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Breadcrumb

Nanomaterials in Academic Research

 

Best practices, Standards, and Guidelines to using engineered nanomaterials

Nanotoolkit

Working Safely with Engineered Nanomaterials in Academic Research Settings

California Nanosafety Consortium of Higher Education

What is the Nanotoolkit?

The Nanotoolkit is an easy to use guide for academic researchers to quickly identify safe handling practices when working with Engineered Nanomaterials (ENMs) based on a low, moderate, or high potential exposure category as described in this document.

How to Use:
Read the Overview of Nanomaterials section to obtain general information on ENMs.
Review the Planning Your Research and Conducting Your Research sections to obtain information on how to plan and conduct your experiment/operation involving ENMs.
Use the Quick Guide: Risk Levels and Control Measures for Nanomaterials to prepare a Standard Operating Procedure (SOP) for your experiment/operation employing the template provided.

Definitions
Nanomaterial: Material or particle with any external dimension in the nanoscale (range 1 nm to 100 nm) or having internal structure or surface structure in the nanoscale (Source: ISO/TS 80004-1:2010, ISO/TS 27687:2008)1, 2

Naturally Occurring Nanomaterial: Particles on the nanoscale occur naturally in the environment. They can also be manufactured and have a variety of commercial applications. More information on naturally occurring nanomaterials can be found in Appendix C.

Engineered Nanomaterials (ENMs): An Engineered Nanomaterial is any intentionally produced material with any external dimension in the nanoscale. It is noted that neither 1 nm nor 100 nm is a “bright line” and some materials are considered engineered nanomaterials that fall outside this range. For example, Buckyballs are also included even though they have a size <1 nm. Excluded are materials that are on the nanoscale, but do not have properties that differ from their bulk counterpart such as single strand polymers. 3

Types of Nanomaterials
Type Examples
Carbon Based Buckyballs or Fullerenes, Carbon Nanotubes*, Dendrimers
Often includes functional groups like PEG (polyethylene glycol), Pyrrolidine, N, N-dimethylethylenediamine, imidazole
Metals and Metal Oxides Titanium Dioxide (Titania)**, Zinc Oxide, Cerium Oxide (Ceria), Aluminum oxide, Iron Oxide, Silver, Gold, and Zero Valent Iron (ZVI) nanoparticles
Quantum Dots ZnSe, ZnS, ZnTe, CdS, CdTe, CdSe, GaAs, AlGaAs, PbSe, PbS, InP
Includes crystalline nanoparticle that exhibits size-dependent properties due to quantum confinement effects on the electronic states (ISO/TS 27687:2008).

* Carbon Nanotubes may be subject to a proposed Recommended Exposure Limit 10 of TWA 7 μg/m3 due to the risk of developing respiratory health effects.
**Nano-Titanium Dioxide is subject to a proposed Permissible Exposure Limit 11 of TWA 0.3 mg/m3 due to the risk of developing lung cancer. There are mixed studies regarding TiO2 skin penetration. Some studies indicate TiO2 and ZnO does not pass through the stratum corneum 6,7, while others indicate significant penetration through the skin. 8


Occupational health and safety concerns

Routes of Exposure

Exposure to engineered nanomaterials may occur via inhalation and dermal contact depending on use and handling; ingestion is unlikely but possible.

Lack of Information on Full Health Effects

With a lack of chronic exposure data and reproductive and developmental toxicity data, a precautionary approach when working with engineered nanomaterials is warranted.

Toxicity
Some potential toxic outcomes can be predicted from what we know about ultrafine particles4 and based on known chemical and structural properties5. Nanomaterials have the potential to:

  1. Deposit in the respiratory tract. Small airborne particles penetrate deep into the lungs.
  2. Cross cell membranes. Some nanomaterials have the ability to cross cell membranes.
  3. Penetrate healthy intact skin/translocation to other organ systems. Reports on this topic are mixed; caution is urged until more is known.

Other
Catalytic effects. In general, nanomaterials are not known to have catalytic effects, however, some nanomaterials are specifically engineered to have catalytic properties.

Fire or explosion. Nanomaterials are generally not explosive or flammable in small laboratory quantities unless the material is inherently reactive, however some of the synthesis methods may use techniques where fire and explosion are potential hazards.


Exposure Limits

Nanomaterials fall under OSHA General Industry Standards 9. Established exposure limits for naturally occurring nanomaterials, and detailed information about current state and federal regulations can be found in Appendix C. Although there are currently no established (legal) exposure limits (US or International) for Engineered Nanomaterials, NIOSH has developed Recommended Exposure Limits (RELs) for carbon nanotubes (TWA 7 μg/m3) and nano-titanium dioxide (TWA 0.3 mg/m3).

Step 1 | Gather Information
Select less-hazardous forms
Whenever possible, select engineered nanomaterials bound in a substrate or matrix or in water-based liquid suspensions or gels.

Review Material Safety Data Sheet (MSDS), if available.
NOTE: Information contained in some MSDSs may not be fully accurate and/or may be more relevant to the properties of the bulk material rather than the nano-size particles. The toxicity of the nanomaterials may be greater than the parent compound. Review your the University's Chemical Hygiene Plan for general laboratory safety guidance.

Step 2 | Determine Potential Risks
Common laboratory operations involving ENMs may be categorized as posing a low, moderate, or high potential exposure risk to researchers depending on the state of the material and the conditions of use. Refer to the Quick Guide: Risk Levels and Control Measures for Nanomaterials. Follow the instructions in this matrix to identify the potential risk of exposure and recommended control measures. Special consideration should be given to the high reactivity of some nanopowders with regard to potential fire and explosion, particularly if scaling up the process. Consider the hazards of the precursor materials in evaluating the process.

Step 3 | Develop a Standard Operating Procedure (SOP)
A standard operating procedure (SOP) is a set of written instructions that describes in detail how to perform a laboratory process or experiment safely and effectively. Employing the hierarchy of controls described in Quick Guide: Risk Levels and Control Measures for Nanomaterials, establish an SOP for operations involving nanomaterials. For an example, refer to Appendix B.

Step 4 | Obtain Training and Consultation / Approval
Training
Principal Investigators or laboratory supervisors must ensure that researchers have both general laboratory safety training pursuant to Cal/OSHA’s Occupational Exposure to Hazardous Chemicals in Laboratories (8 CCR 5191) and lab-specific training relevant to the nanomaterials and associated hazardous chemicals used in the process/experiment. Laboratory-specific training can include a review of this Nanotoolkit, the relevant Material Safety Data Sheets (if available), and the lab’s Standard Operating Procedure (SOP) for the experiment.

Consultation / Approval
Consult with and seek prior approval of the Principal Investigator or laboratory supervisor prior to procuring or working with nanomaterials, and/or if working alone in the laboratory is anticipated. [Follow University rules on working alone.]

Notification
If dosing animals with the nanomaterial, follow University hazard communication processes for advanced notification of animal facility and cage labeling/management requirements. 

Engineering Controls


Control Exposure with Equipment
Minimize airborne release of ENMs by utilizing one of the following devices:

  • Work in a laboratory fume hood or biosafety cabinet. Conduct work inside a fume hood or low flow enclosures to prevent exposure. Biosafety cabinets must be ducted if used in conjunction with volatile compounds.
  • Use a glove box or fully-enclosed system. Where it is not possible to prevent airborne release, such as in grinding operations or in gas phase, use equipment that fully encloses the process. This includes a glove box.
  • Use local capture exhaust hoods. Do not exhaust aerosols containing engineered nanoparticles into the interior of buildings. Use High-Efficiency Particulate Air (HEPA) filtered local exhaust ventilation (LEV). HEPA-filtered LEV should be located as close to the possible source of nanoparticles as possible, and the installation must be properly engineered to maintain adequate ventilation capture. Use HEPA-filtered local capture exhaust hoods to capture any nanoparticles from tube furnaces, or chemical reaction vessels or during filter replacements.

Ensure Performance and Maintenance
Laboratory equipment and exhaust systems used with nanoscale materials should be wet wiped and HEPA vacuumed prior to repair, disposal, or reuse. Make sure fume hoods and any LEV achieves and maintains adequate control of exposure at all times. These systems require regular maintenance and periodic monitoring to ensure controls are working and thorough examination and testing at least once a year.


Administrative Controls


Use Solution of Substrates
To minimize airborne release of engineered nanomaterials to the environment, nanomaterials are to be handled in solutions, or attached to substrates so that dry material is not released.

Locate Safety Equipment
Know the location and proper use of emergency equipment, such as emergency eyewash/safety showers, fire extinguishers, fire alarms, and spill clean-up kits12.

Use Signs and Labels
Restrict access and post signs in area indicating ENM work. When leaving operations unattended, use cautious judgment:

  1. Post signs to communicate appropriate warnings and precautions,
  2. Anticipate potential equipment and facility failures, and
  3. Provide appropriate containment for accidental release of hazardous chemicals.

Clean and Maintain
Line work area with absorbent pad. When working with powders, use antistatic paper and floor sticky mats. Wet wipe and/or HEPA-vacuum work surfaces potentially contaminated with nanoparticles (e.g., benches, glassware, apparatus) at the end of each operation. Consult with your institution regarding the maintenance of HEPA vacuums and replacement of HEPA filters.

Maintain Personal Hygiene
To avoid potential nanoparticle or chemical exposure via ingestion in area where ENMs are used or stored, do not: consume or store food and beverages, apply cosmetics, or use mouth suction for pipetting or siphoning. Remove gloves when leaving the laboratory in order to prevent contamination of doorknobs or other common use objects such as phones, multiuser computers, etc. Wash hands frequently to minimize potential chemical or nanoparticle exposure through ingestion and dermal contact.

Store and Label Properly
Store nanomaterials in a well-sealed container. Label all chemical containers with the identity of the contents (do not use abbreviations/ acronyms); include term “nano” in descriptor (e.g., “nano-zinc oxide particles” rather than just “zinc oxide.” Include hazard warning and chemical concentration information, if known.

Transport in Secondary Containment
Use sealed container with secondary containment when transporting nanomaterials between laboratories or buildings.


Personal Protective Equipment (PPE)

Know the Applications and Limits
The use of PPE is generally considered to be the least desirable option to control employee exposure to occupational safety and health hazards. However, in an academic laboratory, there are often scenarios under which PPE can minimize potential employee exposure to occupational safety and health hazards either as a stand-alone control mechanism, or, as a supplement to either administrative or engineering control approaches.

Many occupational safety and health issues associated with ENM’s are not fully understood (i.e., ENM toxicity, exposure metrics, fate and transport, etc.). The same uncertainty exists with how to select the myriad of available types of PPE and effectively use them to minimize the potential hazards associated with employee exposure to ENM hazards.

There is a growing body of evidence resulting from on-going research which indicates that commonly available PPE does have efficacy against specific sizes and types of ENMs. The PPE described within the Nanotool Quick Guide was selected as a result of a comprehensive review of available guidance and published research available at the time the Guide was developed.

Use The Quick Guide
The user of this Nanotool is directed to the Quick Guide for a description of the recommended PPE. Note that the referenced PPE increases for each Category consistent with the increasing exposure potential. The basic PPE ensemble described under Category 1 is to be augmented by the specific PPE in Category 2 and Category 3. The user is reminded of the following important issues associated with the safe and effective use of PPE:

Respiratory Protection. Mandatory use of respirators will require full adherence to the requirements of your institution’s respiratory protection program. It is imperative that you consult with the University's EH&S representative prior to utilizing respiratory protection, even if that use is voluntary.

Gloves and Clothing. Glove material, fabrication process and thickness are significant issues which impact the permeation of ENM’s. Consequently, consideration should be given to utilizing two layers of gloves. For more information, refer to Table 1 (see below).

The selection of dermal PPE for protection against ENM’s must also take into account other chemicals which may be part of the ENM matrix or use conditions (i.e., solvents, surfactants, carrier gases, etc.). Dermal PPE manufacturers provide permeation/penetration tables which allow the end user to select dermal PPE based upon performance criteria to specific chemical threats. For examples, refer to the Controlled Environments guide by Du Pont®, or the Chemical Resistance Guide by Ansell © 2003. The technique used to remove gloves (and all PPE) is very important so that any material contaminating the outer surfaces of the PPE does not impact the wearer. Consult with your EH&S representative to learn the appropriate technique(s) to remove chemical protective clothing.

Reduce PPE Hazards
Under specific use conditions, utilizing PPE may put the user at risk of occupational injury. PPE may impair vision and dexterity and increase the likelihood of trip, slip, or fall hazards in addition to increasing the potential to develop heat-related illnesses. Consult with your EH&S professional for questions pertaining to the appropriate selection and use conditions for PPE.

Table 1. Glove Choices for Nanomaterials
Select glove based on compatibility with material and solvents to be used and, if possible, permeability studies for that category of ENM. Recommend wearing gauntlet-type/wrist-length gloves with extended sleeves. The table below contains information on select ENMs and the associated reference.

Nanomaterial / State   Glove Type(Recommendation)
Carbon Nanotubes (CNTs) Nitrile over Latex*, **
TiO2 and PT   Latex**, Nitrile, Neoprene***
Graphite  Latex**, Nitrile, Neoprene, Vinyl***

* Consider potential latex allergies in PPE selection.
**Reference: Methner, et. al (NIOSH)
*** Reference: Golanski, et. al (2010)

Purpose

This Quick Guide categorizes common laboratory operations involving engineered nanomaterials according to their potential risk of exposure to personnel, which is based on the state of the material and the conditions of use. Controls are provided in the table to minimize exposures. This guide is intended to be used in conjunction with the academic institutions’ laboratory safety practices or other established guidelines (e.g., Prudent Practices by The National Research Council).

Instructions

Follow these steps to create a Standard Operating Procedure:

Step 1: Determine your risk level
Step 2: Identify the controls needed
Step 3: Develop a SOP
Acknowledgement
 

Contributors
Casimir Scislowicz, California Institute of Technology (CalTech)
Chuck Geraci. National Institute for Occupational Safety and Health (NIOSH)
Frank S. Parr, Department of Toxic Substances Control (DTSC)
Guy DeRose, California Institute of Technology (CalTech)
Hamid Saebfar, Department of Toxic Substances Control (DTSC)
Hilary Godwin, University of California Los Angeles (UCLA)
Jane Bartlett, University of Southern California (USC)
Jay Brakensiek, Claremont University Consortium
Jeff Wong, Department of Toxic Substances Control (DTSC)
Katherine McNamara, University of California Los Angeles (UCLA) 
Khadeeja Abdullah, University of California Los Angeles (UCLA)
Kristin Yamada, University of California Los Angeles (UCLA)
Larry Wong, University of California Office of the President
Lawrence Gibbs, Stanford University
Mary Dougherty, Stanford University
Michelle Lee, University of Southern California (USC)
Rebecca Lally, University of California Irvine (UCI)
Russell Vernon, University of California Riverside (UCR)
Ryan Kinsella, Department of Toxic Substances Control (DTSC)

Thanks
Some of this material is based upon work supported by the California Department of Toxic Substances Control (DTSC) and the University of California Center for Environmental Implications of Nanotechnology in a grant from the National Science Foundation and the Environmental Protection Agency (EPA) under Cooperative Agreement Number DBI-0830117. Generous support for this work, in the form of a graduate fellowship for Khadeeja Abdullah, the doctoral student who worked on this project, was provided by the UCLA Luskin Center of Innovation. We would like to thank Jessica Twining and Adeleye Adeyemi, graduate students from the USCB Bren School of the Environment, for collecting and summarizing the available guidance documents and exposure literature. Acknowledgement is extended to Quantumsphere for opening their doors and allowing their facility to serve as a “working laboratory.” Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation, the Environmental Protection Agency, the California Department of Toxic Substances Control, or the UCLA Luskin Center. This work has not been subjected to EPA review and no official endorsement should be inferred.

Editor
Janette de la Rosa Ducut, Ed.D., University of California Riverside


Preface

Background on California Nanosafety Consortium of Higher Education and Development of the Nanotoolkit

Background
The increasing use of nanomaterials in research and development laboratories along with applications in industry are providing breakthroughs for many technologies and solutions for addressing major problems in our society. However, as with all new technologies, the potential health effects of engineered nanomaterials (ENMs) remain uncertain. The aim of this project is to provide practical guidance as to how ENMs should be handled safely in the research laboratory setting in the face of such uncertainty over possible toxic effects.

Currently many government agencies, academic institutions, and industries have issued detailed guidance documents as to how NMs should be monitored, controlled, and handled in different work settings. Only a portion of these practices have been validated by scientific research or reference to peer reviewed literature. Most guidance documents and exposure studies to date have focused primarily on industrial settings, but academic research settings present their own challenges that also need to be addressed. Much of the initial research and development (R&D) in nanotechnology is still performed in academic research laboratories. In academic laboratories, the quantity of materials used tends to be less than those used in industry, but the variety of nanomaterials used tends to be more diverse. As a result, the potential hazards are also more diverse and exposure monitoring is more challenging. Furthermore, academic practices tend to be less standardized and to vary more from lab to lab and from day to day than typical industrial processes. This means that engineering controls which are commonly used in industry may not be practical to apply in academic laboratory research settings.

The nature of research and training in academic institutions dictates that new students and employees with various backgrounds and levels of training are regularly being introduced into the many diverse laboratory settings. Undergraduate student researchers, graduate students and other laboratory personnel often have minimal formal safety training or are lacking the latest hazard information about such new technological developments. All of these factors make a simple adoption or application of standardized industrial best practices for working with NMs in laboratories difficult.

Goals
The goal of this project is to provide an easy to use tool kit for academic researchers to quickly identify safe handling practices based on whether the work they propose is in a low, moderate, or high potential exposure category. The exposure categories and controls were determined from a review and analysis of many related nanomaterial health and safety guidance documents.

Methods
The analysis of the proposed recommendations included summarizing all the relevant recommendations from the various guidance documents into one matrix, conducting a literature search to see if the recommended practices were appropriately validated, and having a group of experienced environmental health and safety professionals from various California universities use their professional judgment and the research literature provided to rank the applicability of each recommendation as well as rate each recommendation in terms of the need for further research.

The working group summarized documents from 19 academic institutions, 14 government agencies and four industrial sources. This project was a collaborative effort by the California Nanosafety Consortium of Higher Education. The group included representatives from:

Government Agencies
National Institute of Occupational Safety and Health (NIOSH)
Department of Toxic Substances Control (DTSC)

University Environmental Health and Safety Professionals (EH&S)
University of California Los Angeles (UCLA)
University of California Irvine (UCI)
University of California Riverside (UCR)
University of California (UC) Office of the President
University of Southern California (USC)
Stanford University
California Institute of Technology
Claremont University Consortium

In addition, the project involved professor(s) and graduate students from the University of California Los Angeles (UCLA) and University of California Santa Barbara (UCSB).

Through this process we identified existing safety concerns of health and safety professionals and uncovered shortcomings in the current guidance documents, while recommending guidance that is most appropriate and validated by peer reviewed research for application to the research laboratory setting. A practical and easy to use tool kit was developed to help academic researchers to quickly identify proposed laboratory research work with nanomaterials as a low, medium, or high-risk activity and then identify appropriate control measures. Also included are sections with general information about engineered nanomaterials, spill cleanup and waste management.

The user of this tool kit is advised that this document provides a best practice guideline to approaching and understanding how to work safely with engineered nanomaterials in the laboratory. Ultimately, it is the responsibility of the faculty member, the principal investigator, or the laboratory supervisor who is directing such work in the laboratory to provide for the safe conduct of all individuals conducting research in their laboratories. If applied diligently and appropriately, these guidelines will help provide for the safety and health of laboratory personnel conducting research using engineered nanomaterials.