A comparison of 1H8-and 2H8-toluene toxicokinetics in men

Abstract

1. To examine the bioequivalence of an isotope-labelled tracer to study toxicant disposition, we conducted 33 controlled human exposures to a mixture of 50 ppm 1H8-toluene and 50 ppm 2H8-toluene for 2 h, and measured concentrations in blood and breath, and metabolite levels in urine for 100 h post-exposure. 2. A physiologically based kinetic (PBK) model found that compared with 1H8-toluene, 2H8-toluene had a 6.4+/-13% (mean+/-SD) lower AUC, a 6.5+/-13% higher systemic clearance (1.46+/-0.27 versus 1.38+/-0.25 l/h-kg), a 17+/-22% larger terminal volume of distribution (66.4+/-14 versus 57.2+/-10 l/kg) and a 9.7+/-26% longer terminal half-life (38+/-12 versus 34+/-10 h) (p < 0.05 for all comparisons). 3. The higher 2H8-toluene clearance may have been due to an increased rate of ring oxidation, consistent with the 17% higher observed fraction of 2H5- versus 1H5-cresol metabolites in urine. 4. The larger terminal volume and half-lives for 2H8-toluene suggested a higher adipose tissue/blood partition coefficient. 5. Observed isotope differences were small compared with interindividual differences in 1H8-toluene kinetics from previous studies. 6. The PBK model allowed us to ascribe observed isotope differences in solvent toxicokinetics to underlying physiologic mechanisms.

Estimation of absorption of aromatic hydrocarbons diffusing from interior materials in automobile cabins by inhalation toxicokinetic analysis in rats

“…However, in most of the reports, the values of the metabolic parameters used for their models were calculated from the results obtained in animal experimentations (Adams et al, 2005;Borm and de Barbanson, 1988;Droz et al, 1989;Jonsson and Johanson, 2001;Pierce et al, 1996aPierce et al, , 1999Ramsey and Andersen, 1984;Tardif et al, 1995Tardif et al, , 1997. There are a few available reports on models designed on the basis of the values of the metabolic parameters examined in humans (Jarnberg and Johanson, 1999;Lof and Johanson, 1993).…”

Benzene, toluene, ethylbenzene, and xylene: Current analytical techniques and approaches for biological monitoring

“…In acute inhalation exposure, absorbed toluene is excreted predominately in the urine as metabolites and, to a lesser extent (7-20% of absorbed toluene), as unmetabolized form in exhaled air and urine [72,73]. The majority of absorbed toluene is rapidly eliminated from the body [74,75] and a smaller portion (that which accumulated in adipose tissues) is slowly eliminated [73,74,76]. Excretion of unchanged toluene in urine is a minor elimination route based on mass balance.…”