Estimation of Background Exposure to Toluene Using a Physiologically-Based Kinetic Model

Crispin H. PIERCE; Russell L. DILLS; Thomas A. LEWANDOWSKI; Michael S. MORGAN; Mike A. WESSELS; Danny D. SHEN; David A. KALMAN

doi:10.1539/joh.39.130

Crispin H. PIERCE, Russell L. DILLS, Thomas A. LEWANDOWSKI, Michael S. MORGAN, Mike A. WESSELS, Danny D. SHEN, David A. KALMAN

著者情報

キーワード: Toluene, Toxicokinetics, PBPK, Model, Isotope

ジャーナルフリー

1997 年 39 巻 2 号 p. 130-137

DOI https://doi.org/10.1539/joh.39.130

詳細

Published: 1997 Received: 1996/10/17 Available on J-STAGE: 2006/04/07 Accepted: 1996/11/20 Advance online publication: - Revised: -
訂正情報
訂正日: 2006/04/07 訂正理由: - 訂正箇所: 論文抄録訂正内容: Wrong : Estimation of Background Exposure to Toluene Using a Physiologically-Based Kinetic Model: Crispin H. PIERCE, et al. Department of Environmental Health, University of Washington&Mdash;Estimation of environmental exposure to toxicants has generally been limited to concentration measurements in air, water, and foods. Measurement of background levels of toxicants in biological tissues for this purpose has been limited by analytical detection. After developing a sensitive headspace GC-MS method, we conducted 33 controlled human exposures of 50 ppm ¹H₈ toluene and 50 ppm ²H₈ toluene for 2 h, and measured concentrations in blood and breath for 100 h post-exposure. Blood and breath samples from a separate cohort of 9 men exposed to ²H₈ toluene only were also measured for background ¹H₈-toluene levels. A physiologically-based kinetic (PBK) model, previously constructed and validated in an analysis of the ²H₈ toluene data, was used to predict the level of ambient ¹H₈-toluene exposure that produced the observed breath levels. The model-derived estimate of mean background ¹H₈-toluene exposure was 47 ± 44 ppb (mean ± s.d.), which is consistent with indoor air measurements from this and previous studies of 3-27 ppb and outdoor measurements of 2-43 ppb. According to the PBK model, background exposure was expected to produce an average blood concentration of 5.9 nmol/l, which was within a measured range of 3-16 nmol/l, and a corresponding alveolar air concentration of 310 nmol/m³, within a range of 138-764 nmol/m³. This work extends the use of physiologic modeling to back-predict environmental dose, and found that significant differences in inter-individual ¹H₈ toluene background exposures exist. (J Occup Health 1997; 39: 130-137)
Right : Estimation of Background Exposure to Toluene Using a Physiologically-Based Kinetic Model: Crispin H. PIERCE, et al. Department of Environmental Health, University of Washington—Estimation of environmental exposure to toxicants has generally been limited to concentration measurements in air, water, and foods. Measurement of background levels of toxicants in biological tissues for this purpose has been limited by analytical detection. After developing a sensitive headspace GC-MS method, we conducted 33 controlled human exposures of 50 ppm ¹H₈ toluene and 50 ppm ²H₈ toluene for 2 h, and measured concentrations in blood and breath for 100 h post-exposure. Blood and breath samples from a separate cohort of 9 men exposed to ²H₈ toluene only were also measured for background ¹H₈-toluene levels. A physiologically-based kinetic (PBK) model, previously constructed and validated in an analysis of the ²H₈ toluene data, was used to predict the level of ambient ¹H₈-toluene exposure that produced the observed breath levels. The model-derived estimate of mean background ¹H₈-toluene exposure was 47 ± 44 ppb (mean ± s.d.), which is consistent with indoor air measurements from this and previous studies of 3-27 ppb and outdoor measurements of 2-43 ppb. According to the PBK model, background exposure was expected to produce an average blood concentration of 5.9 nmol/l, which was within a measured range of 3-16 nmol/l, and a corresponding alveolar air concentration of 310 nmol/m³, within a range of 138-764 nmol/m³. This work extends the use of physiologic modeling to back-predict environmental dose, and found that significant differences in inter-individual ¹H₈ toluene background exposures exist. (J Occup Health 1997; 39: 130-137)

訂正日: 2006/04/07 訂正理由: - 訂正箇所: 引用文献情報訂正内容: Wrong : 1) Veulemans H, Masschelein R. Experimental human exposure to toluene. Int Arch Occup Environ Health 1978; 42:105-117.
2) Nise G, Attewell R, Skerfving S, Ørbæk P. Elimination of toluene from venous blood and adipose tissue after occupational exposure. Br J Ind Med 1989; 46: 407-411.
3) Mannino D, Schreiber J, Aldous K, et al. Human exposure to volatile organic compounds: a comparison of organic vapor monitoring badge levels with blood levels. Int Arch Occup Environ Health 1995; 67: 59-64.
4) Kawai T, Mizunuma K, Yasugi T, et al. Toluene in blood as a marker of choice for low-level exposure to toluene. Int Arch Occup Environ Health 1994; 66: 309-315.
5) Kawai T, Yasugi T, Mizunuma K, et al. Urinalysis vs. blood analysis, as a tool for biological monitoring of solvent exposure. Tox Lett 1992; 63: 333-343.
6) Kawai T, Yasugi T, Mizunuma K, et al. Comparative evaluation of urinalysis and blood analysis as means of detecting exposure to organic solvents at low concentrations. Int Arch Occup Environ Health 1992; 64: 223-234.
7) Kawai T, Yasugi T, Mizunuma K, et al. Monitoring of workers exposed to a mixture of toluene, styrene and methanol vapours by means of diffusive air sampling, blood analysis and urinalysis. Int Arch Occup Environ Health 1992; 63: 429-435.
8) Etzel R, Ashley D. Volatile organic compounds in the blood of persons in Kuwait during the oil fires. Int Arch Occup Environ Health 1994; 66: 125-129.
9) Ashley D, Bonin M, Cardinali F, et al. Blood concentrations of volatile organic compounds in a nonoccupationally exposed US population and in groups with suspected exposure. Clin Chem 1994; 40: 1401-1404.
10) Brugnone F, Perbellini L, Faccini GB, et al. Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure. Int Arch Occup Environ Health 1989; 61: 303-311.
11) Vrca A, Bozicevic D, Karacic V, et al. Visual evoked potentials in individuals exposed to long-term low concentrations of toluene. Arch Toxicol 1995; 69: 337-340.
12) Brugnone F, Gobbi M, Ayyad K, et al. Blood toluene as a biological index of environmental toluene exposure in the “normal” population and in occupationally exposed workers immediately after exposure and 16 hours later. Int Arch Occup Environ Health 1995; 66: 421-425.
13) Fustinoni S, Buratti M, Giampiccolo R, Colombi A. Biological and environmental monitoring of exposure to airborne benzene and other aromatic hydrocarbons in Milan traffic wardens. Toxicol Let 1995; 77: 387-392.
14) Thomas R, Bigelow P, Keefe T, Yang R. Variability in biological exposure indices using physiologically based pharmacokinetic modeling and monte carlo simulation. Am Ind Hyg Assoc J 1996; 57: 23-32.
15) American Conference of Governmental Industrial Hygienists. 1994-1995 Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati: ACGIH, 1994: 12-36.
16) Leung H. Use of physiologically based pharmacokinetic models to establish biological exposure indexes. Am Ind Hyg Assoc J 1992; 53: 369-374.
17) Georgopoulos P, Roy A, Gallo M. Reconstruction of short-term multi-route exposure to volatile organic compounds using physiologically based pharmacokinetic models. J Expos Anal Environ Epidem 1994; 4: 309-328.
18) Weisel C, Shepard T. Chloroform exposure and the resulting body burden associated with swimming in chlorinated pools. In: Wang R, ed. Drinking water contamination and health. New York: Marcel Dekker, 1993:135-148.
19) Durnin J, Womersley J. Body fat assessed from total body density and its estimation from skin fold thickness-measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 1974; 32: 77-97.
20) Morgan M, Dills RL, Kalman D. Evaluation of stable isotope-labeled probes in the study of solvent pharmacokinetics in human subjects. Int Arch Occup Environ Health 1993; 65 (1 Suppl): S 139-142.
21) Dills RL, Kent S, Checkoway H, Kalman D. Quantification of volatile solvents in blood by static headspace analysis. Talanta 1991; 38: 365-374.
22) US Department of Health, Education, and Welfare. NIOSH Manual of Analytical Methods (NIOSH 84-100). Cincinnati: NIOSH, 1985: 1501-1-1501-7.
23) Pierce C, Dills RL, Morgan M, et al. Interindividual differences in ²H₈-toluene toxicokinetics assessed by a semi-empirical physiologically-based model. Toxicol Appl Pharmacol 1996; 139: 49-61.
24) Tardif R, Laparé S, Krishnan K, Brodeur J. Physiologically based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat. Toxicol Appl Pharmacol 1993; 120: 266-273.
25) Rowland M, Tozer TN. Clinical Pharmacokinetics: Concepts and applications. 2nd ed. Philadelphia: Lea & Febiger, 1989: 132.
26) Gargas ML, Burgess RJ, Voisard DE, et al. Partition coefficients of low-molecular-weight volatile chemicals in various liquids and tissues. Toxicol Appl Pharmacol 1989;98:87-99.
27) Pierce C, Dills RL, Silvey G, Kalman D. Partition coefficients between human blood or adipose tissue and air for aromatic solvents. Scand J Work Environ Health 1996;22:112-118.
28) Mordenti J. Man versus beast: pharmacokinetic scaling in mammals. J Pharm Sci 1986; 75: 1028-1040.
29) Morgan D, Bray K. Lean body mass as a predictor of drug dosage. Clin Pharmacokinet 1994; 26: 292-307.
30) Katayama M, Yamazumi K, Kino K, et al. Changes in liver weight in the elderly. Nippon Ronen Igakkai Zasshi 1990;27:584-588.
31) Girardin E, Bruguerolle B. Pharmacokinetic changes in obesity. Therapie 1993; 48: 397-402.
32) Ings R. Interspecies scaling and comparisons in drug development and toxicokinetics. Xenobiotica 1990; 20: 1201-1231.
33) D''Sousa R, Boxenbaum H. Physiological pharmacokinetic models: some aspects of theory, practice and potential. Tox Ind Health 1988; 4: 151-171.
34) Ritschel W, Vachharajani N, Johnson R, Hussain A. The allometric approach for interspecies scaling of pharmacokinetic parameters. Comp Biochem Physiol 1992; 103C: 249-253.
35) Leggett R, Williams L. Suggested reference values for regional blood volumes in humans. Health Physics 1991; 60:139-154.
36) Davis N, Mapleson W. A physiological model for the distribution of injected agents, with special reference to pethidine. Br J Anaesth 1993; 70: 248-258.
37) Blaak EE, van Blaak MA, Kemerink GJ, et al. Total forearm blood flow as an indicator of skeletal muscle blood flow: effect of subcutaneous adipose tissue blood flow. Clin Science 1994; 87: 559-566.
38) Ferrannini E. The haemodynamics of obesity: a theoretical analysis. J Hypertens 1992; 10: 1417-1423.
39) Wheeler C, Wrighton S, Guenthner T. Detection of human lung cytochromes P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450111A. Biochem Pharmacol 1992; 44: 183-186.
40) Thummel KE, Kharasch ED, Podoll T, Kunze K. Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1. Drug Metab Dispos 1993; 21: 350-357.
41) Carlsson A, Ljungquist E. Exposure to toluene: concentration in subcutaneous adipose tissue. Scand J Work Environ Health 1982; 8: 56-62.
42) Lioy P, Wallace L, Pellizzari E. Indoor/outdoor, and personal monitor and breath analysis relationships for selected volatile organic compounds measured at three homes during New Jersey TEAM-1987. J Expos Anal Environ Epidemiol 1991; 1: 45-61.
43) Kraybill H. Assessment of human exposure to environmental contaminants with special reference to cancer. In: Clayson D, Krewski D, Munro I, eds. Toxicological risk assessment. Vol. II: General criteria and case studies. Boca Raton: CRC Press, Inc., 1985: 17-42.
44) Steiner EC, Rey TD, McCroskey PS. Reference guide-SimuSolv modeling and simulation software. Midland: Dow Chemical Co., 1990: 5-104-5-109.
45) American Conference of Governmental Industrial Hygienists. Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati: ACGIH, 1991: BE1169-BE1174.
46) American Conference of Governmental Industrial Hygienists. 1990-1991 Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati: ACGIH, 1990: 62.
47) Brugnone F, de Rosa E, Perbellini L, et al. Blood and alveolar toluene concentrations in workers during the workshift and the morning after. Appl Ind Hyg 1986; 1: 21-24.
48) Foo S, Jeyaratnam J, Ong C, et al. Biological monitoring for occupational exposure to toluene. Am Ind Hyg Assoc J 1991; 52: 212-217.
49) Löfgren L, Persson K, Strömvall A, Petersson G. Exposure of commuters to volatile aromatic hydrocarbons from petrol exhaust. Sci Total Environ 1991; 108: 225-233.
50) Wallace L, Nelson W, Ziegenfus R. The Los Angeles TEAM study: personal exposures, indoor-outdoor air concentrations, and breath concentrations of 25 volatile organic compounds. J Exp Anal Environ Epidemiol 1991; 1: 157-192.
51) Seifert B, Abraham H. Indoor air concentrations of benzene and some other aromatic hydrocarbons. Ecotoxicol Environ Safety 1982; 6: 190-192.
52) Evans G, Smith D, Somerville M. Measurements of VOCs from the TAMS network. J Air Waste Manage Assoc 1992; 42:1319-1323.
53) Boström C, Almen J, Steen B, Westerholm R. Human exposure to urban air pollution. Env Health Perspec 1994; 102 (Suppl 4): 39-47.
54) Andersen ME, MacNaughton MG, Clewell H III, Paustenbach DJ. Adjusting exposure limits for long and short exposure periods using a physiological pharmacokinetic model. Am Ind Hyg Assoc J 1987; 48: 335-343.

Right : 1) Veulemans H, Masschelein R. Experimental human exposure to toluene. Int Arch Occup Environ Health 1978; 42:105-117.
2) Nise G, Attewell R, Skerfving S, Ørbæk P. Elimination of toluene from venous blood and adipose tissue after occupational exposure. Br J Ind Med 1989; 46: 407-411.
3) Mannino D, Schreiber J, Aldous K, et al. Human exposure to volatile organic compounds: a comparison of organic vapor monitoring badge levels with blood levels. Int Arch Occup Environ Health 1995; 67: 59-64.
4) Kawai T, Mizunuma K, Yasugi T, et al. Toluene in blood as a marker of choice for low-level exposure to toluene. Int Arch Occup Environ Health 1994; 66: 309-315.
5) Kawai T, Yasugi T, Mizunuma K, et al. Urinalysis vs. blood analysis, as a tool for biological monitoring of solvent exposure. Tox Lett 1992; 63: 333-343.
6) Kawai T, Yasugi T, Mizunuma K, et al. Comparative evaluation of urinalysis and blood analysis as means of detecting exposure to organic solvents at low concentrations. Int Arch Occup Environ Health 1992; 64: 223-234.
7) Kawai T, Yasugi T, Mizunuma K, et al. Monitoring of workers exposed to a mixture of toluene, styrene and methanol vapours by means of diffusive air sampling, blood analysis and urinalysis. Int Arch Occup Environ Health 1992; 63: 429-435.
8) Etzel R, Ashley D. Volatile organic compounds in the blood of persons in Kuwait during the oil fires. Int Arch Occup Environ Health 1994; 66: 125-129.
9) Ashley D, Bonin M, Cardinali F, et al. Blood concentrations of volatile organic compounds in a nonoccupationally exposed US population and in groups with suspected exposure. Clin Chem 1994; 40: 1401-1404.
10) Brugnone F, Perbellini L, Faccini GB, et al. Breath and blood levels of benzene, toluene, cumene and styrene in non-occupational exposure. Int Arch Occup Environ Health 1989; 61: 303-311.
11) Vrca A, Bozicevic D, Karacic V, et al. Visual evoked potentials in individuals exposed to long-term low concentrations of toluene. Arch Toxicol 1995; 69: 337-340.
12) Brugnone F, Gobbi M, Ayyad K, et al. Blood toluene as a biological index of environmental toluene exposure in the “normal” population and in occupationally exposed workers immediately after exposure and 16 hours later. Int Arch Occup Environ Health 1995; 66: 421-425.
13) Fustinoni S, Buratti M, Giampiccolo R, Colombi A. Biological and environmental monitoring of exposure to airborne benzene and other aromatic hydrocarbons in Milan traffic wardens. Toxicol Let 1995; 77: 387-392.
14) Thomas R, Bigelow P, Keefe T, Yang R. Variability in biological exposure indices using physiologically based pharmacokinetic modeling and monte carlo simulation. Am Ind Hyg Assoc J 1996; 57: 23-32.
15) American Conference of Governmental Industrial Hygienists. 1994-1995 Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati: ACGIH, 1994: 12-36.
16) Leung H. Use of physiologically based pharmacokinetic models to establish biological exposure indexes. Am Ind Hyg Assoc J 1992; 53: 369-374.
17) Georgopoulos P, Roy A, Gallo M. Reconstruction of short-term multi-route exposure to volatile organic compounds using physiologically based pharmacokinetic models. J Expos Anal Environ Epidem 1994; 4: 309-328.
18) Weisel C, Shepard T. Chloroform exposure and the resulting body burden associated with swimming in chlorinated pools. In: Wang R, ed. Drinking water contamination and health. New York: Marcel Dekker, 1993:135-148.
19) Durnin J, Womersley J. Body fat assessed from total body density and its estimation from skin fold thickness-measurements on 481 men and women aged from 16 to 72 years. Br J Nutr 1974; 32: 77-97.
20) Morgan M, Dills RL, Kalman D. Evaluation of stable isotope-labeled probes in the study of solvent pharmacokinetics in human subjects. Int Arch Occup Environ Health 1993; 65 (1 Suppl): S 139-142.
21) Dills RL, Kent S, Checkoway H, Kalman D. Quantification of volatile solvents in blood by static headspace analysis. Talanta 1991; 38: 365-374.
22) US Department of Health, Education, and Welfare. NIOSH Manual of Analytical Methods (NIOSH 84-100). Cincinnati: NIOSH, 1985: 1501-1-1501-7.
23) Pierce C, Dills RL, Morgan M, et al. Interindividual differences in ²H₈-toluene toxicokinetics assessed by a semi-empirical physiologically-based model. Toxicol Appl Pharmacol 1996; 139: 49-61.
24) Tardif R, Laparé S, Krishnan K, Brodeur J. Physiologically based modeling of the toxicokinetic interaction between toluene and m-xylene in the rat. Toxicol Appl Pharmacol 1993; 120: 266-273.
25) Rowland M, Tozer TN. Clinical Pharmacokinetics: Concepts and applications. 2nd ed. Philadelphia: Lea & Febiger, 1989: 132.
26) Gargas ML, Burgess RJ, Voisard DE, et al. Partition coefficients of low-molecular-weight volatile chemicals in various liquids and tissues. Toxicol Appl Pharmacol 1989;98:87-99.
27) Pierce C, Dills RL, Silvey G, Kalman D. Partition coefficients between human blood or adipose tissue and air for aromatic solvents. Scand J Work Environ Health 1996;22:112-118.
28) Mordenti J. Man versus beast: pharmacokinetic scaling in mammals. J Pharm Sci 1986; 75: 1028-1040.
29) Morgan D, Bray K. Lean body mass as a predictor of drug dosage. Clin Pharmacokinet 1994; 26: 292-307.
30) Katayama M, Yamazumi K, Kino K, et al. Changes in liver weight in the elderly. Nippon Ronen Igakkai Zasshi 1990;27:584-588.
31) Girardin E, Bruguerolle B. Pharmacokinetic changes in obesity. Therapie 1993; 48: 397-402.
32) Ings R. Interspecies scaling and comparisons in drug development and toxicokinetics. Xenobiotica 1990; 20: 1201-1231.
33) D'Sousa R, Boxenbaum H. Physiological pharmacokinetic models: some aspects of theory, practice and potential. Tox Ind Health 1988; 4: 151-171.
34) Ritschel W, Vachharajani N, Johnson R, Hussain A. The allometric approach for interspecies scaling of pharmacokinetic parameters. Comp Biochem Physiol 1992; 103C: 249-253.
35) Leggett R, Williams L. Suggested reference values for regional blood volumes in humans. Health Physics 1991; 60:139-154.
36) Davis N, Mapleson W. A physiological model for the distribution of injected agents, with special reference to pethidine. Br J Anaesth 1993; 70: 248-258.
37) Blaak EE, van Blaak MA, Kemerink GJ, et al. Total forearm blood flow as an indicator of skeletal muscle blood flow: effect of subcutaneous adipose tissue blood flow. Clin Science 1994; 87: 559-566.
38) Ferrannini E. The haemodynamics of obesity: a theoretical analysis. J Hypertens 1992; 10: 1417-1423.
39) Wheeler C, Wrighton S, Guenthner T. Detection of human lung cytochromes P450 that are immunochemically related to cytochrome P450IIE1 and cytochrome P450111A. Biochem Pharmacol 1992; 44: 183-186.
40) Thummel KE, Kharasch ED, Podoll T, Kunze K. Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1. Drug Metab Dispos 1993; 21: 350-357.
41) Carlsson A, Ljungquist E. Exposure to toluene: concentration in subcutaneous adipose tissue. Scand J Work Environ Health 1982; 8: 56-62.
42) Lioy P, Wallace L, Pellizzari E. Indoor/outdoor, and personal monitor and breath analysis relationships for selected volatile organic compounds measured at three homes during New Jersey TEAM-1987. J Expos Anal Environ Epidemiol 1991; 1: 45-61.
43) Kraybill H. Assessment of human exposure to environmental contaminants with special reference to cancer. In: Clayson D, Krewski D, Munro I, eds. Toxicological risk assessment. Vol. II: General criteria and case studies. Boca Raton: CRC Press, Inc., 1985: 17-42.
44) Steiner EC, Rey TD, McCroskey PS. Reference guide-SimuSolv modeling and simulation software. Midland: Dow Chemical Co., 1990: 5-104-5-109.
45) American Conference of Governmental Industrial Hygienists. Documentation of the threshold limit values and biological exposure indices. 6th ed. Cincinnati: ACGIH, 1991: BE1169-BE1174.
46) American Conference of Governmental Industrial Hygienists. 1990-1991 Threshold limit values for chemical substances and physical agents and biological exposure indices. Cincinnati: ACGIH, 1990: 62.
47) Brugnone F, de Rosa E, Perbellini L, et al. Blood and alveolar toluene concentrations in workers during the workshift and the morning after. Appl Ind Hyg 1986; 1: 21-24.
48) Foo S, Jeyaratnam J, Ong C, et al. Biological monitoring for occupational exposure to toluene. Am Ind Hyg Assoc J 1991; 52: 212-217.
49) Löfgren L, Persson K, Strömvall A, Petersson G. Exposure of commuters to volatile aromatic hydrocarbons from petrol exhaust. Sci Total Environ 1991; 108: 225-233.
50) Wallace L, Nelson W, Ziegenfus R. The Los Angeles TEAM study: personal exposures, indoor-outdoor air concentrations, and breath concentrations of 25 volatile organic compounds. J Exp Anal Environ Epidemiol 1991; 1: 157-192.
51) Seifert B, Abraham H. Indoor air concentrations of benzene and some other aromatic hydrocarbons. Ecotoxicol Environ Safety 1982; 6: 190-192.
52) Evans G, Smith D, Somerville M. Measurements of VOCs from the TAMS network. J Air Waste Manage Assoc 1992; 42:1319-1323.
53) Boström C, Almen J, Steen B, Westerholm R. Human exposure to urban air pollution. Env Health Perspec 1994; 102 (Suppl 4): 39-47.
54) Andersen ME, MacNaughton MG, Clewell H III, Paustenbach DJ. Adjusting exposure limits for long and short exposure periods using a physiological pharmacokinetic model. Am Ind Hyg Assoc J 1987; 48: 335-343.

訂正日: 2006/04/07 訂正理由: - 訂正箇所: PDFファイル訂正内容: -

抄録

Estimation of Background Exposure to Toluene Using a Physiologically-Based Kinetic Model: Crispin H. PIERCE, et al. Department of Environmental Health, University of Washington—Estimation of environmental exposure to toxicants has generally been limited to concentration measurements in air, water, and foods. Measurement of background levels of toxicants in biological tissues for this purpose has been limited by analytical detection. After developing a sensitive headspace GC-MS method, we conducted 33 controlled human exposures of 50 ppm ¹H₈ toluene and 50 ppm ²H₈ toluene for 2 h, and measured concentrations in blood and breath for 100 h post-exposure. Blood and breath samples from a separate cohort of 9 men exposed to ²H₈ toluene only were also measured for background ¹H₈-toluene levels. A physiologically-based kinetic (PBK) model, previously constructed and validated in an analysis of the ²H₈ toluene data, was used to predict the level of ambient ¹H₈-toluene exposure that produced the observed breath levels. The model-derived estimate of mean background ¹H₈-toluene exposure was 47 ± 44 ppb (mean ± s.d.), which is consistent with indoor air measurements from this and previous studies of 3-27 ppb and outdoor measurements of 2-43 ppb. According to the PBK model, background exposure was expected to produce an average blood concentration of 5.9 nmol/l, which was within a measured range of 3-16 nmol/l, and a corresponding alveolar air concentration of 310 nmol/m³, within a range of 138-764 nmol/m³. This work extends the use of physiologic modeling to back-predict environmental dose, and found that significant differences in inter-individual ¹H₈ toluene background exposures exist. (J Occup Health 1997; 39: 130-137)

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