NORA Manufacturing Sector Strategic Goals
927Z1LU - Dermal Effects of NanoparticlesStart Date: 10/1/2005
End Date: 9/30/2010
Principal Investigator (PI)Organization: NIOSH
Funded By: NIOSH
Primary Goal Addressed9.0
Secondary Goal AddressedNone
Attributed to Manufacturing100%
Nanoparticles are new materials of emerging technological importance in different industries. Because dermal exposure is likely in a number of occupational settings, it is very important to assess whether nanoparticles could cause adverse effects to skin. Therefore, this project addresses issues of Dermal Disease. The hypothesis is that nanoparticles are toxic to the skin and the toxicity is dependent on their penetration to skin, induction of oxidative stress, and content of transition metals. Results obtained from these studies provide critical knowledge about mechanisms of dermal toxicity of nanoscale materials and will be used by regulatory agencies (OSHA and EPA) and industry in the manufacturing sector, specifically nanotechnology, to address strategies for assurance of healthy work practices and safe environments.
In the last four years, the federal government has provided over one billion dollars in nanotechnology research funding. Carbon Nanotube (CNT) materials are among these newly developed products and are currently of interest for a variety of applications in electronics, reinforced rods, micro-fabricating conjugated polymer activators, supersensitive sensors, enhanced electron/scanning microscopy imaging techniques, and biosensors. Nanostructured or microstructured materials are valuable sources for bone substitutes, bio-mimetic composites, and chemical and genetic probes (Erickson et al., 2004). Nanoengineered particles are already widely used in consumer products, such as sun screens, cosmetics, and toiletries, which are used daily by millions, and the market for these materials is estimated to grow to over eight billion dollars in the next decade. Introduction of novel materials into industry requires evaluating safety and understanding the impact of nanomaterials on the environment, biological species, and human health. To date, little information is available concerning the potential dermal toxicity of nanotubes and ultrafine metal oxides. The objective of this work is to evaluate the dermal toxic effects of nanoparticles both in vitro and in vivo. The project has three specific aims: 1) To establish the extent to which single walled carbon nanotubes (SWCNT) or ultrafine TiO2, NiO, and Co3O4 are toxic to cells in vitro and to characterize the role of oxidative stress and role of transition metals in these effects. 2) To establish the extent to which nanospheres or SWCNT can penetrate into the skin and whether this can cause adverse dermal effects. 3) To establish the extent to which SWCNT or ultrafine metal oxide particles are pro-inflammatory to skin in vivo.
This project addresses a critical gap identified by the NIOSH Nanotechnology Research Center to determine if nanoparticles caused dermal toxicity. The central hypothesis of this project is that topical exposure to nanoparticles causes' skin damage via formation of reactive oxygen species in dermal cells, generation of oxidative stress and antioxidant imbalance in the skin. To test this hypothesis, dermal cells, human in geneered constract tissues and mice will be exposed by to carbon nanotubes, nanosized carnon coated/uncoated NiO, Co3O4 and TiO2. Endothelial dependent dilation or arterioles in the spinotrapezius muscle will be monitored by intravital microscopy. The project has 3 specific Aims.
Nanoparticles are currently being used in sunscreens and cosmetics and their use in skin products is projected to increase dramatically in the next decade. Despite extensive use in skin care products, little is know concerning the potential for these nanoparticles to penetrate the skin and/or cause adverse dermal effects. Production of inflammatory mediators is an important step in the pathogenesis of skin diseases. The approach of this project is to explore the basic molecular mechanisms causing skin disease using state of the art techniques. The NIOSH Nanotechnology Research Center has identified elucidation of the dermal effects of exposure to nanomaterials as a "Critical Issue." The project is relevant to understanding skin injury associated with exposures to nanosize particles. The project hypothesis is that such exposures involve an inflammatory response and oxidant stress following initial exposures. Therefore, skin cell will be exposed to carbon nanotubes and nanometal oxide particles and oxidose stress and alteration in signaling pathways will be evaluated. In addition, inflammatory effects of topical exposure in an animal model will be determined. A greater understanding of mechanisms involved in the initiation and progression of skin inflammation will assist in risk assessment and in the development of strategies for treatment of occupational diseases. This function is being served by offering NIOSH expertise in pathology, molecular biology, and cell biology techniques to this project related to NORA research priorities in Emerging Technology.