Approaches to Safe 

Nanotechnology

Managing the Health and Safety Concerns 

Associated with Engineered Nanomaterials

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health
Photo Credits:

Nanotrees, Ghim Wei Ho and Professor Mark Welland, Nanostructure Center, University of 

Cambridge
Managing the Health and Safety Concerns 

Associated with Engineered Nanomaterials

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

Approaches to Safe Nanotechnology
ii Approaches to Safe Nanotechnology

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DHHS (NIOSH) Publication No. 2009–125

March 2009

Safer • Healthier • PeopleTM
Approaches to Safe Nanotechnology iii

Nanotechnology—the manipulation of matter on a near-atomic scale to produce new structures, 

materials, and devices—offers the promise of unprecedented scientific advancement for many sectors, such as medicine, consumer products, energy, materials, and manufacturing. Nanotechnology 

has the power not only to improve existing technologies, but to dramatically enhance the effectiveness of new applications. 

Research on the potential applications of nanotechnology continues to expand rapidly worldwide. 

New nanotechnology consumer products emerge at a rate of three to four per week. Over the course 

of the next decade, nanotechnology could have a $1 trillion impact on the global economy and employ two million workers—half of them residing in the U.S. 

While nanomaterials present seemingly limitless possibilities, they bring with them new challenges to understanding, predicting, and managing potential safety and health risks to workers. The 

National Institute for Occupational Safety and Health (NIOSH) remains committed to protecting 

workers now and in the future, as nanotechnology applications and uses expand.

As part of these efforts, in October 2005, NIOSH released for public comment the draft document, 

Approaches to Safe Nanotechnology: An Information Exchange with NIOSH. Based on feedback 

received, NIOSH revised and updated the document in July 2006 and sought further public comment. This draft report has been widely cited, and the final version of the report should serve as a 

vital resource for stakeholders (including occupational safety and health professionals, researchers, 

policy makers, risk assessors, and workers in the industry) who wish to understand more about the 

safety and health implications of nanotechnology in the workplace. 

With the publication of the Approaches to Safe Nanotechnology document, NIOSH hopes to: raise 

awareness of the occupational safety and health issues involved with nanotechnology; make recommendations on occupational safety and health best practices in the production and use of nanomaterials; facilitate dialogue between NIOSH and its external partners in industry, labor and academia; 

respond to requests for authoritative safety and health guidelines; and, identify information gaps 

and areas for future study and research. 

As our knowledge of nanoscience increases, so too will our efforts to provide valuable guidance on 

the safe handling of nanoparticles and for protecting the lives and livelihoods of nanotechnology 

workers.

Christine M. Branche, Ph.D.

Acting Director, National Institute 

 for Occupational Safety and Health

Centers for Disease Control and Prevention

Foreword

Approaches to Safe Nanotechnology v

Nanotechnology has the potential to dramatically improve the effectiveness of a 

number of existing consumer and industrial products and could have a substantial 

impact on the development of new products in all sectors, ranging from disease 

diagnosis and treatment to environmental 

remediation. Because of the broad range of 

possible nanotechnology applications, continued evaluation of the potential health 

risks associated with exposure to nanomaterials is essential to ensure their safe handling. Engineered nanoparticles are materials purposefully produced with at least one 

dimension between 1 and 100 nanometers. 

Nanoparticles* often exhibit unique physical 

and chemical properties that impart specific 

characteristics essential in making engineered materials, but little is known about 

what effect these properties may have on 

human health. Research has shown that the 

physicochemical characteristics of particles 

can influence their effects in biological systems. These characteristics include particle 

size, shape, surface area, charge, chemical 

properties, solubility, oxidant generation 

potential, and degree of agglomeration. Until the results from research studies can fully 

elucidate the characteristics of nanoparticles 

that may pose a health risk, precautionary 

measures are warranted. 

NIOSH has developed this document to 

provide an overview of what is known 

about the potential hazards of engineered 

*In an attempt at standardization of terminology, the International Organization for Standardization-Technical 

Committee 229 has used the term nanomaterial to describe 

engineered nanoparticles.

nanoparticles and measures that can be 

taken to minimize workplace exposures. 

Following is a summary of findings and key 

recommendations.

Potential Health Concerns

•	 The potential for nanomaterials to enter the body is among several factors 

that scientists examine in determining 

whether such materials may pose an occupational health hazard. Nanomaterials have the greatest potential to enter 

the body through the respiratory system if they are airborne and in the form 

of respirable-sized particles (nanoparticles). They may also come into contact 

with the skin or be ingested. 

•	 Based on results from human and animal studies, airborne nanoparticles can 

be inhaled and deposit in the respiratory tract; and based on animal studies, nanoparticles can enter the blood 

stream, and translocate to other organs.

•	 Experimental studies in rats have shown 

that equivalent mass doses of insoluble incidental nanoparticles are more 

potent than large particles of similar 

composition in causing pulmonary inflammation and lung tumors. Results 

from in vitro cell culture studies with 

similar materials are generally supportive of the biological responses observed 

in animals.

•	 Experimental studies in animals, cell 

cultures, and cell-free systems have 

shown that changes in the chemical 

Executive Summary
vi Approaches to Safe Nanotechnology

Executive Summary

composition, crystal structure, and size 

of particles can influence their oxidant 

generation properties and cytotoxicity. 

•	 Studies in workers exposed to aerosols 

of some manufactured or incidental 

microscopic (fine) and nanoscale (ultrafine) particles have reported adverse 

lung effects including lung function 

decrements and obstructive and fibrotic lung diseases. The implications of 

these studies to engineered nanoparticles, which may have different particle 

properties, are uncertain. 

•	 Research is needed to determine the 

key physical and chemical characteristics of nanoparticles that determine 

their hazard potential. 

Potential Safety Concerns

•	 Although insufficient information exists to predict the fire and explosion 

risk associated with powders of nanomaterials, nanoscale combustible material could present a higher risk than 

coarser material with a similar mass 

concentration given its increased particle surface area and potentially unique 

properties due to the nanoscale. 

•	 Some nanomaterials may initiate catalytic reactions depending on their 

composition and structure that would 

not otherwise be anticipated based on 

their chemical composition.

Working with Engineered 

Nanomaterials

•	 Nanomaterial-enabled products such as 

nanocomposites, surface-coated materials, and materials comprised of nanostructures, such as integrated circuits, 

are unlikely to pose a risk of exposure 

during their handling and use as materials of non-inhalable size. However, 

some of the processes used in their production (e.g., formulating and applying 

nanoscale coatings) may lead to exposure to nanomaterials, and the cutting 

or grinding of such products could release respirable-sized nanoparticles. 

•	 Maintenance on production systems (including cleaning and disposal of materials from dust collection systems) is likely 

to result in exposure to nanoparticles if 

deposited nanomaterials are disturbed. 

•	 The following workplace tasks can increase the risk of exposure to nanoparticles:

— Working with nanomaterials in 

liquid media without adequate 

protection (e.g., gloves)

— Working with nanomaterials in 

liquid during pouring or mixing 

operations, or where a high degree of agitation is involved

— Generating nanoparticles in nonenclosed systems 

— Handling (e.g., weighing, blending, spraying) powders of nanomaterials 

— Maintenance on equipment and 

processes used to produce or fabricate nanomaterials and the cleaning-up of spills and waste material 

containing nanomaterials 

— Cleaning of dust collection systems 

used to capture nanoparticles 

— Machining, sanding, drilling, or other mechanical disruptions of materials containing nanoparticles
Approaches to Safe Nanotechnology vii

Executive Summary

Exposure Assessment and 

Characterization

•	 Until more information becomes available on the mechanisms underlying 

nanomaterial toxicity, it is uncertain what 

measurement technique should be used 

to monitor exposures in the workplace. 

Current research indicates that mass and 

bulk chemistry may be less important 

than particle size and shape, surface area, 

and surface chemistry (or activity) for 

some nanostructured materials. 

•	 Many of the sampling techniques that 

are available for measuring airborne 

nanoaerosols vary in complexity but can 

provide useful information for evaluating occupational exposures with respect 

to particle size, mass, surface area, number concentration, and composition. 

Unfortunately, relatively few of these 

techniques are readily applicable to routine exposure monitoring. NIOSH has 

initiated exposure assessment studies in 

workplaces that manufacture or use engineered nanoparticles (see Appendix 

Nanoparticle Emission Assessment Technique for Identification of Sources and 

Releases of Engineered Nanomaterials).

•	 Regardless of the metric or measurement 

method used for evaluating nanoaerosol 

exposures, it is critical that background 

nanoscale particle measurements be 

conducted before the production, processing, or handling of nanomaterials. 

•	 When feasible, personal sampling is preferred to ensure an accurate representation of the worker’s exposure, whereas 

area sampling (e.g., size-fractionated 

aerosol samples) and real-time (direct 

reading) exposure measurements may 

be more useful for evaluating the need 

for improvement of engineering controls and work practices.

Precautionary Measures

•	 Given the limited amount of information about health risks that may be associated with nanomaterials, taking 

measures to minimize worker exposures 

is prudent. 

•	 For most processes and job tasks, the 

control of airborne exposure to nanoaerosols can be accomplished using a 

variety of engineering control techniques similar to those used in reducing exposure to general aerosols.

•	 The implementation of a risk management program in workplaces where exposure to nanomaterials exists can help 

to minimize the potential for exposure 

to nanoparticles. Elements of such a 

program should include the following:

— Evaluating the hazard posed by the 

nanomaterial based on available 

physical and chemical property 

data, toxicology, or health-effects 

data

— Assessing the worker’s job task to 

determine the potential for exposure

— Educating and training workers in 

the proper handling of nanomaterials (e.g., good work practices)

— Establishing criteria and procedures for installing and evaluating engineering controls (e.g., 

exhaust ventilation) at locations 

where exposure to nanomaterials 

might occur
viii Approaches to Safe Nanotechnology

— Developing procedures for determining the need for and selecting 

proper personal protective equipment (e.g., clothing, gloves, respirators)

— Systematically evaluating exposures to ensure that control measures are working properly and 

that workers are being provided 

the appropriate personal protective equipment

•	 Engineering control techniques such as 

source enclosure (i.e., isolating the generation source from the worker) and local exhaust ventilation systems should be 

effective for capturing airborne nanoparticles. Current knowledge indicates 

that a well-designed exhaust ventilation 

system with a high-efficiency particulate 

air (HEPA) filter should effectively remove nanomaterials.

•	 The use of good work practices can 

help to minimize worker exposures 

to nanomaterials. Examples of good 

practices include cleaning of work areas using HEPA vacuum pickup and 

wet wiping methods, preventing the 

consumption of food or beverages in 

workplaces where nanomaterials are 

handled, providing hand-washing facilities, and providing facilities for 

showering and changing clothes.

•	 No guidelines are currently available on 

the selection of clothing or other apparel (e.g., gloves) for the prevention 

of dermal exposure to nanoaerosols. 

However, some clothing standards incorporate testing with nanometer-sized 

particles and therefore provide some indication of the effectiveness of protective clothing.

•	 Respirators may be necessary when engineering and administrative controls 

do not adequately prevent exposures. 

Currently, there are no specific limits 

for airborne exposures to engineered 

nanoparticles although occupational 

exposure limits exist for some larger 

particles of similar chemical composition. It should be recognized that 

exposure limits recommended for nonnanoscale particles may not be health 

protective for nanoparticle exposures 

(e.g., the OSHA Permissible Exposure 

Limit [PEL] for graphite may not be a 

safe exposure limit for carbon nanotubes). The decision to use respiratory 

protection should be based on professional judgment that takes into account 

toxicity information, exposure measurement data, and the frequency and 

likelihood of the worker’s exposure. 

While research is continuing, preliminary evidence indicates that NIOSHcertified respirators will be useful for 

protecting workers from nanoparticle 

inhalation when properly selected and 

fit tested as part of a complete respiratory protection program. 

Occupational Health 

Surveillance 

Occupational health surveillance is an essential component of an effective occupational 

safety and health program. The unique physical and chemical properties of nanomaterials, the increasing growth of nanotechnology 

in the workplace, and information suggesting 

that exposure to some engineered nanomaterials can cause adverse health effects in laboratory animals all support consideration of 

an occupational health surveillance program 

for workers potentially exposed to engineered 

Executive Summary
Approaches to Safe Nanotechnology ix

nanomaterials. Continued evaluation of toxicologic research and workers potentially exposed to engineered nanomaterials is needed 

to inform NIOSH and other groups regarding 

the appropriate components of occupational 

health surveillance for nanotechnology workers. NIOSH has formulated interim guidance 

relevant to medical screening (one component of an occupational health surveillance 

program) for nanotechnology workers (see 

NIOSH Current Intelligence Bulletin Interim 

Guidance for Medical Screening and Hazard 

Surveillance for Workers Potentially Exposed 

to Engineered Nanoparticles at www.cdc.gov/

niosh/review/public/115/). In this document 

NIOSH concluded that insufficient scientific 

and medical evidence now exist to recommend the specific medical screening of workers potentially exposed to engineered nanoparticles. However, NIOSH did recommend 

that hazard surveillance be conducted as the 

basis for implementing control measures.

Executive Summary

Approaches to Safe Nanotechnology xi

Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii

Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v

Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2 Purpose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

3 Scope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

4 Descriptions and Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

4.1 Nano-objects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4.2 Ultrafine Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

4.3 Engineered Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

4.4 Nanoaerosol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

4.5 Agglomerate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

4.6 Aggregate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

5 Potential Health Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

5.1 Exposure Routes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

5.2 Effects Seen in Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

5.2.1 Polytetrafluoroethylene fume . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

5.2.2 Carbon nanotubes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

5.3 Observations from Epidemiological Studies Involving Fine and 

Ultrafine Particles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

5.4 Hypotheses from Animal and Epidemiological Studies . . . . . . . . . . . . . . . . . . 18

6 Potential Safety Hazards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

6.1 Fire and Explosion Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

6.2 Risks of Catalytic Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

7 Exposure Assessment and Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

7.1 Workplace Exposures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23

7.1.1 Size-fractionated aerosol sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

7.1.2 Real-time aerosol sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Contents
xii Approaches to Safe Nanotechnology

Contents

7.1.3 Surface-area measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

7.1.4 Particle number concentration measurement . . . . . . . . . . . . . . . . . . . . 29

7.1.5 Surface-area estimation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

7.1.6 Particle number concentration mapping . . . . . . . . . . . . . . . . . . . . . . . . 31

7.2 Sampling Strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

8 Guidelines for Working with Engineered Nanomaterials . . . . . . . . . . . . . . . . . . . . . 35

8.1 Potential for Occupational Exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

8.2 Factors Affecting Exposure to Nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . . 36

8.3 Elements of a Risk Management Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

8.3.1 Engineering controls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

8.3.2 Dust collection efficiency of filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

8.3.3 Work practices . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41

8.3.4 Personal protective clothing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

8.3.5 Respirators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

8.3.6 Cleanup and disposal of nanomaterials . . . . . . . . . . . . . . . . . . . . . . . . . 48

9 Occupational Health Surveillance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53

10 Research Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59

Sources of Additional Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
Approaches to Safe Nanotechnology xiii

This report was developed by the scientists and staff of the National Institute for Occupational Safety and Health (NIOSH) who participate in the NIOSH Nanotechnology Research 

Center (NTRC). Paul Schulte is the manager and Charles Geraci, coordinator of the NIOSH 

NORA nanotechnology cross-sector program. Special thanks go to Ralph Zumwalde and 

Laura Hodson for writing and organizing the report and to Mark Methner for the development of the Appendix: Nanoparticle Emission Assessment Technique for Identification of 

Sources and Releases of Engineered Nanomaterials. 

Others who contributed substantially to the writing and research described here include: 

Eileen Birch, Fred Blosser, Vincent Castranova, Brian Curwin, Douglas Evans, Pengfei Gao, 

Donna Heidel, Mark Hoover, John Howard, Vijia Karra, Bon-Ki Ku, Eileen Kuempel, Robert Mercer, Arthur Miller, Vladimir Murashov, Terri Pearce, Appavoo Rengasamy, Ronald 

Shaffer, Anna Shvedova, Petia Simeonova, Aleksandr Stefaniak, Douglas Trout, and Leonid 

Turkevich. 

The NIOSH NTRC also acknowledges the contributions of Vanessa Becks and Gino Fazio 

for desktop publishing and graphic design, and Elizabeth Fryer for editing the report.

Acknowledgments

Approaches to Safe Nanotechnology 1

Nanotechnology is the manipulation of matter on a near-atomic scale to produce new 

structures, materials, and devices. This technology has the ability to transform many 

industries and can be applied in many ways 

to areas ranging from medicine to manufacturing. Research in nanoscale technologies 

is growing rapidly worldwide. Lux Research 

[2007] projects that new emerging nanotechnology applications will affect nearly every 

type of manufactured product through the 

middle of the next decade, becoming incorporated into 15% of global manufacturing 

output, totaling $2.6 trillion in 2014. 

Nanomaterials present new challenges to 

understanding, predicting, and managing 

potential health risks to workers. As with 

any material being developed, scientific data 

on the health effects in exposed workers are 

largely unavailable. In the case of nanomaterials, the uncertainties are great because 

the characteristics of nanoparticles may 

be different from those of larger particles 

with the same chemical composition. Safety and health practitioners recognize the 

critical lack of specific guidance on the safe 

handling of nanomaterials—especially now, 

when the degree of risk to exposed workers 

is unknown. In the meantime, the extensive 

scientific literature on airborne particles—

including toxicology and epidemiological 

studies, measurement techniques, and engineering controls—provides the best available data from which to develop interim 

approaches for working safely with nanomaterials and to develop hypotheses for 

studies of new nanomaterials. 

The National Institute for Occupational 

Safety and Health (NIOSH) is working in 

parallel with the development and implementation of commercial nanotechnology 

through (1) conducting strategic planning 

and research, (2) partnering with publicand private-sector colleagues from the United States and abroad, and (3), making information widely available. The NIOSH goal is 

to provide national and world leadership for 

incorporating research findings about the 

implications and applications of nanotechnology into good occupational safety and 

health practice for the benefit of all nanotechnology workers. NIOSH has developed 

a strategic plan for coordinating nanotechnology research and for use as a guide for enhancing the development of new research efforts (www.cdc.gov/niosh/topics/nanotech/

strat_plan.html).

1 Introduction

Approaches to Safe Nanotechnology 3

With the publication of this Approaches to Safe 

Nanotechnology document, NIOSH hopes to 

do the following:

•	 Raise awareness of the occupational 

safety and health issues being identified in the rapidly moving and changing science involving implications and 

applications of nanotechnology.

•	 Use the best information available to

make recommendations on occupational safety and health practices in the 

production and use of nanomaterials 

(These recommendations will be updated as appropriate to reflect new information. They will address key components 

of occupational safety and health, including exposure monitoring, engineering 

controls, personal protective equipment, 

and administrative controls. They will 

draw from the ongoing NIOSH assessment of current best practices, technical 

knowledge, and professional judgment. 

Throughout the development of these 

guidelines, the utility of a hazard-based 

approach to risk assessment and control 

was evaluated and, where appropriate, 

recommendations are provided.)

•	 Facilitate an exchange of information 

between NIOSH and its external partners 

from ongoing research, including success 

stories, applications, and case studies.

•	 Respond to requests from industry, labor, academia, and other partners who 

are seeking science-based, authoritative guidelines.

•	 Identify information gaps where few 

or no data exist and where research is 

needed. 

2 Purpose

Approaches to Safe Nanotechnology 5

This document has been developed to provide a resource for stakeholders who wish 

to understand more about the safety and 

health implications and applications of 

nanotechnology in the workplace. The information and guidelines presented here are 

intended to aid in evaluating the potential 

hazard of exposure to engineered nanomaterials and to set the stage for the development of more comprehensive guidelines for 

reducing potential workplace exposures in 

the wide range of tasks and processes that 

use nanomaterials. The information in this 

document will be of specific interest to the 

following:

•	 Occupational safety and health professionals who must (1) understand how 

nanotechnology may affect occupational health and (2) devise strategies 

for working safely with nanomaterials

•	 Researchers working with or planning 

to work with engineered nanomaterials and studying the potential occupational safety and health impacts of 

nanomaterials

•	 Policy and decision makers in government agencies and industry

•	 Risk evaluation professionals

•	 People working with or potentially exposed to engineered nanomaterials in 

the workplace

Established safe work practices are generally 

based on an understanding of the hazards 

associated with the chemical and physical 

properties of a material. Engineered nanomaterials may exhibit unique properties 

that are related to their physical size, shape, 

structure, and chemical composition. Considerable uncertainty still exists as to whether 

these unique properties present occupational 

health risks. Current information about the 

potential adverse health effects of engineered 

nanomaterials, exposure assessment, and exposure control is limited. However, the large 

body of scientific literature that exists on 

exposures to and responses of animals and 

humans to ultrafine and other airborne particles may be useful in making preliminary 

assessments as to the health risks posed by 

engineered nanomaterials. Until further information is available, interim safe working practices should be used based on the 

best available information. The information 

and recommendations in this document are 

intended to aid in assessment of the potential hazard of engineered nanomaterials and 

to set the stage for the development of more 

comprehensive guidelines for reducing potential workplace exposures.

3 Scope

Approaches to Safe Nanotechnology 7

Nanotechnology involves the manipulation 

of matter at nanometer† scales to produce 

new materials, structures, and devices. The 

U.S. National Nanotechnology Initiative (see 

http://nano.gov/html/facts/whatIsNano.

html) defines a technology as nanotechnology only if it involves all of the following: 

•	 Research and technology development 

involving structures with at least one 

dimension in the range of 1–100 nanometers (nm), frequently with atomic/

molecular precision

•	 Creating and using structures, devices, 

and systems that have unique properties and functions because of their 

nanoscale dimensions

•	 The ability to control or manipulate on 

the atomic scale

Nanotechnology is an enabling technology 

that offers the potential for unprecedented 

advances in many diverse fields. The ability to manipulate matter at the atomic or 

molecular scale makes it possible to form 

new materials, structures, and devices that 

exploit the unique physical and chemical 

properties associated with nanoscale structures. The promise of nanotechnology goes 

far beyond extending the use of current 

materials. New materials and devices with 

intricate and closely engineered structures 

will allow for (1) new directions in optics, 

electronics, and optoelectronics, (2) development of new medical imaging and treatment technologies, and (3) production of 

†

1 nanometer (nm) = 1 billionth of a meter (10-9). 

advanced materials with unique properties 

and high-efficiency energy storage and generation.

Although nanotechnology-based products 

are generally thought to be at the precompetitive stage, an increasing number of products 

and materials are becoming commercially 

available. These include nanoscale powders, 

solutions, and suspensions of nanoscale materials as well as composite materials and 

devices having a nanostructure. Nanoscale 

products and materials are increasingly used 

in optoelectronic, electronic, magnetic, medical imaging, drug delivery, cosmetic, catalytic, and materials applications. New nanotechnology consumer products are coming 

on the market at the rate of three to four 

per week, a finding based on the latest update to the nanotechnology consumer product inventory maintained by the Project on 

Emerging Nanotechnologies (PEN)‡ (www.

nanotechproject.org/inventories/consumer). 

The number of consumer products using 

nanotechnology has grown from 212 to 609 

since PEN launched the world’s first online 

inventory of manufacturer-identified nanotech goods in March 2006. 

According to Lux Research [2007], in 2006, 

governments, corporations, and venture capitalists worldwide spent $11.8 billion on nanotechnology research and development (R&D), 

which was up 13% from 2005. By 2014, Lux 

estimates $2.6 trillion in manufactured goods 

‡

The Project on Emerging Nanotechnologies was established in April 2005 as a partnership between the 

Woodrow Wilson International Center for Scholars 

and the Pew Charitable Trusts.

4 Descriptions and Definitions
8 Approaches to Safe Nanotechnology

4 Descriptions and Definitions 

will incorporate nanotechnology—or about 

15% of total global output. 

4.1 Nano-objects 

The International Organization for Standardization Technical Committee 229 (Nanotechnologies) is developing globally recognized 

nomenclature and terminology for nanomaterials. According to ISO/TS 27687:2008, 

nano-object is defined as material with one, 

two, or three external dimensions in the size 

range from approximately 1–100 nm. Subcategories of nano-object are (1) nanoplate, 

a nano-object with one external dimension 

at the nanoscale; (2) nanofiber, a nano-object 

with two external dimensions at the nanoscale with a nanotube defined as a hollow 

nanofiber and a nanorod as a solid nanofiber; 

and (3) nanoparticle, a nano-object with all 

three external dimensions at the nanoscale. 

Nano-objects are commonly incorporated in 

a larger matrix or substrate referred to as a 

nanomaterial. Nano-objects may be suspended in a gas (as a nanoaerosol), suspended in a 

liquid (as a colloid or nanohydrosol), or embedded in a matrix (as a nanocomposite). 

The precise definition of particle diameter 

depends on particle shape as well as how the 

diameter is measured. Particle morphologies 

may vary widely at the nanoscale. For instance, carbon fullerenes represent nanoobjects with identical dimensions in all 

directions (i.e., spherical), whereas single-walled carbon nanotubes (SWCNTs) 

typically form convoluted, fiber-like nanoobjects. Many regular but nonspherical particle morphologies can be engineered at the 

nanoscale, including flower- and belt-like 

structures. Please see www.nanoscience.gatech.edu/zlwang/research.html for examples 

of some nanoscale structures.

4.2 Ultrafine Particles

The term ultrafine particle has traditionally been used by the aerosol research and 

occupational and environmental health 

communities to describe airborne particles 

smaller than 100 nm in diameter. Ultrafine

is frequently used in the context of nanometer-diameter particles that have not been 

intentionally produced but are the incidental products of processes involving combustion, welding, or diesel engines (see Figure 

4–1). The term nanoparticle is frequently 

used with respect to particles demonstrating size-dependent physicochemical properties, particularly from a materials science 

perspective. The two terms are sometimes 

used to differentiate between engineered 

Figure 4–1. Photomicrographs of airborne exposure to ultrafine (nanoscale) particles of 

welding fumes, diesel exhaust, and cerium oxide
Approaches to Safe Nanotechnology 9

4 Descriptions and Definitions

(nanoparticle) and incidental (ultrafine) 

nanoscale particles. 

It is currently unclear whether the use of 

source-based definitions of nanoparticles 

and ultrafine particles is justified from a safety and health perspective. This is particularly the case where data on non-engineered, 

nanometer-diameter particles are of direct 

relevance to the impact of engineered particles. An attempt has been made in this 

document to follow the general convention 

of preferentially using nanoparticle in the 

context of intentionally produced or engineered particles and ultrafine in the context of incidentally produced particles (e.g., 

combustion products). However, this does 

not necessarily imply specific differences in 

the properties of these particles as related to 

hazard assessment, measurement, or control of exposures, and this remains an active 

area of research. Nanoparticle and ultrafine 

particle are not rigid definitions. For example, since the term ultrafine has been in existence longer, some intentionally produced 

particles with primary particle sizes in the 

nanosize range (e.g., TiO2

) are often called 

ultrafine in the literature.

4.3 Engineered Nanoparticles

Engineered nanoparticles are intentionally 

produced, whereas ultrafine particles (often 

referred to as incidental nanoparticles) are 

typically byproducts of processes such as 

combustion and vaporization. Engineered 

nanoparticles are designed with very specific properties or compositions (e.g., shape, 

size, surface properties, and chemistry). Incidental nanoparticles are generated in a relatively uncontrolled manner and are usually 

physically and chemically heterogeneous 

compared with engineered nanoparticles.

4.4 Nanoaerosol

A nanoaerosol is a collection of nanoparticles suspended in a gas. The particles may 

be present as discrete nano-objects, or as aggregates or agglomerates of nano-objects. 

These agglomerates may have diameters 

larger than 100 nm. In the case of an aerosol 

consisting of micrometer-diameter particles 

formed as agglomerates of nano-objects, 

the definition of nanoaerosol is open to interpretation. It is generally accepted that if 

the nanostructure associated with the nanoobject is accessible (through physical, chemical, or biological interactions), then the 

aerosol may be considered a nanoaerosol. 

However, if the nanostructure within individual micrometer-diameter particles does 

not directly influence particle behavior (for 

instance, if the nanoparticles were inaccessibly embedded in a solid matrix), the aerosol 

would not be described as a nanoaerosol.

4.5 Agglomerate

An agglomerate is a group of nanoparticles 

held together by relatively weak forces, including van der Waals forces, electrostatic 

forces, and surface tension [ISO 2006]. 

4.6 Aggregate

An aggregate is a heterogeneous particle in 

which the various components are held together by relatively strong forces, and thus 

not easily broken apart [ISO 2006]. Aggregated nanoparticles would be an example of 

a nanostructured material.

Approaches to Safe Nanotechnology 11

Nanotechnology is an emerging field. As 

such, there are many uncertainties as to 

whether the unique properties of engineered nanomaterials (which underpin 

their commercial and scientific potential) also pose occupational health risks.

These uncertainties arise because of gaps 

in knowledge about the factors that are essential for predicting health risks—factors 

such as routes of exposure, translocation 

of materials once they enter the body, and 

interaction of the materials with the body’s 

biological systems. The potential health risk 

following exposure to a substance is generally associated with the magnitude and duration of the exposure, the persistence of the 

material in the body, the inherent toxicity of 

the material, and the susceptibility or health 

status of the person exposed. More data are 

needed on the health risks associated with 

exposure to engineered nanomaterials. Results of existing studies in animals and humans on exposure and response to ultrafine or other respirable particles provide a 

basis for preliminary estimates of the possible adverse health effects from exposures 

to similar engineered materials on a nanoscale. Experimental studies in rodents and 

cell cultures have shown that the toxicity 

of ultrafine or nanoparticles is greater than 

that of the same mass of larger particles of 

similar chemical composition [Oberdörster 

et al. 1992, 1994a, b; Lison et al. 1997; Tran 

et al. 1999, 2000; Brown et al. 2001; Barlow 

et al. 2005; Duffin et al. 2007]. In addition 

to particle surface area, other particle characteristics may influence toxicity, including surface functionalization or coatings, 

solubility, shape, and the ability to generate 

oxidant species and to adsorb biological 

proteins or bind to receptors [Duffin et al. 

2002; Oberdörster et al. 2005a; Maynard 

and Kuempel 2005; Donaldson et al. 2006]. 

More research is needed on the influence of 

particle properties on interactions with biological systems and the potential for adverse 

effects. International research strategies for 

evaluating the safety of nanomaterials are 

actively being developed through cooperative efforts [Thomas et al. 2006].

Existing toxicity information about a given 

material of larger particle size can provide a 

baseline for anticipating the possible adverse 

health effects that may occur from exposure 

to a nanoscale material that has some of the 

same physicochemical properties (e.g., chemistry, density). However, predicting the toxicity of an engineered nanomaterial based on 

its physicochemical properties may not provide an adequate level of protection. 

5.1 Exposure Routes 

Inhalation is the most common route of exposure to airborne particles in the workplace.

The deposition of discrete nano-objects in the 

respiratory tract is determined by the particle’s 

aerodynamic or thermodynamic diameter 

(i.e., the particle shape and size). Agglomerates of nano-objects will deposit according to 

the diameter of the agglomerate, not constituent nano-objects. Research is ongoing to determine the physical factors that contribute to 

the agglomeration and de-agglomeration of 

nano-objects in air, suspended in aqueous media, or once in contact with lung lining fluid 

and/or biological proteins. Evidence indicates 

5 Potential Health Concerns
12 Approaches to Safe Nanotechnology

5 Potential Health Concerns 

that the degree of agglomeration can affect the 

toxicity of inhaled nano-objects [Shvedova et 

al. 2007].

Discrete nanoparticles are deposited in the 

lungs to a greater extent than larger respirable particles [ICRP 1994], and deposition increases with exercise due to increase 

in breathing rate and change from nasal to 

mouth breathing [Jaques and Kim 2000; 

Daigle et al. 2003] and among persons with 

existing lung diseases or conditions (e.g., 

asthma, emphysema) [Brown et al. 2002]. 

Based on animal studies, discrete nanoparticles may enter the bloodstream from 

the lungs and translocate to other organs 

[Takenaka et al. 2001; Nemmar et al. 2002; 

Oberdörster et al. 2002].

Discrete nanoparticles (35–37-nm median 

diameter) that deposit in the nasal region 

may be able to enter the brain by translocation along the olfactory nerve, as was 

observed in rats [Oberdörster et al. 2004; 

Oberdörster et al. 2005a; Elder et al. 2006]. 

The transport of insoluble particles from 

20–500 nm-diameter to the brain via sensory nerves (including olfactory and trigeminus) was reported in earlier studies in several animal models [De Lorenzo 1970; Adams 

and Bray 1983; Hunter and Dey 1998]. This 

exposure route for nanoparticles and to 

nanoscale biological agents has not been 

studied in humans. 

Some studies suggest that nanomaterials 

could potentially enter the body through 

the skin during occupational exposure. Tinkle et al. [2003] have shown that particles 

smaller than 1 μm in diameter may penetrate into mechanically flexed skin samples. 

A more recent study reported that nanoparticles with varying physicochemical properties were able to penetrate the intact skin of 

pigs [Ryman-Rasmussen et al. 2006]. These 

nanoparticles were quantum dots of different size, shape, and surface coatings. They 

were reported to penetrate the stratum corenum barrier by passive diffusion and localize within the epidermal and dermal layers 

within 8–24 hours. The dosing solutions 

were 2- to 4-fold dilutions of quantum dots 

as commercially supplied and thus represent 

occupationally relevant doses. 

At this time, it is not fully known whether skin 

penetration of nanoparticles would result in 

adverse effects in animal models. However, 

topical application of raw SWCNT to nude 

mice has been shown to cause dermal irritation [Murray et al. 2007]. Studies conducted 

in vitro using primary or cultured human 

skin cells have shown that both SWCNT and 

multi-walled carbon nanotubes (MWCNT) 

can enter cells and cause release of pro-inflammatory cytokines, oxidative stress, and 

decreased viability [Monteiro-Riviere et al. 

2005; Shvedova et al. 2003]. It remains unclear, however, how these findings may be 

extrapolated to a potential occupational 

risk, given that additional data are not yet 

available for comparing the cell model studies with actual conditions of occupational 

exposure. Research on the dermal exposure 

of nanomaterials is ongoing (www.unileipzig.de/~nanoderm/). 

Ingestion can occur from unintentional 

hand to mouth transfer of materials; this 

has been found to happen with traditional 

materials, and it is scientifically reasonable 

to assume that it also could happen during handling of nanomaterials. Ingestion 

may also accompany inhalation exposure 

because particles that are cleared from the 

respiratory tract via the mucociliary escalator may be swallowed [ICRP 1994]. Little is 

known about possible adverse effects from 

the ingestion of nanomaterials.
Approaches to Safe Nanotechnology 13

5 Potential Health Concerns

5.2 Effects Seen in Animal 

Studies 

Experimental studies in rats have shown 

that at equivalent mass doses, insoluble 

ultrafine particles are more potent than 

larger particles of similar composition in 

causing pulmonary inflammation, tissue 

damage, and lung tumors [Lee et al. 1985; 

Oberdörster and Yu 1990; Oberdörster et al. 

1992, 1994a,b; Heinrich et al. 1995; Driscoll 

1996; Lison et al. 1997; Tran et al. 1999, 2000; 

Brown et al. 2001; Duffin et al. 2002; Renwick 

et al. 2004; Barlow et al. 2005]. These studies 

have shown that for poorly-soluble low toxicity (PSLT) particles, the dose-response relationships are consistent across particle sizes when dose is expressed as particle surface 

area. In addition to particle size and surface 

area, studies have shown that other particle 

characteristics can influence toxicity. For 

example, although the relationship between 

particle surface area dose and pulmonary 

inflammation is consistent among PSLT 

particles, crystalline silica is much more inflammogenic than PSLT particles at a given 

surface area dose [Duffin et al. 2007]. 

Reactive oxidant generation on the particle 

surface is an important factor influencing 

lung response to particles, which can be 

related to crystal structure. A recent study 

of the lung effects of rats dosed with either 

ultrafine anatase titanium dioxide (TiO2) or 

ultrafine rutile TiO2

 showed that the anatase

TiO2 had more reactive surfaces and caused 

greater pulmonary inflammation and cell 

proliferation in the lungs of rats [Warheit 

et al. 2007]. In a cell-free assay designed to 

investigate the role of surface area and crystal structure on particle reactive oxygen species (ROS)-generation, Jiang et al. [2008] 

observed that size, surface area, and crystal 

structure all contribute to ROS generation. 

Figure 5–1. Formation of collagen following deposition of SWCNTs in the lungs of mice
14 Approaches to Safe Nanotechnology

5 Potential Health Concerns 

Oxidant generation was apparently associated with the number of defective sites per 

surface area, which varied in nanoparticles 

in some size ranges [Jiang et al. 2008]. 

These studies indicate that for nanoparticles 

with similar properties (e.g., PSLT), the toxicity of a given mass dose will increase with 

decreasing particle size due to the increasing 

surface area. However, the dose-response relationship may differ for particles with different chemical composition and other properties. Consistent with these findings, a recent 

pulmonary instillation study with rats dosed 

with either fine or ultrafine TiO2

 reported 

no significant difference in lung responses 

when compared to controls, while crystalline silica caused more severe lung responses 

at the same dose [Warheit et al. 2006]. However, Warheit et al. [2006] were unable to adequately test the hypotheses about the relationship between particle surface area dose 

and toxicity because the diameters of the fine 

and ultrafine TiO2

-instilled particles did not 

significantly differ due to particle agglomeration, both being in excess of 2 μm. When efforts were made to more effectively disperse 

fine and ultrafine particles, the effect of surface area on the pulmonary response in rats 

after intratracheal instillation was verified 

[Sager et al. 2008]. 

5.2.1 Polytetrafluoroethylene fume

Among ultrafine particles, freshly generated 

polytetrafluoroethylene (PTFE) fume (generated at temperatures of more than 425o

C) is 

known to be highly toxic to the lungs. Freshly 

generated PTFE fume caused hemorrhagic 

pulmonary edema and death in rats exposed 

to less than 60 μg/m3

 [Oberdörster et al. 

1995]. In contrast, aged PTFE fume was much 

less toxic and did not result in mortality. This 

low toxicity was attributed to the increase 

in particle size from accumulation and to 

changes in surface chemistry [Johnston et al. 

2000; Oberdörster et al. 2005a]. Human case 

studies have reported pulmonary edema in 

workers exposed to PTFE fume and an accidental death in a worker when an equipment 

malfunction caused overheating of the PTFE 

resin and release of the PTFE pyrolysis products in the workplace [Goldstein et al. 1987; 

Lee et al. 1997]. While PTFE fume differs 

from engineered nanoparticles, these studies 

illustrate properties of ultrafine particles that 

have been associated with an acute toxic hazard. Enclosed processes and other engineering controls appear to have been effective at 

eliminating worker exposures to PTFE fume 

in normal operations, and thus may provide 

examples of control systems that may be implemented to prevent exposure to nanoparticles that may have similar properties.

5.2.2 Carbon nanotubes 

Carbon nanotubes (CNT) are specialized 

forms or structures of engineered nanomaterials that have had increasing production and 

use [Donaldson et al. 2006]. Consequently, a 

number of toxicologic studies of CNT have 

been performed in recent years. These studies have shown that the toxicity of CNT may 

differ from that of other nanomaterials of 

similar chemical composition. For example, 

single-walled CNTs (SWCNT) have been 

shown to produce adverse effects including 

granulomas in the lungs of mice and rats at 

mass doses at which ultrafine carbon black 

did not produce these adverse effects [Shvedova et al. 2005; Lam et al. 2004]. While both 

SWCNTs and carbon black are carbon-based, 

SWCNTs have a unique, convoluted, fibrous 

structure and specific surface chemistry that 

offers excellent electrical conductive properties. How these characteristics may influence 
Approaches to Safe Nanotechnology 15

5 Potential Health Concerns

toxicity is not known. Carbon nanotubes may 

contain metal catalysts as byproducts of their 

production, which could contribute to their 

toxicity, or the CNTs may provide a structure 

that promotes fibroblast cell growth [Wang 

et al. 2008].

In a study of SWCNTs instilled into the lungs 

of rats, multi-focal granulomas (without transient inflammation or persistent lesions) were 

observed at doses of 1 or 5 mg/kg body weight 

[Warheit et al. 2004]. In a study of mice instilled with one of several types of SWCNTs 

(i.e., raw, purified, iron-containing, and nickel-containing) at doses of 0.1 or 0.5 mg/mouse 

(approximately 3 or 16 mg/kg body weight), 

dose-dependent epithelioid granulomas were 

observed at 7 days, which persisted at 90 days 

[Lam et al. 2004, 2006]. Both the raw and purified forms produced interstitial inflammation, while mortality (5/9 mice) was observed 

in the high dose group of the Ni-containing 

SWCNT. 

NIOSH researchers recently reported adverse 

lung effects following pharyngeal aspiration 

of SWCNTs in mice using doses between 

10–40 μg/mouse (approximately 0.5–2 mg/kg 

body weight) [Shvedova et al. 2005]. The findings showed that exposure to SWCNTs in mice 

lead to transient pulmonary inflammation, 

oxidative stress, decrease in pulmonary function, decrease in bacterial clearance, and early 

onset of interstitial fibrosis. Deposition of agglomerates resulted in development of granulomas, while deposition of dispersed nanotube 

structures in the aspirated suspension resulted 

in the rapid development of interstitial fibrosis (within 7 days), which progressed over a 

30–60 day post-exposure period [Shvedova 

et al. 2005; Mercer et al. 2008]. Evidence indicates that when efforts were made to more 

fully disperse the SWCNT and obtain smaller 

structures in the aspiration suspension, fewer 

granulomas occurred but a 4-fold more potent interstitial fibrotic response was observed 

[Mercer et al. 2008]. 

Exposure to SWCNT has been observed to be 

more fibrogenic than an equal mass of either 

ultrafine carbon black or fine quartz [Shvedova et al. 2005; Lam et al. 2004]. Based on 

their findings in mice, Shvedova et al. [2005] 

estimated that workers may be at risk of developing lung lesions if they were exposed to SWCNT over a period of 20 days at the current 

Figure 5–2. Deposition and clearance of MWCNTs from the conducting airways of mice 

following inhalation exposure
16 Approaches to Safe Nanotechnology

5 Potential Health Concerns 

OSHA PEL for graphite (5 mg/m3). Lam et al. 

[2004, 2006] provided similar estimates and 

suggested that the graphite PEL should not 

be used (e.g., on MSDS) as a safe concentration for workers exposed to CNTs. Compared 

to instillation, the pharyngeal aspiration technique may approximate more closely the particle deposition that occurs during inhalation. 

Inhalation studies of CNTs may provide more 

definitive information about their potential 

toxicity in humans [Donaldson et al. 2006]. 

Recently, NIOSH scientists designed a system 

to generate an aerosol of SWCNT for a rat inhalation study [Baron et al. 2008]. Results of 

the inhalation exposure to SWCNT [Shvedova 

et al. 2008] were qualitatively similar to those 

of the aspiration study [Shvedova et al. 2004] 

with a 4-fold more potent interstitial fibrotic 

response similar to that reported by Mercer 

et al. [2008]. Another NIOSH study found 

markers of inflammation in the lung, aorta, 

and heart tissues of ApoE-/- mice after a single 

intra-pharyngeal instillation dose of SWCNT 

(10 and 40 μg/mouse) and accelerated plaque 

formation after repeated doses (20 μg/mouse 

once every other week for 8 weeks in mice fed 

an atherogenic diet) [Li et al. 2007].

MWCNTs were recently studied by intratracheal instillation in Sprague-Dawley rats receiving 0.5, 2, or 5 mg (approximately 2, 9, 

or 22 mg/kg body weight) of either ground 

MWCNT or unground MWCNT [Muller et 

al. 2005]. Both forms produced pulmonary 

inflammation and fibrosis. Rats that received 

ground MWCNT showed greater dispersion 

in the lungs, and fibrotic lesions were observed in the deep lungs (alveolar region). In 

rats treated with MWCNT (not ground) fibrosis showed mainly in their airways rather 

than in their lungs. The biopersistence of the 

unground MWCNT was greater than that of 

the ground MWCNT, with 81% vs. 36%, respectively, remaining in the lungs at day 60. 

At an equal mass dose, ground MWCNT produced a similar inflammatory and fibrogenic 

response as chrysotile asbestos and a greater 

response than ultrafine carbon black [Muller 

et al. 2005]. Effects from the vehicle (1% 

Tween 80) used for administering ground 

and unground MWCNT to rats were not reported; the control group used in the study 

was exposed to only saline. NIOSH scientists 

have exposed mice by aspiration to MWCNT 

suspended in a simulated alveolar lining fluid 

rather than Tween 80. Control studies show 

that this suspension medium was not inflammatory and did not mask the biological activity of the particle surface. Data indicate that 

aspiration of dispersed MWCNT produced 

pulmonary inflammation, which peaked 

7 days post exposure. The inflammatory response to MWCNT was greater than the inflammatory response to SWCNT [Sriram et 

al. 2007]. 

Two recent studies investigated the hypotheses that CNTs can behave like asbestos. In the 

first study, Takagi et al. [2008] administered 

to p53 (+/-) mice MWCNT, fullerene, or crocidolite asbestos by intraperitoneal injection 

at doses of 3 mg/mouse. The average width 

of the MWCNT was approximately 100 nm, 

and approximately 28% of the particles were 

longer than 5 μm. The particle number concentrations of MWCNT and crocidolite were 

1 × 109

 and 1 × 1010 (in 1-ml suspensions), 

respectively, although the MWCNT sample 

was also reported to contain mainly large aggregates, indicating that the number of MWCNT fibers was vastly underestimated and 

much larger than for the asbestos exposure. 

At the termination of the study (25 weeks), 

mesothelial responses in the MWCNTtreated mice included moderate to severe 

fibrous peritoneal adhesion and peritoneal 

tumors. The asbestos-treated mice had similar responses but to a lesser extent, while the 
Approaches to Safe Nanotechnology 17

5 Potential Health Concerns

fullerene-treated group did not show these 

responses. Mesothelioma was considered by 

the authors as the primary cause of death, 

and constriction of the ileus due to severe 

peritoneal adhesion was considered to be the 

second major cause of death, suggesting that 

3 mg/mouse exceeded the maximum tolerated dose of MWCNT. Whether mesotheliomia was a primary cause of death is somewhat speculative. 

In a second study, Poland et al. [2008] administered to mice either MWCNT (two short 

and two long CNT samples), nanoscale carbon black, or amosite (short or long) at doses of 50 μg/mouse by intraperitoneal injection. The short CNTs were 10 nm or 15 nm 

in width, with no fibers larger than 15 μm in 

length detected; the long CNTs were 85 nm 

or 165 nm in width, and 24% or 84%, respectively, were larger than 15 μm in length 

(the percentage of fibers longer than 5 μm 

was not reported). After either 24 hours or 

7 days, the long MWCNT caused inflammation and granulomatous lesions that were 

qualitatively and quantitatively similar to 

that caused by the long asbestos. The short, 

low-aspect-ratio, tangled aggregates of MWCNT did not produce these responses at the 

doses used in this study. Additional studies 

are needed to determine if this inflammatory response to MWCNT would be persistent 

and result in tumors of the abdominal wall. 

Additionally, the potential for migration of 

MWCNT through the lungs to the mesothelium after inhalation requires investigation. 

Long-term studies are also needed to determine whether CNTs can cause cancer such 

as mesothelioma in laboratory animals, including exposures by typical routes in humans (i.e., inhalation, dermal penetration, 

and ingestion) and at doses that include 

those equivalent to potential workplace exposures. 

These studies indicate the need for more 

data on exposures of workers to CNTs. 

Maynard et al. [2004] reported relatively 

low short-term (approximately 30 min) 

airborne mass concentrations of SWCNT 

(0.007–0.053 mg/m3) in a laboratory production facility. A recent study by Han et al. 

[2008] reported total airborne mass concentrations of MWCNT from 0.21–0.43 mg/m3

(4–6-hr sampling) in a laboratory research 

facility prior to use of engineering control 

measures; after implementing controls, the 

concentration decreased to nondetectable. 

Workers could also be exposed to ground 

CNTs used in polymer composites and 

other matrices or during cutting, grinding, 

or polishing of these materials. Given that 

exposure to SWCNT and MWCNT causes 

interstitial fibrosis and pulmonary inflammation, respectively, in rodent lungs at relatively low mass doses, it is prudent to minimize worker exposure to airborne CNTs 

(see Chapter 8 Guidelines for Working with 

Engineered Nanomaterials). 

5.3 Observations from 

Epidemiological Studies 

Involving Fine and Ultrafine 

Particles 

Epidemiological studies in workers exposed 

to aerosols including fine and ultrafine particles have reported lung function decrements, 

adverse respiratory symptoms, chronic obstructive pulmonary disease, and fibrosis 

[Kreiss et al. 1997; Gardiner et al. 2001; Antonini 2003]. In addition, some studies have 

found lung disease including elevated lung 

cancer and neurological effects among workers exposed to certain ultrafine particles (i.e., 

diesel exhaust particulate) [Steenland et al. 

1998; Garshick et al. 2004, 2006; Hart et al. 

2006] or welding fumes [Antonini 2003; Park 
18 Approaches to Safe Nanotechnology

5 Potential Health Concerns 

et al. 2006; Ambroise et al. 2007; Bowler et al. 

2007]. The implications of these studies to 

engineered nanomaterials, which may have 

different particle properties, are uncertain. 

Studies of airborne particles and fibers in the 

workplace do provide relevant background 

information about the particle-related lung 

diseases and mechanisms, and some limited 

quantitative estimates of exposures and risk 

of adverse health effects. As such, these studies provide a point of reference, including 

baseline information and estimates regarding possible health risks of exposure to other 

nanoscale particles depending on the extent 

to which the exposure conditions and particle-biological interactions may be similar. 

Epidemiological studies in the general population have also shown associations between 

particulate air pollution and increased morbidity and mortality from respiratory and 

cardiovascular diseases [Dockery et al. 1993; 

HEI 2000; Pope et al. 2002, 2004]. Some 

epidemiological studies have shown adverse 

health effects associated with exposure to 

the ultrafine particulate fraction of air pollution [Peters et al. 1997, 2004; Penttinen et 

al. 2001; Ibald-Mulli et al. 2002; Timonen 

et al. 2004; Ruckerl et al. 2006] although 

uncertainty exists about the role of ultrafine particles relative to other air pollutants 

in causing the observed adverse health effects. The associations in these studies have 

been based on measurements of the particle 

number or mass concentrations of particles 

within certain size fractions (e.g., particulate 

matter with diameter of 2.5 μm and smaller 

[PM2.5]). In an experimental study of healthy 

and asthmatic subjects inhaling ultrafine 

carbon particles, changes were observed in 

the expression of adhesion molecules by 

blood leukocyte, which may relate to possible cardiovascular effects of ultrafine particle exposure [Frampton et al. 2006]. Shortterm diesel exhaust exposure (0.3 mg/m3

 for 

1 hr) in healthy volunteers was associated 

with mild systemic inflammation and impaired endothelial-dependent vasodilation 

[Törnqvist et al. 2007].

5.4 Hypotheses from Animal 

and Epidemiological 

Studies

The existing literature on particles and fibers provides a scientific basis from which to 

evaluate the potential hazards of engineered 

nanomaterials. While the properties of engineered nanomaterials can vary widely, 

the basic physicochemical and toxicokinetic 

principles learned from the existing studies 

are relevant to understanding the potential toxicity of nanomaterials. For example, 

it is known from studies in humans that a 

greater proportion of inhaled nanoparticles 

will deposit in the respiratory tract (both at 

rest and with exercise) compared to larger 

particles [ICRP 1994; Jaques and Kim 2000; 

Daigle et al. 2003; Kim and Jaques 2004]. It 

is also known from studies in animals that 

nanoparticles in the lungs can be translocated to other organs in the body; how 

the chemical and physical properties of the 

nanoparticles influence this translocation 

is not completely known [Takenaka et al. 

2001; Kreyling et al. 2002; Oberdörster et al. 

2002, 2004; Semmler et al. 2004; Geiser et al. 

2005]. Due to their small size, nanoparticles 

can cross cell membranes and interact with 

subcellular structures such as mitochondria, 

where they have been shown to cause oxidative damage and to impair function of cells 

in culture [Möller et al. 2002, 2005; Li et al. 

2003; Geiser et al. 2005]. Nanoparticles have 

also been observed inside cell nuclei [Porter 

et al. 2007a, b]. Animal studies have shown 

that nanoparticles are more biologically 
Approaches to Safe Nanotechnology 19

5 Potential Health Concerns

active due to their greater surface area per 

mass compared with larger-sized particles 

of the same chemistry [Oberdörster et al. 

1992; 1994a,b; 2005a; Driscoll 1996; Lison 

et al. 1997; Brown et al. 2001; Duffin et al. 

2002; Renwick et al. 2004; Barlow et al. 2005; 

Sager et al. 2008]. While this increased biological activity is a fundamental component 

to the utility of nanoparticles for industrial, 

commercial, and medical applications, the 

consequences of unintentional exposures of 

workers to nanoparticles are uncertain. 

Research reported from laboratory animal 

studies and from epidemiological studies 

have lead to hypotheses regarding the potential adverse health effects of engineered 

nanomaterials. These hypotheses are based 

on the scientific literature of particle exposures in animals and humans. This literature has been recently reviewed [Donaldson 

et al. 2005; Maynard and Kuempel 2005; 

Oberdörster et al. 2005a, Donaldson et al. 

2006; Kreyling et al. 2006]. In general, the 

particles used in past studies have not been 

characterized to the extent recommended 

for new studies in order to more fully understand the physicochemical properties of the 

particles that influence toxicity [Oberdörster et al. 2005b; Thomas et al. 2006]. As this 

research continues, more data will become 

available to support or refute the following 

hypotheses for engineered nanoparticles. 

Hypothesis 1: Exposure to engineered nanoparticles is likely to cause adverse health effects similar to ultrafine particles that have 

similar physical and chemical characteristics.

Studies in rodents and humans support the 

hypothesis that exposure to ultrafine particles 

poses a greater respiratory hazard than exposure to the same mass of larger particles with 

a similar chemical composition. Studies of 

existing particles have shown adverse health 

effects in workers exposed to ultrafine particles (e.g., diesel exhaust particulate, welding 

fumes), and animal studies have shown that 

ultrafine particles are more inflammogenic 

and tumorigenic in the lungs of rats than an 

equal mass of larger particles of similar composition [Oberdörster and Yu 1990; Driscoll 

1996; Tran et al. 1999, 2000]. If engineered 

nanoparticles have the same physicochemical characteristics that are associated with 

reported effects from ultrafine particles, 

they may pose the same health concerns.

Although the physicochemical characteristics 

of ultrafine particles and engineered nanoparticles can differ, the toxicologic and dosimetric 

principles derived from available studies may 

be relevant to postulating the health concerns 

for newly engineered particles. The biological 

mechanisms of particle-related lung diseases 

(i.e., oxidative stress, inflammation, and production of cytokines, chemokines, and cell 

growth factors) [Mossman and Churg 1998; 

Castranova 2000; Donaldson and Tran 2002] 

appear to be a consistent lung response for respirable particles including ultrafine or engineered nanoparticles [Donaldson et al. 1998; 

Donaldson and Stone 2003; Oberdörster et al. 

2005a]. Toxicological studies have shown that 

the chemical and physical properties that influence the fate and toxicity of ultrafine particles may also be relevant to mechanisms influencing biological exposure and response to 

other nanoscale particles [Duffin et al. 2002; 

Kreyling et al. 2002; Oberdörster et al. 2002; 

Semmler et al. 2004; Nel et al. 2006]. 

Hypothesis 2: Surface area and activity and 

particle number may be better predictors of 

potential hazard than mass.

The greater potential hazard may relate to the 

greater number or surface area of nanoparticles compared with that for the same mass 
20 Approaches to Safe Nanotechnology

5 Potential Health Concerns

concentration of larger particles [Oberdörster et al. 1992, 1994a,b; Driscoll et al. 1996; 

Tran et al. 2000; Brown et al. 2001; Peters et 

al. 1997; Moshammer and Neuberger 2003; 

Sager et al. 2008]. This hypothesis is based 

primarily on the pulmonary effects observed 

in studies of rodents exposed to various types 

of ultrafine or fine particles (i.e., TiO2, carbon black, barium sulfate, carbon black, diesel soot, coal fly ash, toner) and in humans 

exposed to aerosols, including nanoscale 

particles (e.g., diesel exhaust, welding fumes). 

These studies indicate that for a given mass 

of particles, relatively insoluble nanoparticles 

are more toxic than larger particles of similar chemical composition and surface properties. Studies of fine and ultrafine particles 

have shown that particles with less reactive 

surfaces are less toxic [Tran et al. 1999; Duffin et al. 2002]. However, even particles with 

low inherent toxicity (e.g., TiO2

) have been 

shown to cause pulmonary inflammation, 

tissue damage, and fibrosis at sufficiently 

high particle surface area doses [Oberdörster 

et al. 1992, 1994a,b; Tran et al. 1999, 2000].

Through engineering, the properties of nanomaterials can be modified. For example, a recent study has shown that the cytotoxicity of 

water-soluble fullerenes can be reduced by 

several orders of magnitude by modifying 

the structure of the fullerene molecules (e.g., 

by hydroxylation) [Sayes et al. 2004]. These 

structural modifications were shown to reduce the cytotoxicity by reducing the generation of oxygen radicals—which is a probable 

mechanism by which cell membrane damage 

and death occurred in these cell cultures. Increasing the sidewall functionalization of SWCNT also rendered these nanomaterials less 

cytotoxic to cells in culture [Sayes et al. 2005]. 

Cytotoxicity studies with quantum dots have 

shown that the type of surface coating can have 

a significant effect on cell motility and viability [Hoshino et al. 2004; Shiohara et al. 2004; 

Lovric et al. 2005]. Differences in the phase 

composition of nanocrystalline structures 

can influence their cytotoxicity; in a recent 

study comparing two types of TiO2

 nanoparticles exposed to UV radiation, anatase TiO2

was more cytotoxic and produced more reactive species than did rutile TiO2

 with similar 

specific surface area (153 m2

g and 123 m2g of 

TiO2

, respectively) [Sayes et al. 2006]. Reactive 

oxygen species were also associated with the 

cytotoxicity of TiO2 nanoparticles to mouse 

microglia (brain cells) grown in culture [Long 

et al. 2006]. In contrast, in vitro generation 

of oxidant species is relatively low in purified 

SWCNT (contaminating metals removed), 

yet this material caused progressive interstitial 

fibrosis in vivo [Shvedova et al. 2004; 2005]. 

However, recent in vitro studies indicate that 

purified SWCNTs enhance proliferation and 

collagen production in fibroblasts [Wang et al. 

2008]. Therefore, oxidant generation may not 

be the only mechanism driving the biological 

activity of nanomaterials. 

The studies of ultrafine particles may provide useful data to develop preliminary 

hazard or risk assessments and to generate 

hypotheses for further testing. The studies 

in cell cultures provide information about 

the cytotoxic properties of nanomaterials 

that can guide further research and toxicity 

testing in whole organisms. More research 

is needed of the specific particle properties 

and other factors that influence the toxicity 

and disease development, including those 

characteristics that may be most predictive 

of the potential safety or toxicity of newly 

engineered nanomaterials.
Approaches to Safe Nanotechnology 21

Very little is known about the safety risks 

that engineered nanomaterials might pose, 

beyond some data indicating that they possess certain properties associated with safety 

hazards in traditional materials. Based upon 

currently available information, the potential safety concerns most likely would involve catalytic effects or fire and explosion 

hazards if nanomaterials are found to behave similarly to traditional materials. 

6.1 Fire and Explosion Risk

Although insufficient information exists to 

predict the fire and explosion risk associated 

with nanoscale powders, nanoscale combustible material could present a higher risk 

than a similar quantity of coarser material, given its unique properties [HSE 2004]. 

Decreasing the particle size of combustible 

materials can increase combustion potential 

and combustion rate, leading to the possibility of relatively inert materials becoming 

highly reactive in the nanometer size range. 

Dispersions of combustible nanomaterial in 

air may present a greater safety risk than dispersions of non-nanomaterials with similar 

compositions. Some nanomaterials are designed to generate heat through the progression of reactions at the nanoscale. Such materials may present a fire hazard that is unique 

to engineered nanomaterials. In the case of 

some metals, explosion risk can increase significantly as particle size decreases.

The greater activity of nanoscale materials 

forms a basis for research into nanoenergetics. For instance, nanoscale Al/MoO3

 thermites ignite more than 300 times faster than 

corresponding micrometer-scale material 

[Granier and Pantoya 2004].

6.2 Risks of Catalytic 

Reactions

Nanoscale particles and nanostructured porous materials have been used as effective 

catalysts for increasing the rate of reactions 

or decreasing the necessary temperature 

for reactions to occur in liquids and gases. Depending on their composition and 

structure, some nanomaterials may initiate catalytic reactions that, based on their 

chemical composition, would not otherwise be anticipated [Pritchard 2004].

6 Potential Safety Hazards

Approaches to Safe Nanotechnology 23

There are currently no national or international consensus standards on measurement 

techniques for nanomaterials in the workplace. If the qualitative assessment of a process has identified potential exposure points 

and leads to the decision to measure nanomaterials, several factors must be kept in 

mind. Current research indicates that mass 

and bulk chemistry may be less important 

than particle size, surface area, and surface 

chemistry (or activity) for nanostructured 

materials [Oberdörster et al. 1992, 1994a,b; 

Duffin et al. 2002]. Research is ongoing into 

the relative importance of these different 

exposure metrics, and how to best characterize exposures to nanomaterials in the 

workplace. In addition, the unique shape 

and properties of some nanomaterials may 

pose additional challenges. For example, the 

techniques used to measure fiber concentrations in the workplace (e.g., phase contrast 

microscopy) would not be able to detect individual carbon nanotubes with diameters 

less than 100 nm nor bundles of carbon 

nanotubes with diameters less than 250 nm 

[Donaldson et al. 2006]. NIOSH and the 

National Institute of Standards and Technology (NIST) are collaborating on efforts 

to develop nanoscale reference materials for 

exposure assessment. Initial effort is focused 

on development of TiO2 reference material. 

7.1 Workplace Exposures

While research continues to address questions of nanomaterial toxicity, a number 

of exposure assessment approaches can be 

used to help determine worker exposures to 

airborne nanomaterials. These assessments 

can be performed using traditional industrial hygiene sampling methods including 

samplers placed at static locations (area 

sampling), samples collected in the breathing zone of the worker (personal sampling), 

or real-time devices or methods that can be 

personal or static. In general, personal sampling is preferred to ensure an accurate representation of the worker’s exposure, whereas 

area samples (e.g., size-fractionated aerosol 

samples) and real-time (direct-reading) exposure measurements may be more useful 

for evaluating the need for improvement of 

engineering controls and work practices. 

Many of the sampling techniques that are 

available for measuring nanoaerosols vary 

in complexity but can provide useful information for evaluating occupational exposures with respect to particle size, mass, 

surface area, number concentration, composition, and surface chemistry. Unfortunately, relatively few of these techniques are 

readily applicable to routine exposure monitoring. Research is ongoing into developing 

an analytical strategy for determining both 

TiO2 surface area and titanium mass from 

37-mm cassette filter samplers. Current 

measurement techniques are described below along with their applicability for monitoring nanometer aerosols.

For each measurement technique used, it 

is vital that the key parameters associated 

with the technique and sampling methodology be recorded when measuring exposure to nanoaerosols. This should include 

the response range of the instrumentation, 

7 Exposure Assessment and Characterization
24 Approaches to Safe Nanotechnology

7 Exposure Assessment and Characterization 

whether personal or static measurements 

are made, and the location of all potential aerosol sources including background 

aerosols. Comprehensive documentation 

will facilitate comparison of exposure measurements using different instruments or 

different exposure metrics and will aid the 

re-interpretation of historic data as further information is developed on healthappropriate exposure metrics. Regardless 

of the metric and method selected for exposure monitoring, it is critical that measurements be taken before production or 

processing of a nanomaterial to obtain 

background nanoparticle exposure data.

Measurements made during production or 

processing can then be evaluated to determine if there has been an increase in particle 

number concentrations in relation to background measurements and whether that 

change represents worker exposure to the 

nanomaterial. Table 7–1 gives a listing of instruments and measurement methods that 

can be used in the evaluation of engineered 

nanoparticle exposures.

Figure 7–1. Examples of different sampling instruments used to measure occupational 

exposures to nanoparticles including the determination of real-time particle number 

concentrations and size-fractionated mass concentrations

7.1.1 Size-fractionated aerosol 

sampling

Studies indicate that particle size plays an 

important role in determining the potential 

adverse effects of nanomaterials in the respiratory system: by influencing the physical, 

chemical, and biological nature of the material; by affecting the surface-area dose of deposited particles; and by enabling deposited 

particles to more readily translocate to other 

parts of the body. Animal studies indicate 

that the toxicity of inhaled nanoparticles 

is more closely associated with the particle 

surface area and particle number than with 

the particle mass concentration when comparing aerosols with different particle size 

distributions. However, mass concentration 

measurements may be applicable for evaluating occupational exposure to nanometer 

aerosols where a good correlation between 

the surface area of the aerosol and mass 

concentration can be determined or if toxicity data based on mass dose are available 

for a specific nanoscale particle associated 
Approaches to Safe Nanotechnology 25

7 Exposure Assessment and Characterization

with a known process (e.g., diesel exhaust 

particulate). 

Aerosol samples can be collected using inhalable, thoracic, or respirable samplers, 

depending on the region of the respiratory 

system most susceptible to the inhaled particles. Since prevailing information suggests 

that a large fraction of inhaled nanoparticles will deposit in the gas-exchange region of the lungs [ICRP 1994], respirable 

samplers would be appropriate. Respirable 

samplers will also collect a nominal amount 

of nanoscale particles that can deposit in the 

upper airways and ultimately be cleared or 

transported to other parts of the body. 

Table 7–1. Summary of instruments and measurement methods used in the evaluation 

of nanomaterial exposures*

Metric Instrument or method Remarks

Mass-Direct (total and/

or elemental) 

Size Selective Static 

Sampler

The only instruments offering a cut point around 

100 nm are cascade impactors (Berner-type low 

pressure impactors, or Micro orifice impactors). 

Allows gravimetric and chemical analysis of 

samples on stages below 100 nm.

TEOM®

(Tapered Element 

Oscillating 

Microbalance)

Sensitive real-time monitors such as the TEOM 

may be useable to measure nanoaerosol mass 

concentration on-line with a suitable size 

selective inlet.

Filter collection and 

elemental analysis

Filters may be collected with size selective presamplers or open face. Elemental analysis (e.g., 

carbon, metals) for mass determination.

Mass-Indirect 

(calculation)

ELPITM

(Electrical Low Pressure 

Impactor)

Real time size-selective (aerodynamic diameter) 

detection of active surface area concentration 

giving aerosol size distribution. Mass 

concentration of aerosols can be calculated when 

particle charge and density are known or assumed.

MOUDI

(Micro-Orfice Uniform 

Deposit Impactor)

Real time size-selective (aerodynamic diameter) 

by cascade impaction.

DMAS

(Differential Mobility 

Analyzing System)

Real time size-selective (mobility diameter) 

detection of number concentration, giving 

aerosol size distribution. Mass concentration of 

aerosols can be calculated when particle shape 

and density are known or assumed.

(continued)

See footnotes at end of table.
26 Approaches to Safe Nanotechnology

7 Exposure Assessment and Characterization 

Table 7–1 (Continued). Summary of instruments and measurement methods used in 

the evaluation of nanomaterial exposures*

Metric Instrument or method Remarks

Number-Direct CPC

 (Condensation Particle 

Counter)

CPCs provide real time number concentration 

measurements between their particle diameter 

detection limits. Without a nanoparticle preseparator they are not specific to the nanometer 

size range. Some models have diffusion screen 

to limit top size to 1 μm.

OPC

(Optical Particle 

Counter)

OPCs provide real time number concentration 

measurements between their particle diameter 

detection limits. Particle size diameters begin at 

300 nm and may go up to 10,000 nm.

DMAS and SMPS

(Scanning Mobility 

Particle Sizer)

Real time size-selective (mobility diameter) 

detection of number concentration giving 

number-based size distribution.

 Electron Microscopy Off-line analysis of electron microscope samples 

can provide information on size-specific aerosol 

number concentration.

Number-Indirect ELPITM and MOUDI Real time size-selective (aerodynamic diameter) 

detection of active surface-area concentration 

giving aerosol size distribution. Data may be 

interpreted in terms of number concentration. 

Size-selective samples may be further analyzed 

off-line.

Surface Area-Direct Diffusion Charger Real-time measurement of aerosol active surfacearea. Active surface-area does not scale directly 

with geometric surface-area above 100 nm. Note 

that not all commercially available diffusion 

chargers have a response that scales with particle 

active surface-area below 100 nm. Diffusion 

chargers are only specific to nanoparticles if used 

with appropriate inlet pre-separator.

ELPITM and MOUDI Real-time size-selective (aerodynamic diameter) 

detection of active surface-area concentration. 

Active surface-area does not scale directly with 

geometric surface-area above 100 nm.

(continued)

See footnotes at end of table.
Approaches to Safe Nanotechnology 27

7 Exposure Assessment and Characterization

Table 7–1 (Continued). Summary of instruments and measurement methods used in 

the evaluation of nanomaterial exposures*

Metric Instrument or method Remarks

Surface Area-Direct

(continued)

 Electron Microscopy Off-line analysis of electron microscope samples 

(previously collected on filters or other media) 

can provide information on particle surface-area 

with respect to size. TEM analysis provides direct 

information on the projected area of collected 

particles which may be related to geometric area 

for some particles shapes.

Surface Area-Indirect 

(calculation)

DMAS and SMPS Real time size-selective (mobility diameter) 

detection of number concentration. Data may be 

interpreted in terms of aerosol surface-area under 

certain circumstances. For instance, the mobility 

diameter of open agglomerates has been shown to 

correlate with projected surface area.

DMAS and ELPITM used 

in parallel

Differences in measured aerodynamic and 

mobility can be used to infer particle fractal 

dimension which can be further used to 

estimate surface-area. 

*Adapted from ISO/TR 12885

Note: Inherent to all air sampling instruments in this table is the fact that they cannot discriminate the 

nanoaerosol of interest from other airborne particles. Also, there is a general lack of validation regarding 

the response of these air sampling instruments to the full spectrum of nanoparticles that may be found in 

the workplace, including varieties of primary particles, agglomerates or aggregates, and other physical and 

chemical forms. A suite of nanoparticle reference materials are required to perform the needed validations. 

Respirable samplers allow mass-based exposure measurements to be made using gravimetric and/or chemical analysis [NIOSH 

1994]. However, they do not provide information on aerosol number, size, or surface-area 

concentration, unless the relationship between 

different exposure metrics for the aerosol (e.g., 

density, particle shape) has been previously 

characterized. Currently, no commercially 

available personal samplers are designed to 

measure the particle number, surface area, or 

mass concentration of nanoaerosols. However, 

several methods are available that can be used 

to estimate surface area, number, or mass concentration for particles smaller than 100 nm. 

The use of conventional impactor samplers 

to assess nanoparticle exposure is limited 

since the impaction collection efficiencies 

are 200–300 nm. Low-pressure cascade impactors that can measure particles to 50 nm 

and larger may be used for static sampling 

since their size and complexity preclude their 

use as personal samplers [Marple et al. 2001; 

Hinds 1999]. A personal cascade impactor 

is available with a lower aerosol cut point of 
28 Approaches to Safe Nanotechnology

7 Exposure Assessment and Characterization 

250 nm [Misra et al. 2002], allowing an approximation of nanoscale particle mass concentration in the worker’s breathing zone. 

For each method, the detection limits are on 

the order of a few micrograms of material on 

a filter or collection substrate [Vaughan et al. 

1989]. Cascade impactor exposure data gathered from worksites where nanomaterials are 

being processed or handled can be used to 

make assessments as to the efficacy of exposure control measures. 

7.1.2 Real-time aerosol sampling 

The real-time (direct-reading) measurement of nanometer aerosol concentrations is limited by the sensitivity of the 

instrument to detect small particles. Many 

real-time aerosol mass monitors used in 

the workplace rely on light scattering from 

groups of particles (photometers). This 

methodology is generally insensitive to particles smaller than 100 nm [Hinds 1999]. 

Optical instruments that size individual 

particles and convert the measured distribution to a mass concentration are similarly limited to particles larger than 100 nm. 

Quantitative information gained by optical 

particle counters may also be limited by relatively poor counting efficiencies at smaller 

particle diameters (i.e., less than 500 nm). 

These instruments are capable of operating 

within certain concentration ranges that, 

when exceeded, affect the count or mass 

determination efficiencies due to coincidence errors at the detector. Similarly, the 

response of optical particle counters may 

be material-dependent according to the refractive index of the particle. The Scanning 

Mobility Particle Sizer (SMPS) is widely 

used as a research tool for characterizing 

nanoscale aerosols although its applicability for use in the workplace may be limited 

because of its size, cost, and the inclusion of 

a radioactive source. Additionally, the SMPS 

may take 2–3 minutes to scan an entire size 

distribution; thus, it may be of limited use 

in workplaces with highly variable aerosol size distributions, such as those close 

to a strong particle source. Fast (less than 1 

second), mobility-based, particle-sizing instruments are now available commercially; 

however, having fewer channels, they lack 

the finer sizing resolution of the SMPS. The 

Electrical Low Pressure Impactor (ELPI) 

is an alternative instrument that combines 

diffusion charging and a cascade impactor 

with real-time (less than 1 second) aerosol 

charge measurements providing aerosol size 

distributions by aerodynamic diameter [Keskinen et al. 1992]. 

7.1.3 Surface-area measurements

Relatively few techniques exist to monitor 

exposures with respect to aerosol surface 

area. Particle surface is composed of internal surface area attributable to pores (cavities 

more deep than wide), external surface area 

due to roughness (cavities more wide than 

deep), and total surface area (the accessible 

area of all real particle surfaces). A standard 

gas adsorption technique (i.e., BET) is used 

to measure the total surface area of powders 

and can be adapted to measure the specific 

surface area (surface area per unit mass) of 

engineered nanomaterials [Brunauer et al. 

1938]. However, surface-area analysis by gas 

adsorption requires relatively large quantities 

of material, is not element specific, and must 

be performed in a laboratory. 

The first instrument designed to measure 

aerosol surface area was the epiphaniometer 

[Baltensperger et al. 1988]. This device measures the Fuchs, or active surface area, of the 

aerosols by measuring the attachment rate of 
Approaches to Safe Nanotechnology 29

7 Exposure Assessment and Characterization

radioactive ions. For aerosols less than approximately 100 nm in size, measurement of 

the Fuchs surface area is probably a good indicator of external surface area (or geometric 

surface area). However, for aerosols greater 

than approximately 1 μm, the relationship 

with geometric particle surface area is lost 

[Fuchs 1964]. Measurements of active surface 

area are generally insensitive to particle porosity. The epiphaniometer is not well suited 

to widespread use in the workplace because 

of the inclusion of a radioactive source and 

the lack of effective temporal resolution. 

This same measurement principle can be 

applied with the use of a portable aerosol 

diffusion charger. Studies have shown that 

these devices provide a good estimate of 

aerosol external surface area when airborne 

particles are smaller than 100 nm in diameter. For larger particles, diffusion chargers 

underestimate aerosol surface area. However, further research is needed to evaluate 

the degree of underestimation. Extensive 

field evaluations of commercial instruments 

are yet to be reported. However, laboratory 

evaluations with monodisperse silver particles have shown that two commercially 

available diffusion chargers can provide 

good measurement data on aerosol external surface area for particles smaller than 

100 nm in diameter but underestimate the 

aerosol surface area for particles larger than 

100 nm in diameter [Ku and Maynard 2005, 

2006].

7.1.4 Particle number concentration 

measurement

Particle number concentration has been associated with adverse responses to air pollution in some human studies [Timonen 

et al. 2004; Ruckerl et al. 2005], while in 

toxicologic studies, particle surface area has 

generally been shown to be a better predictor than either particle number, mass, or volume concentration alone [Oberdörster and 

Yu 1990; Tran et al. 1999; Duffin et al. 2002]. 

A two-variable dose metric of particle size 

and volume has been shown to be the best 

predictor of lung cancer in rats from various types of particles [Borm et al. 2004; Pott 

and Roller 2005]. This illustrates some of 

the complexity of interpreting existing data 

on particle dose metric and response. While 

adverse health effects appear to be more 

closely related with particle surface area, the 

number of particles depositing in the respiratory tract or other organ systems may also 

play an important role. 

Aerosol particle number concentration can 

be measured relatively easily using Condensation Particle Counters (CPCs). These are 

available as hand-held static instruments, 

and they are generally sensitive to particles 

greater than 10–20 nm in diameter. Condensation Particle Counters designed for the 

workplace do not have discrete size-selective 

inputs, and so they are typically sensitive to 

particles less than 1 μm in diameter. Com in diameter. Commercial size-selective inlets are not available 

to restrict CPCs to the nanoparticle size range; 

however, the technology exists to construct 

size-selective inlets based on particle mobility or possibly on inertial pre-separation. An 

alternative approach to estimating nanoparticle number concentrations using a CPC is 

to use the instrument in parallel with an optical particle counter (OPC). The difference 

in particle count between the instruments 

will provide an indication of particle number 

concentration between the lower CPC detectable particle diameter and the lower OPC 

particle diameter (typically 300–500 nm).

A critical issue when characterizing exposure using particle number concentration 
30 Approaches to Safe Nanotechnology

7 Exposure Assessment and Characterization 

is selectivity. Nanoscale particles are ubiquitous in many workplaces, from sources 

such as combustion, vehicle emissions, and 

infiltration of outside air. Particle counters 

are generally insensitive to particle source 

or composition making it difficult to differentiate between incidental and process-related nanoparticles using number 

concentration alone. In a study of aerosol 

exposures during a carbon black bagging 

process, Kuhlbusch et al. [2004] found that 

peaks in number concentration measurements were associated with emissions from 

fork lift trucks and gas burners in the vicinity, rather than with the process itself. In a 

similar manner, during an ultrafine particle 

mapping exercise in an automotive facility, 

Peters et al. [2006] found that direct gasfired heating systems systematically produced high particle number concentrations 

throughout the facility when the heating 

system was in operation. Through follow 

up measurements, Heitbrink et al. [2007] 

found a high proportion of ultrafine particles produced from these burners, yet little 

if any mass was associated with their emissions. Other non-process ultrafine sources 

were identified in an adjacent foundry [Evans et al. 2008]. Together with roof mounted 

gas-fired heating units, additional sources 

included cigarette-smoking and the exhaust 

from a propane fueled sweeper vehicle, with 

the latter contributing a large fraction of the 

ultrafine particles. Although these issues are 

not unique to particle number concentration measurements, orders of magnitude 

difference can exist in particle number 

concentrations depending on concomitant 

sources of particle emissions. 

Although using nanoparticle number concentration as an exposure measurement may 

not be consistent with exposure metrics being used in animal toxicity studies, such 

measurements may be useful for identifying nanoscale particle emissions and determining the efficacy of control measures.

Portable CPCs are capable of measuring localized particle concentrations allowing the 

assessment of particle releases occurring at 

various processes and job tasks [Brouwer et 

al. 2004].

7.1.5 Surface-area estimation

Information about the relationship between 

different measurement metrics can be used 

for approximating particle surface area. If 

the size distribution of an aerosol remains 

consistent, the relationship between particle 

number, surface area, and mass metrics will 

be constant. In particular, mass concentration measurements can be used for deriving 

surface-area concentrations, assuming the 

constant of proportionality is known. This 

constant is the specific surface area (surface 

to mass ratio). 

Size distribution measurements may be obtained through the collection of filter samples 

and analysis by transmission electron microscopy to estimate particle surface area. If 

the measurements are weighted by particle 

number, information about particle geometry will be needed to estimate the surface 

area of particles with a given diameter. If the 

measurements are weighted by mass, additional information about particle density 

will be required. Estimates of particle-specific 

surface area from geometric relation with external particle dimensions depends upon the 

morphology regime of the material of interest and is only appropriate for smooth, regularly shaped, compact particles [Stefaniak et al. 

2003; Weibel et al. 2005]. For example, Weibel 

et al. [2005] report that estimates of ultrafine 

TiO2

 surface area determined using a geometric relationship with the physical particle size 
Approaches to Safe Nanotechnology 31

7 Exposure Assessment and Characterization

(using TEM) were 50% lower than measured 

using nitrogen gas adsorption. 

If the airborne aerosol has a lognormal size 

distribution, particle surface-area concentration can be derived using three independent measurements. An approach has been 

proposed using three simultaneous measurements of the aerosol that included mass 

concentration, number concentration, and 

charge [Woo et al. 2001]. With knowledge of 

the response function of each instrument, 

minimization techniques can be used to estimate the parameters of the lognormal distribution leading to the three measurements 

used in estimating the particle surface area. 

An alternative approach has been proposed 

whereby independent measurements of particle number and mass concentration are 

made, and the surface area is estimated by assuming the geometric standard deviation of 

the (assumed) lognormal distribution [Maynard 2003]. This method has the advantage of 

simplicity by relying on portable instruments 

that can be used in the workplace. Theoretical calculations have shown that estimates 

may be up to a factor of 10 different from 

the actual particle surface area, particularly 

when the aerosol has a bimodal distribution. 

Field measurements indicate that estimates 

are within a factor of 3 of the active surface 

area, particularly at higher concentrations. 

In workplace environments, particle surfacearea concentrations can be expected to span 

up to 5 orders of magnitude; thus, surfacearea estimates may be suited for initial or 

preliminary appraisals of occupational exposure concentrations. 

Although such estimation methods are unlikely to become a long-term alternative to 

more accurate methods, they may provide 

a viable interim approach to estimating the 

surface area of nanoscale particles in the 

absence of precise measurement data. Additional research is needed on comparing 

methods used for estimating particle surface 

area with a more accurate particle surfacearea-measurement method. NIOSH is conducting research in this area and will communicate results as they become available. 

7.1.6 Particle number 

concentration mapping

To better understand particle sources and 

contaminant migration, some investigators 

have adopted an aerosol mapping technique, 

which integrated measurements of respirable mass, ultrafine particle number, and 

active surface-area concentrations in automotive manufacturing facilities [Peters et al. 

2006; Heitbrink et al. 2007, 2008; Evans et al. 

2008]. The process relies on portable aerosol 

sampling instrumentation for simultaneous 

measurements at predetermined positions 

throughout a facility. The technique is somewhat measurement-intensive but is useful 

for locating contaminant sources and determining the extent of contaminant migration. 

Leaks and other less obvious particle sources 

have been identified in this way and the procedure provides a powerful tool for facility staff to target their contaminant control 

approaches most effectively. This technique 

relies on successive measurements at various 

locations, making facilities with continuous 

processes or those likely to achieve steady 

state particle number concentrations most 

appropriate for this approach. The approach 

is less successful for facilities with batch processes or those likely to experience rapid concentration changes as, depending on where 

in the measurement cycle the release occurs, 

it may be overlooked. A high degree of variability between mapping events is expected in 
32 Approaches to Safe Nanotechnology

7 Exposure Assessment and Characterization 

facilities where sporadic or batch processing 

occurs.

7.2 Sampling Strategy

Currently, there is not one sampling method 

that can be used to characterize exposure to 

nanoscale aerosols. Therefore, any attempt to 

characterize workplace exposure to nanomaterials must involve a multifaceted approach 

incorporating many of the sampling techniques mentioned above. Brouwer et al. [2004] 

recommend that all relevant characteristics of 

nanomaterial exposure be measured, and a 

sampling strategy similar to theirs would provide a reasonable approach to characterizing 

workplace exposure. NIOSH has developed 

the Nanoparticle Emission Assessment Technique (NEAT) to qualitatively determine the 

release of engineered nanomaterials in the 

workplace (see Appendix). This approach may 

be helpful to others for the initial evaluation of 

workplaces where engineered nanomaterials 

are manufactured or used. If material release 

is found and if resources allow, then a more 

comprehensive and quantitative approach 

may be adopted [Methner et al. 2007].

The first step to characterizing workplace exposures would involve identifying the source 

of nanomaterial emissions. A CPC used in 

parallel with an OPC provides acceptable 

capability for this purpose. It is critical to 

determine ambient or background particle 

counts before measuring particle counts 

during the manufacturing, processing, or 

handling of engineered nanomaterials.

However, investigators need to be aware that 

background nanoscale particle counts can 

vary both spatially and temporally depending on the unique conditions of the workplace. Subtraction of background nanoscale 

particle counts will be most challenging in 

these situations. In cases where nanomaterial 

handling or processing operations contribute only small elevations in particle counts, 

it may not be possible to adequately characterize these increases, particularly if the background particle count is relatively high. 

If nanomaterials are detected in the process area at elevated concentrations relative to background particle number concentrations, then a pair of filter-based, area 

air samples should be collected for particle 

analysis via transmission electron microscopy (TEM) and for determining mass concentration. Transmission electron micros Transmission electron microscopy can provide an estimate of the particle 

size distribution and, if equipped with an 

energy dispersive X-ray analyzer (EDS), a 

determination of elemental composition 

Figure 7–2. Photomicrographs of airborne engineered nanomaterials (airborne samples 

of engineered nanoparticles of silver, nickel, and MWCNT analyzed by TEM and EDS) 
Approaches to Safe Nanotechnology 33

7 Exposure Assessment and Characterization

can be made to identify the nanomaterial 

(see Figure 7–2).

Analysis of filters for mass determination of 

air contaminants of interest can help identify 

the source of the particles. Standard analytical chemical methodologies (e.g., NMAM 

5040 for carbon, NMAM 7303 for metals) 

should be employed [NIOSH 1994]. 

The combination of particle counters and 

samples for chemical analysis allows for an 

assessment of worker exposure to nanomaterials (see Figure 7–3) and the characterization of the important aerosol metrics. However, since this approach relies primarily on 

static or area sampling, some uncertainty 

will exist in estimating worker exposures. 

Figure 7–3. Combined use of the OPC, 

CPC, and two filter samples to determine 

the presence of nanomaterials

Approaches to Safe Nanotechnology 35

Engineered nanomaterials are diverse in 

their physical, chemical, and biological nature. The processes used in research, material development, production, and use 

or introduction of nanomaterials have the 

potential to vary greatly. Until further information on the possible health risks and 

extent of occupational exposure to nanomaterials becomes available, interim protective measures should be developed and 

implemented. These measures should focus 

on the development of engineering controls 

and safe working practices tailored to the 

specific processes and materials where workers might be exposed. Hazard information 

that is available about common materials 

being manufactured in the nanoscale range 

(e.g., TiO2

,beryllium) should be considered 

as a starting point in developing appropriate 

controls and work practices. 

The following recommendations are designed to aid in the assessment and control 

of workplace exposures to engineered nanomaterials. Using a hazard-based approach to 

evaluate exposures and for developing precautionary measures is consistent with good 

occupational safety and health practices 

[The Royal Society and The Royal Academy 

of Engineering 2004; Schulte et al. 2008].

8.1 Potential for Occupational 

Exposure

Few workplace measurement data exist on 

airborne exposure to nanomaterials that are 

purposely produced and not incidental to an 

industrial process. In general, it is likely that 

processes generating nanomaterials in the 

gas phase (after removal of the nanomaterial 

from an enclosed generation system), or using or producing nanomaterials as powders 

or slurries/suspensions/solutions (i.e., in liquid media), pose the greatest risk for releasing nanoparticles. In addition, maintenance 

on production systems (including cleaning 

and disposing of materials from dust collection systems) is likely to result in exposure 

to nanoparticles if deposited nanomaterials are disturbed. Exposures associated with 

waste streams containing nanomaterials may 

also occur.

The magnitude of exposure to nanomaterials 

when working with nanopowders depends 

on the likelihood of particles being released 

from the powders during handling. NIOSH 

is actively conducting research to quantitatively determine how various nanomaterials 

are dispersed in the workplace. Studies on 

exposure to SWCNTs and MWCNTs have indicated that the raw material may release visible particles into the air when handled, that 

the particle size of the agglomerate can be a 

few millimeters in diameter, and that the release rate of inhalable and respirable particles 

is relatively low (on a mass or number basis) 

compared with other nanopowders. Maynard et al. [2004] reported concentrations of 

respirable dust from 0.007 to 0.053 mg/m3

when energy was applied (vortexing) to 

bulk SWCNT for approximately 30 minutes. 

Similar findings were reported by Han et al. 

[2008] at a laboratory producing MWCNTs 

in which exposure concentrations as high as 

0.4 mg/m3 were observed prior to the implementation of exposure controls. In a health 

hazard evaluation conducted by NIOSH at a 

Guidelines for Working with Engineered 8 Nanomaterials
36 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

university-based research laboratory the potential release of airborne carbon nanotubes 

(CNFs) was observed at various processes 

[Methner et al. 2007]. General area exposure 

measurements indicated slight increases in 

airborne particle number and mass concentrations relative to background measurements during the transfer of CNFs prior to 

weighing and mixing, and during wet saw 

cutting of a composite material. Since data 

are lacking on the generation of inhalable/

respirable particles during the production 

and use of engineered nanomaterials, further research is required to determine exposures under various conditions. NIOSH 

researchers are conducting both laboratory 

and field-based evaluations in order to address some of these knowledge gaps.

Devices comprised of nanostructures, such 

as integrated circuits, pose a minimal risk 

of exposure to nanomaterials during handling. However, some of the processes used 

in their production may lead to exposure 

to nanomaterials (e.g., exposure to commercial polishing compounds that contain 

nanoscale particles, exposure to nanoscale 

particles that are inadvertently dispersed or 

created during the manufacturing and handling processes). Likewise, large-scale components formed from nanocomposites will 

most likely not present significant exposure 

potential. However, if such materials are 

used or handled in such a manner that can 

generate nanoparticles (e.g., cutting, grinding) or undergo degradation processes that 

lead to the release of nanostructured material, then exposure may occur by the inhalation, ingestion, and/or dermal penetration 

of these particles.

8.2 Factors Affecting Exposure 

to Nanomaterials

Factors affecting exposure to engineered 

nanomaterials include the amount of material being used and whether the material can 

be easily dispersed (in the case of a powder) 

or form airborne sprays or droplets (in the 

case of suspensions). The degree of containment and duration of use will also influence 

exposure. In the case of airborne material, 

particle or droplet size will determine whether the material can enter the respiratory tract 

and where it is most likely to deposit. Respirable particles are those capable of depositing 

in the alveolar (gas exchange) region of the 

lungs, which includes particles smaller than 

approximately 10 μm in diameter [Lippmann 

1977; ICRP 1994; ISO 1995]. The proportion 

of inhaled nanoparticles likely to deposit in 

any region of the human respiratory tract is 

approximately 30%–90% depending on factors such as breathing rate and particle size. 

Up to 50% of nanoparticles in the 10–100 nm 

size range may deposit in the alveolar region, 

while nanoparticles smaller than 10 nm are 

more likely to deposit in the head and thoracic regions [ICRP 1994]. The mass deposition fraction of inhaled nanoparticles in the 

gas-exchange region of the lungs is greater 

than that for larger respirable particles.

At present there is insufficient information 

to predict all of the situations and workplace 

scenarios that are likely to lead to exposure 

to nanomaterials. However, there are some 

workplace factors that can increase the potential for exposure:

•	 working with nanomaterials in liquid 

media without adequate protection 

(e.g., gloves)

•	 working with nanomaterials in liquid 

during pouring or mixing operations 
Approaches to Safe Nanotechnology 37

8 Guidelines for Working with Engineered Nanomaterials

or where a high degree of agitation is 

involved 

•	 generating nanomaterials in the gas phase 

in non-enclosed systems 

•	 handling (e.g., weighing, blending, spraying) powders of nanostructured materials 

•	 maintenance on equipment and processes used to produce or fabricate nanomaterials 

•	 cleaning up spills or waste material 

•	 cleaning dust collection systems used 

to capture nanoparticles 

•	 machining, sanding, drilling of nanomaterials, or other mechanical disruptions of nanomaterials can potentially 

lead to the aerosolization of nanoparticles. 

8.3 Elements of a Risk 

Management Program

Given the limited information about the 

health risks associated with occupational 

exposure to engineered nanomaterials, appropriate steps should be taken to minimize 

the risk of worker exposure through the 

implementation of a risk management program [Schulte et al. 2008]. Risk management 

programs for nanomaterials should be seen 

as an integral part of an overall occupational 

safety and health program for any company 

or workplace producing or using nanomaterials or nanoenabled products. A critical element of the program should be the capability 

to anticipate new and emerging risks (hazard 

determination) and whether they are linked 

to changes in the manufacturing process, 

equipment, or the introduction of new materials. This will require an ongoing assessment of the potential risks to workers (risk 

evaluation) through the systematic collection 

of job and product information so that determinations can be made regarding scenarios (e.g., laboratory research, production and 

manufacture, nanoenabled product use) that 

place the worker in contact with nanomaterials (see Figure 8–1). This assessment should 

be an ongoing cyclic process that provides 

feedback on potential sources of exposure 

and solutions taken to correct those problems. For example, operations and job tasks 

that have the potential to aerosolize nanomaterials (e.g., handling dry powders, spray applications) deserve more attention and more 

stringent controls than those where the nanomaterials are imbedded in solid or liquid matrices. Elements of the risk management program should include guidelines for installing 

and evaluating engineering controls (e.g., 

exhaust ventilation, dust collection systems), 

the education and training of workers in the 

proper handling of nanomaterials (e.g., good 

work practices), and the selection and use of 

personal protective equipment (e.g., clothing, gloves, respirators). 

When controlling potential exposures within 

a workplace, NIOSH has recommended a 

hierarchical approach to reduce worker exposures (see Table 8–1) [NIOSH 1990]. The 

philosophical basis for the hierarchy of controls is to eliminate the hazard when possible 

(i.e., substitute with a less hazardous material) or, if not feasible, control the hazard at 

or as close to the source as possible. 

8.3.1 Engineering Controls

If the potential hazard can not be eliminated or substituted with a less hazardous or 

non-hazardous substance, then engineering controls should be installed and tailored to the process or job task. The type of 

engineering control used should take into 
38 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

Figure 8–1. Workplaces with potential for occupational exposure to engineered 

nanomaterials. The figure illustrates the life cycle of nanomaterials from laboratory 

research development through product development, use, and disposal. Each step of 

the life cycle represents opportunities for potential worker exposure to nanomaterials. 

Adapted from Schulte et al. 2008a. 
Approaches to Safe Nanotechnology 39

8 Guidelines for Working with Engineered Nanomaterials

account information on the potential hazardous properties of the precursor materials and intermediates as well as those of the 

resulting nanomaterial. In light of current 

scientific knowledge about the generation, 

transport, and capture of aerosols [Seinfeld 

and Pandis 1998; Hinds 1999], airborne ex airborne exposure to nanomaterials can most likely be 

controlled at most processes and job tasks 

using a wide variety of engineering control 

techniques similar to those used in reducing 

exposures to general aerosols [Ratherman 

1996; Burton 1997]. 

Engineering control techniques such as 

source enclosure (i.e., isolating the generation source from the worker) and local exhaust ventilation systems should be effective 

for capturing airborne nanomaterials, based 

on what is known of nanomaterial motion 

and behavior in air (see Figure 8–2). The 

quantity of the bulk nanomaterial that is 

synthesized or handled in the manufacture 

of a product will significantly influence the 

selection of the exposure controls. 

Other factors that influence selection of engineering controls include the physical form of 

the nanomaterial and task duration and frequency. For instance, working with nanomaterial in the slurry form in low quantities would 

require a less rigorous control system than 

those that would be required for large quantities of nanomaterials in a free or fine powder form (see Figure 8–3). Unless cutting or 

grinding occurs, nanomaterials that are not in 

free form (encapsulated in a solid, nanocomposites, and surface coated materials) typically 

wouldn’t require engineering controls. 

Handling research quantities typically occurs in laboratories with ventilation controls. Since quantities are small, local containment and control can be applied, such 

as low-flow vented work stations and small 

glove box chambers. However, as quantities 

are increased, care must be taken to reduce 

the amount of nanomaterial that is released 

from the process equipment and to prevent the migration of nanomaterials into 

adjacent rooms or areas. For example, the 

installation of local exhaust ventilation at a 

Table 8–1. Hierarchy of exposure controls* 

Control method Process, equipment, or job task 

1. Elimination Change design to eliminate hazard

2. Substitution Replace a high hazard for a low hazard

3. Engineering Isolation/enclosure, ventilation (local, general)

4. Administrative Procedures, policies, shift design

5. Personal protective equipment Respirators, clothing, gloves, goggles, ear plugs

*Control methods are typically implemented in this order to limit worker exposures to an acceptable 

concentration (e.g., occupational exposure limit or other pre-established limit). 

Sources: Plog et al. 2002; NIOSH 1990.
40 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

reactor used to make nanoscale engineered 

metal oxides and metals was found to reduce nanoparticle exposures by 96% (mean 

particle number concentration) [Methner 

2008]. The use of exhaust ventilation systems should be designed, tested, and maintained using approaches recommended by 

the American Conference of Governmental 

Industrial Hygienists [ACGIH 2001]. 

A secondary but nonetheless important 

issue concerning the control of nanoparticle emissions is that of product loss. The 

properties of nanomaterials, along with the 

unique methods that may be employed for 

producing them, may mean that traditional 

exhaust ventilation may be more energetic 

than necessary for removing incidentally 

released nanoscale particles. For this reason, engineering controls need to be applied 

judiciously to ensure protection of workers 

without compromising production.

8.3.2 Dust collection efficiency of 

filters

Current knowledge indicates that a welldesigned exhaust ventilation system with a 

Figure 8–2. Exposure control of particles (illustration of how particle diameter-related 

diffusion and inertia influence particle capture efficiency in a ventilation system). Particles 

with a diameter of 200–300 nm have minimal diffusion and inertial properties and are 

easily transported by moving air and captured. Particle motion by diffusion increasingly 

dominates as particle diameter decreases below 200 nm. The inertial behavior of larger 

particles, especially those ejected from energetic processes such as grinding, increases 

significantly with particle diameter, enabling them to cross the streamlines of moving air 

and avoid capture. Adapted from Schulte et al. 2008a.
8 Guidelines for Working with Engineered Nanomaterials 

Figure 8–3. Factors influencing control selection. Several factors influence the selection of 

exposure controls for nanomaterials including quantity of nanomaterial handled or produced, 

physical form, and task duration. As each one of theses variables increase, exposure risk 

becomes greater as does the need for more efficient exposure control measures. 

HEPA filter should effectively remove nanoparticles [Hinds 1999]. Limited studies have 

reported the effi cacy of filter media typically 

found in control systems (including respirators) in capturing nanoparticles. The dearth 

of data on filtration performance against 

nanoparticles (in particular nanoparticles 

smaller than 20 nm) is primarily due to the 

challenges in generating and quantifying 

particles in those size ranges. Despite these 

limitations, the results of some studies [Van 

Osdell et al. 1990] using different fi lter media challenged with monodispersed aerosols (silver 4–10 nm and dioctylphthalate 

32–420 nm) were in agreement with classical 

single-fiber theory showing an increase in fi ltration efficacy for smaller size particles. No 

evidence for particle thermal rebound was 

observed. Similar results have been recently 

reported by Kim et al. [2007] using different 

filter media challenged with particles ranging 

in size from 2.5–20 nm, indicating that other 

filter medias—including those used in air purifying respirators—would behave similarly. 

If HEPA filters are used in the dust collection system, they should be coupled with 

well-designed filter housings. If the fi lter 

is improperly seated within the housing, 

nanoparticles have the potential to bypass 

the filter, leading to fi lter effi ciencies much 

less than predicted [NIOSH 2003]. 

8.3.3 Work practices 

An integral step in establishing good work 

practices is having knowledge of the potential 

Approaches to Safe Nanotechnology 41 
42 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

hazards in the workplace and developing 

formal procedures that describe actions to 

be taken to ensure the protection of workers. 

Incorporated in these procedures should be 

guidelines for good work practices intended 

to minimize worker exposure to nanomaterials and other potentially hazardous chemicals. Management should systemically review and update these procedures. Actions 

taken to resolve and/or improve workplace 

conditions should be routinely conveyed by 

management to workers. 

Good practices for management

•	 Educating workers on the safe handling of engineered nano-objects or 

nano-object-containing materials to 

minimize the likelihood of inhalation 

exposure and skin contact. 

•	 Providing information, as needed, on 

the hazardous properties of the precursor materials and those of the resulting 

nanomaterials product with instruction on measures to prevent exposure.

•	 Encouraging workers to use handwashing facilities before eating, smoking, or leaving the worksite. 

•	 Providing additional control measures 

(e.g., use of a buffer area, decontamination facilities for workers if warranted 

by the hazard) to ensure that engineered 

nanomaterials are not transported outside the work area [US DOE 2007].

•	 Providing facilities for showering and 

changing clothes to prevent the inadvertent contamination of other areas 

(including take-home) caused by the 

transfer of nanomaterials on clothing 

and skin. 

Good practices for workers

•	 Avoiding handling nanomaterials in 

the open air in a ‘free particle” state. 

•	 Storing dispersible nanomaterials, whether suspended in liquids or in a dry particle 

form in closed (tightly sealed) containers 

whenever possible.

•	 Cleaning work areas at the end of each 

work shift, at a minimum, using either 

a HEPA-filtered vacuum cleaner or wet 

wiping methods. Dry sweeping or air 

hoses should not be used to clean work 

areas. Cleanup should be conducted in 

a manner that prevents worker contact 

with wastes. Disposal of all waste material should comply with all applicable 

Federal, State, and local regulations.

•	 Avoiding storing and consuming food 

or beverages in workplaces where nanomaterials are handled. 

8.3.4 Personal protective clothing 

Currently, there are no generally acceptable 

guidelines available based on scientific data 

for the selection of protective clothing or 

other apparel against exposure to nanomaterials. This is due in part to minimal data 

being available on the efficacy of existing 

protective clothing, including gloves. In any 

case, although nanoparticles may penetrate 

the epidermis, there has been little evidence 

to suggest that penetration leads to disease; 

and no dermal exposure standards have been 

proposed. However, based on a recent survey 

of nanotechnology workplaces [ICON 2006], 

84% of employers recommended personal 

protective equipment and clothing for employees working with nanomaterials. These 

recommendations were generally based on 

conventional occupational hygiene practices 
Approaches to Safe Nanotechnology 43

8 Guidelines for Working with Engineered Nanomaterials

but also varied with the size of the company, 

the type of nanomaterials being handled, and 

the commercial sector. While some guidelines on the use of protective clothing and 

gloves have been developed by organizations 

for use in their own laboratories (e.g., US 

DOE 2007) or countries (e.g., British Standards Institute BSI 2008) or by consensus 

standards development organizations (e.g., 

ASTM, 2007), these are generally based upon 

good industrial hygiene practices rather than 

scientific data specific to nanomaterials. 

A challenge to making appropriate recommendations for dermal protection against 

nanoparticles is the need to strike a balance 

between comfort and protection. Garments 

that provide the highest level of protection 

(e.g., an impermeable Level A suit) are also 

the least comfortable to wear for long periods of time, while garments that are probably 

the least protective (e.g., thin cotton lab coat) 

are the most breathable and comfortable for 

employees to wear. The two primary routes 

of exposure to particulates for workers using protective clothing are direct penetration 

through the materials and leakage through 

gaps, seams, defects, and interface and closure areas [Schneider et al. 1999, 2000]. The 

relative contributions from these two inward 

leakage sources are not well-understood. 

NIOSH has an active research program designed to assess the efficacy of barrier materials and ensembles for protection against particulate hazards, including nanoparticles. 

The lack of available data is further complicated by the limitations and difficulties of 

current test methods, which fall into two basic categories: penetration tests on material 

swatches to determine barrier efficiency and 

system-level aerosol testing to determine 

product ensemble integrity. The former are 

usually bench-scale testing methods, while 

the latter require an exposure chamber that 

is large enough for at least one human test 

subject or mannequin. Chamber design requirements for system level aerosol testing 

have been reviewed by Gao et al. [2007]. 

Little scientific data exists, but some systems 

level test methods are available. ISO standard 

method 13982 [ISO 2004a] and EN standard method 943 [CEN 2002] specify the 

use of sodium chloride (NaCl) with a mass 

median aerodynamic diameter (MMAD) of 

0.6 μm to determine the barrier efficiency of 

protective clothing against aerosols of dry, 

fine dusts. The standard method issued by 

National Fire Protection Association [2007] 

is a method that is not dependent on filtration-based approaches. Penetration of fluorophore-impregnated silica particles with a 

MMAD of 2.5 μm and a geometric standard 

deviation of 2.6 are qualitatively visualized 

by black light that causes the fluorescent 

glow of the challenge aerosol particles. Note 

that the polydisperse particle challenges 

used in these methods include a large number of nanoscale particles when measured 

by count rather than by mass. 

Particle penetration test methods can be further categorized into those that are analogous 

to the process used in respirator filter testing 

and those that are not dependent on filtration-based approaches. Test methods that involve measuring aerosol concentrations using a sampling flow rate do not mimic in-situ 

situations because the skin does not “breathe.” 

Standardized methodology is needed that is 

not dependent on filtration-based approaches 

for examining the overall barrier-effectiveness 

of the full protective clothing ensemble for different materials to particulate hazards. In this 

respect, NIOSH has presented preliminary results [Wang and Gao 2007] on development 

of a magnetic passive aerosol sampler for more 

accurate determination of particle penetration 
44 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

through protective clothing. NIOSH is conducting research in this area and will communicate results as they become available. 

The bulk of the penetration data available 

on clothing has been done with filtration 

based testing. One study found that penetration levels of 30–2,000-nm-sized potassium chloride particles through an unidentified military garment ranged from about 

20%–60%, with the maximum penetration 

occurring in the range of 100–400 nm [Hofacre 2006]. Another group of researchers 

studied the barrier efficiency of 10 unidentified fabric samples (woven, non-woven, 

and laminated fabrics) using 477-nm-sized 

latex spheres at a flow rate of 1.8 cm/second 

[Shavlev et al. 2000]. Particle penetration 

measurements ranged from 0%–54%, with 

three of the fabrics exhibiting a measurable 

pressure drop and having penetration levels less than 1%. In general, these findings 

suggest that increased external air pressure 

(e.g., from wind) results in increased particle 

penetrations. Thus, only impermeable barrier materials are likely to provide complete 

barrier protection against aerosol penetration. Body movement (i.e., bellows effect) 

can also impact penetration [Bergman et al. 

1989]. NIOSH will theoretically and empirically investigate wind-driven nanoparticle 

penetration through protective clothing 

in an attempt to obtain a predictive model 

based upon single-fiber theory. Results will 

be communicated as they become available.

Another widely used test method incorporates testing with nanoscale particles in 

solution, and therefore also provides some 

indication of the effectiveness of protective 

clothing to nanoparticles. ASTM standard 

F1671–03 [ASTM 2003] and ISO standard 

16604 [ISO 2004b] specify the use of a 27-nm 

bacteriophage to evaluate the resistance of 

materials used in protective clothing from 

the penetration of blood-borne pathogens. 

One study [Edlich et al. 1999] evaluated the 

integrity of powder-free examination gloves 

and found that no bacteriophage penetration was detected for powder-free nitrile 

gloves, powder-free latex gloves, nor polyvinyl chloride synthetic gloves. 

Based upon the uncertainty of the health effects of dermal exposure to nanoparticles, it 

is prudent to consider using protective equipment, clothing, and gloves to minimize dermal exposure, with particular attention given 

to preventing exposure of nanomaterials to 

abraded or lacerated skin. Until scientific data 

exist specific to the performance of protective clothing and gloves against nanomaterials, current industrial hygiene best practices 

should be followed. 

8.3.5 Respirators 

The use of respirators is often required when 

engineering and administrative controls do 

not adequately keep worker exposures to 

an airborne contaminant below a regulatory limit or an internal control target. Currently, there are no specific exposure limits 

in the United States for airborne exposures 

to engineered nanomaterials although occupational exposure limits and guidelines 

exist for airborne particles of similar chemical composition regardless of particle size. 

Current scientific evidence indicates that 

nanoparticles may be more biologically reactive than larger particles of similar chemical composition and thus may pose a greater 

health risk when inhaled. In determining the 

need for respirators, it would therefore be 

prudent to consider current exposure limits or guidelines (e.g., OSHA PELs, NIOSH 

RELs, ACGIH TLVs) for larger particles of 

similar composition, existing toxicologic 
Approaches to Safe Nanotechnology 45

8 Guidelines for Working with Engineered Nanomaterials

data on the specific nanoparticle, and the 

likelihood of worker exposure (e.g., airborne 

concentration, time exposed, job task). 

The decision to institute respiratory protection should be based on a combination 

of professional judgment and the results 

of the hazard assessment and risk management practices recommended in this document. The effectiveness of administrative, 

work-practice, and engineering controls 

can be evaluated using the measurement 

techniques described in Chapter 7 Exposure Assessments and Characterization. If 

worker exposure to airborne nanomaterials 

remains a concern after instituting control 

measures, the use of respirators can provide 

further worker protection. Several classes of 

respirators exist that can provide different 

levels of protection when properly fit tested 

on the worker. Table 8–2 lists various types 

of particulate respirators that can be used; 

information is also provided on the level 

of exposure reduction that can be expected 

along with the advantages and disadvantages 

of each respirator type. To assist respirator 

users, NIOSH has published the document 

NIOSH Respirator Selection Logic (RSL) that 

provides a process that respirator program 

administrators can use to select appropriate 

respirators [NIOSH 2004] (see www.cdc.

gov/niosh/docs/2005-100/default.html). As 

new toxicity data for individual nanomaterials become available, NIOSH will review 

the data and make recommendations for 

respirator protection. 

When respirators are required for use in 

the workplace, the Occupational Safety and 

Health Administration (OSHA) respiratory 

protection standard [29 CFR 1910.134] requires that a respiratory program be established that includes the following program 

elements: (1) an evaluation of the worker’s 

ability to perform the work while wearing 

a respirator, (2) regular training of personnel, (3) periodic environmental monitoring, 

(4) respirator fit testing, and (5) respirator maintenance, inspection, cleaning, and 

storage. The standard also requires that the 

selection of respirators be made by a person 

knowledgeable about the workplace and the 

limitations associated with each type of respirator. OSHA has also issued guidelines for 

employers who choose to establish the voluntary use of respirators [29 CFR 1910.134 

Appendix D].

Table 8–2 lists the NIOSH assigned protection factors (APF) for various classes of 

respirators. The APF is defined as the minimum anticipated protection provided by a 

properly functioning respirator or class of 

respirators to a given percentage of properly fitted and trained users. The APF values 

developed by NIOSH are based in part on 

laboratory studies and take into consideration a variety of factors including the inward leakage caused by penetration through 

the filter and leakage around the respirator 

face seal. The relative contributions of these 

two sources of inward leakage are critical 

because for many applications the predominant source of exposure to the respirator 

wearer results from leakage around the face 

seal (due to a poor fit) and not penetration 

directly through the filter media. In 2006, 

OSHA published updated APF values that 

supersede the NIOSH APF values [Federal 

Register 2006]. In general there is good 

agreement between the NIOSH and OSHA 

APF values, but management should consult the OSHA standard prior to using the 

values in Table 8–2 directly. 

NIOSH is not aware of any data specific 

to respirator face seal leakage of nanoparticles. However, numerous studies have 
46 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

been conducted on larger particles and on 

gases/vapors with one total inward leakage 

(TIL) study that used nanoparticles. For example, work done by researchers at the U.S. 

Army RDECOM on a head-form showed 

that mask leakage (i.e., simulated respirator fit factor) measured using submicron 

aerosol challenges (0.72 μm polystyrene 

latex spheres) was representative of vapor 

challenges such as sulfur hexafluoride (SF6

) 

and isoamyl acetate (IAA) [Gardner et al. 

2004]. Other studies using particles larger 

than 100 nm have shown that face seal leakage can be affected by particle size, however, the impact of this is still the subject of 

some debate. A recently completed laboratory study to measure TIL protection factors of four NIOSH certified N95 filtering 

facepiece respirator models donned by human test subjects exposed to 40–1,300 nm 

particles found that the minimal protection 

factors were observed for particles between 

80–200 nm [Lee 2008]. The geometric mean 

of the protection factors for all four models 

across all particle sizes tested was 21.5; but 

wide model-to-model variation was observed. NIOSH is conducting a laboratory 

study to determine whether nanoparticle 

face seal leakage is consistent with the leakage observed for larger particles and gases/

vapors. Results will be communicated as 

they become available. 

NIOSH certifies respirators in accordance 

with 42 CFR Part 84. As noted earlier, the 

NIOSH RSL contains a process for selecting respirators for protection against particular hazards. The two respirator classes 

(air purifying respirators and powered air 

purifying respirators) most commonly used 

for protection against particulates use filter 

media to collect/trap particles before they 

reach the user’s breathing zone. Among the 

various test methods and criteria NIOSH 

uses as part of the certification process, 

respirator filter performance testing is the 

one most affected by the particle size. Since 

respirator users are exposed to a variety of 

hazards in different scenarios, respirator 

certification filtration testing was designed 

to use worst-case test conditions (e.g., different particle sizes and flow rates), so that 

filter performance in the workplace would 

not be worse. The NIOSH certification test 

for N-designated respirators uses a polydisperse distribution of NaCl particles with a 

count median diameter (CMD) of 0.075 

+/-0.020 μm and a geometric standard deviation (GSD) of less than 1.86 [NIOSH 

2005a]. NIOSH tests R- and P-designated 

respirators using a polydispersal of dioctyl 

phthalate (DOP) particles with a CMD of 

0.185 +/-0.020 μm and a GSD of less than 

1.60 [NIOSH 2005b]. For the lognormal 

distribution of NaCl aerosols used in the 

N series certification test, a broad range of 

particle sizes (e.g., 95% of the particles lie 

in the range of 22–259 nm) with a MMD of 

about 240 nm is used to determine whether 

the respirator filter performance is at least 

95, 99, or 99.97% efficient. Most of the particles penetrating through the filter are measured simultaneously using a forward light 

scattering photometer. However, as noted in 

a recent review, the instrumentation used in 

the NIOSH certification test is not capable 

of measuring the light scattering of all particles less than 100 nm [Eninger et al. 2008a].

Particles larger than 0.3 μm are collected 

most efficiently by impaction, interception, 

and gravitational settling, while particles 

smaller than 0.3 μm are collected most efficiently by diffusion or electrostatic attraction [Hinds 1999]. In the development of 

the test method used for respirator certification, penetration by particles with an approximate 0.3 μm diameter was considered 
Approaches to Safe Nanotechnology 47

8 Guidelines for Working with Engineered Nanomaterials

to be the worst case because these particles 

were considered to be in the range of the 

most penetrating particle size [Stevens and 

Moyer 1989; TSI 2005; NIOSH 1996]. However, in practice, the most penetrating particle size range (MPPS) for a given respirator 

can vary based on the type of filter media 

employed and the condition of the respirator. For example, the most penetrating particle size for N95 air purifying respirators 

containing electrostatically charged filter 

media can range from 50–100 nm [Martin 

and Moyer 2000; Richardson et al. 2005] to 

30–70 nm [Balazy et al. 2006; Eninger et al. 

2008b]. These test results were recently confirmed by NIOSH [Rengasamy et al. 2007] 

in which five different models of respirators 

with N95 filters were challenged with 11 different monodisperse NaCl particles ranging 

in size from 20–400 nm. The monodisperse 

aerosol penetrations showed that the MPPS 

was in the 40-nm range for all respirator 

models tested. Under the aggressive laboratory test conditions employed in the study, 

mean penetration levels for 40-nm particles 

ranged from 1.4%–5.2%, which suggested 

that the respirators would be effective at 

capturing nanoparticles in the workplace. 

The NIOSH study also investigated whether 

there was a correlation between filtration 

performance using the existing NIOSH 

certification protocol for N series air purifying respirators and the filtration performance against monodisperse particles at the 

MPPS. A good correlation (r = 0.95) was 

found (e.g., respirators that performed better using the NIOSH certification test also 

had higher filter efficiencies against monodisperse 40-nm nanoparticles), which is not 

surprising given that changes in filtration 

performance follow a consistent trend as a 

function of particle size.

According to single fiber filtration theory, 

below the most penetrating particle size, 

filtration efficiency will increase as particle 

size decreases. This trend will continue until 

the particles are so small that they behave 

like vapor molecules. As particles approach 

molecular size, they may be subject to thermal rebound effects, in which particles literally bounce through a filter. As a result, 

particle penetration will increase. The exact 

size at which thermal rebound will occur 

is unclear. However, a study by Heim et al. 

[2005] found that there was no discernable 

deviation from classical single-fiber theory 

for particles as small as 2.5-nm diameter. 

Subsequently, a NIOSH-funded contract 

with the University of Minnesota [Kim et 

al. 2007; Pui et al. 2006] and another study 

[Kim et al. 2006] showed that the penetration of nanoparticles through fibrous filter 

media decreased down to 2.5 nm as expected by the single fiber filtration theory. Thermal rebound phenomena were observed for 

nanoparticles below 2 nm diameter [Kim 

et al. 2006]. Recent studies provide additional data on nanoparticle penetration 

for NIOSH certified N95 and P100 filtering face-piece respirators [Rengasamy et al. 

2008a], NIOSH certified N95 and European Certified FFP1 respirators [Huang et al. 

2007], and FFP3 filter media [Golanski et al. 

2008] using particles greater than 4 nm. 

Based on these preliminary findings, 

NIOSH-certified respirators should provide 

the expected levels of protection if properly 

selected and fit tested as part of a complete 

respiratory protection program. However, 

as noted elsewhere [Rengsamy et al. 2007], 

in the unlikely event that the workplace exposure consists of a large percentage of particles in the most penetrating particle size 

range, management should take this information into account during the respirator 
48 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

selection process, perhaps by choosing a respirator with higher levels of filtration performance (e.g., changing from an N95 to a 

P100, even though the APF will remain the 

same) as suggested by OSHA [Federal Register 2006] or by selecting a respirator with 

a higher APF (e.g., full face-piece respirator 

or powered air purifying respirator). Dust 

masks, commercially available at hardware/

home improvement stores, are often confused with NIOSH approved N95 filtering 

facepiece respirators because of their similar appearance. However, dust masks are not 

respirators and are not approved by NIOSH 

for respiratory protection. One study found 

that penetration of 40-nm NaCl nanoparticles range from 4.3%–81.6% for the seven 

dust mask models studied [Rengasamy et al. 

2008b]. Dust masks should not be used in 

place of NIOSH-approved respirators for 

protection against nanoparticles. 

NIOSH is continuing to study the protection afforded by NIOSH-certified respirators against emerging hazards such 

as engineered nanomaterials—including 

workplace-protection-factor studies—to ensure they provide expected levels of protection. NIOSH is also committed to updating 

42 CFR Part 84—the regulatory language 

that provides NIOSH the authority to certify the performance of respirators in the 

United States—using a modular approach 

to rulemaking. Recently, NIOSH proposed 

the use of a TIL test as part of the respirator certification process for half-mask air 

purifying particulate respirators, including those having elastomeric and filtering 

face-pieces. The test protocol used to obtain 

benchmark TIL data for 101 half-face piece 

respirator models used 40–60 nm size ambient nanoparticles [NIOSH 2007]. Once 

implemented as part of the NIOSH certification process, the TIL tests should result in 

half-mask respirators with increased fitting 

performance. Future rulemaking activities 

may also include revisions to the filtration 

test to reflect changes in filtration performance resulting from use of new technologies (e.g., electret filter media). Results will 

be communicated as they become available.

8.3.6 Cleanup and disposal of 

nanomaterials

No specific guidance is currently available on 

cleaning up nanomaterial spills or contamination on surfaces; however, recommendations 

developed in the pharmaceutical industry for 

the handling and cleanup of pharmaceutical 

compounds might be applicable to worksites 

where engineered nanomaterials are manufactured or used [Wood 2001]. Until relevant 

information is available, it would be prudent 

to base strategies for dealing with spills and 

contaminated surfaces on current good practices, together with available information on 

exposure risks including the relative importance of different exposure routes. Standard 

approaches for cleaning powder spills include using HEPA-filtered vacuum cleaners, 

or wiping up the powder using damp cloths 

or wetting the powder prior to dry wiping. 

Liquid spills are typically cleaned by applying 

absorbent materials/liquid traps. 

Damp cleaning methods with soaps or 

cleaning oils are preferred. Cleaning cloths 

should be properly disposed. Use of commercially available wet or electrostatic microfiber cleaning cloths may also be effective 

in removing particles from surfaces with 

minimal dispersion into the air. Drying and 

reusing contaminated cloths can result in 

re-dispersion of particles.

Energetic cleaning methods such as dry 

sweeping or the using of compressed air 
Approaches to Safe Nanotechnology 49

8 Guidelines for Working with Engineered Nanomaterials

should be avoided or only used with precautions that assure that particles suspended 

by the cleaning action are trapped by HEPA 

filters. If vacuum cleaning is employed, care 

should be taken that HEPA filters are installed 

properly and bags and filters changed according to manufacturer’s recommendations. 

While vacuum cleaning may prove to be effective for many applications, the following 

issues should be considered. Forces of attraction may make it difficult to entrain particles off surfaces with a vacuum cleaner. The 

electrostatic charge on particles will cause 

them to be attracted to oppositely charged 

surfaces and repelled by similarly charged 

surfaces. A similarly charged vacuum brush 

or tool may repel particles, making it difficult to capture the aerosol or even causing 

it to be further dispersed. Vigorous scrubbing with a vacuum brush or tool or even 

the friction from high flow rates of material 

or air on the vacuum hose can generate a 

charge. The vacuum cleaners recommended 

for cleaning copier and printer toners have 

electrostatic-charge-neutralization features 

to address these issues. 

When developing procedures for cleaning 

up nanomaterial spills or contaminated 

surfaces, consideration should be given to 

the potential for exposure during cleanup. 

Inhalation exposure and dermal exposure 

will likely present the greatest risks. Consideration will therefore need to be given to appropriate levels of personal protective equipment. Inhalation exposure in particular will 

be influenced by the likelihood of material 

reaerosolization. In this context, it is likely 

that a hierarchy of potential exposures will 

exist, with dusts presenting a greater inhalation exposure potential than liquids, and 

liquids in turn presenting a greater potential risk than encapsulated or immobilized 

nanomaterials and structures.

As in the case of any material spill or cleaning 

of contaminated surfaces, the handling and 

disposal of the waste material should follow 

existing federal, state, or local regulations.

Table 8–2. Air-purifying particulate respirators 

Respirator

type 

NIOSH

assigned

protection

factor Advantages Disadvantages 

Filtering facepiece 

(disposable)

10 – Lightweight

– No maintenance or cleaning 

needed

– No effect on mobility 

– Provides no eye protection

– Can add to heat burden

– Inward leakage at gaps in face 

seal

– Some do not have adjustable 

head straps

– Difficult for a user to do a seal 

check

– Level of protection varies greatly 

among models

– Communication may be difficult

(continued)
50 Approaches to Safe Nanotechnology

8 Guidelines for Working with Engineered Nanomaterials 

Table 8–2 (Continued). Air-purifying particulate respirators 

Respirator

type 

NIOSH

assigned

protection

factor Advantages Disadvantages 

Filtering facepiece 

(disposable)

(continued)

– Fit testing required to select 

proper facepiece size

– Some eyewear may interfere with 

the fit 

Elastomeric halffacepiece 10 – Low maintenance

– Reusable facepiece and 

replaceable filters and 

cartridges

– No effect on mobility 

– Provides no eye protection

– Can add to heat burden

– Inward leakage at gaps in face 

seal

– Communication may be difficult

– Fit testing required to select 

proper facepiece size

– Some eyewear may interfere with 

the fit 

Powered with loosefitting facepiece 25 – Provides eye protection

– Offers protection for 

people with beards, missing 

dentures or facial scars

– Low breathing resistance

– Flowing air creates cooling 

effect

– Face seal leakage is generally 

outward

– Fit testing is not required

– Prescription glasses can be 

worn

– Communication easier 

than with elastomeric halffacepiece or full-facepiece 

respirators

– Reusable components and 

replaceable filters 

– Added weight of battery and 

blower

– Awkward for some tasks

– Battery requires charging

– Air flow must be tested with flow 

device before use 

(continued)
Approaches to Safe Nanotechnology 51

8 Guidelines for Working with Engineered Nanomaterials

Table 8–2 (Continued). Air-purifying particulate respirators 

Respirator

type 

NIOSH

assigned

protection

factor Advantages Disadvantages 

Elastomeric fullfacepiece with 

N-100, R-100, or 

P-100 filters

50 – Provides eye protection

– Low maintenance

– Reusable facepiece and 

replaceable filters and 

cartridges

– No effect on mobility

– More effective face seal than 

that of filtering facepiece or 

elastomeric half-facepiece 

respirators 

– Can add to heat burden

– Diminished field-of-vision 

compared to half-facepiece

–Inward leakage at gaps in face seal

–Fit testing required to select 

proper facepiece size

–Facepiece lens can fog without 

nose cup or lens treatment

–Spectacle kit needed for people 

who wear corrective glasses 

Powered with tightfitting half-facepiece 

or full-facepiece 

50 –Provides eye protection with 

full-facepiece

–Low breathing resistance

–Face seal leakage is generally 

outward

–Flowing air creates cooling 

effect

–Reusable components and 

replaceable filters 

–Added weight of battery and 

blower

–Awkward for some tasks

–No eye protection with halffacepiece

–Fit testing required to select 

proper facepiece size

–Battery requires charging

–Communication may be difficult

–Spectacle kit needed for people 

who wear corrective glasses with 

full face-piece respirators

–Air flow must be tested with flow 

device before use 

Approaches to Safe Nanotechnology 53

Occupational health surveillance is an essential component of an effective occupational 

safety and health program. The unique physical and chemical properties of nanomaterials, the increasing growth of nanotechnology 

in the workplace, and information suggesting 

that exposure to some engineered nanomaterials can cause adverse health effects in laboratory animals all support consideration of 

an occupational health surveillance program 

for workers potentially exposed to engineered 

nanomaterials [Schulte et al. 2008a]. Continued evaluation of toxicologic research and 

workers potentially exposed to engineered 

nanomaterials is needed to inform NIOSH 

and other groups regarding the appropriate 

components of occupational health surveillance for nanotechnology workers. 

NIOSH has developed interim guidance 

relevant to medical screening (one component of an occupational health surveillance 

program) for nanotechnology workers (see 

NIOSH Current Intelligence Bulletin: Interim Guidance on Medical Screening and 

Hazard Surveillance for Workers Potentially 

Exposed to Engineered Nanoparticles, www.

cdc.gov/niosh/review/public/115/). Medical 

screening is only part of a complete safety 

and health management program that follows the hierarchy of controls and involves 

various occupational health surveillance 

measures. Since specific medical screening of 

workers exposed to engineered nanoparticles 

has not been extensively discussed in the scientific literature, this document is intended 

to fill the knowledge gap on an interim basis. 

Increasing evidence indicates that exposure 

to some engineered nanoparticles can cause 

adverse health effects in laboratory animals, 

but no studies of workers exposed to the few 

engineered nanoparticles tested in animals 

have been published. The current body of 

evidence about the possible health risks of 

occupational exposure to engineered nanoparticles is quite small. Insufficient scientific and medical evidence now exists to recommend the specific medical screening of 

workers potentially exposed to engineered 

nanoparticles. Nonetheless, the lack of evidence on which to recommend specific 

medical screening does not preclude its consideration by employers interested in taking precautions beyond standard industrial 

hygiene measures [Schulte et al. 2008b]. If 

medical screening recommendations exist for chemical or bulk materials of which 

nanoparticles are composed, they would apply to nanoparticles as well. 

Ongoing research on the hazards of engineered nanoparticles is needed along with the 

continual reassessment of available data to 

determine whether specific medical screening 

is warranted for workers who are producing 

or using nanoparticles. In the meantime, the 

following recommendations are provided for 

the management of workplaces where employees may be exposed to engineered nanoparticles in the course of their work:

•	 Take prudent measure to control workers’ exposures to nanoparticles.

•	 Conduct hazard surveillance as the basis for implementing controls.

9 Occupational Health Surveillance
54 Approaches to Safe Nanotechnology

9 Occupational Health Surveillance

•	 Continue use of established medical 

surveillance approaches.

NIOSH will continue to examine new research findings and update its recommendations about medical screening programs 

for workers exposed to nanoparticles. Additionally, NIOSH is seeking comments on 

the strengths and weaknesses of exposure 

registries for workers potentially exposed to 

engineered nanoparticles. 
Approaches to Safe Nanotechnology 55

NIOSH has developed a strategic plan for 

research on several occupational safety and 

health aspects of nanotechnology. The plan 

is available at www.cdc.gov/niosh/topics/

nanotech/strat_plan.html. NIOSH has focused its research efforts in the following 

10 critical topic areas to guide in addressing 

knowledge gaps, developing strategies, and 

providing recommendations. 

1. Exposure Assessment

— Determine key factors that influence 

the production, dispersion, accumulation, and re-entry of nanomaterials 

into the workplace.

— Determine how possible exposures to nanomaterials differ by 

work process.

— Assess possible exposure when 

nanomaterials are inhaled or settle on the skin.

2. Toxicity and Internal Dose

— Investigate and determine the 

physical and chemical properties 

(e.g., size, shape, solubility, surface area, oxidant generation potential, surface functionalization, 

surface charge, chemical composition) that influence the potential toxicity of nanomaterials.

— Determine the deposition pattern 

of nanoparticles in the lung and 

their translocation to the interstitium and to extrapulmonary organs.

— Evaluate short- and long-term effects of pulmonary exposure to 

nanomaterials in various organ 

systems and tissues (e.g., lungs, 

brain, cardiovascular).

— Determine if intratracheal instillation or pharyngeal aspiration 

can mimic the biological response 

to inhalation exposure to nanomaterials.

— Determine the dermal effects of 

topical exposure to nano-objects, 

whether these nano-objects can 

penetrate into the skin, and whether 

they can cause immune alterations.

— Determine the genotoxic and carcinogenic potential of nano-objects.

— Determine biological mechanisms 

for potential toxic effects.

— Determine whether in vitro screening tests can be predictive on in 

vivo response.

— Create and integrate models to 

help assess potential hazards.

— Determine whether a measure 

other than mass is more appropriate for determining toxicity.

3. Epidemiology and Surveillance

— Evaluate existing exposure and 

health data for workers employed 

in workplaces where nanomaterials are produced and used, 

with emphasis on improving our 

understanding of the value and 

10 Research Needs
56 Approaches to Safe Nanotechnology

10 Research Needs 

utility of establishing exposure 

registries for workers potentially 

exposed to engineered nanomaterials. 

— Assess the feasibility of industrywide exposure and epidemiological studies of workers exposed to 

engineered nanomaterials, with 

emphasis on workers potentially 

exposed to engineered carbonaceous nanomaterials.

— Integrate nanotechnology safety 

and health issues into existing hazard surveillance mechanisms and 

continue reassessing guidance related to occupational health surveillance for workers potentially 

exposed to engineered nanomaterials.

— Build on existing public health 

geographical information systems 

and infrastructure to enable effective and economic development 

of methods for sharing nanotechnology safety and health data. 

4. Risk Assessment 

— Determine how existing exposure-response data for fine and 

ultrafine particles (human or animal) may be used to identify the 

potential hazards and estimate 

the potential risks of occupational 

exposure to nanomaterials.

— Develop a framework for assessing 

the potential hazards and risks of 

occupational exposure to nanomaterials, using new toxicologic 

data on engineered nanomaterials and standard risk assessment 

models and methods.

5. Measurement Methods

— Evaluate methods used to measure 

the mass of respirable particles in 

the air and determine whether 

this measurement can be used to 

measure nanomaterials.

— Develop and field-test practical 

methods to accurately measure 

airborne nanomaterials in the 

workplace. 

— Develop, test, and evaluate systems 

to compare and validate sampling.

6. Engineering Controls and Personal 

Protective Equipment 

— Evaluate the effectiveness of engineering controls in reducing 

occupational exposures to nanoaerosols and developing new controls when needed.

— Evaluate the suitability of controlbanding techniques when additional information is needed and 

evaluate the effectiveness of alternative materials.

— Evaluate and improve current personal protective equipment.

— Develop recommendations (e.g., 

use of respiratory protection) to 

prevent or limit occupational exposures to nanomaterials.

7. Fire and Explosion Safety

— Identify physical and chemical 

properties that contribute to dustiness, combustibility, flammability, 

and conductivity of nanomaterials.
Approaches to Safe Nanotechnology 57

10 Research Needs

— Recommend alternative work practices to eliminate or reduce work 

place exposures to nanomaterials.

8. Recommendations and Guidance

— Use the best available science to 

make interim recommendations for 

workplace safety and health practices during the production, use, 

and handling of nanomaterials.

— Evaluate and update mass-based 

occupational exposure limits for 

airborne particles to ensure good, 

continuing precautionary practices.

9. Communication and Information

— Establish partnerships to allow 

for identification and sharing of 

research needs, approaches, and 

results.

— Develop and disseminate training and education materials to 

workers, employers, and occupational safety and health professionals.

10. Applications

— Identify uses of nanotechnology for 

application in occupational safety 

and health.

— Evaluate and disseminate effective 

applications to workers, employers, and occupational safety and 

health professionals.

Approaches to Safe Nanotechnology 59

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Approaches to Safe Nanotechnology 71

1.0 Introduction

This appendix describes a technique that can 

be used by industrial hygienists for conducting initial workplace assessments for possible 

nanoparticle emissions. It allows a semiquantitative evaluation of processes and 

tasks in the workplace where releases of engineered nanoparticles may occur. NIOSH uses 

several sampling approaches simultaneously 

with the goal of obtaining key physicochemical particle metrics: number concentration, 

qualitative size, shape, degree of agglomeration, and mass concentration of elemental 

constituents of interest. 

2.0 Scope

Employers, workers, and researchers engaged in the production and use of engineered nanomaterials have expressed an 

interest in determining whether these nanomaterials are hazardous and if the potential 

for worker exposure exists. NIOSH has an 

active toxicology program to assess the potential hazards of engineered nanoparticles. 

Unfortunately these studies require long 

time periods and fall behind the pace of production and use of these nanomaterials. To 

assist in answering the latter of these questions, NIOSH established a nanotechnology field research team tasked with visiting 

facilities and collecting information about 

the potential for release of nanomaterials 

and worker exposure at those facilities. The 

initial challenges that the field research team 

encountered were: 1) determining which 

exposure metric (e.g., mass, particle number concentration, particle surface area) for 

engineered nanoparticles would provide a 

consistent body of knowledge to align with 

the toxicological results observed in experimental animal studies; and 2) selecting a 

sampling method based on metrics that 

were practical and would provide reproducible results. Engineered nanomaterials can 

be measured in the workplace using a variety of instrumentation including: condensation particle counter (CPC); optical particle 

counter (OPC); scanning mobility particle 

sizer (SMPS); electric low pressure impactor (ELPI); aerosol diffusion charger; and 

tapered element oscillating microbalance 

(TOEM), which vary in complexity and field 

portability. Unfortunately, relatively few of 

the above instruments are readily applicable to routine exposure monitoring due to 

non-specificity, lack of portability, difficulty 

of use, and high cost. NIOSH researchers 

have developed and used a field assessment 

strategy for determining exposures to engineered nanoparticles that could be adopted 

by other health and safety professionals in 

the evaluation of occupational exposures 

[Methner, et. al. 2007; Methner, 2008]. 

Since there are currently no exposure limits specific to engineered nanomaterials, 

this technique is used to determine whether 

Nanoparticle Emission Assessment Technique for Identification 

of Sources and Releases of Engineered Nanomaterials

Appendix
72 Approaches to Safe Nanotechnology

Appendix 

airborne releases of engineered nanomaterials occur. This assessment, which compares 

particle number concentrations and relative 

particle size at the potential emission source 

to background particle number concentrations and particle size, provides a semiquantitative means for determining the effectiveness of existing control measures in 

reducing engineered nanoparticle exposures.

This procedure utilizes portable direct-reading instrumentation supplemented by filterbased air samples (source-specific and personal breathing zone [PBZ]). The use of filter 

samples is crucial for particle identification 

because direct-reading instruments used for 

determining particle number concentrations 

are incapable of identifying the composition 

of the particles. 

3.0 Summary of the On-Site 

Initial Assessment

The initial assessment uses a combination of 

direct-reading, handheld instruments (CPC 

and OPC) and filter-based sampling (e.g. 

37-mm diameter filter cassettes) for subsequent chemical and microscopic analyses 

(Figure 1). This semi-quantitative approach 

was first described by Maynard et al. [2004] 

and NIOSH has adopted a similar approach. 

The technique includes determining particle 

number concentration using direct-reading, handheld particle counters at potential 

emission sources and comparing those data 

to background particle number concentrations. If elevated concentrations of suspected nanoparticles are detected at potential 

emission sources, relative to the background 

particle number concentrations, then a pair 

of filter-based, source-specific air samples 

are collected with one sample analyzed by 

transmission electron microscopy (TEM) 

or scanning electron microscopy (SEM) for 

particle identification and characterization, 

and the other used for determining the elemental mass concentration (Figure 2). A 

second pair of filter-based air samples may 

also be collected in the personal breathing 

zone of workers. Breathing zone samples are 

analyzed in the same manner as the area air 

samples (i.e., by TEM and elemental mass).

4.0 Air Sampling 

Instrumentation and Filter 

Media Used in the Initial 

Assessment 

The following instrumentation is used by 

NIOSH; however, use does not constitute 

endorsement. 

4.1 TSI model 3007 (or model 8525) (TSI 

Inc, Shoreview, MN), handheld condensation particle counter (CPC), 

which uses isopropanol to condense 

on particles so they can be counted

The TSI units provide a non-specific measure of the total number 

of particles independent of chemical identity per cubic centimeter of 

air (P/cm3

). The measureable range 

is between 10–1,000 nm for model 

3007, or between 20–1,000 nm for 

model 8525. The range of detection for these instruments is reported by the manufacturer to be 

0–100,000 P/cm3.

4.2 ART Instruments Hand Held Particle 

Counter (HHPC-6, ART Instruments, 

Grants Pass, Oregon), which operates 

on optical counting principles using 

laser light scattering.

The HHPC-6 optical particle counter (OPC) can measure the total 

number of particles per liter (P/L) 
Approaches to Safe Nanotechnology 73

Appendix

of air independent of chemical identity within six specific size ranges. 

The OPC used by the NIOSH field 

research team provides particle 

counts in the following size cutpoints: 300 nm; 500 nm; 1,000 nm; 

3,000 nm; 5,000 nm; and 10,000 nm. 

The range of detection for this instrument is reported by the manufacturer 

to be 0−70,000 P/L. Different manufacturers’ OPCs may have slightly different particle size ranges and could 

be substituted.

4.3 Appropriate air sampling filter media 

(e.g. mixed cellulose ester, quartz fiber filter) are selected depending on 

nanoparticle type and desired analytical information (e.g., determination 

of particle morphology using TEM 

or SEM, elemental analysis for metals, elemental analysis for carbon) 

4.4 Air sampling pumps capable of sampling at high flow rates (e.g., 7 liters 

per minute or other flow rate depending upon the duration of the task and 

the appropriate NIOSH method, if a 

method is available)

4.5 Sampling pump flow calibrator

4.6 If desired, personal cascade impactor 

or respirable cyclone (see 5.3.3)

4.7 If desired, cassette conductive cowl 

(see 5.3.3)

4.8 Optional research-grade particle 

analyzers for expanded surveys (see 

5.6.1)

4.9 Optional surface sampling supplies such as substrate (e.g., Ghost 

WipesTM), disposable 10 cm × 10 

cm templates, sterile containers, and 

nitrile gloves for handling media (see 

5.6.2)

5.0 Evaluation of Potential 

Releases of Engineered 

Nanomaterials

5.1 Identify Potential Sources of 

Emissions

The overall purpose of this step is to 

develop a list of target areas and tasks 

that will be evaluated with the particle analyzers. 

The initial assessment involves identifying the potential sources of engineered nanomaterial emissions by 

reviewing the type of process, process 

flow, material inputs and discharges, 

tasks, and work practices. When 

available, literature (e.g., MSDS, records of feedstock materials) is reviewed to gain an understanding of 

the engineered nanomaterials being 

produced or used, including their 

physicochemical properties such as 

size, shape, solubility, and reactivity. 

Once the potential sources of emissions have been identified from the 

process review, the industrial hygienist (or other qualified person):

•	 Conducts an observational walkthrough survey of the production area and processes to locate 

potential sources of emissions.

•	 Determines the frequency and 

duration of each operation and 

the type of equipment used for 

handling and containment of 

the material.
74 Approaches to Safe Nanotechnology

Appendix 

•	 Determines the presence/absence 

of general and local exhaust ventilation and other engineering 

controls. (This initial assessment includes identifying points 

of potential system failure that 

could result in emission from 

the containment/control system 

[e.g., hole in duct, deteriorated 

sealing gasket]).

•	 Determines the process points 

where containment is deliberately breached (e.g., opening 

system for product retrieval or 

for cleaning).

5.2 Conduct Particle Concentration 

Sampling

5.2.1 Background measurements

Determining the contribution of 

background particle concentrations 

on measurements made for the particles of interest (e.g., engineered nanoparticles) is an important evaluation 

of assessing the possible airborne release of engineered nanoparticles.

Ideally, during the initial assessment, 

the industrial hygienist (or other qualified person), will determine the average airborne particle concentration at 

various processes and adjacent work 

areas with the CPC and OPC before 

the processing or handling of nanomaterials begins. If the background 

particle concentrations are high (values are relative and will vary with processes and facilities), an assessment 

is made as to whether there may be a 

source of incidental nanoparticles in 

the area. Incidental nanoparticles may 

be generated from a variety of sources, 

including vacuum pumps, natural gas 

heating units, gasoline/propane/diesel powered fork lift trucks, or other 

combustion activities such as welding, 

soldering, or heat-sealing. The CPC 

and OPC can be used to check these 

sources for incidental nanoparticle 

releases. Outdoor or re-circulated air 

supply from the building ventilation 

system should also be considered as a 

possible source of nanoparticles [Peters et al. 2006]. 

Measurements of background particle concentrations are repeated after 

the active processing, manufacturing, 

or handling of the nanomaterial has 

ended. An average background concentration is then computed and subtracted from the measurements made 

during processing, manufacturing, or 

the handling of engineered nanomaterials. This approach is acceptable 

only if background particle counts 

remain relatively stable throughout 

the measurement period and particle 

emissions from the process under investigation are sufficiently elevated 

above background. For other situations, correcting for particle background concentrations becomes 

more complex requiring additional 

sampling over an extended time period to determine the source(s) and 

magnitude of background particle 

concentrations. This type of evaluation is generally outside the scope of 

the initial assessment described here.

5.2.2 Area sampling

Once initial background particle concentrations have been determined, 

measurements of airborne particle 

concentrations and size ranges are 
Approaches to Safe Nanotechnology 75

Appendix

made with the CPC and OPC simultaneously at locations near the suspected or likely emission source (e.g., 

opening a reactor, handling product, 

potential leak points in the ventilation system). Airborne particle concentrations are determined before, 

during, and after each task or operation to identify those factors (e.g., 

controls, worker interaction, work 

practices) that may affect airborne 

particle concentrations. This information is used to identify processes, 

locations, and personnel for filterbased air sampling (5.3).

5.3 Conduct Filter-based Area and 

Personal Air Sampling

5.3.1 Area air sampling

A pair of filter-based, air samples are 

collected at process/task locations 

and/or workers engaged in process 

operations where suspected engineered nanomaterial emissions may 

occur, based on air sampling results 

using the CPC and OPC. 

Filter-based area air samples provide 

more specific information on the 

engineered nanomaterial of interest (e.g., size, shape, mass). The pair 

of air samples includes one sample 

analyzed for elemental mass and one 

sample analyzed by electron microscopy. For example, one sample might 

be collected for metals determination 

(e.g., NIOSH Method 7300, 7303) 

or elemental carbon (e.g., NIOSH 

Method 5040) depending on the 

composition of the engineered nanomaterial. The other sample would be 

collected for particle characterization 

(e.g., size, shape, dimension, degree 

of agglomeration) by TEM or SEM 

using the measurement techniques 

specified in NIOSH Methods 7402, 

7404, or other equivalent methods 

[NIOSH 1994]. 

The source-specific air samples are 

collected as close as possible to the 

suspected emission source but outside of any existing containment, to 

increase the probability of detecting 

any possible release of engineered 

nanomaterials. Sampling duration 

generally matches the length of time 

in which the potential exposure to the 

engineered nanomaterial exists at the 

task or specific process. In cases where 

the duration of the tasks associated 

with the potential airborne release 

of nanomaterials is short (e.g., minutes), a relatively high air sampling 

flow rate may be required (approximately 7 liters per minute) to ensure 

adequate particle loading on the filter 

media. If specific information is desired on the worker’s potential exposure to the engineered nanomaterial 

then PBZ samples should be collected using the two- sample filter-based 

sampling strategy described above.

If the particle number concentrations 

(using CPC or OPC) are substantially 

high, then shorter sampling times for 

the TEM or SEM sample may be necessary to avoid overloading the filter 

and interfering with particle characterization. The specific sampling time 

should be based on direct-reading 

instrument results and professional 

judgment of the industrial hygienist. In general, filter samples are collected for the duration of a given 

task, normally 15–30 minutes. If the 
76 Approaches to Safe Nanotechnology

Appendix 

direct-reading instruments indicate a 

high particle number concentration 

the sampling time can be shortened 

to 5–10 minutes, or both a short- and 

long-duration sample may be collected to ensure an adequate sample 

for electron microscopy analysis. See 

Table 1 for additional sampling time 

guidance. However, the sampling 

times in Table 1 were based on collection of asbestos fibers by NIOSH 

Method 7402 and may not be applicable for much smaller engineered 

nanoparticles. See Figures 3–5 for example TEM micrographs.

A minimum of 2 background filter 

samples are collected distant from 

the potential sources of engineered 

nanoparticle exposure to serve as an 

indicator of ambient particle identification and concentration.

5.3.2 Personal air samples

When possible, personal breathing 

zone (PBZ) air samples are collected 

on workers likely to be exposed to engineered nanomaterials (e.g., engaged 

in active handling of nanomaterials 

or operating equipment previously 

identified as emitting nanoparticles). 

If measurements obtained with the 

CPC and OPC indicate that nanoparticles are being emitted at a specific process where a worker is located, 

then the collection of PBZ samples 

may be warranted.

PBZ samples are analyzed in the 

same manner as the area air samples 

(i.e., by TEM and elemental mass). It 

may be necessary to collect samples 

at a relatively high flow rate (e.g., 7 

liters per minute) if the duration of 

the task and the resulting potential 

exposure is short. 

5.3.3 Optional sample collection

In the event that measurements 

made by the OPC indicate a large 

fraction (over 50%) of particles exceeding 1,000 nm in size, the use of 

a personal cascade impactor or respirable cyclone sampler in tandem with 

a filter-based air sampling cassette 

may be required for both the mass 

and TEM/SEM analyses to eliminate 

large particles that may interfere with 

analysis and be of limited interest. 

The use of an impactor or cyclone 

will require using a flow rate appropriate for the particle cut size and is 

usually in the range of 1.7–2.5 liters 

per minute. Open-face, and impactor 

or cyclone samples may be collected 

side by side to allow a more thorough 

interpretation of analytical results. 

Additionally, if it is anticipated that 

the nanoparticles of interest will have 

a tendency to be electrostatically attracted to the sides of the plastic air 

sampling cassette, a conductive cowl 

may be necessary to eliminate particle loss and subsequent underestimation of the airborne nanoparticle 

concentration. The use of a personal 

cascade impactor, respirable cyclone, 

or conductive cowl is made at the discretion of the industrial hygienist (or 

other qualified person). 

If the facility is manufacturing or using TiO2

, then the sampling should include the sampling recommendations 

found in the NIOSH Draft Document: 

Evaluation of Health Hazard and Recommendations for Occupational Exposure 

to Titanium Dioxide (www.cdc.gov/
Approaches to Safe Nanotechnology 77

Appendix

niosh/review/public/TiO2/default.

html),which recommends collecting 

a mass-based airborne measurement 

using NIOSH Method 0600. 

5.4 Quality Assurance and Quality 

Control

To ensure valid emission measurements, the following quality assurance 

and control steps should be taken: 

•	 Use factory calibrated directreading particle analyzers

•	 Perform daily zero-checks on all 

particle counters before each use

•	 Calibrate pumps before and after each sampling day

•	 Submit for analysis any process, 

background, and bulk material samples along with field 

and media blanks to a laboratory accredited by the American 

Industrial Hygiene Association 

(AIHA)

5.5 Data Interpretation

Since the size of airborne engineered 

nanoparticles and the degree of agglomeration may be unknown at 

the time of sample collection, the 

use of direct-reading, particle sizing/

counting instruments may provide a 

semi-quantitative indication of the 

magnitude of potential emissions, 

provided background particle number subtraction can be successfully 

accomplished. The particle number 

concentration measurements taken 

with the CPC and OPC will provide a 

measurement of particles larger than 

the ASTM definition of nanoparticles 

(1–100 nm) [ASTM 2006]. However, 

the two particle counters can be used 

simultaneously to obtain a semiquantitative size differential evaluation of the aerosol being sampled. 

The CPC provides a measure of total particles per cm3

 in the size range 

of 10–1,000 nm (or 20–1,000 nm). 

The OPC provides the total number 

of particles per liter of air within six 

specific size ranges: 300 nm; 500 nm; 

1,000 nm, 3,000 nm, 5,000 nm and 

> 10,000 nm. If necessary, the data 

from the CPC and OPC can be used 

together to determine the number 

concentration of nanoscale particles. 

For example, a high particle number 

concentration on the CPC, in combination with a high particle number concentration in the small size 

ranges (300–500 nm) on the OPC, 

may indicate the possible presence of 

nanoscale particles. Conversely, a low 

CPC particle number concentration, 

in combination with a high OPC 

particle number concentration in the 

larger size ranges (> 1,000 nm) may 

indicate the presence of larger particles and/or engineered nanoparticle 

agglomerates. These assumptions of 

nanoparticles versus larger particles 

and/or nanoparticle agglomerates 

may be verified by TEM or SEM analysis.

5.5.1 Selectivity

Selectivity is a critical issue when 

characterizing exposure using airborne particle number concentration. 

Airborne nanoparticles are present 

in many workplaces and often originate from multiple sources such as 

combustion, vehicle emissions, and 
78 Approaches to Safe Nanotechnology

Appendix 

infiltration of outside air. Particle 

counters are generally not selective to 

particle source or composition, making it difficult to differentiate between 

incidental and process-related nanoparticles using number concentration 

alone. The CPC and OPC are used to 

identify sources of nanoparticles and 

the filter-based samples are used to 

verify the size, shape, and chemical 

composition of the nanoparticles with 

the goal of differentiating between 

incidental and engineered nanoparticles.

5.5.2 Limitations

The exposure assessment technique 

does have some limitations including:

•	 Although this issue is not unique 

to particle number concentration measurements, orders of 

magnitude difference can exist 

in aerosol number concentrations, depending on the number 

and types of sources of particle 

emissions. Monitoring over several days and during different 

seasons can provide a better understanding of the variability that 

might exist in airborne particle 

number concentrations found 

in background measurements 

and in measurements made at 

sources where engineered nanomaterials are handled. 

•	 The upper dynamic range of 

the CPC is 100,000 P/cm3. A 

dilutor, consisting of a modified HEPA filter cartridge placed 

upstream of the inlet, can extend the range of the CPC when 

particle number concentrations 

are greater than 100,000 P/cm3

[Peters et al. 2006; Heitbrink et 

al. 2007; Evans et al. 2008].

•	 The analysis of air samples by 

TEM or SEM with energy dispersive X-ray spectrometry can 

provide information on the elemental composition of the 

nanomaterials. However, TEM 

and SEM analysis can be compromised if there is particle 

overload on the filter. Alternatively, if the loading is too sparse, 

an accurate assessment of particle characteristics may not be 

possible (see 5.3.1).

•	 Note that area samples are collected as closely as possible to 

the source of emission to allow 

for more accurate determination 

of a nanoparticle release and to 

identify locations most likely 

to result in worker exposure. 

Therefore, results from this 

type of sampling should not be 

interpreted as representative 

of worker exposure. However, 

samples collected in such a fashion should serve as an indicator 

of material release and the possible need for controls.

5.6 Expanded Research (In Depth 

Assessments)

5.6.1 Research instrumentation

A major obstacle in conducting more 

specific measurement of engineered 

nanomaterials in the workplace is a 

lack of field-portable instruments 

that can be easily maneuvered within 
Approaches to Safe Nanotechnology 79

Appendix

a facility or easily worn by a worker to 

provide an indication of PBZ exposure. Additionally, there is no single 

instrument capable of measuring the 

numerous potential exposure metrics 

associated with engineered nanomaterials (e.g., number concentration, 

surface area, size, shape, mass concentration) [Maynard and Aitken 2007]. 

Although the following instruments 

lack field portability and ease of use, 

they can measure many of the desirable exposure metrics and provide 

information about the particle size 

distribution. These research-grade 

particle analyzers are not usually part 

of the initial assessment but are used 

when additional knowledge about 

the nanoscale particle temporal or 

spatial exposure variation or size distribution is desired.

5.6.1.1 Particle Surface-Area Analyzers

Toxicology studies have indicated that 

surface area of nanoparticles may be 

an important exposure dose metric. 

Portable aerosol diffusion chargers 

may be used to provide estimates of 

external aerosol surface area when 

airborne particles are smaller than 

100 nm in diameter, but these may 

tend to overestimate external surface 

area when particles are larger than 

100 nm in diameter. These instruments are based on diffusion charging 

followed by detection of the charged 

aerosol using an electrometer.

The TSI AerotrakTM 9000 Nanoparticle 

Aerosol Monitor does not measure total active surface area but indicates the 

surface area of particles which may be 

deposited in the lung in units of square 

micrometers per cubic centimeter, 

corresponding to either the tracheobronchial or alveolar regions of the 

lung. The Ecochem DC 2000-CE 

measures the total particle surface 

area. These devices are currently being 

evaluated as part of the process used 

by NIOSH to conduct initial assessments. These particle surface analyzers are used as area samplers.

5.6.1.2. Scanning Mobility Particle Sizer

More specific depictions of particles 

by size (diameter) and number can 

greatly improve the ability to evaluate 

possible releases of engineered nanoparticles. One particular instrument, 

the Scanning Mobility Particle Sizer 

(SMPS) measures particle diameters 

from 2.5–1,000 nm and can display 

data as a size and number distribution using up to 167 size channels. 

The SMPS is widely used as a research tool for characterizing nanoscale aerosols. The SMPS employs a 

continuous, fast-scanning technique 

to provide high-resolution measurements. However, the SMPS may take 

2–3 minutes to scan which may not 

be useful for the process screening in 

workplaces with highly variable aerosol size distributions. Its applicability 

for use in the workplace may be limited because of its size, cost, and use 

of an internal radioactive source.

The Fast Mobility Particle Sizer 

(FMPS) is similar to the SMPS but has 

a much faster response time (approximately 1 second). However, because 

it has fewer particle size channels, it 

does not include the same level of detail on particle size distributions that 

can be determined with the SMPS. 
80 Approaches to Safe Nanotechnology

Appendix 

The FMPS and SMPS are used as area 

samplers.

5.6.1.3 Low Pressure Impactors

The Electrical Low Pressure Impactor 

(ELPI) combines diffusion charging 

and a cascade impactor to provide 

aerosol size distributions by aerodynamic diameter as determined real 

time by mass and number collected 

on a series of plates.

Low pressure cascade impactors offer 

the ability to size particles and then 

conduct secondary analyses (e.g., 

metals analysis). However, these instruments are sensitive to harsh field 

conditions and are not considered 

portable. The ELPI is used as an area 

sampler. 

5.6.1.4 Tapered Element Oscillating Microbalance

The tapered element oscillating microbalance (TEOM) is commonly 

used for sampling aerosols less than 

1 μm in diameter, however, the sampling inlet can be set to select different 

size fractions. The TEOM determines 

mass by detecting a change in vibration frequency across a particle-collecting substrate. The TEOM can be 

configured to provide size-differentiated mass measurements and is used 

as an area sampler.

5.6.2 Surface sampling

Surface sampling to detect the presence of engineered nanomaterials is 

not routinely part of the initial assessment but may be conducted to determine if surface contamination exists. 

Surface sampling does not provide 

size-specific information but may be 

useful for determining whether engineered nanomaterials have migrated 

away from active production or handling areas and have contaminated 

nonproduction work areas. The decision to collect surface samples is 

made in the field at the discretion 

of the industrial hygienist (or other 

qualified person), and is dependent 

on direct observation and the nanomaterial of interest. For example, 

surface sampling was completed at 

a quantum dot facility after observing dusty surfaces in areas adjacent to 

the production area. In order to determine if the dust was contaminated 

with quantum dots, surface samples 

were collected and analyzed for the 

chemical components of the quantum dots produced by that facility. 

Surface wipe samples are collected 

using a pre-moistened substrate such 

as Ghost WipeTM towelettes in accordance with NIOSH Method 9102 

for elements or the NIOSH method 

for specific elements (e.g., NIOSH 

Method 9100 for lead). When collecting wipe samples, the following steps 

should be followed:

•	 Don a pair of nitrile disposable 

gloves

•	 Wipe the surface within a disposable 10 cc × 10 cc template using 

four horizontal s-shaped strokes

•	 Fold the exposed side of the wipe 

in and wiping the same area with 

four vertical s-shaped strokes

•	 Fold the wipe, exposed side in, and 

placing it into a sterile container
Approaches to Safe Nanotechnology 81

Appendix

Gloves and template are discarded after each sample collection to 

eliminate the possibility of crosscontaminating successive samples. 

Wipe samples may be collected from 

undisturbed horizontal surfaces 

throughout the facility at locations 

suspected to be contaminated and 

in areas expected to be free of engineered nanomaterials. Wipe samples 

are analyzed following the appropriate NIOSH method for the chemical 

substance of interest.

6.0 Conclusions

The NIOSH initial assessment technique uses complimentary approaches 

to semi-quantitatively evaluate the potential releases of engineered nanoparticles. Two different particle counters 

are used in a parallel and differential 

manner to evaluate the total particle 

number relative to background and 

the relative size distribution of the 

particles. If this initial evaluation indicates an elevated number of small 

particles, which could potentially be 

the engineered nanoparticle of interest, then the particle counters are used 

to detect the source of the emissions. 

If nanoparticles are found and determined to be emitted from a specific 

process (versus background incidental 

nanoscale particles), then additional 

samples are collected for qualitative 

measurement of particle size and 

shape, (by TEM or SEM analysis) and 

for determination of elemental mass 

concentration (by chemical analysis). 

The initial assessment technique 

is useful for determining whether airborne releases of engineered 

nanomaterials are occurring at potential emission sources. This assessment provides a semi-quantitative 

means for determining whether existing measures are adequate for controlling nanomaterial emissions or if 

additional controls may be required. 

The NIOSH emission assessment 

technique may be useful to health 

and safety professionals who are interested in determining whether release of nanomaterials occurs in the 

workplace. Where possible, use of 

the technique should be repeated 

in workplaces of interest to gain a 

better understanding of the daily 

fluctuations in airborne exposures 

at processes and tasks in which engineered nanomaterials occur and 

for determining potential sources of 

background particle number concentrations. A more systematic and routine assessment of the workplace can 

provide more definitive information 

on the performance of control measures and if additional actions are 

needed to reduce worker exposure. 

The initial assessment technique can 

be expanded or modified to determine 

additional metrics (Figure 6). Research 

initiatives addressing more comprehensive process monitoring, particle 

metrics, personal exposure monitoring, 

and method/approach development 

and validation are currently underway 

within NIOSH. As this information 

becomes available, revisions to the Approaches to Safe Nanotechnology document will be made. 

Information about contacting the 

nanotechnology field research team 

is available at: [www.cdc.gov/niosh/
82 Approaches to Safe Nanotechnology

Appendix 

docs/2008-121], see the Fact Sheet: 

NIOSH Nanotechnology Field Research Effort [NIOSH 2008]. 

7.0 References

ASTM International [2006] ASTME2456–06 Standard terminology relating to nanotechnology

Evans DE, Heitbrink WA, Slavin TJ, 

Peters TM [2008]. Ultrafine and respirable particles in an automotive 

grey iron foundry. Ann Occup Hyg 

52(1):9–21.

Heitbrink WA, Evans DE, Peters TM, 

Slavin TJ [2007]. The characterization and mapping of very fine particles in an engine machining and 

assembly facility. J Occup Environ 

Hyg 4:341–351.

NIOSH [2008]. NIOSH Fact Sheet: 

NIOSH Nanotechnology Field Research Effort, Cincinnati, OH: U.S. 

Department of Health and Human 

Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and 

Health. DHHS (NIOSH) Publication 

No. 2008–121 [http://www.cdc.gov/

niosh/docs/2008-121/].

NIOSH [1994]. NIOSH manual of 

analytical methods (NMAM®), 4th 

ed. By Schlecht PC, O’Conner PF, eds. 

Cincinnati, OH: U.S. Department of 

Health and Human Services, Centers 

for Disease Control and Prevention, 

National Institute for Occupational 

Safety and Health. DHHS (NIOSH) 

Publication No. 94–113 [www.cdc.

gov/niosh/nmam/].

Maynard A, Aitken R [2007]. Assessing 

exposure to airborne nanomaterials: 

current abilities and future requirements. Nanotoxicology 1(1):26–41.

Maynard A, Baron P, Foley M, Shvedova A, Kisin E, Castranova V [2004] 

Exposure to carbon nanotube material: Aerosol release during the 

handling of unrefined single walled 

carbon nanotubes material. J Toxicology. Environmental Health Part A, 

67: 1; 87–107.

Methner MM, Birch ME, Evans DE, 

Ku BK, Crouch KG, Hoover MD 

[2007]. Mazzukelli LF, ed: Case study: 

Identification and characterization 

of potential sources of worker exposure to carbon nanofibers during 

polymer composite laboratory operations. J Occup Environ Hyg 4(12): 

D125–D130.

Methner M [2008]. Engineering case 

reports. Old L, ed. Effectiveness of local exhaust ventilation in controlling 

engineered nanomaterial emissions 

during reactor cleanout operations. J 

Occup Environ Hyg 5(6): D63–D69.

Peters T, Heitbrink W, Evans D, Slavin 

T, Maynard A [2006]. The mapping 

of fine and ultrafine particle concentrations in an engine machining and 

assembly facility. Ann Occup Hyg 

50(3):1–9. 
 

 

 

 

 

 

 

 

 

 

Appendix 

Table 1. Approximate sampling times for TEM grid based on particle 

number concentrations*. 

Open-faced cassettes 

TEM grid 25-mm 37-mm 47-mm 

Diameter (mm) 3.0 25.0 37.0 47.0 

Effective diameter (mm) 3.0 22.2 34.2 44.2 

Effective collection area 7 385 916 1531 

(mm2

)

Flow (L/min) 0.1 7 7 7 

Desired Loading (#/mm2

) 1.E+06 1.E+06 1.E+06 1.E+06 

Air concentration 


(#/cm3

) Time (min)
 

250 282.7 220.2 523.4 874.8 

500 141.4 110.1 261.7 437.4 

1,000 70.7 55.0 130.8 218.7 

2,000 35.3 27.5 65.4 109.4 

4,000 17.7 13.8 32.7 54.7 

8,000 8.8 6.9 16.4 27.3 

16,000 4.4 3.4 8.2 13.7 

32,000 2.2 1.7 4.1 6.8 

64,000 1.1 0.9 2.0 3.4 

128,000 0.6 0.4 1.0 1.7 

*

NIOSH NMAM Method 7402 Asbestos by TEM and personal communication with 

Dr. Aleksandr Stefaniak (NIOSH) 

Approaches to Safe Nanotechnology 83 
84 Approaches to Safe Nanotechnology

Appendix 

Figure 1. A demonstration of the initial assessment 

technique with side-by-side sampling using (from left 

to right) the OPC, co-located open-face filter cassettes, 

and the CPC: examples of PBZ and source-specific 

filter-based sampling setup.
Approaches to Safe Nanotechnology 85

Appendix

Figure 2. Summary of the initial assessment technique

Figure 4. Electron microscopy micrograph 

of a carbon nanofiber and carbon 

nanotube

Figure 3. Electron microscopy micrograph 

of a carbon nanofiber

Carbon Nanotube

Carbon Nanofiber
86 Approaches to Safe Nanotechnology

Appendix

Figure 5. Electron microscopy micrograph of an 

agglomerated nanoparticle of nickel oxide

Figure 6. Considerations for expanded nanomaterial assessments

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