Investigation of potential early key events and mode of action for 1,2‐dichloroethane‐induced mammary tumors in female rats

Abstract

1,2‐dichloroethane (DCE or EDC) is a chlorinated hydrocarbon used as a chemical intermediate, including in the synthesis of polyvinyl chloride. Although DCE has induced tumors in both rats and mice, the overall weight‐of‐evidence suggests a lack of in vivo mutagenicity. The present study was conducted to explore a potential mode of action further for tumor formation in rat mammary tissue. Fischer 344 rats were exposed to target concentrations of 0 or 200 ppm of DCE vapors (6 hours/day, 7 days/week) for at least 28 days; 200 ppm represents a concentration of ~20% higher than that reported to induce mammary tumors. Endpoints examined included DNA damage (via Comet assay), glutathione (reduced, oxidized and conjugated), tissue DNA adducts, cell proliferation and serum prolactin levels. Exposure to DCE did not alter serum prolactin levels with consistent estrous stage, did not cause cell proliferation in mammary epithelial cells, nor result in histopathological alterations in the mammary gland. DNA adducts were identified, including the N7‐guanylethyl glutathione adduct, with higher adduct levels measured in liver (nontumorigenic target) compared with mammary tissue isolated from the same rats; no known mutagenic adducts were identified. DCE did not increase the Comet assay response in mammary epithelial cells, whereas DNA damage in the positive control (N‐nitroso‐N‐methylurea) was significantly increased. Although the result of this study did not identify a specific mode of action for DCE‐induced mammary tumors in rats, the lack of any exposure‐related genotoxic responses further contributes to the weight‐of‐evidence suggesting that DCE is a nongenotoxic carcinogen.

Derivation of human health hazard assessment values of 1,2-dichloroethane under the Japan Chemical Substances Control Law

“…Regarding carcinogenic mechanisms, a 28-day inhalation study in rats following 1,2-dichloroethane exposure (LeBaron et al, 2021) reported negative results in the comet assay and DNA adduct tests in mammary glands and liver, and no genotoxic effects or specific DNA adducts associated with carcinogenesis in the mammary tissue were detected. However, the compound was positive for DNA binding ability in vitro (Cheever et al, 1990;Reitz, 1980Reitz, , 1982 and in vivo studies (Banerjee, 1988;Arfellini et al, 1984;Baertsch et al, 1991).…”

Scaling up the Process of Catalytic Decomposition of Chlorinated Hydrocarbons with the Formation of Carbon Nanostructures

“…Thus, the production of one ton of vinyl chloride is accompanied by the appearance of nearly 50 kg of organochlorine wastes, represented by a complex mixture of chlorinated derivatives of ethane and ethylene. All these substances are xenobiotics, i.e., they are foreign to the body or to an ecological system and therefore exert highly toxic effects on living forms, including humans [3][4][5].…”