title: Toxicity of new emerging pollutant tris-(2,3-dibromopropyl) isocyanurate on BALB/c mice.
abstract: The emerging heterocyclic brominated flame retardant tris-(2,3-dibromopropyl) isocyanurate (TBC), widely used in reinforced plastics, has demonstrated toxicity to fish. However, little is known about its toxicity in rodents. This study aims to determine the effect of TBC on growth, biochemical parameters in serum, organs and related gene expression of both male and female BALB/c mice after gastro-gavage administration of 0, 2, 10 and 50 mg kg⁻¹ TBC for 28 days. Results indicated that exposure to TBC had no effects on basic growth and food intake of mice, but significantly increased serum alanine aminotransferase levels in male mice. Histopathological analyses showed that focal necrosis (2, 10 and 50 mg kg⁻¹ TBC-exposed groups) and ballooning degeneration (10 and 50 mg kg⁻¹ TBC-exposed groups) were found in mouse liver, whereas transmission electron microscopy revealed dose-dependent hepatocyte apoptosis, mitochondrial degeneration and endoplasmic reticulum dilation. Histopathological and ultrastructural assessments in the lung showed dose-dependent hyperplasia of pulmonary alveolar epithelium, bronchial congestion, infiltration of inflammatory cells and mitochondrial swelling following TBC exposure. Our results also indicated that mitochondria are one of the major target cytoplasmic organelles for TBC, suggesting that damage in mitochondria is one of the pathways that led to toxic effects in the liver and lung of TBC-treated groups. Moreover, TBC effectively activated the gene expression of p53 in mice liver. Our findings provide strong evidence that TBC induces significant toxicity in mice organs, especially in liver and lung, which play vital roles in detoxification and gas exchange, respectively. This research will contribute to characterize the toxic effects of TBC, which was introduced as one of the candidates for brominated flame retardant replacement.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, PO Box 2871, Beijing, 100085, People's Republic of China; Key Laboratory of Subtropical Agriculture and Environment, Ministry of Agriculture, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Jieqing
authors.initials: J
authors.lastname: Bao
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Liu
authors.forename: Junfeng
authors.initials: J
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Aiqian
authors.initials: A
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D005260:Female; D005411:Flame Retardants / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000187:drug effects / Q000648:ultrastructure; D009336:Necrosis; D011897:Random Allocation; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D013047:Specific Pathogen-Free Organisms; D023382:Toxicity Tests, Acute; D014227:Triazines / Q000008:administration & dosage / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D005411:Flame Retardants; D014227:Triazines; D016159:Tumor Suppressor Protein p53; C541743:tris(2,3-dibromopropyl)isocyanurate
keywords: brominated flame retardants (BFRs); liver; lung; mitochondria; tris-(2,3-dibromopropyl) isocyanurate (TBC); ultrastructure