Metabolism and disposition of [¹⁴C]dibromoacetonitrile in rats and mice following oral and intravenous administration

Abstract

1. Tissue distribution, metabolism, and disposition of oral (0.2–20 mg/kg) and intravenous (0.2 mg/kg) doses of [2-¹⁴C]dibromoacetonitrile (DBAN) were investigated in male rats and mice.

2. [¹⁴C]DBAN reacts rapidly with rat blood in vitro and binds covalently. Prior depletion of glutathione (GSH) markedly diminished loss of DBAN. Chemical reaction with GSH readily yielded glutathionylacetonitrile.

3. About 90% of the radioactivity from orally administered doses of [¹⁴C]DBAN was absorbed. After intravenous administration, 10% and 20% of the radioactivity was recovered in mouse and rat tissues, respectively, at 72 h. After oral dosing, three to four times less radioactivity was recovered, but radioactivity in stomach was mostly covalently bound.

4. Excretion of radioactivity into urine exceeded that in feces; 9–15% was exhaled as labeled carbon dioxide and 1–3% as volatiles in 72 h.

5. The major urinary metabolites were identified by liquid chromatography-mass spectrometry, and included acetonitrile mercaptoacetate (mouse), acetonitrile mercapturate, and cysteinylacetonitrile.

6. The primary mode of DBAN metabolism is via reaction with GSH, and covalent binding may be due to reaction with tissue sulphydryls.

Keywords::

• Dibromoacetonitrile
• alkylation
• metabolism
• disinfection by-products

Acknowledgements

The authors are grateful to Drs. Suramya Waidyanatha, J. Michael Sanders, Ronald Melnick, and Ms. Amy Etheridge for their review of this manuscript, and Ms. Kathy Ancheta for her assistance in preparation of the manuscript. This work was performed under the National Institute of Environmental Health Sciences contracts N01-ES-25482 and N01-ES-75407.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.