The Effect of Workload on Biological Monitoring of Occupational Exposure to Toluene and N-Hexane: Contribution of Physiologically Based Toxicokinetic Modeling

Abstract

A physiologically based toxicokinetic model was used to examine the impact of work load on the relationship between the airborne concentrations and exposure indicator levels of two industrial solvents, toluene and n-Hexane. The authors simulated occupational exposure (8 hr/day, 5 days/week) at different concentrations, notably 20 ppm and 50 ppm, which are the current threshold limit values recommended by ACGIH for toluene and n-hexane, respectively. Different levels of physical activity, namely, rest, 25 W, and 50 W (for 12 hr followed by 12 hr at rest) were simulated to assess the impact of work load on the recommended biological exposure indices: toluene in blood prior to the last shift of the workweek, urinary o-cresol (a metabolite of toluene) at the end of the shift, and free (nonhydrolyzed) 2,5-hexanedione (a metabolite of n-hexane) at the end of the shift at the end of the workweek. In addition, urinary excretion of unchanged toluene was simulated. The predicted biological concentrations were compared with the results of both experimental studies among human volunteers and field studies among workers. The highest predicted increase with physical exercise was noted for toluene in blood (39 microg/L at 50 W vs. 14 microg/L at rest for 20 ppm, i.e., a 2.8-fold increase). The end-of-shift urinary concentrations of o-cresol and toluene were two times higher at 50 W than at rest (for 20 ppm, 0.65 vs. 0.33 mg/L for o-cresol and 43 vs. 21 microg/L for toluene). Urinary 2,5-hexanedione predicted for 50 ppm was 1.07 mg/L at 50 W and 0.92 mg/L at rest (+16%). The simulations that best describe the concentrations among workers exposed to toluene are those corresponding to 25 W or less. In conclusion, toxicokinetic modeling confirms the significant impact of work load on toluene exposure indicators, whereas only a very slight effect is noted on n-hexane kinetics. These results highlight the necessity of taking work load into account in risk assessment relative to toluene exposure.

Aliphatic Hydrocarbons

“…Hexane concentrations in exhaled air increased between 7 and 20% with increasing workload intensity (221). PBTK modeling of hexane exposures predict urinary 2,5-hexanedione increased 35% with increasing workload in the same hexane exposure (222). Steady-state levels of hexane in blood were linearly dose dependent following inhalation of up to 200 ppm.…”

Sex Differences in Urinary Levels of Several Biological Indicators of Exposure: A Simulation Study Using a Compartmental-Based Toxicokinetic Model

“…Interestingly, urinary levels following TLV exposures to MEK and 1M2P were found to be higher than the current BEI (see Figure 8), suggesting that work load can have a significant impact on biological exposure indicators. (35) The poorest fit of the model to data occurred in the elimination phases of the urinary biomarkers of exposure, mainly for urinary MEK and urinary 1M2P (free and total). In fact agreement between observed and predicted values is weaker and this can lead to an over-or underestimation of the corresponding exposure level.…”

Accounting for the impact of short-term variations in the levels of trihalomethane in drinking water on exposure assessment for epidemiological purposes. Part II: Biological aspects

“…18 Modeling can describe the absorption, distribution, metabolism and elimination of a contaminant within an organism, thereby serving to estimate biological exposure indicators or assess the effect of various factors on their levels. 19 The relevance and usefulness of such assessments have been investigated several times in recent years. 6,[20][21][22][23]…”