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Methodological considerations when conducting in vitro, air-liquid interface exposures to engineered nanoparticle
Lynn E Secondo1, Nathan J Liu2,3, Nastassja A Lewinski1,2
1a Department of Chemical and Life Science Engineering , Virginia Commonwealth University , Richmond , VA , USA.
Critical Reviews in Toxicology
|September 21, 2016
Summary
Standardizing toxicological testing for engineered nanoparticles (ENPs) in air-interfaced culture (AIC) systems is crucial. This review highlights methodological inconsistencies and offers recommendations for reliable in vitro risk assessment.
Area of Science:
- Nanotoxicology and Environmental Health Sciences
- In Vitro Toxicology and Risk Assessment
Background:
- Significant inconsistencies exist in the methodologies for toxicological testing of aerosolized engineered nanoparticles (ENPs) using in vitro air-interfaced culture (AIC) exposure systems.
- These variations in particle types, exposure durations, systems, and dose metrics hinder inter-laboratory comparisons and the identification of adverse effect dose thresholds.
Purpose of the Study:
- To critically analyze the methodologies employed in ENP toxicological assessments within AIC exposure systems.
- To determine whether administered or deposited dose better correlates with biological response.
- To compare different AIC systems, assess consistency for similar nanomaterials, and evaluate the correlation between in vitro and in vivo deposited doses and AIC model reliability for acute toxicity.
Main Methods:
- Systematic literature screening of 10,241 studies, with 110 publications meeting eligibility criteria for review.
- Critical analysis of methodologies for delivering, measuring, and reporting ENP aerosol doses in vitro.
- Comparative case studies on silver, zinc oxide, titanium dioxide, and multi-walled carbon nanotube exposures, examining dosimetry and biological responses across AIC, conventional suspensions, and in vivo models.
Main Results:
- Methodological heterogeneity in ENP toxicological testing using AIC systems is prevalent, affecting dose-response relationship clarity.
- Variability exists in dose metrics and exposure system performance, impacting the comparability of results.
- Case studies reveal discrepancies in how different ENPs behave and elicit responses across various exposure models.
Conclusions:
- Standardization of methodologies in ENP toxicological testing via AIC systems is urgently needed.
- Recommendations are provided for designing future AIC experiments to enhance standardization, facilitate inter-laboratory comparisons, and improve the reliability of in vitro risk assessment for ENPs.
- Improved dosimetry and reporting are essential for accurate risk assessment and understanding nanoparticle toxicity.

