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 μg/L at 50 W vs. 14 μg/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 μg/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.

Keywords:

• free 2,5-hexanedione
• industrial solvents
• o-cresol
• physical activity
• toluene in blood and urine
• toxicokinetic models

ACKNOWLEDGMENTS

This study was funded by the Agence française de sécurité sanitaire de l'environnement et du travail (Afsset), France (EST-2007-n°78) and by the Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST # 099–170), Québec, Canada. Irène Sari-Minodier was a recipient of a grant from the Association pour le développement des recherches biologiques et médicales au centre hospitalier régional de Marseille (A.DE.REM), France.

Notes

^A From Hamelin et al.^{( 29 )}

^B The values in parentheses are for n-hexane model.

^C From Åstrand (for rest and 50 W),^{( 3 )} for toluene model only; blood flow for 25 W was calculated by linear interpolation between the values at rest and 50 W.

^D From Kumagai and Matsunaga,^{( 35 )} for toluene model only.

^A From Sato.^{( 36 )}

^B From Fisher et al.^{( 32 )}

^C From Thrall et al.^{( 37 )} (saline:air partition coefficient)

^D From Gargas et al.^{( 34 )}

^E Determined in our laboratory according to Sato and Nakajima.^{( 39 )}

^F From Tardif et al.^{( 31 )}

^G From Ali and Tardif.^{( 38 )}

^H From this study; based on the best fit of the simulation to the time-course data on o-CR excretion over the three periods (0–3 hr, 3–7 hr, and 7–24 hr) from Tardif et al.'s experimental study.^{( 40 )}

^I From Hamelin et al.^{( 29 )}

^J From Laparé et al.^{( 33 )}

^A Bold type: sampling times that are relevant for biological monitoring.

^A Bold type: sampling times that are relevant for biological monitoring.

^A Expressed in ppm as AM ± ASD; median; GM(GSD); min-max (as specified by the authors.)

^B Toluene only (if specified by the authors).

^C End (or second half) of workweek (if specified by the authors).

^D Estimated mean toluene exposure during the workweek.

^E Number of regression equations.

^F Mean of values obtained from regression equations.

^G Mean of values obtained from regression equations, weighted by the number of subjects (or samples) included in each regression equation.

^A Expressed in ppm as AM ± ASD; median; GM(GSD); min-max (as specified by the authors).

^B 29 workers over 5 consecutive days.

^C Toluene only (if specified by the authors).

^D End of the first half of the shift (4 hr).

^E End (or second half) of workweek (if specified by the authors).

^F 30 exposed M and 20 nonexposed M.

^G The author's equation stated as T(ppm) = 0,89(μg/L)+5.26 was inconsistent with the plots showing solvent in urine concentration on the y axis.

^H 57 exposed M, and 20 nonexposed M.

^I 86 exposed workers (76 M + 10 W) and 11 nonexposed controls (6 M + 5 W).

^J Number of regression equations.

^K Mean of values obtained from regression equations.

^L Mean of values obtained from regression equations, weighted by the number of subjects (or samples) included in each regression equation.

^A Expressed in ppm as AM ± ASD; median; GM(GSD); min-max (as specified by the authors).

^B End (or second half) of workweek (if specified by the authors).

^C Toluene only (if specified by the authors).

^D 14 workers over 3 consecutive days.

^E 6 workers over 5 consecutive days.

^F 452 exposed workers (206 M + 246 W) and 517 nonexposed controls (246 M + 271 W).

^G 122 exposed M and 30 nonexposed M.

^H Number of regression equations.

^I Mean of values obtained from regression equations.

^J Mean of values obtained from regression equations, weighted by the number of subjects (or samples) included in each regression equation.

^A Expressed in ppm as AM ± ASD; median; GM(GSD); min-max (as specified by the authors).

^B HEX was combined with other solvents (TOL, ethyl acetate …).

^C 28 workers with gloves and 59 workers without gloves.

^D End (or second half) of workweek (if specified by the authors).

^E 123 exposed workers (104 M + 19 W) and 53 nonexposed controls.

^F 30 exposed M and 20 nonexposed M.

^G Urine samples were taken from Monday to Friday.

^H Number of regression equations.

^I Mean of values obtained from regression equations.

^J Mean of values obtained from regression equations, weighted by the number of subjects (or samples) included in each regression equation.