Breaking the routine: is there room for modern techniques of neuropathology assessment in routine preclinical safety studies

Details

• Personal Author:
  O'Callaghan JP ; Toscano CD
• Description:
  Neurotoxicity in routine preclinical safety studies is traditionally assessed with three H&E-stained brain sections; an approach that is not optimal, considering the brain's complex neuroanatomy. The need to increase the sensitivity of this approach is supported by the finding that routine neuropathology assessments would fail to detect MPTP, ethanol and carbonyl sulfide induced-CNS lesions. Increasing the number of brain sections sampled and inclusion of additional histology stains have been recommended but there is no expert consensus on the feasibility of incorporating modern methods of assessment into routine preclinical safety studies. We will explore and comment on the adequacy of the traditional approach to neuropathology assessment in routine preclinical safety studies. We will also examine the current regulatory guidance on neurotoxicity assessment in routine preclinical safety studies and discuss the feasibility of changing the current approach. Examples of emerging methods, such as MRI-directed histology and detection of circulating biomarkers of CNS damage, along with strategies for incorporating these techniques into standard preclinical safety studies will also be discussed. Finally, we will attempt to build consensus on appropriate approaches for improving the sensitivity of neurotoxicity assessment in routine preclinical safety studies by fostering a discussion between the audience and panel members. This discussion will focus on the feasibility of employing the proposed new markers, endpoints, and approaches and potential issues with interpretation of results of these studies. In conclusion, we believe that by examining the adequacy of current approaches of neuropathology assessment, discussing possible improvements to regulatory guidance and presenting emerging approaches of neurotoxicity assessment that this workshop will allow for a much needed dialogue on the need and feasibility of improving the current methods of neuropathology assessment in routine preclinical safety studies. [Description provided by NIOSH]
• Subjects:
  Biomarkers Clinical Laboratory Techniques Diagnosis Environmental Monitoring Ethanol Histology Laboratories Nervous System Occupational Health Pyridines Safety Sulfides Toxicology

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• Keywords:
  Brain-electrical-activity Brain-function Carbonyls Central-nervous-system Clinical-diagnosis Clinical-pathology Clinical-techniques Clinical-tests Ethanols Exposure-assessment Laboratory-techniques Neurological-reactions Neuropathology Neurotoxicity Safety-practices

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; OSHA Region 6 ; Texas ; 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:
  132
• Issue:
  1
• NIOSHTIC Number:
  nn:20042434
• Citation:
  Toxicologist 2013 Mar; 132(1):344
• CAS Registry Number:
  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (CAS RN 28289-54-5) ; Carbonyl sulfide (CAS RN 463-58-1) ; Ethanol (CAS RN 64-17-5)
• Federal Fiscal Year:
  2013
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:416a445652fc942ef5c2a755feec81b2e0bf28b34e12ea743e70c06902274b5d64b30e3648de3925c5bb1388f44afd11c92174bdbdebc977c324f88ba006c422
• Download URL:
  https://stacks.cdc.gov/view/cdc/194659/cdc_194659_DS1.pdf
• File Type:
  [PDF - 567.74 KB ]