exploring the biotic-abiotic interface: implications for ... presentation … · exploring the...
TRANSCRIPT
![Page 1: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/1.jpg)
Exploring the Biotic-Abiotic Interface:
Implications for Nano Toxicity
December 16, 2013
National Capitol Area Chapter
Society of Toxicology
Christopher P. Weis, Ph.D., DABT.
National Institutes of Environmental health Science
![Page 2: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/2.jpg)
Objectives
• What’s going on at the Biotic – Abiotic interface?
• Why is the Biotic-Abiotic interface important?
• What are the implications for Health Risks and Regulations?
![Page 3: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/3.jpg)
Basic Respiratory Anatomy
Images developed under contract to the National Institutes of Health
![Page 4: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/4.jpg)
Anatomy of the bronchiolar alveolus clusters
![Page 5: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/5.jpg)
Bronchiole Alveolar Structure Maina & van Gils (2001) Comp. Biochem and Physiol. 130(4)781-798.
![Page 6: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/6.jpg)
Gas exchange in the lung
The alveolar- capillary membrane is just 0.2 microns thick!
Blood volume in capillary space Is about 70 mL.
Blood flow through the lung is about 5L/min.
![Page 7: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/7.jpg)
![Page 8: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/8.jpg)
Water: the molecule of life
![Page 9: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/9.jpg)
Solid – Liquid Interface
Nel et
al. (2
00
9)
Nat
. M
ater.
8:5
43
![Page 10: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/10.jpg)
Qiao, R. et al. (2007) Nano Lett. 7(3):614
“C60 molecule can readily “jump” into the bilayer and translocate the membrane within a few milliseconds”
![Page 11: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/11.jpg)
“The simulation results indicate that, although a pristine C60 molecule can readily “jump” into the bilayer and translocate the membrane within a few milliseconds, the C60(OH)20 molecule can barely penetrate the bilayer.”
Small chemical modifications Can have big Consequences
Qiao, R. et al. (2007) Nano Lett. 7(3):614
![Page 12: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/12.jpg)
ENM – Biomolecule Interactions
Nel et al. (2009) Nat. Mater. 8:543
![Page 13: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/13.jpg)
Nel et al. (2009) Nat. Mater. 8:543
Nanoparticle endocytosis at the cell membrane: The clathrin-coated vessicle
![Page 14: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/14.jpg)
Clathrin coated vessicles transporting materials across the cell
membrane
Attribution: University of British Columbia Dept. of Zoology (Permission requested)
![Page 15: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/15.jpg)
Objectives
• What’s going on at the Biotic – Abiotic interface?
• Why is the Biotic-Abiotic interface important?
• What are the implications for OELs?
![Page 16: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/16.jpg)
Attribution: F.A. Murphy, Univ.Texas Medical Branch
Coronavirus on a Mouse epithelial cell ~40,000X mag.
Coronavirus
(~70 - 200nm)
![Page 17: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/17.jpg)
Corona Virus on Cultured Cell Surface Attribution: Dr. Steve Patterson
![Page 18: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/18.jpg)
Targeted Docetaxel Nanoparticle
Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile.
Hrkach et al. (2012) Sci. Trans. Med 4:128ra39
~90 nm
Docetaxel MW=807
![Page 19: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/19.jpg)
Strain-specific differential response to TOPO-PMAT Cd-
Se/ZnS QDs
Oropharyngeal aspiration 10 nM solution, 8 h PE
BALF Neutrophils
Mouse Strains
Univ. Washington Nanotoxicology Center
![Page 20: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/20.jpg)
Ceria nanowires introduced
shape-dependent toxicity
Inflammasome activation
N
pro-IL-1β IL-1β
lysosome
IL-1β NALP3
Macrophage AR 0= 1
Ф = 7 nm
AR 7>200
L = 1~2 μm
0
50
100
150
200
250
300
0 25 50 75 100 125
IL-1
β a
cti
vit
y (
pg
/mL
)
Concentration (µg/mL)
R0R1R2R3R4
AR 6
AR 0-5
AR7
THP-1 cells
AR7
Lysosomal Damage
AR7
SEM TEM
Frustrated endocytosis
AR: aspect ratio
IL-1β T
HP
-1 c
ell
s
TH
P-1
cell
s
Ceria nanowires introduced shape-dependent toxicity NIEHS-funded Center for Nanobiology and Predictive Toxicology
![Page 21: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/21.jpg)
Objectives
• What’s going on at the Biotic – Abiotic interface?
• Why is the Biotic-Abiotic interface important?
• What are the implications for Risks and Regulations?
![Page 22: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/22.jpg)
Att
ribut
ion:
CP
Weis
![Page 23: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/23.jpg)
Nano-sized mineral fibrils from Western Montana A
ttribu
tion:
![Page 24: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/24.jpg)
Phagocytosis of asbestos fibers
pulmonary alveolar macrophage cell attempting to engulf and ingest several long mineral fibers incomplete ingestion of bio-persistent fibers can lead to extensive ‘selective release’ of proteolytic enzymes and ROS from the ‘frustrated’ PAMs
![Page 25: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/25.jpg)
Microscopic and macroscopic lung abnormalities caused by durable fibers
‘mineral bodies’
‘ferruginous bodies’
Radiograph of Pleural plaques
Anatomy of Pleural plaques
Attribution: Med. Digital Library. Univ. of Michigan
![Page 26: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/26.jpg)
High Resolution Computed Tomography (HRCT) of a pleural plaque
HRCT scan of a 45 Y.O. female with secondary (take home) exposure to nano particle taconite dust in the Upper Peninsula of Michigan.
Harbut et al. (2009) Int J Occup Environ Health 15(3):269-
273.
![Page 27: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/27.jpg)
“Fibres shorter than 5 mm have traditionally not been counted by methods used for regulatory standards for asbestos because these methods were developed to provide a reproducible index of fibre exposure. The findings from our analysis show that cumulative exposures to all fibre size indices, including fibres <5 mm in length, were highly statistically significant predictors of lung cancer or asbestosis mortality.”
Stayner et al. (2008) Occ. Env. Med 65(9):613
Size–based Risk Management: a good idea?
![Page 28: Exploring the Biotic-Abiotic Interface: Implications for ... Presentation … · Exploring the Biotic-Abiotic Interface: Implications for Nano Toxicity December 16, 2013 National](https://reader034.vdocuments.mx/reader034/viewer/2022042605/5f54355198ff392224791ff2/html5/thumbnails/28.jpg)
Summary
• Biophysical chemistry at the abiotic-biotic
interface is critical to understanding
toxicity of engineered nanomaterials;
• Characterization of nanomaterials
(especially effects on the A-B interface) is
key;
• Toxicity studies for nanomaterials must
include minimal physico-chemical
characterization.