[14C]bis(2-chloroethoxy)methane: comparative absorption, distribution, metabolism and excretion in rats and mice.
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.
Black
S R
SR
RTI International, Research Triangle Park, NC 27709, USA. sherryb@rti.org
Decosta
K S
KS
Patel
P R
PR
Mathews
J M
JM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005019:Ethyl Ethers / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000378:metabolism*
D005019:Ethyl Ethers; C495703:bis(2-chloroethoxy)methane