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

Autor: LeBaron MJ; The Dow Chemical Company, Toxicology & Environmental Research & Consulting, Midland, Michigan, USA., Hotchkiss JA; The Dow Chemical Company, Toxicology & Environmental Research & Consulting, Midland, Michigan, USA., Zhang F; The Dow Chemical Company, Toxicology & Environmental Research & Consulting, Midland, Michigan, USA., Koehler MW; The Dow Chemical Company, Toxicology & Environmental Research & Consulting, Midland, Michigan, USA., Boverhof DR; The Dow Chemical Company, Toxicology & Environmental Research & Consulting, Midland, Michigan, USA.
Jazyk: angličtina
Zdroj: Journal of applied toxicology : JAT [J Appl Toxicol] 2021 Mar; Vol. 41 (3), pp. 362-374. Date of Electronic Publication: 2020 Aug 24.
DOI: 10.1002/jat.4048
Abstrakt: 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 N 7 -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.
(© 2020 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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