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Derivation of an occupational exposure limit for benzene using epidemiological study quality assessment tools
Toxicology Letters ( IF 3.5 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.toxlet.2020.05.036
A Robert Schnatter 1 , Martijn Rooseboom 2 , Neslihan Aygun Kocabas 3 , Colin M North 4 , Abigail Dalzell 5 , Johannes Twisk 6 , Frank Faulhammer 7 , Erik Rushton 8 , Peter J Boogaard 2 , Viktorija Ostapenkaite 5 , Stephen D Williams 5
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This paper derives an occupational exposure limit for benzene using quality assessed data. Seventy-seven genotoxicity and 36 haematotoxicity studies in workers were scored for study quality with an adapted tool based on that of Vlaanderen et al, 2008 (Environ Health. Perspect. 116 1700-5). These endpoints were selected as they are the most sensitive and relevant to the proposed mode of action (MOA) and protecting against these will protect against benzene carcinogenicity. Lowest and No- Adverse Effect Concentrations (LOAECs and NOAECs) were derived from the highest quality studies (i.e. those ranked in the top tertile or top half) and further assessed as being "more certain" or "less certain". Several sensitivity analyses were conducted to assess whether alternative "high quality" constructs affected conclusions. The lowest haematotoxicity LOAECs showed effects near 2 ppm (8 h TWA), and no effects at 0.59 ppm. For genotoxicity, studies also showed effects near 2 ppm and showed no effects at about 0.69 ppm. Several sensitivity analyses supported these observations. These data define a benzene LOAEC of 2 ppm (8 h TWA) and a NOAEC of 0.5 ppm (8 h TWA). Allowing for possible subclinical effects in bone marrow not apparent in studies of peripheral blood endpoints, an OEL of 0.25 ppm (8 h TWA) is proposed.

中文翻译:

使用流行病学研究质量评估工具推导出苯的职业接触限值

本文使用质量评估数据推导出苯的职业接触限值。使用基于 Vlaanderen 等人,2008 年 (Environ Health. Perspect. 116 1700-5) 的改编工具对工人的 77 项基因毒性和 36 项血液毒性研究进行了研究质量评分。选择这些终点是因为它们对提议的作用模式 (MOA) 最敏感且最相关,并且防止这些终点将防止苯致癌。最低和无副作用浓度(LOAEC 和 NOAEC)来自最高质量的研究(即排在前三分位数或前半部分的研究),并进一步评估为“更确定”或“不太确定”。进行了几项敏感性分析以评估替代的“高质量”结构是否影响结论。最低的血液毒性 LOAEC 在 2 ppm(8 小时 TWA)附近显示出影响,在 0.59 ppm 时没有影响。对于遗传毒性,研究还表明在 2 ppm 附近有影响,在 0.69 ppm 左右没有影响。一些敏感性分析支持了这些观察结果。这些数据定义了 2 ppm (8 h TWA) 的苯 LOAEC 和 0.5 ppm (8 h TWA) 的 NOAEC。考虑到在外周血终点研究中不明显的骨髓亚临床效应,建议 OEL 为 0.25 ppm(8 小时 TWA)。
更新日期:2020-11-01
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