Abstract
Numerous n-heptane metabolites have been identified and quantified by gas chromatography and mass spectrometry in some tissues and in the urine of Sprague Dawley rats exposed for 6 h to 1800 ppm n-heptane. 2-Heptanol and 3-heptanol were the main biotransformation products of the solvent. 2-Heptanone, 3-heptanone, 4-heptanol, 2,5-heptanedione, γ-valerolactone, 2-ethyl-5-methyl-2, 3-dihydrofuran and 2,6-dimethyl-2,5-dihydropyran were also found as metabolites of n-heptane. In five shoe factory workers and in three rubber factory workers the mean exposure to technical heptane was measured (n-heptane ranged between 5 and 196 mg/m3). In the urine collected at the end of their work shift some n-heptane biotransformation products were found: 2-heptanol, 3-heptanol, 2-heptanone, 4-heptanone and 2,5-heptanedione. 2-Heptanol was the main n-heptane metabolite and its urinary concentrations ranged between 0.1 and 1.9 mg/l. Urinary 2,5-heptanedione was detectable only in some samples and at very low concentration (0.1–0.4 mg/1).
These data suggest that n-heptane can be considered as a neurotoxic product, since it gives rise to 2,5-heptanedione, but the small amount of the urinary metabolite is very unlikely to cause clinical damage to the peripheral nervous system.
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References
Bahima J, Cert A, Menendez, Gallego M (1984) Identification of volatile metabolites of inhaled n-heptane in rat urine. Toxicol Appl Pharmacol 76: 473–482
Crespi V, Di Costanzo M, Ferrario F, Tredici G (1979) Electrophysiological findings in workers exposed to n-heptane fumes. J Neurol 222: 135–138
Di Vincenzo G, Kaplan CJ, Dedinas J (1976) Characterization of the metabolites of methyl n-butyl ketone, methyl iso-butyl ketone, and methyl ethyl ketone in guinea pig serum and their clearance. Toxicol Appl Pharmacol 36: 511–552
Frommer U, Ullrich V, Staudinger H, Orrenius S (1972) The monooxygenation of n-heptane by rat liver microsomes. Biochim Biophys Acta 280: 487–494
Frontali N, Amantini MC, Spagnolo A, Guarcini AM, Saltari MA, Brugnone F, and Perbellini L (1981) Experimental neurotoxicity and urinary metabolites of the C5–C7 aliphatic hydrocarbons used as glue solvents in shoe manufacture. Clin Toxicol 18: 1357–1367
Heller SR, Milne GWA (1978) EPA/NIH mass spectral data base. National Bureau of Standards. EPA/NIH Washington
Katz GV, O'Donoghue JL, Di Vincenzo GD, Terhaar CJ (1980) Comparative neurotoxicity and metabolism of ethyl n-butyl ketone and methyl n-butyl ketone in rats. Toxicol Appl Pharmacol 52: 153–158
Misumi J, Nagano M (1984) Neurophysiological studies on the relation between the structural properties and neurotoxicity of aliphatic hydrocarbon compounds in rats. Br J Ind Med 41: 526–532
Perbellini L, Brugnone F, Silvestri R, Gaffuri E (1981) Measurement of the urinary metabolites of n-hexane, cyclohexane and their isomers by gas chromatography. Int Arch Occup Environ Health 48: 99–106
Perbellini L, Brugnone F, Pavan I (1980) Identification of the metabolites of n-hexane, cyclohexane, and their isomers in men's urine. Toxicol Appl Pharmacol 53: 220–229
Perbellini L, Bartolucci GB, Brugnone F, De Rosa E, Valentini F (1985a) Il 2,5-esandione nel controllo biologico dell'esposizione professionale a n-esano. Med Lav 76: 35–43
Perbellini L, Brugnone F, Caretta D, Maranelli G (1985b) Partition coefficients of some industrial aliphatic hydrocarbons (C5–C7) in blood and in human tissues. Br J Ind Med 42: 162–168
Savolainen H, Pfaffli P (1980) Neurochemical effects on rats of n-heptane inhalation exposure. Arch Environ Contam Toxicol 9: 727–732
Spencer PS, Schaumburg HH, Sabri MI, Veronesi B (1980) The enlarged view of hexacarbon neurotoxicity. Crit Rev Toxicol 7: 279–356
Takeuchi Y, Ono Y, Hisanaga N, Kitoh J, Sugiura Y (1980) A comparative study on the neurotoxicity of n-pentane, n-hexane and n-heptane in the rat. Br J Ind Med 37: 241–247
Truhaut R, Laget P, Piat G, Nguyen Phu-Lich, Dutertre-Catella H, Vu Ngoc Huyen (1973) Premiers resultats électro-physiologiques après intoxications experimentales par l'hexane et par l'heptane techniques chez le rat blanc. Arch Mal Prof 34: 417–426
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Perbellini, L., Brugnone, F., Cocheo, V. et al. Identification of the n-heptane metabolites in rat and human urine. Arch Toxicol 58, 229–234 (1986). https://doi.org/10.1007/BF00297111
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DOI: https://doi.org/10.1007/BF00297111