[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. © 2007 Informa UK Ltd.