Department of Pharmacology and Toxicology, Universität Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany.
Olin Corporation, 2205 Ridgewood Dr., Midland, MI, 48642 USA.
Regul Toxicol Pharmacol. 2021 Mar;120:104858. doi: 10.1016/j.yrtph.2020.104858. Epub 2020 Dec 31.
Dichloromethane (DCM) is a high production volume chemical (>1000 t/a) mainly used as an industrial solvent. Carcinogenicity studies in rats, mice and hamsters have demonstrated a malignant tumor inducing potential of DCM only in the mouse (lung and liver) at 1000-4000 ppm whereas human data do not support a conclusion of cancer risk. Based on this, DCM has been classified as a cat. 2 carcinogen. Dose-dependent toxicokinetics of DCM suggest that DCM is a threshold carcinogen in mice, initiating carcinogenicity via the low affinity/high capacity GSTT1 pathway; a biotransformation pathway that becomes relevant only at high exposure concentrations. Rats and hamsters have very low activities of this DCM-metabolizing GST and humans have even lower activities of this enzyme. Based on the induction of specific tumors selectively in the mouse, the dose- and species-specific toxicokinetics in this species, and the absence of a malignant tumor response by DCM in rats and hamsters having a closer relationship to DCM toxicokinetics in humans and thus being a more relevant animal model, the current classification of DCM as human carcinogen cat. 2 remains appropriate.
二氯甲烷（DCM）是一种高产量的化学品（>1000 t/a），主要用作工业溶剂。在大鼠、小鼠和仓鼠中的致癌性研究表明，DCM 仅在小鼠（肺和肝）中以 1000-4000 ppm 的浓度具有潜在的恶性肿瘤诱导作用，而人类数据并不支持致癌风险的结论。基于此，DCM 被归类为 2 类致癌物。DCM 的剂量依赖性毒代动力学表明，DCM 是一种在小鼠中具有阈值致癌性的物质，通过低亲和力/高容量 GSTT1 途径引发致癌性；这是一种只有在高暴露浓度下才相关的生物转化途径。大鼠和仓鼠的这种 DCM 代谢 GST 活性非常低，而人类的这种酶活性甚至更低。基于在小鼠中选择性诱导特定肿瘤、该物种中特定剂量和物种的毒代动力学，以及在与人的 DCM 毒代动力学更接近的大鼠和仓鼠中未观察到 DCM 引起恶性肿瘤反应，目前将 DCM 归类为人类致癌物 2A 类仍然是合适的。
