Skip to main content
Log in

Distribution, metabolism, and excretion of musk xylene in rats

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

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

References

  • Akagi M, Aoki I (1962) Studies on food additives. VI. Metabolism of 2,6-di-tert-butyl-p-cresol (BHT) in a rabbit. (1). Determination and paper Chromatography of a metabolite. Chem Pharm Bull 10: 101–105

    Google Scholar 

  • Aoki I (1962) Studies on food additives. VII. Metabolism of 2,6-di-tert-butyl-p-cresol in a rabbit. (2). Isolation of a metabolite. Chem Pharm Bull 10: 105–112

    Google Scholar 

  • Astill BD, Fassett DW, Roudabush RL (1960) The metabolism of phenolic antioxidants. 2. The metabolism of butylated hydroxyanisole in the rat. Biochem J 75: 543–551

    PubMed  Google Scholar 

  • Astill BD, Mills J, Fassett DW, Roudabush RI, Terhaar CJ (1962) Fate of butylated hydroxyanisole in man and dog. J Agr Food Chem 10: 315–319

    Article  Google Scholar 

  • Bray HG, Humphris BG, Thorpe WV (1949) Metabolism of derivatives of toluene. III.o-, m-, andp-xylenes. Biochem J 45: 241–244

    Google Scholar 

  • Dacre JC (1961) The metabolism of 3∶5-di-tert-butyl-4-hydroxytoluene and 3 ∶ 5-di-tert-butyl-4-hydroxybenzoic acid in the rabbit. Biochem J 78: 758–766

    Google Scholar 

  • Dacre JC, Denz IA, Kennedy TH (1956) The metabolism of butylated hydroxyanisole in the rabbit. Biochem J 64: 777–782

    PubMed  Google Scholar 

  • Daniel JW, Gage JC, Jones DI (1968) The metabolism of 3,5-di-tert-butyl-4-hydroxytoluene in the rat and in man. Biochem J 106: 783–790

    PubMed  Google Scholar 

  • DeBethizt JD, Rickert DE (1984) Metabolism of nitrotoluenes by freshly isolated Fischer 344 Rat hepatocytes. Drug Metab Dispos 12: 45–50

    PubMed  Google Scholar 

  • Goldman P (1978) Biochemical Pharmacology of the intestinal flora. Ann Rev Pharmacol Toxicol 18: 523–539

    Article  Google Scholar 

  • Jaffe M (1878) Zur Kenntnis der Synthetischen Vorgänge im Tierkörper. Hoppe-Seyler's Z Physiol Chem 2: 47–64

    Google Scholar 

  • Maekawa A, Matsushima Y, Onodera H, Shibutani M, Ogasawara H, Kodama Y, Kurokawa Y, Hayashi Y (1990) Long-term toxicity carcinogenicity of musk xylol in B6C3F1 mice. Food Chem Toxicol 28: 581–586

    Article  PubMed  Google Scholar 

  • McKillop A, Ford ME (1974) Mercury-assisted solvolysis of alkyl halide. Simple procedures for the preparation of nitrate esters, acetate esters, alcohols and ethers. Tetrahedron 30: 2467–2475

    Article  Google Scholar 

  • Mori M, Naruse Y, Kozuka H (1981) Identification of urinary metabolites 2,4-dinitrotoluene (2,4-DNT) in rats. Chem Pharm Bull 29: 1147–1150

    PubMed  Google Scholar 

  • Nair J, Oshima H, Malaveille C, Friesen M, O'Neil IK, Hautefeuille A, Bartsch H (1986) Identification, Occurrence and mutagenicity inSalmonella typhimurium of two synthetic nitroarenes, musk ambrette and musk xylene, in Indian Chewing Tobacco and Betel Quid. Food Chem Toxicol 24: 27–32

    Article  PubMed  Google Scholar 

  • Nambaru S, Fukuoka M, Tanaka A, Minegishi K, Nishimaki-Mogami T, Takahashi A (1988) Metabolic studies on musk xylene (3). Syntheses of labeled musk xylene and its metabolites. 107th Annual Meeting of the Pharmaceutical Society of Japan, p 657

  • Rickert DE, Long RM (1981) Metabolism and excretion of 2,4-dinitro-toluene in male and female Fischer 344 rats after different doses. Drug Metab Dispos 9: 226–232

    PubMed  Google Scholar 

  • Rickert DE, Long RM, Krakowka S, Dent JG (1981) Metabolism and excretion of 2,4-(14C) Dinitrotoluene in conventional and axenic Fischer-344 rats. Toxicol Appl Pharmacol 59: 574–579

    Article  PubMed  Google Scholar 

  • Robinson D, Smith JN, Williams RT (1951) Studies in detoxication 40. The metabolism of nitrobenzene in the rabbit,o-, m-, andp-nitrophenols,o-, m- andp-aminophenols and 4-nitrocatechol as metabolites of nitrobenzene. Biochem J 50: 228–235

    PubMed  Google Scholar 

  • Schelline RR (1973) Metabolism of foreign compounds by gastrointestinal microorganisms. Pharmacol Rev 25: 451–523

    PubMed  Google Scholar 

  • Shoji M, Mori M, Moto-o K, Kozuka H, Honda T (1985) High-performance liquid chromatographic determination of urinary metabolites of 2,4-dinitrotoluene in Wistar rats. Chem Pharm Bull 33: 1687–1693

    PubMed  Google Scholar 

  • Williams RT (1959) Detoxication mechanisms, 2nd edition, Chapman and Hall, London, pp 194–195

    Google Scholar 

  • Yamagishi T, Miyazaki T, Horil S, Akiyama K (1983) Synthetic musk residues in biota and water from Tama River and Tokyo Bay (Japan). Arch Environ Contam Toxicol 12: 83–89

    Article  PubMed  Google Scholar 

  • Yurawecz MP, Puma BJ (1983) Nitro musk fragrances as potential contaminants in pesticide residue analysis. J Assoc Off Anal Chem 66: 241–247

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01968961

Key words

Navigation