Details

Autor(en) / Beteiligte

• Dekant, Wolfgang
• Jean, Paul
• Arts, Josje

Titel

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

Ist Teil von

• Regulatory toxicology and pharmacology, 2021-03, Vol.120, p.104858, Article 104858

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. •DCM inhalation resulted in lung and liver tumors in mice but not in rats and hamsters.•Toxicokinetics show DCM is a threshold carcinogen via the low affinity GSTT1 pathway.•The order of DCM-related GSTT1 activity is: mice ≫ rats/hamsters ≫ humans.•Epidemiology data do not convincingly support a conclusion of cancer hazard of DCM.