[¹⁴C]bis(2-chloroethoxy)methane: Comparative absorption, distribution, metabolism and excretion in rats and mice

Abstract

bis(2-Chloroethoxy)methane (BCM) is used primarily as a precursor in the synthesis of polysulfide elastomers. After administration of [¹⁴C]BCM, radioactivity is readily absorbed from the gastrointestinal tract and moderately absorbed through skin. Following absorption, BCM-derived radioactivity is rapidly distributed to all tissues, rapidly metabolized and excreted primarily in urine. Minimal effects of sex, species or dose in the range studied (0.1–10 mg kg⁻¹) were observed on the fate of BCM in rats and mice after all routes of administration. The major metabolite (about 40% of the dose) of BCM in rat was isolated and identified as thiodiglycolic acid (TDGA) indicating that the ether linkage of BCM is cleaved to form 2-chloroethyl fragments that may be further metabolized to 2-chloracetaldehyde, conjugated with glutathione and the latter subsequently metabolized to TDGA. 2-chloroacetaldehyde has also been shown to be cardiotoxic, possibly accounting for BCM cardiotoxicity observed in repeated dose studies.

Key Words::

• bis(2-Chloroethoxy)methane
• 2-chloroacetate
• 2-chloroacetaldehyde
• thiodiglycolic acid
• metabolism
• glutathione conjugation

Acknowledgements

The authors are grateful to Kathy Ancheta for her assistance in the preparation of the manuscript. This work was performed under National Institute of Environmental Health Sciences contract N01-ES-75407.