Urinary excretion of heptanones, heptanoles and 2, 5-heptanedione after controlled acute exposure of volunteers to n-heptane. (1st December 2018)

• Record Type: Journal Article
• Authors: Rossbach, Bernd; Kegel, Peter; Letzel, Stephan
• Is Part Of: Toxicology letters. Volume 298(2018)
• Page Start: 81
• Page End: 90
• Publication Date: 2018-12-01
• Subjects: n-Heptane -- Biological monitoring -- Volunteer study -- Experimental exposure -- SPDE -- Metabolites -- Urine; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2018.03.031
• Languages: English
• ISSNs: 0378-4274

Abstract

Abstract: A lack of well-established parameters and assessment values currently impairs biomonitoring of n-heptane exposure. Using controlled inhalation experiments, we collected information on urinary n-heptane metabolite concentrations and the time course of metabolite excretion. Relationships between external and internal exposure were analysed to investigate the suitability of selected metabolites to reflect n-heptane uptake. Twenty healthy, non-smoking males (aged 19–38 years, median 25.5) were exposed for 3 h to 167, 333 and 500 ppm n-heptane, each. Spot urine samples of the volunteers, collected before exposure and during the following 24 h, were analysed for heptane-2-one, 3-one, 4-one, 2, 5-dione, 1-ol, 2-ol, 3-ol, and 4-ol using headspace solid phase dynamic extraction gas chromatography/mass spectrometry (HS-SPDE-GC/MS). Starting from median pre-exposure concentrations between <0.5 (3-one) and 82.9 μg/L (4-one), exposure increased the concentrations for all parameters except for 4-one. Median post-exposure concentrations ranged up to 840.4 μg/L (2-ol) and decreased with half-lifes <3 h after exposure. Non-parametric correlation analyses (n = 47, p < 0.05) revealed weak to moderate associations of volume related metabolite excretion with external exposure for 2-one, 3-one and 2, 5-dione (R = 0.332–0.753). Heptanol excretion was moderately associated with exposure (R ≥ 0.509) only after creatinine adjustment. Lacking association with external exposure impedes the use of 4-one as heptane biomarker, whereas 2-ol and 3-ol turned out to be sensitive indicators of exposure if creatinine correction is applied. By providing fundamental data on a panel of eight potential heptane metabolites, our study can help to promote biological monitoring of n-heptane exposure.