Abstract
Distribution, metabolism and excretion of musk xylene (MX) were investigated in male Wistar rats. Urinary and fecal excretion accounted for 10 and 75% of the dose (70 mg/kg), respectively, on day 7 after orally administration of3H-MX to rats. Total residue of radioactivity in tissues on day 7 was less than 2.0% of the administered dose. The highest concentration was found in adipose tissue and the second was in liver. Some metabolites of MX were identified using GC-MS and NMR after purification by column or thin layer chromatography of feces, bile and urine extracts. MX, 2-NH2-MX, 2-Ac-MX, 2-NH2-3-CH2OH-MX, and 2-NH2-5-tert-BuOH-MX were found in feces, bile and urine. 4-NH2-MX and metabolite X were found in feces and urine. 4-NH2-3-CH2OH-MX was found in urine. HO-MX was found in bile. The major route of excretion for MX was the feces via bile. The reduction of the 2-nitro group of MX to the amino group was a key step in metabolism. Further metabolism of 2-NH2-MX may proceed by decreased steric hindrance of functional group.
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Abbreviations
- MX (M-1):
-
5-tert-butyl-2,4,6-trinitroxylene
- 2-NH2, MX (M-2):
-
2-amino-5-tert-butyl-4,6-dinitroxylene
- 4-NH2-MX (M-3):
-
4-amino-5-tert-butyl-2,6-dinitroxylene
- 2-Ac-MX (M-4):
-
2-acetylamino-5-tert-butyl-4,6-dinitroxylene
- 2-NH2-3-CH2OH-MX (M-5):
-
2-amino-5-tert-butyl-1-methyl-3-hydroxymethyl-4,6-dinitrobenzene
- 2-NH2-5-tert-BuOH-MX (M-6):
-
2-amino-5-tert-hydroxybutyl-4,6-dinitroxylene
- 4-NH2-3-CH2OH-MX (M-7):
-
4-amino-5-tert-butyl-1-methyl-3-hydroxymethyl-4,6-dinitrobenzene
- HO-MX (M-8):
-
5-tert-butyl-1-methyl-3-hydroxymethyl-4,6-dinitrobenzene or 5-tert-hydroxybutyl-4,6-dinitroxylene metabolite X (M-9), 8-tert-butyl-1,2,4,4-tetrahydro-2,6-dimethyl-5,7-dinitrobenzoxazine
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Minegishi, Ki., Nambaru, S., Fukuoka, M. et al. Distribution, metabolism, and excretion of musk xylene in rats. Arch Toxicol 65, 273–282 (1991). https://doi.org/10.1007/BF01968961
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DOI: https://doi.org/10.1007/BF01968961