PNNL

Abstract

It's assumed that the skin contributes minor amounts to the total uptake of solvent vapors, relative to the respiratory tract. Contrary, glycol ether solvent,2-butoxyethanol(BE),has been reported to be more effectively absorbed through the skin(75% of the total uptake)than through the lungs of humans(Johanson and Boman,Br.J.Ind.Med.1991,48,788). The possibility that the finger prick blood sampling technique used in the J.and B.study was confounded by locally high concentrations of BE at the site of absorption was suggested using a previously-developed PBPK model(Corley et al.,Tox. Appl.Pharm.1994,129,61). The study was to verify the PBPK analysis and to determine whether or not the skin was the major site for absorption of BE vapor by exposing one arm from each of six volunteers to 50 ppm 13C2-BE vapor for two hr. Samples were taken from both the unexposed arm (catheter; during and after exposure) and the exposed arm (fingerprick; end of the exposure only) for analysis of both BE and butoxyacetic acid(BAA). The concentration of BE in the finger prick blood samples averaged 1500 times higher than the corresponding concentration in venous blood sampled from a catheter in the unexposed arm at the end of the exposure. Blood BAA levels were within a factor of 4 of each other for the two techniques and was considered a better indicator of systemic absorbtion. Urine was collected for 24 hr and analyzed for the following metabolites found in rat metabolism studies: free and conjugated BE, BAA, ethylene glycol(EG) and glycolic acid(GA),with only BAA detected in the human urine. Urinary BAA was found to be extensively conjugated(~67%)with glutamine. The results, coupled with PBPK modeling of worst-case exposure scenarios(no clothing) demonstrated that no more than 15-27%(low-to-high relative temperatures and humidities),not 75%, of the total uptake of BE could be attributed to the skin of humans during simulated 8-hr exposures to the ACGIH TLV concentra- tration of 25ppm.