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Respiratory Toxicology: Specialized Investigations

With the US FDA’s authority to regulate tobacco products and the need to assess consumer products and pharmaceuticals that may result in pulmonary exposures, IIVS has expanded its capabilities to include inhalation toxicology. Active engagement with industry stakeholders, regulatory authorities, and experts in pulmonary toxicity has led toward development and characterization of relevant in vitro models to guide decision making processes .

Using Ex Vivo Precision Cut Lung Slices and Reconstructed Human Airway Models

Customized programs to address your specific respiratory/airway concerns:

  • Evaluate hazards of ingredients and products
  • Acute airway and oral mucosal tissue toxicology
  • Chronic/repeat exposure
  • Inflammatory biomarker induction and fibrosis evaluations

Precision Cut Lung Slices (PCLS)

  • Human lung tissues cultured long-term at ALI
  • Cytotoxicity Endpoints
    LDH, AK, ALP release assays
  • Viability Endpoint
    WST-8 conversion
  • Histological Evaluations
    H&E architectural and cellular changes
    Masson’s Trichrome (collagen deposition)
    Custom IHC staining (e.g. macrophages)
  • Fibrosis Evaluations
    Inflammatory Cytokine Analyses
    Tissue collagen content by ELISA

Reconstructed Human Oral Buccal/Gingival Models

  • Human oral tissue models cultured at ALI
  • Cytotoxicity/Viability Endpoints
    LDH, AK release assays
    MTT, WST-8 conversion
  • Inflammatory Cytokine Analyses

Reconstructed Human Airway Models

  • Human bronchial tissue models cultured long-term at ALI
  • Cytotoxicity/Viability Endpoints
    LDH, AK release assays
    MTT, WST-8 conversion
  • Mucociliary clearance by ciliary beat frequency (CBF) analyses
  • Mucin production -Inflammatory Cytokine Analyses

Holger Behrsing, PhD., Principal Investigator

Holger P. Behrsing, PhD

Dr. Behrsing is Principal Scientist at IIVS and Principal Investigator (PI) for the Respiratory Toxicology Program. Bringing 20 years of experience in in vitro toxicology and expertise in the use of models for pulmonary toxicology, Dr. Behrsing conducts and oversees laboratory studies, as well as teaches and serves as an industry resource for workshops, webinars, and other educational activities. He serves as the PI for the respiratory toxicology workshop series.

Dr. Behrsing attended the University of CA, at Santa Barbara for his undergraduate degree, majoring in both Biology and German Studies. He completed his Doctoral degree in Pharmacology and Toxicology at UC Davis. He has spoken at internationally-recognized meetings and has experience with numerous in vitro and ex vivo models systems, with a well-documented background in the use of pulmonary models (Amin et al. 2006; Behrsing et al. 2004; Behrsing et al. 2013; Behrsing et al. 2006; Tyson et al. 2005).

Contact Dr. Behrsing to discuss a customized protocol.

Workshop Series

IIVS held its first workshop in respiratory toxicology in December of 2014, “Assessment of In Vitro COPD Models for Tobacco Regulatory Science”. The workshop was attended by more than 60 participants of diverse backgrounds, including FDA-CTP attendees and an FDA-CTP speaker. Conclusions from this first-in-series workshop prompted a second (technical) workshop, “In Vitro Models for Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays”, held in June 2015. This was followed by inter-lab exercises to establish standardized assay protocols.

Most recently, in April 2016, we held our second workshop the series and the only known event of its kind, “In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products”, attended by stakeholders from industry, government, and academia to discuss considerations for exposure and dosimetry for non-animal testing.

Workshop Report: Assessment of In Vitro COPD Models for Tobacco Regulatory Science (12/2014)

Funding for this conference was made possible, in part, by the Food and Drug Administration through grant 1 R13 FD 005299-01, views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does any mention of trade names, commercial practices, or organization imply endorsement by the United States Government.

Posters and Presentations


Workshop Report: In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products

Assessment of In Vitro COPD Models for Tobacco Regulatory Science: Workshop Proceedings, Conclusions and Paths Forward for In Vitro Model Use ALTA, May 2016

Digital Dispensing onto 3D Airway Tissue: Delivery of Patterned, Picoliter Volumes for Direct Apical Surface Coverage with Precise Quantities of Test Materials (“In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products”, IIVS Workshop, April 2016)

Effect of Acclimation Conditions on 3D Human in vitro ALI Airway Models: Exposure-induced Inflammatory Response and Sampling Location-specific Results (SOT 2016)

Type Document
Poster 2014 CORESTA: Toxic Insult to Rat Precision Cut Lung Slices Increases Tissue Cytokine Levels and Activation of Macrophages, and Causes Acute Damage, While Prolonged Insult May Lead to Increased Deposition of Collagen - a Marker of Fibrosis
Poster 2014 TSRC: The Use of Precision-cut Lung Slices to Assess Inflammation, Parenchymal Damage, and Collagen Deposition: Three Markers of Tobacco Exposure-induced Pulmonary Toxicity
Presentation 2014 IIVS Workshop: Assessment of In Vitro COPD Models for Tobacco Regulatory Science

Day 1: Overview: Etiology of COPD and In Vitro Models
Day 3: Detection of Inflammation and Parenchymal Damage Using Precision-cut Lung Slices
Presentation 2015 SOT Ancillary Meeting (IIVS): 2015 TSRC: 3D Reconstructed Human Airway Models: Effect of Acclimation Conditions on Biomarker and Inflammatory Response Following Tissue Challenge