Summary
The urinary excretion of hippuric acid (HA) and ortho-cresol (O-cr) in man was measured in two studies of 7-h exposure to toluene in a climate chamber, either constant concentration of 100 ppm or varying concentrations containing peaks of 300 ppm but with a time-weighted average of 100 ppm. In Study A, four males were exposed to clean air and to constant and varying concentrations of toluene in combination with rest and with 100 W exercise in 140 min. Exercise increased end exposure excretion rate of HA and O-cr by 47 and 114%, respectively. After exposure, all excess HA was excreted within 4 h, while O-cr was eliminated with a half life of about 3 h. Alveolar air concentration of toluene varied between 21 and 31 ppm during constant exposure and between 13 and 57 ppm during varying exposure, but no difference in mean alveolar toluene concentration or in metabolite excretion was seen between the exposure schedules. In Study B, 32 males and 39 females aged between 31 and 50 years were exposed once to either clean air, constant or varying concentrations of toluene. Background excretion rate of HA was 0.97 ± 0.75 mg/min (1.25 ± 1.05 g/g creatinine) and rose to 3.74 ± 1.40 mg/min (3.90 ± 1.85 g/g cr) during the last 3 h of exposure to 100 ppm toluene. The corresponding figures for O-cr were 0.05 ± 0.05 μg/min (0.08 ± 0.14 mg/g cr), and 2.04 ± 0.84 μg/min (2.05 ± 1.18 mg/g cr). The individual creatinine excretion rate was considerably influenced by sex, body weight and smoking habits, thus influencing the metabolite concentration standardised in relation to creatinine. It is concluded that both metabolites are estimates of toluene exposure. O-cr is more specific than HA, but the individual variation in excretion of both metabolites is large, and when implementing either of them as biological exposure indices, the influence of sex, body size, age as well as consumption of tobacco and alcohol has to be considered.
Similar content being viewed by others
References
Allessio L, Berlin A, Dell Orto A, Toffoletto F, Ghezzi I (1985) Reliability of urinary creatinine as a parameter used to adjust values of urinary biological indicators. Int Arch Occup Environ Health 55:99–106
American Conference of Governmental Industrial Hygienists (1984) Supplemental documentation. Biological exposure indices, Cincinnati, Ohio
American Conference of Governmental Industrial Hygienist (1984-5). Threshold limit values for chemical substances and physical agents in the work environment. Cincinnati, Ohio
Andersen I, Lundqvist GR, Mølhave L, Pedersen OF, Proctor DF, Væth M, Wyon DP (1983) Human response to controlled levels of toluene in six-hour exposure. Scand J Work Environ Health 9:405–418
Andersson R, Carlsson A, Byfält-Nordqvist M, Sollenberg J (1983) Urinary excretion of hippuric acid and O-cresol after laboratory exposure of humans to toluene. Int Arch Occup Environ Health 53:101–108
Apostoli P, Brugnone F, Perbellini L, Cocheo V, Bellomo ML, Silvestri R (1982) Biomonitoring of occupational toluene exposure. Int Arch Occup Environ Health 50:153–168
Armitage P (1971) Statistical methods in medical research. Blackwell Scientific Publications, Oxford
Åstrand I, Ehrner-Samuel H, Kilbom Å, Övrum P (1972) Toluene exposure I. Concentration in alveolar air and blood at rest and during exercise. Work Environ Health 9:119–130
Åstrand PO (1977) Textbook of work physiology, 2nd ed. McGraw Hill Book Company, New York
Bonsnes RW, Tanssky HH (1945) On colorimetric determination of creatinine by Jaffe reaction. J Biol Chem 158:581–591
Bülow J (1982) Adipose tissue blood flow during exercise. Lægeforeningens forlag, Copenhagen
Carlsson A (1982) Exposure to toluene. Uptake, distribution and elimination in man. Scand J Work Environ Health 8:43–55
De Rosa E, Brugnone F, Bartolucci GB, Perbellini L, Bellomo ML, Gori GP, Signon M, Chiesura Corona P (1985) The validity of urinary metabolites as indicators of low exposures to toluene. Int Arch Occup Environ Health 56:135–145
Døssing M, Bælum J, Hansen SH, Lundqvist GR, Andersen NT (1983) Urinary hippuric acid and ortho-cresol excretion in man during experimental exposure to toluene. Br J Ind Health 40:470–473
Døssing M, Bælum J, Hansen SH, Lundqvist GR (1984) Effect of ethanol, cimetidine and propranolol on toluene metabolism in man. Int Arch Occup Environ Health 54:309–315
Downey HF, Crystal GJ, Bashour FA (1982) Regional renal and splancnic blood flows during nicotine infusion: effects of alpha and of combined alpha and beta adrenergic blocade. J Pharmacol Exp Ther 220:375–381
Droz PO, Berode M, Boillat MA, Lob M (1984) Biological monitoring and health surveillance of rotagravure printing workers exposed to toluene. Presented at the ACS meeting, St. Louis
Hansen SH, Døssing M (1982) Determination of urinary hippuric acid and O-cresol as indices of toluene exposure by liquid chromatography on dynamically modified silica. J Chromatogr229:141–148
Hasegawa K, Shiojima S, Koizumi A, Ikeda M (1983) Hippuric acid and O-cresol in the urine of workers exposed to toluene. Int Arch Occup Environ Health 52:197–208
Kjærgaard S, Mølhave L, Bælum J (1985) Variations in the burden of solvent vapours among printers. Arbejdsmiljøfondet, Copenhagen (In Danish)
Numeric Algorithms Group (1980) GENSTAT. A general statistic program. Rothamsted Experimental Station, UK
Övrum P, Hultengren M, Lindqvist T (1978) Exposure to toluene in a photogravure printing plant. Scand J Work Environ Health 4:237–245
Pfäffli P, Savolainen H, Kalliomäki PL, Kaaliokoski P (1979) Urinary O-cresol in toluene exposure. Scand J Work Environ Health 5:286–289
Sato A, Nakajima T (1984) Dietary carbohydrate and ethanol induces alteration of the metabolism and toxicity of chemical substances. Nutr Cancer 6:121–132
Veulemans H, Masschelein R (1978) Experimental human exposure to toluene. II. Toluene in venous blood during and after exposure. Int Arch Environ Health 42:105–117
Veulemans H, Masschelein R (1979) Experimental human exposure to toluene. III. Urinary hippuric acid excretion as a measure of individual solvent uptake. Int Arch Environ Health 43:53–62
Waldron HA, Cherry N, Johnston JD (1983) The effects of ethanol on blood toluene concentration. Int Arch Occup Environ Health 51:365–369
WHO, Technical Report Series no. 664 (1981) Recommended health-based limits in occupational exposure to selected organic solvents. WHO, Geneva
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bælum, J., Døssing, M., Hansen, S.H. et al. Toluene metabolism during exposure to varying concentrations combined with exercise. Int. Arch Occup Environ Heath 59, 281–294 (1987). https://doi.org/10.1007/BF00377740
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00377740