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

Details

• Personal Author:
  Brown VJ ; Carratt SA ; Edwards PC ; Kelty JS ; Keum C ; Van Winkle LS
• 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. [Description provided by NIOSH]
• Subjects:
  Animals Cytotoxins Hazardous Substances Lung Occupational Exposure Occupational Health Respiratory System Safety Toxicology
• Keywords:
  Acute Toxicity Animal Studies Author Keywords: 4-Methylimidazole Chronic Exposure Club Cell Toxicity Cytotoxic Effects Food Contaminants Naphthalene Pulmonary Effects Respiratory Toxic Effects

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• ISSN:
  0273-2300
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  116
• NIOSHTIC Number:
  nn:20062591
• Citation:
  Regul Toxicol Pharmacol 2020 Oct; 116:104761
• Contact Point Address:
  Laura S. Van Winkle, Center for Health and the Environment, University of California, Davis, Bldg 3792, Rm 129, 1250 Old Davis Road, Davis, CA 95616, USA
• Email:
  lsvanwinkle@ucdavis.edu
• CAS Registry Number:
  4-Methylimidazole (CAS RN 822-36-6) ; Naphthalene (CAS RN 91-20-3)
• Federal Fiscal Year:
  2021
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of California - Davis
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Regulatory Toxicology and Pharmacology
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cb76efba0a75431aaa8ca7099faaad0b6b009385ba6150c64a66609b27f471053d807c255934302fa185569d8bc3d40e89704cd477879f39a7f899359f25d6e2
• Download URL:
  https://stacks.cdc.gov/view/cdc/225801/cdc_225801_DS1.pdf
• File Type:
  [PDF - 8.43 MB ]