Olfactory and Central Neurotoxicity of Occupationally Relevant Inhaled Aerosols

Details

• Personal Author:
  Antonini JM ; Fedan, Jeffery S. ; Hubbs, Ann F. ; Lin X ; McKinney W ; Sriram K
• Description:
  Fine and ultrafine particles generated at the workplace can aerosolize and thus inhalation exposure is a major occupational concern. Aerosolized particles deposited in nose and/or lung can reach the brain via retrograde transport across the olfactory sensory neurons (OSNs) or through the systemic circulation. The OSNs extend into the brain from the air-interface in the nose and thus have direct access to airborne pollutants and toxic chemicals. Indeed, environmental air pollutants are known to cause nasal pathology, neuroinflammation, and neurodegenerative changes, both in humans and animals. Toxicant-mediated olfactory damage often manifests as loss of olfaction, which precedes the hallmark clinical signs of neurodegeneration seen in Parkinson's (PD) and Alzheimer's diseases. Our recent experimental data suggest that olfactory and central neurotoxicity is elicited by a variety of chemicals and particulate aerosols. Here, we present evidence of neurotoxicity associated with exposure to two occupationally-relevant agents, welding fumes (WF) and diesel exhaust (DE). Welding generates fumes with high concentrations of fine and ultrafine metal aerosols composed of iron, manganese, chromium, and nickel, besides gaseous agents. There is growing concern that inhalation of WF causes PD-like manifestation, thus warranting extensive characterization of the neurotoxic potential of WF. Rats (male Sprague-Dawley; approx. 3 m old) were exposed to fumes generated by gas metal arc-stainless steel welding (GMA-SS / WF; 15 mg/m3; 3 h/d × 10 d) and humanely euthanized after 7 d for neurotoxicity assessments. WF increased serotonin (5-HT; 43 %) levels in the olfactory bulb (OB), while reducing tyrosine hydroxylase protein (TH; 39 %) and glial fibrillary acidic protein (GFAP; 45 %). In the striatum (STR) and midbrain, brain regions typically affected in PD, WF reduced dopamine levels by 33 % and 14 %, respectively. A concordant reduction (22 - 33 %) in TH, alpha-synuclein (SNCA), and ubiquitin C-terminal hydrolase L1 (UCHL1 / PARK5) proteins was also seen in the STR, suggesting that a short-term repeated exposure to WF causes dopaminergic neurotoxicity. DE is a complex mixture of particulates and gases. The particulate fraction mainly consists of an insoluble elemental carbon core and an organic solvent soluble coating adsorbed on the carbon core that make up the bulk of the particulate matter in DE. The gaseous components primarily include oxides of carbon, nitrogen, and sulfur, as well as some low molecular weight hydrocarbons. Rats (male Sprague-Dawley; approx. 3 m old) were exposed to DE from a tier 2 engine (1 mg/m3 particulate; 6 h/d × 4 d) and humanely euthanized after 1 d for neurotoxicity assessments. DE caused upregulation (3 to 5-fold) of mRNA transcripts for matrix metalloproteinase 9 (Mmp9), claudins (Cldn1 and Cldn2), and Gfap (1.6-fold) in the OB, suggestive of altered blood-brain barrier integrity and reactive gliosis. A reduction (20 %) in olfactory marker protein was also evident. In the hippocampus, DE caused a robust increase in 5-HT (1000 %), tyrosine 3-monooxygenase/ tryptophan 5-monooxygenase activation protein epsilon (YWHAE / 14-3-3-e; 130 %), and GFAP protein (63 %). Activation of serotonergic receptors by 5-HT is known to inhibit hippocampal pyramidal neurons, which in turn is linked to cognitive impairment and cognitive dysfunction. Further, increased YWHAE is indicative of injury/damage to neural cells. Collectively, our findings show that occupationally-relevant incidental aerosols can elicit olfactory and central neurotoxicity and calls for extensive investigation of the long-term effects to assess progressive neurodegeneration and neurobehavioral outcomes, if any. [Description provided by NIOSH]
• Subjects:
  Aerosols Nervous System Nose Occupational Health Respiratory System Safety Sense Organs
• Keywords:
  Central Nervous System Inhalation Nasal Cavity Neurotoxicity Olfactory System Ultrafine Particles
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  192
• NIOSHTIC Number:
  nn:20067221
• Citation:
  Toxicologist 2023 Mar; 192(S1):298
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1a0689796a7d7690e5af1fc58d84381777e5f4a720156c451dfaf106e057d6cd7df1d8b5a393e88ce1f2f8cfd44c958a0fc2597f7a5b2a59f99c214749242a5e
• Download URL:
  https://stacks.cdc.gov/view/cdc/231348/cdc_231348_DS1.pdf
• File Type:
  [PDF - 1.11 MB ]