分析法评估静脉血中苯乙烯暴露情况。针对空气中苯乙烯暴露量为25 ppm或血液中苯乙烯暴露量为0.275 mg/l所定义的苯乙烯暴露分层，对肝脏生化变量进行评估，并对年龄、性别、体重指数和乙醇摄入量进行校正。
在两项研究中，通过空气和血液监测均发现，随着苯乙烯暴露量增加，直接胆红素和直接/总胆红素比值呈现出一致且显著的线性趋势。在对照中，平均直接胆红素浓度从0.05 - 0.08 mg%增加到苯乙烯暴露量高于25 ppm的工人中的0.12 - 0.19 mg%，呈现出显著的暴露 - 反应趋势（p<0.005）。苯乙烯暴露与直接/总胆红素比值显著升高相关，范围从0.22至0.35（p<0.001），表明结合胆红素的肝脏清除率降低。此外，在汇总回归分析中发现肝转氨酶ALT和AST与苯乙烯暴露之间存在显著的线性关联，在两项研究的汇总分析中，苯乙烯暴露量高于空气中25 ppm或血液中0.275 mg/l的工人中，AP升高约10 IU/ml。
这两项独立研究中一致发现直接胆红素和AP浓度升高，为接触苯乙烯的工人中结合胆红素肝脏清除率降低及相关胆汁淤积提供了证据。汇总分析中肝转氨酶浓度与苯乙烯暴露之间存在显著线性关联，这与轻度肝损伤及相关代谢功能障碍相符。
