Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy

Günter Oberdörster¹ , Andrew Maynard² , Ken Donaldson³ , Vincent Castranova⁴ , Julie Fitzpatrick⁵ , Kevin Ausman⁶ , Janet Carter⁷ , Barbara Karn⁸^,9 , Wolfgang Kreyling¹⁰ , David Lai¹¹ , Stephen Olin⁵ , Nancy Monteiro-Riviere¹² , David Warheit¹³ , Hong Yang¹⁴ and A report from the ILSI Research Foundation/Risk Science Institute Nanomaterial Toxicity Screening Working Group

¹Department of Environmental Medicine, University of Rochester, 601 Elmwood Avenue, P.O. Box EHSC, Rochester, NY 14642, USA

²Project on Emerging Nanotechnologies, Woodrow Wilson International Center for Scholars, 1300 Pennsylvania Avenue, N.W., Washington, DC 20004-3027, USA

³MRC/University of Edinburgh Centre for Inflammation Research, ELEGI Colt Laboratory Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

⁴Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA

⁵Risk Science Institute, ILSI Research Foundation, International Life Sciences Institute, One Thomas Circle, N.W., Suite 900, Washington, DC 20005-5802, USA

⁶Center for Biological and Environmental Nanotechnology, MS-63, P.O. Box 1892, Rice University, Houston, TX 77251-1892, USA

⁷Respiratory/Inhalation Toxicology, Central Product Safety, Procter & Gamble Company, PO Box 538707, Cincinnati, OH 45253-8707, USA

⁸Office of Research and Development, United States Environmental Protection Agency, Ariel Rios Building, Mail Code: 8722F, 1200 Pennsylvania Avenue, N.W., Washington, DC 20460, USA

⁹Project on Emerging Nanotechnologies, Woodrow Wilson International Center for Scholars, 1300 Pennsylvania Avenue, N.W., Washington, DC 20004-3027, USA

¹⁰Institute for Inhalation Biology & Focus Network: Aerosols and Health, GSF National Research Centre for Environment and Health, Ingolstadter Landstrasse 1, 85764 Neuherberg, Munich, Germany

¹¹Risk Assessment Division, Office of Pollution Prevention & Toxics, United States Environmental Protection Agency, 7403M, 1200 Pennsylvania Avenue, N.W., Washington, DC 20460, USA

¹²Center for Chemical Toxicology and Research Pharmacokinetics, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA

¹³DuPont Haskell Laboratory for Health and Environmental Sciences, P.O. Box 50, 1090 Elkton Road, Newark, DE 19714-0050, USA

¹⁴Department of Chemical Engineering, University of Rochester, Gavett Hall 253, Rochester, NY 14627, USA

author email corresponding author email

Particle and Fibre Toxicology 2005, 2:8doi:10.1186/1743-8977-2-8


Published:	6 October 2005

Abstract

The rapid proliferation of many different engineered nanomaterials (defined as materials designed and produced to have structural features with at least one dimension of 100 nanometers or less) presents a dilemma to regulators regarding hazard identification. The International Life Sciences Institute Research Foundation/Risk Science Institute convened an expert working group to develop a screening strategy for the hazard identification of engineered nanomaterials. The working group report presents the elements of a screening strategy rather than a detailed testing protocol. Based on an evaluation of the limited data currently available, the report presents a broad data gathering strategy applicable to this early stage in the development of a risk assessment process for nanomaterials. Oral, dermal, inhalation, and injection routes of exposure are included recognizing that, depending on use patterns, exposure to nanomaterials may occur by any of these routes. The three key elements of the toxicity screening strategy are: Physicochemical Characteristics, In Vitro Assays (cellular and non-cellular), and In Vivo Assays.

There is a strong likelihood that biological activity of nanoparticles will depend on physicochemical parameters not routinely considered in toxicity screening studies. Physicochemical properties that may be important in understanding the toxic effects of test materials include particle size and size distribution, agglomeration state, shape, crystal structure, chemical composition, surface area, surface chemistry, surface charge, and porosity.

In vitro techniques allow specific biological and mechanistic pathways to be isolated and tested under controlled conditions, in ways that are not feasible in in vivo tests. Tests are suggested for portal-of-entry toxicity for lungs, skin, and the mucosal membranes, and target organ toxicity for endothelium, blood, spleen, liver, nervous system, heart, and kidney. Non-cellular assessment of nanoparticle durability, protein interactions, complement activation, and pro-oxidant activity is also considered.

Tier 1 in vivo assays are proposed for pulmonary, oral, skin and injection exposures, and Tier 2 evaluations for pulmonary exposures are also proposed. Tier 1 evaluations include markers of inflammation, oxidant stress, and cell proliferation in portal-of-entry and selected remote organs and tissues. Tier 2 evaluations for pulmonary exposures could include deposition, translocation, and toxicokinetics and biopersistence studies; effects of multiple exposures; potential effects on the reproductive system, placenta, and fetus; alternative animal models; and mechanistic studies.