Evaluation of the carcinogenicity of dichloromethane in rats, mice, hamsters and humans

被引：21

作者：

Dekant, Wolfgang ^{[1
]}

Jean, Paul ^{[2
]}

Arts, Josje ^{[3
]}

机构：

[1] Univ Wurzburg, Dept Pharmacol & Toxicol, Versbacherstr 9, D-97078 Wurzburg, Germany

[2] Olin Corp, 2205 Ridgewood Dr, Midland, MI 48642 USA

[3] Nouryon Ind Chem, POB 60192, NL-6800 JD Arnhem, Netherlands

来源：

REGULATORY TOXICOLOGY AND PHARMACOLOGY | 2021年 / 120卷

关键词：

Carcinogenicity; Dichloromethane; Methylene chloride; Classification and labeling;

D O I：

10.1016/j.yrtph.2020.104858

中图分类号：

DF [法律]; D9 [法律]; R [医药、卫生];

学科分类号：

0301 ; 10 ;

摘要：

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.

引用

页数：8

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