Black S R, Decosta K S, Patel P R, Mathews J M
RTI International, Research Triangle Park, NC 27709, USA.
Xenobiotica. 2007 Apr;37(4):427-40. doi: 10.1080/00498250701206872.
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.
双（2-氯乙氧基）甲烷（BCM）主要用作合成聚硫橡胶的前体。给予[(14)C]BCM后，放射性物质很容易从胃肠道吸收，并可通过皮肤适度吸收。吸收后，BCM衍生的放射性物质迅速分布到所有组织，迅速代谢并主要经尿液排泄。在研究的剂量范围（0.1 - 10 mg kg(-1)）内，观察到性别、物种或剂量对大鼠和小鼠经所有给药途径后BCM的代谢情况影响极小。在大鼠中，BCM的主要代谢产物（约占剂量的40%）被分离并鉴定为硫代二甘醇酸（TDGA），这表明BCM的醚键被裂解形成2-氯乙基片段，该片段可能进一步代谢为2-氯乙醛，与谷胱甘肽结合，后者随后代谢为TDGA。2-氯乙醛也已被证明具有心脏毒性，这可能是重复剂量研究中观察到BCM心脏毒性的原因。
