Exponential Modeling, Washout Curve Reconstruction, and Estimation of Half-Life of Toluene and its Metabolites

Abstract

Health risks from ostensible occupational and environmental toxicant exposure are difficult to quantify. Maximal use of limited biological measurements of xenobiotic or metabolite concentration in the body is therefore essential. Elimination rates of exhaled [²H8]toluene and urinary metabolites were analyzed from 33 exposures of males to 50 ppm [²H8]toluene for 2 h at rest. It was hypothesized that the shapes from our decay curves would be applicable to any occupational or environmental toluene exposure. Except for a rapid decline in toluene blood and breath levels in the 0–0.1 h period, this “curve reconstruction” method successfully fit data from published studies. Urinary hippuric acid concentrations were not well fit due to substantial background levels, whereas o-cresol levels were accurately described. Our approach was able to reconstruct data from studies where exposure duration ranged from 10 min to 7 h, and where activity level ranged from rest to 150 W (strenuous exercise). Using this approach, limited biological data following toluene exposure could be back-extrapolated to immediate postexposure concentrations, which in turn could be compared to biological indicators of exposure to determine risk.

We thank Russell Dills and David Kalman for laboratory support during the original exposures, and Danny Shen and Robert Hink for valuable discussion. This work was supported by the Superfund Basic Research program, NIEHS ES 04696, and by NIOSH SERCA grant 5 K01 OH00164.