Institute for Occupational, Social and Environmental Medicine, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Arch Toxicol. 2023 Apr;97(4):1033-1045. doi: 10.1007/s00204-023-03447-x. Epub 2023 Jan 30.
The solvent 1,3-dichlorobenzene (1,3-DCB) is formed during thermal decomposition of the initiator 2,4-dichlorobenzoylperoxide in the production of silicone rubber with potential exposure of production workers as shown in previous works. Despite a threshold limit value (MAK value) of 2 ppm in air, there are currently no data about the corresponding internal exposure that would allow for the derivation of a biological limit value. In the present study, we have investigated the absorption of 1,3-DCB and urinary kinetics of its metabolites in 10 human volunteers after controlled inhalative exposure. Due to the strong odour of 1,3-DCB, a subjective evaluation of odour nuisance was also performed. Ten male human volunteers (23-36 yrs.) were exposed 6 h/day to a concentration of 0.7 ppm and 1.5 ppm in the Aachen workplace simulation laboratory (AWSL) with one week between each experiment. In order to investigate potential dermal absorption, the volunteers were exposed to 1.5 ppm wearing a suitable filter mask that prevented inhalative exposure in a third exposure. 1,3-DCB in blood was measured after 3 and 6 h exposure and the urinary metabolites 3,5-dichlorocatechol (3,5-DCC), 2,4-dichlorophenol (2,4-DCP) and 3,5-dichlorophenol (3,5-DCP) were measured over 24 h after exposure via LC/MS/MS. There were clear dose-response relations for all investigated parameters. The maximum excretion of the metabolites was reached at the end of exposure and corresponded to 5.2 ± 0.7 mg/g crea, 1.5 ± 0.35 mg/g crea and 0.07 ± 0.011 mg/g crea at 0.7 ppm and to 12.0 ± 3 mg/g crea, 3.5 ± 1.1 mg/g crea and 0.17 ± 0.05 mg/g crea at 1.5 ppm for 3,5-DCC, 2,4-DCP and 3,5-DCP, respectively. The use of filter masks decreased the internal exposure for about 85-90%, indicating substantial dermal absorption. Odour perception did not show a dose-response, probably due to fast olfactory adaption. The human study presented here provides an excellent basis for deriving a biological limit value for 1,3-DCB.
溶剂 1,3-二氯苯（1,3-DCB）是在硅橡胶生产中引发剂 2,4-二氯过氧化苯甲酰热分解时形成的，生产工人可能会接触到该物质。尽管空气中的阈限值（MAK 值）为 2 ppm，但目前尚无关于相应的内部暴露的数据，无法推导出生物限值。在本研究中，我们对 10 名男性志愿者进行了受控吸入暴露，以研究 1,3-DCB 的吸收和其代谢物的尿动力学。由于 1,3-DCB 气味强烈，因此还进行了气味危害的主观评估。10 名男性志愿者（23-36 岁）在亚琛工作场所模拟实验室（AWSL）中以 0.7 ppm 和 1.5 ppm 的浓度暴露 6 小时/天，每次实验之间间隔一周。为了研究潜在的皮肤吸收，志愿者在第三次暴露时佩戴合适的过滤面罩，以防止吸入暴露，该暴露的浓度为 1.5 ppm。在暴露 3 和 6 小时后测量血液中的 1,3-DCB，并通过 LC/MS/MS 在暴露后 24 小时内测量尿代谢物 3,5-二氯邻苯二酚（3,5-DCC）、2,4-二氯苯酚（2,4-DCP）和 3,5-二氯苯酚（3,5-DCP）。所有调查参数均显示出明显的剂量反应关系。代谢物的最大排泄量在暴露结束时达到，分别为 0.7 ppm 时的 5.2±0.7 mg/g·肌酐、1.5±0.35 mg/g·肌酐和 0.07±0.011 mg/g·肌酐，以及 1.5 ppm 时的 12.0±3 mg/g·肌酐、3.5±1.1 mg/g·肌酐和 0.17±0.05 mg/g·肌酐。使用过滤面罩可将内部暴露量减少约 85-90%，表明存在大量皮肤吸收。气味感知没有表现出剂量反应，可能是由于嗅觉快速适应。本研究为推导 1,3-DCB 的生物限值提供了良好的基础。
