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

Xenobiotica. 2007 Apr;37(4):427-40. doi: 10.1080/00498250701206872.

Abstract

bis(2-Chloroethoxy)methane (BCM) is used primarily as a precursor in the synthesis of polysulfide elastomers. After administration of [(14)C]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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Ethyl Ethers / pharmacokinetics*
  • Ethyl Ethers / toxicity
  • Female
  • Intestinal Absorption / drug effects*
  • Male
  • Mice
  • Rats
  • Rats, Inbred F344
  • Skin / metabolism*

Substances

  • Ethyl Ethers
  • bis(2-chloroethoxy)methane