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Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air

I. Toluene and m-xylene

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Summary

The present study was undertaken to investigate the influence of different exposure scenarios on the elimination of toluene and m-xylene in alveolar air and other biological fluids in human volunteers. The study was also aimed at establishing the effectiveness of physiologically based toxicokinetic models in predicting the value of biological monitoring data after exposure to toluene and m-xylene. Two adult male and two adult female white volunteers were exposed by inhalation, in a dynamic, controlled-environment exposure chamber, to various concentrations of toluene (21–66 ppm) or mxylene (25–50 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on respective biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of hippuric acid and m-methylhippuric acid were determined. The results show that doubling the exposure concentration for both solvents led to a proportional increase in the concentrations of unchanged solvents in alveolar air and blood at the end of a 7-h exposure period. Cumulative urinary excretion of the respective metabolites exhibited a nearly proportional increase. Adjustment of exposure concentration to account for a prolongation of the duration of exposure resulted in essentially identical cumulative urinary excretion of the metabolites. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar concentration for both solvents, depending on whether or not sampling preceded or followed peak exposure to solvent. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of both solvents were increased by 40%. Experimental data collected during the present study were adequately simulated by physiologically based toxicokinetic modeling. These results suggest that alveolar air solvent concentration is a reliable index of exposure to both toluene and m-xylene under various experimental exposure scenarios. For clinical situations likely to be encountered in the workplace, physiologically based toxicokinetic modeling appears to be a useful tool both for developing strategies of biological monitoring of exposure to volatile organic solvents and for predicting alveolar air concentrations under a given set of exposure conditions.

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References

  • ACGIH (1986) Documentation of the threshold limit values and biological exposure indices. ACGIH, Cincinnati, Ohio

    Google Scholar 

  • ACGIH (1991) Threshold limit values and biological exposure indices for 1991–92. ACGIH, Cincinnati, Ohio

    Google Scholar 

  • Andersen ME (1989) Physiological modeling of tissue dosimetry. CUT Activities 9:1–8

    Google Scholar 

  • Andersen ME, Clewell HJ III, Gargas ML, MacNaughton MG, Reitz RH, Nolan RJ, McKenna MJ (1991) Physiologically based pharmacokinetic modeling with dichloromethane, its metabolites, carbon monoxide, and blood carboxyhemoglobin in rats and humans. Toxicol Appl Pharmacol 108:14–27

    Google Scholar 

  • Andersen ME, Krishnan K, Conolly RB, McClellan RO (1992) Mechanistic toxicology research and biologically-based modeling: partners for improving quantitative risk assessments. CIIT Activities 12:1–7

    Google Scholar 

  • Arms AD, Travis CC (1988) Reference physiological parameters in pharmacokinetic modeling. Office of Health and Environmental Assesment, U.S. EPA, Washington, D.C., NTIS PB 88-196019

    Google Scholar 

  • Astrand I (1983) Effect of physical exercise on uptake, distribution and elimination of vapors in man. In: Fiserova-Bergerova V (ed) Modeling of inhalation exposure to vapors: uptake, distribution and elimination. vol 2. CRC Press, Boca Raton, pp 107–129

    Google Scholar 

  • Astrand I, Samuel E, Kilbom A, Ovrum P (1972) Toluene exposure — I. Concentration in alveolar air and blood at rest and during exercise. Work Environ Health 9:119–130

    Google Scholar 

  • Baelum J (1990) Toluene in alveolar air during controlled exposure to constant and varying concentrations. Int Arch Occup Environ Health 62:59–64

    Google Scholar 

  • Baelum J (1991) Human solvent exposure. Factors influencing the pharmacokinetics and acute toxicity. Pharmacol Toxicol 68 [Suppl]:1–36

    Google Scholar 

  • Baelum J, Dossing M, Steen HH, Lundgvist GR, Andersen NT (1987) Toluene metabolism during exposure to varying concentrations combined with exercise. Int Arch Occup Environ Health 59:281–294

    Google Scholar 

  • Berlin MJ, Gage B, Gullberg B (1980) Breath concentration as an index of the health risk from benzene. Scand J Work Environ Health 6:104–111

    Google Scholar 

  • Bois FY, Zeise L, Tozer TN (1990) Precision and sensitivity of pharmacokinetic models for cancer risk assessment: tetrachloroethylene in mice, rats, and humans. Toxicol Appl Pharmacol 102:300–315

    Google Scholar 

  • Bois FY, Woodruff TJ, Spear RC (1991) Comparison of three physiologically based pharmacokinetic models of benzene disposition. Toxicol Appl Pharmacol 110:79–88

    Google Scholar 

  • Droz PO (1985) The use of simulation models for setting BEIs for organic solvents. Ann Am Conf Ind Hyg 12:339–350

    Google Scholar 

  • Droz PO, Fernandez JG (1977) Effect of physical workload on retention and metabolism of inhaled organic solvents: a comparative theoretical approach and its application with regards to exposure monitoring. Int Arch Occup Environ Health 38:231–246

    Google Scholar 

  • Droz PO, Wu MM, Cumberland WG (1989a) Variability in biological monitoring of solvent exposure. 11. Application of a population physiological model. Br J Ind Med 46:547–558

    Google Scholar 

  • Droz PO, Wu MM, Cumberland WG, Berode M (1989b) Variability in biological monitoring of solvent exposure. I. Development of a population physiological model. Br J Ind Med 46:447–460

    Google Scholar 

  • D'Souza RW, Boxenbaum H (1988) Physiological pharmacokinetic models: some aspects of theory, practice and potential. Toxicol Ind Health 4:151–171

    Google Scholar 

  • Engstrom K, Husman K, Pfaffli P, Riihimaki V (1978) Evaluation of occupational exposure to xylene by blood, exhaled air and urine analysis. Scand J Work Environ Health 4:114–121

    Google Scholar 

  • Farrar D, Allen B, Crump K, Shipp A (1989) Evaluation of uncertainty in input parameters to pharmacokinetic models and the resulting uncertainty in output. Toxicol Lett 49:371–385

    Google Scholar 

  • Fiserova-Bergerova V (1985) Toxicokinetics of organic solvents. Scand J Work Environ Health 11 [Suppl]:7–21

    Google Scholar 

  • Fiserova-Bergerova V (1987) Simulation models as a tool for adjustment of biological exposure indices to exposure conditions. In: Ho MH, Dillon HK (eds) Biological monitoring of exposure to chemicals: organic compounds. Wiley, New York, pp 29–57

    Google Scholar 

  • Fiserova-Bergerova V (1990) Application of toxicokinetic models to establish biological exposure indicators. Ann Occup Hyg 34:639–651

    Google Scholar 

  • Fiserova-Bergerova V, Vlach J, Cassady JC (1980) Predictable “individual differences” in uptake and excretion of gases and lipid soluble vapours: simulation study. Br J Ind Med 37:42–49

    Google Scholar 

  • Fiserova-Bergerova V, Tichy M, DiCarlo FJ (1984) Effect of biosolubility on pulmonary uptake and disposition of gases and vapors of lipophilic chemicals. Drug Metabol Rev 15:1033–1070

    Google Scholar 

  • Graves DA, Locke CS Jr, Muir KT, Miller RP (1989) The influence of assay variability on pharmacokinetic parameter estimation. J Pharmacol Biopharm 17:571–592

    Google Scholar 

  • Guberan E, Fernandez J (1974) Control of industrial exposure to tetrachloroethylene by measuring alveolar concentrations: theoretical approach using a mathematical model. Br J Ind Med 31:159–167

    Google Scholar 

  • Johanson G, Naslund PH (1988) Spreadsheet programming. A new approach in physiologically based modeling of solvent toxicokinetics. Toxicol Lett 41:115–127

    Google Scholar 

  • Kaneko T (1990) A physiological simulation model of m-xylene pharmacokinetic behaviour: its development and application to biological exposure monitoring. Thesis, Medical University of Yamanashi, Tamaho, Yamanashi, Japan

    Google Scholar 

  • Koizumi A (1989) Potential of physiologically based pharmacokinetics to amalgamate kinetic data of trichloroethylene and tetrachloroethylene obtained in rats and man. Br J Ind Med 46:239–249

    Google Scholar 

  • Krishnan K, Andersen ME (1990) The role of physiological modeling in reducing animal use in toxicology research. In: Goldberg AM (ed) Alternative methods in toxicology, vol 8. In vitro toxicology: mechanisms and new technology. Ann Liebert, New York, pp 113–133

    Google Scholar 

  • Leung HW (1991) Development and utilization of physiologically based pharmacokinetic models for toxicological applications. J Toxicol Environ Health 32:247–268

    Google Scholar 

  • Leung HW (1992) Use of physiologically based pharmacokinetic models to establish biological exposure indexes. Am Ind Hyg Assoc J 53:369–374

    Google Scholar 

  • Liira J, Riihimaki V, Pfaffli P (1988) Kinetics of methyl ethyl ketone in man: absorption, distribution and elimination in inhalation exposure. Int Arch Occup Environ Health 60:195–200

    Google Scholar 

  • Liira J, Johanson G, Riihimaki V (1990) Dose-dependent kinetics of inhaled methylethylketone in man. Toxicol Lett 50:195–201

    Google Scholar 

  • Perbellini I, Mozzo P, Olivato D, Brugnone F (1990) “Dynamic” biological exposure indexes for n-hexane and 2,5-hexanedione, suggested by a physiologically based pharmacokinetic model. Am Ind Hyg Assoc J 51:356–362

    Google Scholar 

  • Purcell KJ, Gregory HC, Gargas ML, Andersen ME, Travis CC (1990) In vivo metabolic interactions of benzene and toluene. Toxicol Lett 52:141–152

    Google Scholar 

  • Ramsey JC, Andersen ME (1984) A physiologically-based description of the inhalation pharmacokinetics of styrene in rats and humans. Toxicol Appl Pharmacol 73:159–175

    Google Scholar 

  • Sato A (1991) The effect of environmental factors on the pharmacokinetic behaviour of organic solvent vapours. Ann Occup Hyg 35:525–541

    Google Scholar 

  • Sato A, Nakajima T, Fujiwara Y (1975) Determination of benzene and toluene in blood by means of a syringe-equilibration method using a small amount of blood. Br J Ind Med 32:210–214

    Google Scholar 

  • Sato A, Endoh K, Kaneko T, Johanson G (1991) A simulation study of physiological factors affecting pharmacokinetic behaviour of organic solvent vapours. Br J Ind Med 48:342–347

    Google Scholar 

  • Sherwood RJ (1972) Benzene: the interpretation of monitoring results. Ann Occup Hyg 15:409–421

    Google Scholar 

  • Tardif R, Plaa GL, Brodeur J (1989) Simultaneous high-performance liquid chromatographic analysis of hippuric acid and ortho-, meta- and para-methylhippuric acids in urine. J Anal Toxicol 13:313–316

    Google Scholar 

  • Tardif R, Lapare S, Krishnan K, Brodeur J (1992) In vivo characterization of the metabolic interaction between toluene and xylene in rats. Can Fed Biol Soc 35:101

    Google Scholar 

  • Wallen M, Holm S, Nordgvist MB (1985) Co-exposure to toluene and p-xylene in man: uptake and elimination. Br J Ind Med 42:111–116

    Google Scholar 

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Authors and Affiliations

  1. Département de médecine du travail et d'hygiéne du milieu, Faculté de médecine, Université de Montreal, C.P. 6128, Succ. “A”, H3C 3J7, Montréal, Québec, Canada

    S. Laparé, R. Tardif & J. Brodeur

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  1. S. Laparé
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  2. R. Tardif
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  3. J. Brodeur
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Laparé, S., Tardif, R. & Brodeur, J. Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air. Int. Arch Occup Environ Heath 64, 569–580 (1993). https://doi.org/10.1007/BF00517703

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  • DOI: https://doi.org/10.1007/BF00517703

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