Impact of Physiochemical Properties on Skin Absorption of Manufactured NanomaterialsEPA Grant Number: R833328
Title: Impact of Physiochemical Properties on Skin Absorption of Manufactured Nanomaterials
Investigators: Xia, Xin-Rui , Monteiro-Riviere, Nancy A. , Riviere, Jim E.
Institution: North Carolina State University
EPA Project Officer: Hahn, Intaek
Project Period: September 1, 2006 through August 31, 2009
Project Amount: $391,617
RFA: Exploratory Research: Nanotechnology Research Grants Investigating Environmental and Human Health Effects of Manufactured Nanomaterials: a Joint Research Solicitation-EPA, NSF, NIOSH, NIEHS (2006) RFA Text | Recipients Lists
Research Category: Health Effects , Nanotechnology , Health , Safer Chemicals
The wide applications of manufactured nanomaterials will create enormous potential for human exposure and environmental release. Skin, as the largest organ protecting the body from exogenous toxins and particulates, will be a major portal of entry for nanomaterials. Our preliminary study has shown that fullerene nanoparticles can penetrate deep into the stratum corneum (the primary barrier of the skin) and be modulated by solvents and ion-pairing agents. Currently, there is no method available for quantitative assessment of the skin absorption of the manufactured nanomaterials.
The objective of this project is to establish a structure-permeability relationship for skin absorption of manufactured nanomaterials for safety evaluation and risk assessment. Four dominant physiochemical properties (particle size, surface charge, hydrophobicity and solvent effects) in skin absorption will be studied. Fullerene and its derivatives will be used as model nanomaterials. The absorption and disposition kinetics and dose-response relationships will be measured experimentally for quantitative model development.
The novelty of this project is to study one parameter of interest (e.g., size) while keeping other parameters (e.g., surface charges and hydrophobicity) constant, in contrast to most of the current research focusing on the toxicological effects of the nanomaterials. Three well-developed experimental methods will be used in consideration of throughput, cost and biological complexity. Diffusion experiments will provide in-vitro absorption kinetic information by measuring the nanomaterial flux across the skin. Tape-stripping is designed to provide in-vitro disposition kinetic information of the nanomaterials in the stratum corneum. An isolated perfused porcine skin flap (IPPSF) technique will provide ex-vivo absorption kinetic information that has proven to be effective for human in vivo prediction.
The ion-pairing effects, solvent effects, and the impact of particle size and hydrophobicity on skin absorption of nanomaterials will be quantitatively measured to provide three sets of absorption kinetic data: in-vitro absorption, ex-vivo absorption, and in-vitro disposition kinetics. The quantitative data obtained in this project will be used to develop quantitative structure-permeability relationships based on the physiochemical properties of nanomaterials, which will define a general applicable approach for quantitative risk assessment and safety evaluation of manufactured nanomaterials.