Seminar Series: Kevin L. Dreher, Ph.D. – Friday 4/13/2018, 11:00 A.M.
JSNN Seminar Series
Title: “Alternative Pulmonary Toxicity Assessment of a Nano-Enabled Outdoor Wood Preservative.”
Speaker: Kevin L. Dreher, Ph.D.
Job Title: Senior Investigator
Toxicity Assessment Division
National Health and Environmental Effects Laboratory
Office of Research and Development
US Environmental Protection Agency
Research Triangle Park, NC
Date and Time: Friday, 04/13/2018, 11:00 A.M.
Location: JSNN Auditorium
Existing and emerging engineered nanomaterials (ENMs) represent potential health risks depending on their physiochemical properties and exposure risks related to their applications. Applications and products containing multiple ENMs used in highly dispersive manner and in products with a high risk of ENM exposure via multiple routes of exposure are of particular concern. For example, cerium oxide (CeO2) is replacing TiO2 ENM as a surface coating for protection against ultra violet (UV) light/scratch resistant applications whereas copper(Cu)-based ENMs are increasingly being employed in wood preservatives and pesticides. Cu-based and CeO2 ENMs now exist in treated and UV-coated outdoor wood. These uses represent exposures to multiple ENMs via inhalation, dermal, and oral routes across treated wood’s life cycle (J. G. Clar et al., Science and the Total Environment 613-614:714-723, 2018; J. L. Griggs et al., Science and the Total Environment 598:413-420, 2017). Predictive alternative toxicity testing approaches are critically need to assess ENMs and nano-enabled products due to their number, applications, and changes of over their life cycle.
The seminar will present results of joint interagency case study between the US Environmental Protection Agency and the Consumer Product Safety Commission on nanoscale CuCO3 (1 – 400 nm) and CeO2 (5 – 7 nm) particles are employed as a preservative and ultra violet (UV) coating for outdoor wood, respectively. CuCO3 and CeO2 treated outdoor wood provide a product and application with a risk of dermal and/or inhalation exposures to a mixture of ENMs with unknown health effects. To address this uncertainty, research was conducted to assess the potential pulmonary toxicity of CuCO3 and CeO2 employed in outdoor wood preservation and UV coating. CuCO3 underwent ball-milling to produce CuCO3 nano/micro particles (NMPs) differing in size distribution but overlapping with commercial CuCO3 products Osmose and Arch employed as outdoor wood preservatives. Saw dust (SD) samples were obtained from untreated, CuCO3, and CuCO3+CeO2 treated outdoor wood. A thiobarbituric acid reactive substance (TBARS) assay was employed to assess the inherent reactivity of samples. TBARS analysis of CuCO3 NMPs demonstrated that samples with the smallest size distribution displayed the highest reactivity, whereas CeO2 NPs were found to have no TBARS reactivity. CeO2 NPs inhibited the TBARS reactivity of CuCO3 ball-milled samples in a dose-dependent manner. CuCO3 treated outdoor wood SD displayed TBARS reactivity similar to CuCO3 ball-milled samples. SD from untreated outdoor wood was negative in the TBARS assay. SD suspensions and centrifuged extracts from CuCO3-treated outdoor wood SD retained TBARS reactivity but the reactivity was lost when filtered through a 3kDal filter but not a 0.2 μm filter. Human bronchial epithelial BEAS 2B cells were exposed to ball-milled CuCO3 NMPs over a concentration range of 25 – 200 μg/ml for 24h and cytotoxicity was assessed using the WST1 assay. CuCO3 ball-milled NMPs with the smallest size distribution were most cytotoxic to BEAS 2B cells at 24hr post-exposure. CeO2 NPs were not cytotoxic to BEAS 2B cells. Finally, results of recent qRT-PCR studies has demonstrated the ability of CuCO3 NMPs with the most TBARS reactivity to induce greatest increase in IL-6 and IL-8 gene expression by BEAS 2B cells. These findings demonstrate CuCO3 NMPs employed as wood preservatives have inherent reactivity which correlated with human airway epithelial cell cytotoxicity and proinflammatory gene induction. In addition, results demonstrate the ability of alternative assays to link physicochemical properties to potential adverse pulmonary health effects. (This abstract does not represent EPA policy)
Since 1991 Dr. Dreher has been a senior principal investigator at the U.S. Environmental Protection Agency (USEPA), Office of Research and Development (ORD), National Health and Environmental Effects Research Laboratory. He is also an adjunct professor at the North Carolina State University and member in the Curriculum of Toxicology at the University of North Carolina, Chapel Hill. Dr. Dreher has managed over his career obtained and managed $9 million in research grant funding. He has given numerous invited national and international presentations. Dr. Dreher has served as co-chair of ILSI, HESI’s Cardiac Safety Technical Committee Leadership and Advisory Panel and resides on several of its working groups including its Cardiac Stem Cell Group. Dr. Dreher has published over 75 peer-reviewed scientific papers, co-authored 9 Agency and Federal research strategy and regulatory documents. Dr. Dreher serves on several national and international science advisory boards and review boards for major toxicology journals. He is past Councilor of the Inhalation Specialty Section of the Society of Toxicology and served as President, and co-founder of the Cardiovascular Toxicology Specialty Section within the Society of Toxicology.