Kezic S, Meuling W J A, Jakasa I
Coronel Laboratory, Faculty of Medicine, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands.
Int Arch Occup Environ Health. 2004 Nov;77(8):580-6. doi: 10.1007/s00420-004-0540-3. Epub 2004 Nov 17.
To assess excretion kinetics of free and total (free + conjugated) 2-butoxyacetic acid (BAA) following dermal and inhalation exposure to butoxyethanol (BE).
Six male volunteers were dermally exposed for 4 h to a 50% aqueous solution of BE on an area of 40 cm(2) of the volar forearm. Six other male volunteers were exposed by inhalation (mouth only) to 93 mg m(-3) BE for 30 min. As biological indices of exposure, BE in blood and total and free BAA in urine were measured.
Following inhalation exposure, the 24-h cumulative excretion of free and total BAA in urine amounted to 5.5 +/- 2.7 and 12.8 +/- 4.0 mg, respectively. After dermal exposure, 147.1 +/- 61.0 and 346 +/- 52 mg, respectively, of free and total BAA were excreted in urine up to 48 h after the onset of exposure. The proportion of conjugated BAA in single urine samples increased after dermal exposure in time from 45+/-30% in the first collection period to 92+/-2% after 48 h. The elimination half-life of total BAA following dermal exposure was longer than that of free BAA (5.1 +/- 0.6 and 3.8 +/- 0.4 h, respectively). The interindividual variation in the cumulative excreted amount after inhalatory exposure was higher (49%) for free BAA than for total BAA (31%). The average dermal flux amounted to 3.5 mg cm(-2) h(-1) independently of whether free or total BAA was used for the calculation, and, again, the interindividual variation in the estimated fluxes was higher for free BAA than for total BAA (41% and 15%, respectively).
The interindividual variation in the extent of conjugation is large, and the degree of conjugation increases with time. Due to lower interindividual variability, total BAA is superior to free BAA as a biomarker of exposure.
评估在经皮和经吸入接触丁氧基乙醇(BE)后,游离及总(游离 + 结合态)2 - 丁氧基乙酸(BAA)的排泄动力学。
6名男性志愿者在前臂掌侧40 cm²的面积上经皮接触50%的BE水溶液4小时。另外6名男性志愿者经吸入(仅通过口腔)接触93 mg/m³的BE 30分钟。测量血液中的BE以及尿液中的总BAA和游离BAA作为接触的生物学指标。
经吸入接触后,尿液中游离和总BAA的24小时累积排泄量分别为5.5±2.7 mg和12.8±4.0 mg。经皮接触后,在接触开始后48小时内,尿液中游离和总BAA分别排泄了147.1±61.0 mg和346±52 mg。单次尿液样本中结合态BAA的比例在经皮接触后随时间增加,从第一个采集期的45±30%增加到48小时后的92±2%。经皮接触后总BAA的消除半衰期长于游离BAA(分别为5.1±0.6小时和3.8±0.4小时)。经吸入接触后,游离BAA累积排泄量的个体间差异(49%)高于总BAA(31%)。无论计算时使用游离还是总BAA,平均经皮通量均为3.5 mg/cm²·h⁻¹,并且,游离BAA估计通量的个体间差异再次高于总BAA(分别为41%和15%)。
结合程度的个体间差异很大,且结合程度随时间增加。由于个体间变异性较低,总BAA作为接触生物标志物优于游离BAA。