Nanomaterials: Are small particles a big problem?Occupational health and safety issues associated with nanoparticle

exposures

Nanomaterials: Are small particles a big problem?Occupational health and safety issues associated with nanoparticle

exposures

Susan Woskie

Professor

Department of Work Environment

University of Massachusetts Lowell, USA

Susan Woskie

Professor

Department of Work Environment

University of Massachusetts Lowell, USA

Mahidol University & UMass Lowell Center for Work Environment Nutrition and Development (CWEND)GeoHealth Hub for Occupational & Environmental Health

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*over 3000 NM in Nanowerks database

*over 1600 products in Nanotechnology Consumer Products Inventory.

Nanomaterial CategoriesICON, 2008

• Oxides: TiO2, ZnO, CeO2, Fe3O4 MnO2, SiO2

• Metals: Ag, Co, Ni, Fe, Pt, Pd, Rh, Au, Al, Cu

• Carbon Based Nanoparticles

– Nanotubes….single & multiwall

– Nano Carbon black

• Quantum Dots: fluorescent crystalline semiconductor

nanoparticles for biolabels, LEDs, solar cells

• Macromolecules: hyperbranched polymeric organic

molecules for drug delivery, coatings, ion exchange resins

Kosnett & Woskie Chap 81 Patty’s Industrial Toxicology 2012

Nano Silver…antibacterial• Used in many commerical products

– Athletic clothing, linens, cosmetics, baby bottles, toothpaste, food containers, kitchen and washing machine surfaces & sprayed in Hong Kong subways

• Used in many medical productes– Hospital equipment including catheters, bandages, wheelchair

seats and door handles.

• Concern about bacterial resistance and damage to sewage treatment bacteria

• Unconverted silver shown to be toxic to fish, algae and crustaceans. – Some converted to more stable silver sulfides in wastewater (O2-

free environments where sulfates present)

Oberdoster et al. EHP 2005; 113 (7)Oberdoster et al. EHP 2005; 113 (7)

Translocation via olfactory neurons (Oberdoster, EHP, 2005)

-non-human primates :monkey & 50 nm colloidal gold particles (DeLorenzo, 1970)-rodents: ultrafine particles ~30 nm (G. Oberdörster 1990s)- rodents & cats: axonal transport 20-200 nm rhodamine labeled microspheres

(Katz et al. 1983)-fish: soluble Mn (Tjalve, 1990s)

Chronic Inflammation- Linked to various diseases

Reactive Oxygen Species /ROSCause Oxidative Damage

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Bello et al Nanotoxicology, 2013 (5):989

Nanoparticle Emissions from Commercial Photocopiers

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Biomarkers in Nasal Lavage

Khatri et al Nanotoxicology,2013 Aug;7(5):1014

•10 key inflammatory markers increased, such as:

• IL-6, IL-8, TNF-a, GCSF, MCP-1

•Total Protein UP•PMN (white blood cells) UP

•Several inflammatory markers stay significantly elevated at 24-30 hrs post-exposure (IL-6, IL-8, EGF and fractalkine)

0 6hr 12hr 24hr

IL6

GCSF

IL8 TNF-a

PMN

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Excreted in Urine

8-OHdG – Sensitive Marker of Systemic Oxidative Damage from Photocopier Exposure

ln

8-O

HD

G

• 8-OH-dG (oxidative state of deoxyguanine DNA amino acid) increased in urine after photocopier exposure

• Stays significantly elevated at 24-30 hrs post-exposure

• Increases with average daily particle count (#/cm3)

• Partilce count of ~30,000 is ~10x higher than background

0 6hr 12hr 24hr

Av Daily Particle countKhatri et al Nanotoxicology, 2013

We need Epidemiologic Studies of NM Exposed Workers….NIOSH has proposed a prospective cohort

Reactive Oxygen Species /ROSCause Oxidative Damage

Tagaki et al. 2008 “Induction of mesothelioma in p53+/− mouse by

intraperitoneal application of multi-wall carbon nanotube”:

• Administer MWCNT intraperitoneally to asbestos sensitive mice.

• MWCNT induced mesothelioma (purple line) as did positive control, crocidolite asbestos (orange line), compared to no mesothelioma from fullerene negative control.

• MWCNT ~10 to 20 micrometers length with an aspect ratio of more than three…..asbestos fiber-like

J. Toxicol. Sci., Vol. 33: No. 1, 105-116. (2008) .

Fiber Production with Machining of Composites

• Cutting of CNT-hybrid composites produced respirable size fibers (though not specifically CNTs)

• Using NIOSH counting rules the concentrations of fibers were: 1.6-3.8 fibers/cm3 (0.1 f/cm3 = USA PEL)

• CNT-Alumina composites produced fewer fibers than CNT-carbon composites

Bello et al, J Nanopart Res 2009

Examples of Potential Exposures

Some Photos courtesy of M. Methner, NIOSH 3-16

17X2012; dhimiter_bello@uml.edu

PRIMARY MANUFACTURING TiO2

Thousands of tons/yr.

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Instrumentation

Real time Characterization

Integrated Sampling off-line Characterization

Number ConcentrationFast Mobility Particle Sizer

(FMPS), Aerodynamic Particle Sizer (APS),

Condensation Particle Counter (CPC)(p/cm3)

Size distribution FMPS, APS

(dN/dLogDp, p/cm3)

P. Boonruksa UML 2014

NIOSH NEAT screening….• if process < 25% background

count then stop…• If process > 25% background

then further samples

Instrumentation

Real time Characterization

Integrated Sampling off-line

Characterization

Morphology- ESP TEM- Filters SEM/EDX

Chemical composite- TGA CNT

content- XPS Surface

chem.

Fiber Count, Shape (BZ) Filters SEM

200-mesh Cu with C film

Nucleopore, 0.4 um

Thermal Gravimetric Analysis (TGA)

Xray Photoelectron Spectroscopy (XPS)

P. Boonruksa UML 2014

Electrostatic precipitator (ESP)

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REGULATIONS: RELs

USA (NIOSH)• CNTs

– NIOSH, 1ug/m3, EC, 8-hr TWA

– (asbestos = 0.1 f/cc)

• Nano TiO2 – 300 ug/m3, 8-TWA

(vs. 2.4mg/m3 for non-nano TiO2)

International• CNTs

– 0.01 fibers/cm3 (British Stand Inst 2007, German Social Accident Insurance IFA 2009)

– 30 ug/m3 (Japanese National Institute of Advanced Industrial Science and Technology)

dhimiter_bello@uml.edu

No standard or criteria for counting potential CNT fibers, (now use asbestos fiber count method, NIOSH 7400, 7402, WHO 1997)

Consider ALARA: As Low As Reasonably Achievable.

Precautionary PrincipleUnited Nations Rio Declaration 1992

Lack of full scientific certainty shall not be used to postpone measures to prevent threats of serious or irreversible damage to the environment or human health

spinning operations for asbestos thread (1930–1960) and spinning SWCNT into high-strength ‘super rope’ (early 2000s)

Engineering Controls

• LEV during reactor cleanout reduces exposures 74-96% (Methner JOEH 2008)

• ICON survey reported only 47% of those handling dry powder use lab hood or ventilation

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Transfer Al2O3

Tsai et al Ann Occ Hyg 2010

Controls for Nano Exposures• Respiratory Protection Program Requirements

• NIOSH approved P100/N95 filters “achieve expected levels of filtration efficiency for nanoparticles” (NIOSH-allowed penetration levels of < 5% N95 and < 0.03% P100 filter materials)

• Dermal Exposure & PPE•Nitrile, latex, neoprene, and butyl rubber gloves tested with

powder and colloidal nano TiO2 by IRRST Canada 2013.•Generally good protection but replace gloves used under

mechanically stressful conditions, especially if colloidal material

• Training • 42% of 82 International nano companies reported they did not

perceive nanomaterials as risky so they :

• Did have not nano specific training or EHS program (64%)• Did not require PPE (40%)• Did not do exposure monitoring (51%)• Did not use nanospecific waste disposal methods (47%)

• Conti et al. EST 2008, 42 (9)

(1) Sotiriou et al., Curr Opin Chem Eng 2011, 1, 3 – 10(2) Xia et al., ACS Nano 2011, 5, 1223 – 1235 (3) Napierska et al., Particle and Fibre Toxicology 2010, 7,39(4) Teleki et al., Chem. Mater. 2009, 21, 2094–2100(5) Sotiriou et al., Adv. Funct. Mater. 2010, 20, 4250–4257 Source: Prof. P. Demokritou HSPH

Next generation ENM: Safer-by design• Incorporate high throughput

screening prior to marketing• Utilize screening to design safer

materials

Thank You for your Attention!

Sunscreens,

ZnO nano vs macro

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Q-Dots

http://www.nanoandme.org/nano-products/cosmetics-and-sunscreen/

Larson, Science, 2003, 300:1434

Hardman, EHP 2006, 114 (2)

Macrophage with carbon nanotube