title: Didecyldimethylammonium chloride induces pulmonary inflammation and fibrosis in mice.
abstract: Didecyldimethylammonium chloride (DDAC) is used worldwide as a germicide, in antiseptics, and as a wood preservative, and can cause adverse pulmonary disease in humans. However, the pulmonary toxicity of DDAC has not yet been thoroughly investigated. Mice were intratracheally instilled with DDAC to the lung and the bronchoalveolar lavage (BAL) fluid and lung tissues were collected to assess dose- and time-related pulmonary injury. Exposure to 1500 μg/kg of DDAC caused severe morbidity with pulmonary congestive oedema. When the BAL fluid from survivors was examined on day 3 after treatment, exposure to 150 μg/kg of DDAC caused weakly induced inflammation, and exposure to 15μg/kg did not cause any visible effects. Next, we observed pulmonary changes that occurred up to day 20 after 150 μg/kg of DDAC exposure. Pulmonary inflammation peaked on day 7 and was confirmed by expression of interleukin-6, monocyte chemotactic protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, and regulated upon activation, normal T-cell expressed and secreted in the BAL fluid; these changes were accompanied by altered gene expression of their chemokine (C-C motif) receptor (Ccr) 1, Ccr2, Ccr3, and Ccr5. Cytotoxicity evoked by DDAC was related to the inflammatory changes and was confirmed by an in vitro study using isolated mouse lung fibroblasts. The inflammatory phase was accompanied or followed by pulmonary remodeling, i.e., fibrosis, which was evident in the mRNA expression of type I procollagen. These results suggest that administering DDAC by intratracheal instillation causes pulmonary injury in mice, and occupational exposure to DDAC might be a potential hazard to human health.
authors.affiliation: Laboratory of Pathology, Toxicology Division, Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso, Ibaraki, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ohnuma
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yoshida
authors.forename: Haruka
authors.initials: H
authors.lastname: Tajima
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayashi
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ohtsuka
authors.forename: Junya
authors.initials: J
authors.lastname: Sasaki
authors.forename: Junko
authors.initials: J
authors.lastname: Fukumori
authors.forename: Mariko
authors.initials: M
authors.lastname: Tomita
authors.forename: Sayuri
authors.initials: S
authors.lastname: Kojima
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Maki
authors.initials: M
authors.lastname: Kuwahara
authors.forename: Makio
authors.initials: M
authors.lastname: Takeda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kosaka
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Nakashima
authors.forename: Takanori
authors.initials: T
authors.lastname: Harada
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced*; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D000644:Quaternary Ammonium Compounds / Q000633:toxicity*; D019707:Receptors, Chemokine / Q000235:genetics
chemical_list: D024042:Collagen Type I; D000644:Quaternary Ammonium Compounds; D019707:Receptors, Chemokine; C027118:didecyldimethylammonium