Publications, Reports, and Posters Related to Respiratory Toxicity

Publications: Method Development and Application

• Stucki AO, Sauer UG, Allen DG, Kleinstreuer NC, Perron MM, Yozzo KL, Lowit AB, Clippinger AJ. Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments. Regul Toxicol Pharmacol. 2024;150:105648.
• Sharma M, Stucki AO, Verstraelen S, Stedeford TJ, Jacobs A, Maes F, Poelmans D, Van Laer J, Remy S, Frijns E, Allen DG, Clippinger AJ. Human cell-based in vitro systems to assess respiratory toxicity: a case study using silanes. Toxicol Sci. 2023;195(2):213-230.
• Paudel I, Barutcu AR, Samuel R, Moreau M, Slattery SD, Scaglione J, Recio L. Increasing confidence in new approach methodologies for inhalation risk assessment with multiple end point assays using 5-day repeated exposure to 1,3-dichloropropene. Toxicology. 2023;499:153642.
• Patel VS, Amin K, Wahab A, Marimoutou M, Ukishima L, Alvarez J, Battle K, Stucki AO, Clippinger AJ, Behrsing HP. Cryopreserved human precision-cut lung slices provide an immune competent pulmonary test system for “on-demand” use and long-term cultures. Toxicol Sci. 2023;191(2):253-265.
• Ramanarayanan T, Szarka A, Flack S, Hinderliter P, Corley R, Charlton A, Pyles S, Wolf D. Application of a new approach method (NAM) for inhalation risk assessment. Regul Toxicol Pharmacol. 2022;133:105216.
• Moreau M, Fisher J, Andersen ME, Barnwell A, Corzine S, Ranade A, McMullen PD, Slattery SD. NAM-based prediction of point-of-contact toxicity in the lung: A case example with 1,3-dichloropropene. Toxicology. 2022;481(July):153340.
• Da Silva E, Vogel U, Hougaard KS, Pérez-Gil J, Zuo YY, Sørli JB. An adverse outcome pathway for lung surfactant function inhibition leading to decreased lung function. Curr Res Toxicol. 2021;2:225-236.
• Luettich K, Sharma M, Yepiskoposyan H, Breheny D, Lowe FJ. An adverse outcome pathway for decreased lung function focusing on mechanisms of impaired mucociliary clearance following inhalation exposure. Front Toxicol. 2021;3:750254.
• Welch J, Wallace J, Lansley AB, Roper C. Evaluation of the toxicity of sodium dodecyl sulphate (SDS) in the MucilAir^™ human airway model in vitro. Regul Toxicol Pharmacol. 2021;125:105022.
• Petersen EJ, Sharma M, Clippinger AJ, Gordon J, Katz A, Laux P, Leibrock LB, Luch A, Matheson J, Stucki AO, Tentschert J, Bierkandt FS. Use of cause-and-effect analysis to optimize the reliability of in vitro inhalation toxicity measurements using an air-liquid interface. Chem Res Toxicol. 2021;34(6):1370-1385.
• Hargrove MM, Parr-Dobrzanski B, Li L, Constant S, Wallace J, Hinderliter P, Wolf DC, Charlton A. Use of the MucilAir airway assay, a new approach methodology, for evaluating the safety and inhalation risk of agrochemicals. Appl In Vitro Toxicol. 2021;7(2):50-60.
• Corley RA, Kuprat AP, Suffield SR, Kabilan S, Hinderliter PM, Yugulis K, Ramanarayanan TS. New approach methodology for assessing inhalation risks of a contact respiratory cytotoxicant: computational fluid dynamics–based aerosol dosimetry modeling for cross-species and in vitro comparisons. Toxicol Sci. 2021;182(2):243-259.
• Da Silva E, Hickey C, Ellis G, Hougaard KS, Sørli JB. In vitro prediction of clinical signs of respiratory toxicity in rats following inhalation exposure. Curr Res Toxicol. 2021;2:204-209.
• Ladics GS, Price O, Kelkar S, Herkimer S, Anderson S. A weight-of-the-evidence approach for evaluating, in lieu of animal studies, the potential of a novel polysaccharide polymer to produce lung overload. Chem Res Toxicol. 2021;34(6):1430-1444.
• Barosova H, Maione AG, Septiadi D, Sharma M, Haeni L, Balog S, O’Connell O, Jackson GR, Brown D, Clippinger AJ, Hayden P, Petri-Fink A, Stone V, Rothen-Rutishauser B. Use of EpiAlveolar lung model to predict fibrotic potential of multiwalled carbon nanotubes. ACS Nano. 2020;14(4):3941-3956.
• Zavala J, Freedman AN, Szilagyi JT, Jaspers I, Wambaugh JF, Higuchi M, Rager JE. New approach methods to evaluate health risks of air pollutants: critical design considerations for in vitro exposure testing. Int J Environ Res Public Health. 2020;17(6):2124.
• Ritter D, Knebel J, Niehof M, Loinaz I, Marradi M, Gracia R, Te Welscher Y, van Nostrum CF, Falciani C, Pini A, Strandh M, Hansen T. In vitro inhalation cytotoxicity testing of therapeutic nanosystems for pulmonary infection. Toxicol In Vitro. 2020;63:104714.
• Mistry A, Bowen LE, Dzierlenga MW, Hartman JK, Slattery SD. Development of an in vitro approach to point-of-contact inhalation toxicity testing of volatile compounds, using organotypic culture and air-liquid interface exposure. Toxicol In Vitro. 2020;69:104968.
• Halappanavar S, van den Brule S, Nymark P, Gaté L, Seidel C, Valentino S, Zhernovkov V, Høgh Danielsen P, De Vizcaya A, Wolff H, Stöger T, Boyadziev A, Poulsen SS, Sørli JB, Vogel U. Adverse outcome pathways as a tool for the design of testing strategies to support the safety assessment of emerging advanced materials at the nanoscale. Part Fibre Toxicol. 2020;17(1):16.
• Bluhmki T, Bitzer S, Gindele JA, Schruf E, Kiechle T, Webster M, Schymeinsky J, Ries R, Gantner F, Bischoff D, Garnett J, Heilker R. Development of a miniaturized 96-Transwell air–liquid interface human small airway epithelial model. Sci Rep. 2020;10:13022.
• Septiadi D, Rodriguez-Lorenzo L, Balog S, Spuch-Calvar M, Spiaggia G, Taladriz-Blanco P, Barosova H, Chortarea S, Clift M, Teeguarden J, Sharma M, Petri-Fink A, Rothen-Rutishauser B. Quantification of carbon nanotube doses in adherent cell culture assays using UV-VIS-NIR spectroscopy. Nanomaterials. 2019;9(12):176.
• Felder M, Trueeb B, Stucki AO, Borcard S, Stucki JD, Schnyder B, Geiser T, Guenat OT. Impaired wound healing of alveolar lung epithelial cells in a breathing lung-on-a-chip. Front Bioeng Biotechnol. 2019;7:3.
• Marescotti D, Serchi T, Luettich K, Xiang Y, Moschini E, Talikka M, Martin F, Baumer K, Dulize R, Peric D, Bornand D, Guedj E, Sewer A, Cambier S, Contal S, Chary A, Gutleb AC, Frentzel S, Ivanov NV, Peitsch MC, Hoeng J. How complex should an in vitro model be? Evaluation of complex 3D alveolar model with transcriptomic data and computational biological network models. ALTEX. 2019; 36(3):388-402.
• Luettich K, Talikka M, Lowe F, Haswell L, Park J, Gaca M, Hoeng J. The adverse outcome pathway for oxidative stress-mediated EGFR activation leading to decreased lung function. Appl In Vitro Toxicol. 2017;3(1):99-109.
• Behrsing HP, Huang S, Constant S. The use of human 3D reconstructed airway cultures for tobacco product evaluation: precision low-volume exposures at the apical site. Appl In Vitro Toxicol. 2017;3(1):56-67.
• Mottas I, Milosevic A, Petri-Fink A, Rothen-Rutishauser B, Bourquin C. A rapid screening method to evaluate the impact of nanoparticles on macrophages. Nanoscale. 2017;9(7):2492-2504.
• Sørli JB, Da Silva E, Bäckman P, Levin M, Thomsen BL, Koponen IK, Larsen ST. A proposed in vitro method to assess effects of inhaled particles on lung surfactant function. Am J Respir Cell Mol Biol. 2016; 54(3):306-311.
• Wiemann M, Vennemann A, Sauer UG, Wiench K, Ma-Hock L, Landsiedel R. An in vitro alveolar macrophage assay for predicting the short-term inhalation toxicity of nanomaterials. J Nanobiotechnology. 2016;14:16.
• Corvaro M, Gehen S, Andrews K, Chatfield R, Arasti C, Mehta J. GHS additivity formula: a true replacement method for acute systemic toxicity testing of agrochemical formulations. Regul Toxicol Pharmacol. 2016;82:99-110.
• Weisensee D, Poth A, Roemer E, Conroy LL, Schlage WK. Cigarette smoke–induced morphological transformation of Bhas 42 cells in vitro. Altern Lab Anim. 2013;41(2):181-189.
• Mathis C, Poussin C, Weisensee D, Gebel S, Hengstermann A, Sewer A, Belcastro V, Xiang Y, Ansari S, Wagner S, Hoeng J, Peitsch MC. Human bronchial epithelial cells exposed in vitro to cigarette smoke at the air-liquid interface resemble bronchial epithelium from human smokers. Am J Physiol Lung Cell Mol Physiol. 2013;304(7):L489-L503.

Publications: Workshop Proceedings and Reviews

• Sullivan K, Allen DG, Clippinger AJ, Wilson DM, Edwards SW, Glover K, Mansouri K, Settivari R, Wijeyesakere S, Casey W. Mind the gaps: prioritizing activities to meet regulatory needs for acute systemic lethality. ALTEX. 2021;38(2):327-335.
• Clippinger AJ, Allen D, Behrsing H, BéruBé KA, Bolger MB, Casey W, DeLorme M, Gaça M, Gehen SC, Glover K, Hayden P, Hinderliter P, Hotchkiss JA, Iskandar A, Keyser B, Luettich K, Ma-Hock L, Maione A, Makena P, Melbourne J, Milchak L, Ng S, Paini A, Page K, Patlewicz G, Prieto P, Raabe H, Reinke E, Roper C, Rose J, Sharma M, Spoo W, Thorne PS, Wilson DM, Jarabek AM. Pathway-based predictive approaches for non-animal assessment of acute inhalation toxicity. Toxicol In Vitro. 2018;52:131-145.
• Clippinger AJ, Allen D, Behrsing H, Hinderliter PM, Landsiedel R, Reinke EN, Stone V. Nonanimal approaches to assessing the toxicity of inhaled substances: current progress and future promise. Appl In Vitro Toxicol. 2018;4(2):82-88.
• Clippinger AJ. Application of in silico and in vitro approaches to assess the toxicity of inhaled substances. Appl In Vitro Toxicol. 2018;4(2):81.
• Strickland J, Clippinger AJ, Brown J, Allen D, Jacobs A, Matheson J, Lowit A, Reinke EN, Johnson MS, Quinn MJ Jr., Mattie D, Fitzpatrick SC, Ahir S, Kleinstreuer N, Casey W. Status of acute systemic toxicity testing requirements and data uses by US regulatory agencies. Regul Toxicol Pharmacol. 2018;94:183-196.
• Lacroix G, Koch W, Ritter D, Gutleb A, Larsen ST, Loret T, Zanetti F, Constant S, Chortarea S, Rothen-Rutishauser B, Hiemstra PS, Frejafon E, Hubert P, Gribaldo L, Kearns P, Aublant J, Diabaté S, Weiss C, de Groot A, Kooter I. Air-liquid interface in vitro models for respiratory toxicology research: consensus workshop and recommendations. Appl In Vitro Toxicol. 2018;4(2):91-106.
• Clippinger AJ, Allen D, Jarabek AM, Corvaro M, Gaça M, Gehen S, Hotchkiss JA, Patlewicz G, Melbourne J, Hinderliter P, Yoon M, Huh D, Lowit A, Buckley B, Bartels M, BéruBé K, Wilson DM, Indans I, Vinken M. Alternative approaches for acute inhalation toxicity testing to address global regulatory and non-regulatory data requirements: an international workshop report. Toxicol In Vitro. 2018;48:53-70.
• Behrsing H, Hill E, Raabe H, Tice R, Fitzpatrick S, Devlin R, Pinkerton K, Oberdörster G, Wright C, Wieczorek R, Aufderheide M, Steiner S, Krebs T, Asgharian B, Corley R, Oldham M, Adamson J, Li X, Rahman I, Grego S, Chu PH, McCullough S, Curren R. In vitro exposure systems and dosimetry assessment tools for inhaled tobacco products: workshop proceedings, conclusions and paths forward for in vitro model use. Altern Lab Anim. 2017;45(3):117-158.
• Hamm J, Sullivan K, Clippinger AJ, Strickland J, Bell S, Bhhatarai B, Blaauboer B, Casey W, Dorman D, Forsby A, Garcia-Reyero N, Gehen S, Graepel R, Hotchkiss J, Lowit A, Matheson J, Reaves E, Scarano L, Sprankle C, Tunkel J, Wilson D, Xia M, Zhu H, Allen D. Alternative approaches for identifying acute systemic toxicity: moving from research to regulatory testing. Toxicol In Vitro. 2017;41:245-259.
• Clippinger AJ, Ahluwalia A, Allen D, Bonner JC, Casey W, Castranova V, David RM, Halappanavar S, Hotchkiss JA, Jarabek AM, Maier M, Polk W, Rothen-Rutishauser B, Sayes CM, Sayre P, Sharma M, Stone V. Expert consensus on an in vitro approach to assess pulmonary fibrogenic potential of aerosolized nanomaterials. Arch Toxicol. 2016;90(7):1769-1783.
• Polk WW, Sharma M, Sayes CM, Hotchkiss JA, Clippinger AJ. Aerosol generation and characterization of multi-walled carbon nanotubes exposed to cells cultured at the air-liquid interface. Part Fibre Toxicol. 2016;13:20.
• Sharma M, Nikota J, Halappanavar S, Castranova V, Rothen-Rutishauser B, Clippinger AJ. Predicting pulmonary fibrosis in humans after exposure to multi-walled carbon nanotubes (MWCNTs). Arch Toxicol. 2016;90(7):1605-1622.
• Sharma M, Shatkin J, Cairns C, Canady R, Clippinger AJ. Framework to evaluate exposure relevance and data needs for risk assessment of nanomaterials using in vitro testing strategies. Risk Anal. 2016;36(8):1551-1563.
• Behrsing H, Raabe H, Manuppello J, Bombick B, Curren R, Sullivan K, Sethi S, Phipps R, Tesfaigzi Y, Yan S, D’Ruiz C, Tarran R, Constant S, Phillips G, Gaça M, Hayden P, Cao X, Mathis C, Hoeng J, Braun A, Hill E. Assessment of in vitro COPD models for tobacco regulatory science: workshop proceedings, conclusions and paths forward for in vitro model use. Altern Lab Anim. 2016;44(2):129-166.
• Manuppello JR, Sullivan KM. Toxicity assessment of tobacco products in vitro. Altern Lab Anim. 2015;43(1):39-67.
• Godwin H, Nameth C, Avery D, Bergeson L, Bernard D, Beryt E, Boyes W, Brown S, Clippinger AJ, Cohen Y, Doa M, Olgilvie Hendren C, Holden P, Houck K, Kane A, Klaessig F, Kodas T, Landsiedel R, Lynch I, Malloy T, Miller M, Muller J, Oberdorster G, Petersen EJ, Pleus R, Sayre P, Stone V, Sullivan K, Tentschert J, Wallis P, Nel AE. Nanomaterial categorization for assessing risk potential to facilitate regulatory decision-making. ACS Nano. 2015;9(4):3409-3417.

Reports

• OECD. Case Study No. 367 on the use of an Integrated Approach for Testing and Assessment (IATA) for New Approach Methodology (NAM) for Refining Inhalation Risk Assessment from Point of Contact Toxicity of the Pesticide, Chlorothalonil. 2022.
• US Environmental Protection Agency. FIFRA Scientific Advisory Panel meeting minutes and final report no 2019-01 – peer review on evaluation of a proposed approach to refine the inhalation risk assessment for point of contact toxicity: a case study using a new approach methodology (NAM). 19 April 2019.
• Federal Register. Revocation of significant new use rule for a certain chemical substance (P-16-581). 1 April 2020.

Posters

• Sharma M, Stucki AO, Verstraelen S, Jacobs A, Roldan N, Hollanders K, Van Laer J, Remy S, Frijns E, Clippinger AJ. The INSPIRE initiative: using human cell-based in vitro systems to assess respiratory toxicity of surfactants delivered as liquid or aerosols. Poster presented at: Society of Toxicology 63^rd Annual Meeting; 2024; Salt Lake City, UT.
• Marimoutou M, Patel VS, Amin K, Ukishima L, Wahab AF, Alvarez J, Battle K, Hughes J, Stucki AO, Clippinger AJ, Behrsing HP. Application of a performance characterization protocol for the assessment of normal and diseased cryopreserved human precision-cut lung slices. Poster presented at: Society of Toxicology 62^nd Annual Meeting; 2023; Nashville, TN.
• Behrsing HP, Marimoutou M, Amin K, Stucki AO, Clippinger AJ, Wahab A, Ukishima L, Patel VS. Cryopreservation of human precision-cut lung slices provides an immune competent, pulmonary test system for “on-demand” use. Poster presented at: Society of Toxicology 61^stAnnual Meeting; 2022; San Diego, CA.
• Sharma M, Stucki AO, Verstraelen S, Jacobs A, Poelmans D, Remy S, Maes F, Frijns E, Hollanders K, Geerts L, Voorspoels S, Laer JV, Clippinger AJ. Human cell–based in vitro systems to assess respiratory toxicity of chemicals. Poster presented at: Society of Toxicology 61^st Annual Meeting; 2022; San Diego, CA.
• Jarabek AM, Stedeford T, Ladics GS, Price OT, Tveit A, Hayes MP, Tremblay RT, Snyder SA, Salazar KD, Osman-Sypher S, Irwin W, Odin M, Melia J,  Carlson-Lynch H,  Sharma M, Clippinger AJ,  Stucki AO, Henry TR. Poorly soluble, low toxicity (PSLT) polymer category: an integrated approach to testing and assessment (IATA) including new approach methods (NAMs) under the Toxic Substances Control Act (TSCA). Poster presented at: Society of Toxicology 60^th Annual Meeting; 2021; Virtual.