Consideration of ADME/PK in Safety Assessments for Engineered

42 Pages·2015·3.43 MB·English

Application of ADME/PK
Studies to Improve Safety
Assessments for Food and
Cosmetics
February 23, 2015
Consideration of ADME/PK in Safety
Assessments for Engineered
Nanomaterials: Example with Silver
Nanoparticles
William K. Boyes, PhD.
Office of Research and Development
US Environmental Protection Agency
Research Triangle Park, NC
Dr. Boyes has no financial conflicts of interest

The materials in this presentation do not represent
endorsement of commercial products or official
policies of the Environmental Protection Agency
What is nanotechnology?
 Nanotechnology is science, engineering, and
“There is plenty of room at the
technology conducted at the nanoscale
bottom” (Richard Feynman)
 Nanoparticles are usually defined as having at
least 1 dimension between 1 to 100 nanometers.

 1 nm = 10-9 m
 1 nm x 109 = 1 m
 1 m x 107 = size of earth
90 nm size of HIV
200 nm = 2 x 10-7 m (limit visible microscope)
400-700 nm, wavelengths of visible light
10-9 10-7 10-5 10-3 10-1 101 103 105 107 109
1 nm 100 nm
meters
Visible Earth (http://visibleearth.nasa.gov/)
Nanotechnology is growing
President’s Council of Advisors on Science and Technology, 2014
Categories of commercial nanomaterials

Category # product Examples
listings
Carbon nanotubes 714 SWCNT, MWCNT
Fullerenes 136 Pure or functionalized
Graphene 38 Film, on substrate
Nanoparticles of elements 549 Metals (silver, gold etc.)
Binary compounds 750 metal oxides, salts, carbonates
Complex compounds 205 Doped metal oxides
Quantum Dots 183 Cadmium selenide
Biomedical Quantum Dots 205 Peg modified Qdots, Antibody coated
Nanowires 26 Copper, gold, indium
Nanofibers 30 Carbon
Non-carbon nanowires 1 Titania
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http://www.nanowerk.com/phpscripts/n_dbsearch.php
Accessed Aug 6, 2012
Health and Safety Issues for
Engineered Nanomaterials (ENM)
 High surface area / mass causes high reactivity
 High reactivity may lead to inadvertent toxicity
 Small size may enable them to distribute widely in biological
systems
 Evaluating ENM risks will require methods and technology
beyond traditional toxicological tools
 Rapid development and application exceeds capacity to test
potential toxicity using conventional approaches
 Risk assessments will need to consider:
alternative testing strategies (ATS)
–
in vitro - in vivo extrapolation (IV-IVE)
–
Transformative Science
 Toxicity Testing in the 21st Century: A Vision and a Strategy
(NRC, 2007)
 Growing number of ENM; can’t afford to test one-by-one
 Behavior of ENM depends on their inherent chemical and
physical properties and how those properties interact with
the environment and sensitive species in the environment
 Transformative science will understand the influence of
ENM material properties and build predictive models so that
each new material does not need to be fully tested
Chemical Safety for Sustainability
Objectives: Emerging Materials/
Nanomaterials
 Developing test systems that are adequate for
evaluation of nanomaterials
 Identifying critical parameters that influence their
behavior in the environment
 Determining how the inherent properties influence
behavior in biological systems and act in adverse
outcome pathways
Research Approach
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