Inhalation and epidermal exposure of volunteers to ethylene glycol: Kinetics of absorption, urinary excretion, and metabolism to glycolate and oxalate

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• 作者：Swapna Upadhyay ; Joern Carstens ; Dominik Klein ; Thomas H. Faller ; Stephan Halbach ; Werner Kirchinger ; Winfried Kessler ; Gyö ; rgy A. Csaná ; dy ; Johannes G. Filser
• 关键词：Ethylene glycol ; Human ; Health risk ; Epidermal exposure ; Inhalation exposure ; Permeability constant
• 刊名：Toxicology Letters
• 出版年：2008
• 出版时间：5 May 2008
• 年：2008
• 卷：178
• 期：2
• 页码：131-141
• 全文大小：1027 K

文摘

Ethylene glycol (EG) is a widely used liquid. Limited data are published regarding inhaled EG and no data regarding transdermal EG uptake in humans. In order to gain information on the quantitative fate of EG, four male volunteers inhaled between 1340 and 1610 μmol vaporous ¹³C-labeled EG (¹³C₂-EG) for 4 h. Separately, three of these subjects were epidermally exposed for up to 6 h to liquid ¹³C₂-EG (skin area 66 cm²). Plasma concentrations and urinary amounts of ¹³C₂-EG were determined by gas chromatography with mass selective detection. Additionally, plasma was assayed for ¹³C-labeled glycolic acid (¹³C₂-GA) and urine for ¹³C₂-GA and ¹³C-labeled oxalic acid (¹³C₂-OA). Both EG metabolites were nephrotoxic in animals and humans and embryotoxic in rodents. ¹³C-labels enabled to differentiate from also determined endogenous EG, glycolic acid (GA), and oxalic acid (OA). Of ¹³C₂-EG inhaled, 5.5 ± 3.0 % , 0.77 ± 0.15 % , and 0.10 ± 0.12 % were detected in urine as ¹³C₂-EG, ¹³C₂-GA, and ¹³C₂-OA, respectively. The skin permeability constant of liquid EG was 2.7 × 10⁻⁵ ± 0.5 × 10⁻⁵ cm/h. Of the dose taken up transdermally, 8.1 ± 3.2 % and up to 0.4 % were excreted in urine as ¹³C₂-EG and ¹³C₂-GA, respectively. It is calculated that equally long-lasting exposure to 10 ppm vaporous EG or wetting of both hands by liquid EG leads to about the same body burden by EG and metabolites. The amounts of GA and OA excreted daily in urine as a result of exposure (8 h/day) to 10 ppm EG are about 15 % and 2 % , respectively, of those excreted from naturally occurring endogenous GA and OA.