Comparison of Acute Respiratory Epithelial Toxicity for 4-Methylimidazole and Naphthalene Administered by Oral Gavage in B6C3F1 Mice

Details

• Alternative Title:
  Regul Toxicol Pharmacol
• Personal Author:
  Kelty, Jacklyn S ; Keum, Chayoung ; Brown, Veneese J ; Edwards, Patricia C ; Carratt, Sarah A ; Van Winkle, Laura S
• Description:
  4-Methylimidazole (4MEI) is a contaminant in food and consumer products. Pulmonary toxicity and carcinogenicity following chronic dietary exposures to 4MEI is a regulatory concern based on previous rodent studies. This study examined acute pulmonary toxicity in B6C3F1 mice from 6 h to 5 days after oral gavage with a single dose of 150 mg/kg 4MEI, a double dose delivered 6 h apart, or vehicle controls. Oral gavage of 150 mg/kg naphthalene, a prototypical Club cell toxicant, was used as a positive control. Intrapulmonary conducting airway cytotoxicity was assessed in fixed-pressure inflated lungs using qualitative histopathology scoring, quantitative morphometric measurement of vacuolated and exfoliating epithelial cells, and immunohistochemistry. 4MEI treatment did not change markers of cytotoxicity including the mass of vacuolated epithelium, the thickness of the epithelium, or the distributions of epithelial proteins: secretoglobin 1A1, proliferating cell nuclear antigen, calcitonin gene-related peptide, and myeloperoxidase. 4MEI and vehicle controls caused slight cytotoxicity with rare vacuolization of the epithelium relative to the severe bronchiolar epithelial cell toxicity found in the naphthalene exposed mice at terminal bronchioles, intrapulmonary airways, or airway bifurcations. In summary, 4MEI caused minimal airway epithelial toxicity without characteristic Club Cell toxicity when compared to naphthalene, a canonical Club Cell toxicant.
• Subjects:
  Administration, Oral Animals Environmental Pollutants Female Imidazoles Male Mice Naphthalenes Respiratory Mucosa
• Keywords:
  4-Methylimidazole Acute Toxicity Club Cell Toxicity Naphthalene Respiratory
• Source:
  Regul Toxicol Pharmacol. 116:104761
• Pubmed ID:
  32768664
• Pubmed Central ID:
  PMC7983601
• Document Type:
  Journal Article
• Funding:
  R01 ES020867/ES/NIEHS NIH HHSUnited States/ ; T32 ES007148/ES/NIEHS NIH HHSUnited States/ ; T32 HL007013/HL/NHLBI NIH HHSUnited States/ ; P30 ES023513/ES/NIEHS NIH HHSUnited States/ ; U54 OH007550/OH/NIOSH CDC HHSUnited States/ ; U54OH007550/ACL/ACL HHSUnited States/
• Volume:
  116
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f9b212ed6a4fa27108ec5392d4b2989293be160c31977a29d07a23b88d14cb5a
• Download URL:
  https://stacks.cdc.gov/view/cdc/104382/cdc_104382_DS1.pdf
• File Type:
  [PDF - 866.04 KB ]