Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Derivation of an Inhalation Reference Concentration Based Upon Olfactory Neuronal Loss in Male Rats Following Subchronic Acetaldehyde Inhalation

Journal Article · · Inhalation Toxicology
 [1];  [2];  [2];  [3];  [2];  [4];  [5];  [2];  [2];  [2];  [6];  [7];  [1]
  1. CIIT Centers for Health Research
  2. CIIT at The Hamner Institutes for Health Sciences
  3. CIIT at The Hamner Institutes for health Sciences
  4. Unknown
  5. EPL, Inc.
  6. BATTELLE (PACIFIC NW LAB)
  7. ENVIRON Health Sciencies Institute
+ Show Author Affiliations
Acetaldehyde inhalation induces neoplastic and nonneoplastic responses in the rodent nasal cavity. This experiment further characterizes the dose-response relationship for nasal pathology, nasal epithelial cell proliferation, and DNA-protein cross link formation in F-344 rats exposed subchronically to acetaldehyde. Animals underwent whole-body exposure to 0, 50, 150, 500, or 1500 ppm acetaldehyde for 6 hr/day, five days/week for up to 65 exposure days. Respiratory tract histopathology was evaluated after 4, 9, 14, 30, and 65 exposure days. Acetaldehyde exposure was not associated with reduced body weight gain or other evidence of systemic toxicity. Histologic evaluation of the nasal cavity showed an increased incidence of olfactory neuronal loss (ONL) following acute to subchronic exposure to = 150 ppm acetaldehyde and increased olfactory epithelial cell proliferation following exposure to 1500 ppm acetaldehyde. The severity of the ONL demonstrated dose- and temporal-dependent behaviors with minimal effects noted at 150-500 ppm acetaldehyde and moderately severe lesions seen in the highest exposure group with increased lesion severity and extent as the exposure duration increased. Acetaldehyde exposure was also associated with inflammation, hyperplasia, and squamous metaplasia of the respiratory epithelium. These responses were seen in animals exposed to = 500 ppm acetaldehyde. Acetaldehyde exposure was not associated with increased DNA-protein cross link formation in the respiratory or olfactory epithelium. A model of acetaldehyde pharmacokinetics in the nose was used to derive an Inhalation Reference Concentration (RfC) of 0.4 ppm, based on the NOAEL of 50 ppm for the nasal pathology seen in this study. 2
Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC05-76RL01830
OSTI ID:
1601373
Report Number(s):
PNWD-SA-8184
Journal Information:
Inhalation Toxicology, Journal Name: Inhalation Toxicology Journal Issue: 3 Vol. 20
Country of Publication:
United States
Language:
English

References (39)

Effect of variable versus fixed exposure levels on the toxicity of acetaldehyde in rats journal October 1986
Chemically-induced nasal carcinogenesis and epithelial cell proliferation: a brief review journal October 1997
Proliferation in the Rat Olfactory Epithelium: Age-Dependent Changes journal May 1997
The Nose Revisited: A Brief Review of the Comparative Structure, Function, and Toxicologic Pathology of the Nasal Epithelium journal April 2006
Repeated Exposure to Acetaldehyde Vapor: Studies in Syrian Golden Hamsters journal September 1975
Computer Simulation of Inspiratory Airflow in All Regions of the F344 Rat Nasal Passages journal August 1997
Human Respiratory Tract Cancer Risks of Inhaled Formaldehyde: Dose-Response Predictions Derived From Biologically-Motivated Computational Modeling of a Combined Rodent and Human Dataset journal July 2004
Airflow, Gas Deposition, and Lesion Distribution in the Nasal Passages journal April 1990
Dosimetric adjustment factors for methyl methacrylate derived from a steady-state analysis of a physiologically based clearance-extraction model journal October 2008
A PBPK Model for Evaluating the Impact of Aldehyde Dehydrogenase Polymorphisms on Comparative Rat and Human Nasal Tissue Acetaldehyde Dosimetry journal January 2008
mRNA Induction and Cytokine Release of Inflammatory Mediators During In Vitro Exposure of Human Nasal Respiratory Epithelia to Acetaldehyde journal January 2006
Inhalation toxicity of acetaldehyde in rats. IV. Progression and regression of nasal lesions after discontinuation of exposure journal December 1987
The effect of inhibition of aldehyde dehydrogenase on nasal uptake of inspired acetaldehyde journal June 1999
Identification and molecular regulation of neural stem cells in the olfactory epithelium journal June 2005
Differentiating between local cytotoxicity, mitogenesis, and genotoxicity in carcinogen risk assessments: the case of vinyl acetate journal April 2003
1, N 2 -Deoxyguanosine Adducts of Acrolein, Crotonaldehyde, and trans -4-Hydroxynonenal Cross-link to Peptides via Schiff Base Linkage journal December 2002
Dna-Protein Cross-Links Produced by Various Chemicals in Cultured Human Lymphoma Cells journal April 1997
Olfactory Horizontal Basal Cells Demonstrate a Conserved Multipotent Progenitor Phenotype journal June 2004
Inhalation toxicity of acetaldehyde in rats. I. Acute and subacute studies journal January 1982
Decreased extractability of DNA from proteins in the rat nasal mucosa after acetaldehyde exposure journal April 1986
Neurogenesis and cell death in olfactory epithelium journal May 1996
Physiologically Based Modeling of Vinyl Acetate Uptake, Metabolism, and Intracellular pH Changes in the Rat Nasal Cavity journal February 1997
Effects of Exposure to Acetaldehyde in Syrian Hamsters Simultaneously Treated with Benzo(a)pyrene or Diethylnitrosamine1 book January 1979
Approaches to the Identification and Recording of Nasal Lesions in Toxicology Studies journal November 1991
Inhalation toxicity of acetaldehyde in rats. III. Carcinogenicity study☆ journal October 1986
Upper respiratory tract deposition of inspired acetaldehyde journal May 1992
Cell death in the olfactory epithelium journal July 1995
Covalent binding of inhaled formaldehyde to DNA in the respiratory tract of rhesus monkeys: Pharmacolinetics, rat-to-monkey interspecies scaling, and extrapolation to man journal August 1991
Respiratory tract tumours in hamsters exposed to acetaldehyde vapour alone or simultaneously to benzo(a)pyrene or diethylnitrosamine journal January 1982
Effects of formaldehyde exposure on the extractability of DNA from proteins in the rat nasal mucosa journal August 1983
Unit Length as the Denominator for Quantitation of Cell Proliferation in Nasal Epithelia journal January 1990
A Physiologically Based Pharmacokinetic Model for Nasal Uptake and Metabolism of Nonreactive Vapors journal November 1993
Inhalation toxicity of acetaldehyde in rats II. Carcinogenicity study: Interim results after 15 months journal May 1984
Changes in the Nasal Epithelium of Rats Exposed by Inhalation to Mixtures of Formaldehyde, Acetaldehyde, and Acrolein journal February 1996
Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment journal March 1991
Caspases 3 and 9 Send a Pro-Apoptotic Signal from Synapse to Cell Body in Olfactory Receptor Neurons journal September 2001
Application of a Hybrid Computational Fluid Dynamics and Physiologically Based Inhalation Model for Interspecies Dosimetry Extrapolation of Acidic Vapors in the Upper Airways journal September 1998
DNA–Protein Cross-link Formation in Burkitt Lymphoma Cells Cultured with Benzaldehyde and the Sedative Paraldehyde journal January 2007
Benchmark Dose Risk Assessment for Formaldehyde Using Airflow Modeling and a Single-Compartment, DNA-Protein Cross-Link Dosimetry Model to Estimate Human Equivalent Doses journal June 2003

Similar Records

Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice
Journal Article · Mon Jun 01 00:00:00 EDT 1987 · Environ. Health Perspect.; (United States) · OSTI ID:6061037
Toxicity of dimethylamine in F-344 rats and B6C3F1 mice following a 1-year inhalation exposure
Journal Article · Sun Mar 31 23:00:00 EST 1985 · Fundam. Appl. Toxicol.; (United States) · OSTI ID:5225786
Proliferative responses of rat nasal epithelia to ozone
Journal Article · Wed Mar 14 23:00:00 EST 1990 · Toxicology and Applied Pharmacology; (USA) · OSTI ID:6852912

Related Subjects

toxicology
risk assessment