|This study indicates that the observed in vitro effects of nanoparticles are not necessarily predictive of in vivo pulmonary effects. In vitro assays will need to be standardized and validated relative to in vivo effects before they can provide useful screening data on the relative toxicity of inhaled nanoparticles.|
Reviewed by Annette Santamaria, Ph.D., DABT, ENVIRON International Corporation.
- Sayes, C.M., Reed, K.L. and Warheit, D.B. (2007). “Assessing Toxicity of Fine and Nanoparticles: Comparing In Vitro Measurements to In Vivo Pulmonary Toxicity Profiles” Toxicological Sciences (97)1: 163-180. DOI: 10.1093/toxsci/kfm018
Previous studies have reported little correlation between the relative toxicity of particle types when comparing lung toxicity rankings following in vivo instillation versus in vitro cell culture exposures. This study was designed to assess the capacity of in vitro screening studies to predict in vivo pulmonary toxicity of several fine or nanoscale particle types in rats.
To assess the impact of many limitations of in vitro toxicity studies with the goal of developing an in vitro system that may provide a reasonably accurate, predictive early screen for assessing the pulmonary toxicity of fine and nano-sized particles.
An in vivo intratracheal pulmonary bioassay study and in vitro assays were conducted to assess the toxicity of five different fine or nano-sized particles, including carbonyl iron (CI) (800-3000nm) , crystalline silica (CS) (Min-U-Sil 5, a-quartz) (1800 nm), precipitated amorphous silica (AS) (1000-3000nm), nano-sized zinc oxide (NZO) (50-70nm), or fine-sized zinc oxide (FZO) (<1000nm). Inflammation and cytotoxicity indices were used as biomarkers to compare observed effects from the in vitro and in vivo studies. Several variables which strongly impact the ability of in vitro screening studies to accurately reflect in vivo pulmonary toxicity of several particle types in rats were evaluated, including particle dose, time course, duration of treatment exposure, and pulmonary cell types.
A recently published commentary focusing on the safe handling of nanotechnology recommended strategic research strategies to support sustainable nanotechnologies by maximizing benefits and minimizing environmental and health risks (Maynard et al., 2006). This international panel of scientists recommended five grand challenges which were selected to stimulate research and to bring focus to a range of complex multidisciplinary issues. One of the five key grand challenges cited in the commentary is to develop and validate alternatives (e.g., in vitro studies) to in vivo toxicity testing of engineered nanomaterials within the next 5–15 years. However, several studies have been conducted to evaluate the correlation between in vitro and in vivo pulmonary effects of a variety of chemical substances and particles and in many instances, there was little concordance between the observed cytotoxicity and inflammatory responses between the in vivo and in vitro studies.
Results of the in vivo pulmonary toxicity studies demonstrated that instilled CI particles produced little toxicity, CS exposures produced sustained inflammation and cytotoxicity, AS particles produced reversible and transient inflammatory responses and NZO and FZO particle instillations produced potent but reversible inflammation which was resolved at
1 month. Results of in vitro pulmonary cytotoxicity and inflammation assays demonstrated a variety of responses to the different particle types that demonstrated little correlation to the in vivo observations. Under the conditions of this study, the results of in vivo and in vitro cytotoxicity and inflammatory cell measurements demonstrated little correlation and the authors concluded that there is a need for better in vitro systems to predict the pulmonary toxicity potential of nanoparticles.