Advanced Continuing Education Course on Inhalation Toxicology Highlights Methods Innovations

By Gary Rankin posted 03-24-2014 19:02


On Sunday afternoon, March 23, I attended one of the advanced Continuing Education (CE) Courses offered at the 53rd Annual Society of Toxicology meeting in Phoenix, Arizona. The course was PM10 Innovations in Methodologies for Inhalation Exposure and Interpretations of In Vivo Toxicity. This CE course, chaired by Drs. Urmila Kodavanti, US Environmental Protection Agency (EPA), and Juergen Pauluhn, Bayer HealthCare, Germany, provided an update on many of the advances in methodology for studies that utilize inhalation exposure techniques to answer questions about toxicity of airborne chemicals and particles. The five speakers covered a wide range of topics ranging from evaluating nanoparticle exposure to studying complex environmental mixtures in the atmosphere.

Dr. Kodavanti welcomed everyone to the course and turned the session over to Dr. Pauluhn, who gave a brief introduction describing how the speakers will be presenting recent advances in inhalation methods for studying a wide range of emerging inhalants with a focus on the generation of atmospheres for both in vivo and in vitro toxicity studies.

Dr. Pauluhn then gave the first presentation, which focused on exposure methodologies in rodents and non-rodent species with an emphasis on measurements of cardiopulmonary function. His presentation highlighted the importance of understanding the link between pulmonary and cardiac events and suggested that early characterization of cardiopulmonary reflexes could be a new pathway to improve translational inhalation toxicology.

Dr. Pauluhn was followed by Dr. Jake McDonald from the Lovelace Respiratory Research Institute, Albuquerque, New Mexico, who talked about various aspects (aerosol generation, chemistry, and exposure conditions) of inhalation studies that involve complex mixtures. He made it very clear that studies examining complex mixtures must use relevant exposures both in terms of composition and concentrations of toxicants. It was particularly impressive to note the lengths to which his laboratory has gone to appropriately reproduce environmental exposure of humans to airborne toxicants. My favorite example was a study that examined gasoline emissions: His group removed engines from three Chevy S-10 pickup trucks and installed them in a laboratory setting, where they could effectively measure gasoline emissions. He also discussed how difficult it is to create and maintain the infrastructure needed to appropriately generate and determine the composition of complex mixtures to which we are exposed.

Dr. Bean Chen from the National Institute for Occupational Health and Safety in Morgantown, West Virginia, followed Dr. McDonald and described advances in methodologies for studying inhalation exposure and toxicity of manufactured nanoparticles. Nanomaterial toxicity is an area of growing concern and investigation, and his presentation highlighted studies that bridge inhalation toxicology and industrial hygiene. He described how studies of this type need to simulate the workplace in an exposure chamber and gave three cases as examples of how to properly conduct these types of studies. Of particular interest to me was a case study examining the potential toxicity of titanium dioxide nanoparticles that could be released from a gas-propelled spray can. He found that the occasional use of these antimicrobial spray products should not be a problem.

Dr. Chen was followed by Dr. Kenneth G. Sexton from the University of North Carolina, who discussed the use of exposure chambers to study air pollutants and the effect on sunlight to “age” the gases/pollutants to more toxic metabolites. It was very interesting to learn that as the day goes on, many types of airborne pollutant mixtures can become more toxic as the sunlight activates components of the air to more toxic chemical species. Dr. Sexton noted that some of these reactive species (e.g. ozone) can generate even more toxicants as the day goes on as part of the reason for the increased toxicity seen from air samples of pollutants later in the day.

The last presentation of the course was made by Dr. Mark Higuchi from the US EPA. His presentation covered advances in methodologies for conducting in vitro exposures to aerosols and vapors. He discussed the pros and cons of using primary cells versus cell lines for these studies, and it was interesting to learn that in vitro studies are now being conducted using cells obtained from humans that could be susceptible (asthmatics, smokers, genetic conditions, etc.) to airborne substances. He discussed advances in exposure chambers and how chambers used for in vivo exposures can also be adapted for in vitro exposures. I was amazed to learn how many new cook stoves are sent to the US EPA each year to be evaluated for emissions and how in vitro exposure to these emissions may someday be helpful in determining the safety of these stoves.

Overall, the session was very informative and highlighted the complexity of studying the safety, toxic potential, and potential mechanisms of toxicity following “real life” exposure to airborne toxicants and the concept that as the day goes on, air pollutants may have a greater risk of inducing toxicity was something that stayed with me as I left the course.