Free and total urinary 2-butoxyacetic acid following dermal and inhalation exposure to 2-butoxyethanol in human volunteers

Objectives: To assess excretion kinetics of free and total (free + conjugated) 2-butoxyacetic acid (BAA) following dermal and inhalation exposure to butoxyethanol (BE). Methods: Six male volunteers were dermally exposed for 4 h to a 50% aqueous solution of BE on an area of 40 cm² 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. Results: 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). Conclusion: 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.