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Manufacturing

NORA Manufacturing Sector Strategic Goals

927Z1LU - Dermal Effects of Nanoparticles

Start Date: 10/1/2005
End Date: 9/30/2010

Principal Investigator (PI)
Organization: NIOSH
Sub-Unit: HELD
Funded By: NIOSH

Primary Goal Addressed
9.0

Secondary Goal Addressed
None


Attributed to Manufacturing
100%

Project Description

Short Summary

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.



Description

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.



Results are expected to impact the state of knowledge in the field and guide future research by the scientific community. Results will be presented at scientific conferences and published in journals, will be disseminated by the NIOSH Nanotechnology Research Center, and will impact hazard identification and development of prevention strategies.



Objectives

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.

• To establish the extent to which SWCNT or ultrafine TiO2, NiO, and Co3O4 are toxic to skin cells in vitro and to characterize the role of oxidative stress and the role of transition metals in these effects.

• To establish the extent to which nanosized SWCNT can penetrate into the skin and whether this can cause adverse dermal effects.

• To establish the extent to which SWCNT or ultrafine metal oxides are pro-inflammatory to skin in vivo.

Results obtained from these studies provide critical knowledge about the mechanisms of dermal effects of nanoparticles and will be used for hazard identification, risk assessment and management. Initial outputs from the project will be abstracts and presentations followed by scientific publications. Scientific impact of such publications will be evaluated by the number of citations by extramural scientists. If the major goals are accomplished, the impact of the study will be to identify new workplace hazards, improve the assessment of risk for workplace exposures to carbon nanotubes, NiO, and Co3O4 induced coetaneous damage and skin inflammation. Data obtained from these studies will help to clarify effects of nanoparticles on skin cells and tissues, and to elucidate mechanisms of ultrafine TiO2, NiO, and Co3O4 or SWCNT-induced toxicity via inflammation and oxidative stress. These results will provide critical knowledge about the mechanisms of dermal toxicity of nanoscale materials with respect to occupational exposures.

Outputs of this project will be presentations and publications of the result in scientific conferences and journals. Outcomes will impact of results on the state of science in the field, impact on the direction of scientific research by other institutions, impact on recommendations by NIOSH on "Good Handling Practice for Nanomaterials", and impact on development of prevention strategies and risk assessment efforts by NIOSH, OSHA, EPA, and DOD.

Achievement of project goals will be determined by: 1) completion of project milestones, 2) number of presentations and publications, 3) the number of times these outputs are cited by the scientific community and/or mentioned in the lay press, 4) the influence on NIOSH publications such as "Frequently Asked Questions" and "Good Workplace Practices" documents, and 5) the usefulness in development of prevention strategies and risk assessment efforts by NIOSH, OSHA, EPA, and DOD. This information will be transmitted to NASA via an Interagency Agreement and to industry via articles in the lay press and summaries on the NIOSH Nanotechnology Web site.

Data obtained from these studies will help to clarify effects of nanoparticles on skin cells and tissues, and to elucidate mechanisms of ultrafine TiO2, NiO, and Co3O4 or SWCNT-induced toxicity via inflammation and oxidative stress. Results obtained from these studies provide critical knowledge about the mechanisms of dermal toxicity of nanoscale particles with respect to occupational exposures to nano-engineered materials and will impact future research by the scientific community and be used by regulatory agencies (OSHA and EPA) and industry to address strategies for assurance of healthy work practices and safe environment.

Initial outputs from the project will be abstracts and presentations followed by scientific publications. Scientific impact of such publications will be evaluated by the number of citations by extramural scientists. If the major goals are accomplished, the impact of the study will be to identify new workplace hazards, improve the assessment of risk for workplace exposures to carbon nanotubes and ultrafine metal oxide materials, introduction of tests for the potential toxicity of ultrafine materials, and the development of preventive strategies targeting of dermal exposure and adverse pulmonary outcomes. This information will be transmitted to NASA via an Interagency Agreement and to industry via articles in the lay press and summaries on the NIOSH Nanotechnology Web site. Impact will be evaluated by citations of these publications by extramural scientists and the use of results in instituting safe work practices and prevention measures in the workplace.



Mission Relevance

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.



Results will support the Manufacturing Sector (100%), Goal 9 "Enhance the state of knowledge related to emerging risks to occupational safety and health in manufacturing."



Results also support the Immune and Dermal Sector (100%) Goal 1 "Contribute to the reduction of occupational skin disease". Activity/Output goal 1.1.3 (09DRMAOG1.1.3) "Develop and validate improved laboratory ůmethodology for hazard identification".



Lastly, results support Nanotechnology (100%) Goal 1 "Determine if nanoparticles and nanomaterials pose risks for work-related illness." Intermediate Goal 2.1 (09PPNANIG2.1) "Key factors and mechanisms" Performance Measure 2.1 "Determine in vitro effects of SWCNT and metal oxide nanoparticles on skin cells and the in vivo effects of topical exposure".



Page last updated: June 3, 2011
Page last reviewed: May 23, 2011
Content Source: National Institute for Occupational Safety and Health (NIOSH) Office of the Director

 

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