Chemicals

The inhalation of dust, fumes, or mists containing beryllium or beryllium compounds present a very serious health hazard. Laboratory processes that can produce fumes or inhalable dust include heating, grinding, and machining of beryllium and its alloys.

In humans, beryllium causes both acute and chronic lung disease and lung cancer. Acute beryllium disease has been seen after brief exposures to soluble beryllium compounds. Symptoms range from a mild inflammation of nasal passages to bronchitis and lung inflammation.

Chronic beryllium disease is characterized by lung fibrosis (scarring) and inflammation, causing breathlessness upon exertion, weakness, chest pain, enlarged heart, and ultimately death. Beryllium has been documented to cause lung cancer in industrial beryllium production facilities. Beryllium can also cause allergic skin reactions.

To work safely with beryllium, all labs and shops must do the following:

• All procedures that potentially generate beryllium particulates, such as heating or machining or aerosols of beryllium salts, must be evaluated by the EHS Office to insure that air levels are safe.
• All researchers working with beryllium in a manner that creates airborne exposure can enroll in the Beryllium Surveillance Program at MIT Medical by calling (617) 452-3477. The program is voluntary and free.
• Standard operating procedures for specific operations should be established before working with beryllium and its compounds. These will normally include the use of fume hoods or local exhaust ventilation.
• Prior to working with beryllium, employees must receive training from their supervisor. Beryllium users must also complete either Chemical Hygiene or Hazard Communication training and Managing Hazardous Waste training.

Best practice for dispensing liquid from a low pressure container to a dewar:

• Don a face shield and safety glasses, cryogenic gloves, long pants without cuffs, closed-toed shoes, and a laboratory coat.
• Next connect a transfer line to the liquid valve, if one is not already present, making sure the fittings match.  Please note that the valve will be labeled.  The transfer line should have a phase separator attached to reduce turbulence and the release of gas while filling.
• Check the pressure in the cylinder.  It should read approximately 22 pounds per square inch.  Position the Dewar on the floor at the base of the cylinder, or on some other support below waist level and insert the transfer line into the Dewar.  The end of the transfer line should extend to the bottom, or just off the bottom, of the Dewar.  Keep bystanders at least four feet away while filling in case of splashing.
• Open the liquid valve one half to three quarters of a turn to begin cooling down the transfer hose and adding the cryogen to the Dewar.  The warm hose and Dewar will vaporize the cryogen as it cools and this could create splashing particularly if it is added too quickly.  The pressure in the container will drive the liquid out through the valve.
• Once the hose and Dewar have cooled, open the liquid valve to obtain the desired rate of flow.  However, if you fully open the valve, be sure to close it a quarter turn.  A fully opened valve may freeze in that position causing a spill.  A good flow rate is typically evident by a moderate vapor trail coming from the mouth of the Dewar.  Listen for the change in sound as the Dewar fills – a higher pitch indicates the Dewar is getting full.
• When full, close the liquid valve. Remove the transfer line but be careful not to drop it or allow the phase separator to hit a solid object which will cause it to break.  Watch out for any cryogen that continues to spill out of the transfer hose.   Finally, place the top on the Dewar, pushing it all the way on and then pulling it up so that it is loose.

Best practice for dispensing gas from a high pressure container to equipment or system:

• Don cryogenic gloves, safety glasses, long pants without cuffs, closed-toed shoes, and a laboratory coat.
• Check the pressure in the cylinder.  It should be approximately 230 pounds per square inch, but this will vary with the gas dispensed.
• Next connect the inlet of a suitable regulator to the gas use valve or a transfer line from this valve to an appropriate wall mounted regulator.  Please note that the gas withdrawal valve will be labeled. The regulator should be designed for use with cryogens and adjustable over the desired pressure range.
• The outlet of the regulator is connected to the system receiving the gas using the appropriate transfer line – in this case it’s a dedicated gas line.
• Next close the regulator valve and open the gas use valve.  Adjust the gas regulator to deliver the gas at the desired pressure, for example, 90 pounds per square inch.   At this point you may begin withdrawing gas.
• In applications where large volumes of gas will be withdrawn from the container, the pressure building valve will be opened.  This valve operates an internal circuit that allows more liquid to vaporize then would naturally occur through evaporation alone.  The vendor supplying the container generally knows your application and opens or closes this valve when delivered.

The transportation of cryogenic containers in elevators represents a potential asphyxiation risk if researchers become trapped in an elevator with a container of cryogen.  If a passenger elevator must be used, the first person rolls the container into the elevator, posts a clearly visible sign that warns staff and students not to enter the elevator.  The first person pushes the elevator button for the appropriate floor and immediately gets off the elevator.  The second person meets the elevator, removes the container and the sign.

This table lists the change in volume as the gas transitions from liquid to gas at room temperature. The resulting pressure that would be generated inside a container from trapped liquid under these conditions is also listed.

Note 1: Although CO2, which has a slightly higher boiling is technically not cryogenic liquid but has similar properties and is often included in this category. (Note: Source Argonne National Laboratory)

MIT must identify all laboratory activities that are above the OSHA action level or short term exposure level (STEL) through initial air monitoring and provide training, medical surveillance, and engineering and work practice controls if air levels warrant it. The Industrial Hygiene Program (IHP) in the EHS Office has performed extensive air sampling for formaldehyde during a variety of lab activities such as animal perfusion, dissections, and tissue fixation and found the results to be below OSHA levels provided that suitable exhaust ventilation is used.

With proper exhaust ventilation, you should not detect any odors from formaldehyde work nor experience any symptoms of exposure such as eye tearing or throat irritation. If you do, please contact EHS immediately at (617) 452-3477 for an evaluation.

EHS sends a questionnaire annually to laboratory EHS Representatives to survey formaldehyde use and conducts air sampling of procedures where there may be a potential for exposure. Notify EHS for an evaluation if your procedures change and you work with large quantities of formaldehyde, perform animal perfusions, or do extensive tissue dissection work.

Any suspected skin exposures to HF should be immediately flooded with water, decontaminated with calcium gluconate gel, and be treated at MIT Medical”.

“In case of:

• ​Large area of skin exposure (greater than the palm of the hand) and the HF concentration is greater than 5%
• Eye exposure
• Inhalation exposure
• Ingestion

Immediately call 100 or 617-253-1212, ask for Advanced Life Support (ALS) Ambulance, follow appropriate irrigation protocol and go directly to the hospital.

All laboratories using HF must have unexpired calcium gluconate decontamination gel on hand. You may obtain it from the EHS Office by completing this form.

Calcium Gluconate Gel Request Form

All employees are required to be trained by the EHS Office before beginning work with HF. The training covers safe use, personal protective equipment, and decontamination procedures. The training can be taken on the web or in the classroom. Visit Atlas and select Learning Center to search and register for the training.

Upon completion of your experiment using lithium or sodium metals or powders, specifically, follow these guidelines or contact the EHS Office for assistance in preparing the waste or surplus materials for hazardous waste pick-up:

1. Within the glove box or controlled environment, containerize your waste materials and submerge them in oil.
2. Remove the container of waste from the glove box, label it with a red tag, spell out the constituents, indicate Ignitable/Reactive as the associated hazards, date the container, and place it in your lab’s SAA.
3. Upon dating, place a waste collection pickup request online for removal from the lab within 3-days.

Nanoparticles are generally similar in size to proteins in the body and are considerably smaller than many cells in the body. Human alveolar macrophages are 24 um in diameter and red blood cells are 7-8 um in diameter. Cells growing in tissue culture will pick up most nanoparticles.

Particles in the nanometer size range do occur both in nature and as an incidental byproduct of existing industrial processes. Nanosized particles are part of the range of atmospheric particles generated by natural events such as volcanic eruptions and forest fires. They also form part of the fumes generated during welding, metal smelting, automobile exhaust, and other industrial processes. One concern about small particles that are less than 10 um is that they are respirable and reach the alveolar spaces of the lungs.

The ability to be taken up by cells is being used to develop nanosized drug delivery systems and does not inherently indicate toxicity.

Quantum Dots

Quantum dots are nanocrystals containing 1,000 to 100,000 atoms and exhibiting unusual “quantum effects” such as prolonged fluorescence. They are being investigated for use in immunostaining as alternatives to fluorescent dyes. The most commonly used material for the core crystal is cadmium-selenium, which exhibits bright fluorescence and high photostability. Both bulk cadmium and selenium are toxic to cells. One of the primary sites of cadmium toxicity in vivo is the liver.

Carbon Nanotubes

Carbon Nanotubes (CNT) can have either single or multiple layers of carbon atoms arranged in a cylinder. The dimensions of typical single-wall carbon nanotubes (SWCNT) are about 1-2 nm in diameter by 0.1 um in length. Multiple wall carbon nanotubes (MWCNT) are 20 nm in diameter and 1 mm long.

CNT may behave like fibers in the lung. They have properties very different from bulk carbon or graphite. They have great tensile strength and are potentially the strongest, smallest fibers known. CNT have been tested in short term animal tests of pulmonary toxicity and the results suggest the potential for lung toxicity though there are questions about the nature of the toxicity observed and the doses used.

Fullerenes

Fullerenes are another category of carbon-based nanoparticles. The most common type has a molecular structure of C60 which takes the shape of a ball-shaped cage of carbon particles arranged in pentagons and hexagons. Fullerenes have many potential medical applications as well as applications in industrial coatings and fuel cells, so a number of preliminary toxicology studies have been done with them.

The toxicity of most nanomaterials is currently unknown. Studies suggest that the levels of toxicity depend on the base material of the nanoparticle, its size and structure, and its substituents and coatings.

The preliminary conclusions to be drawn from the toxicology studies to date is that some types of nanomaterials can be toxic, if they are not bound up in a substrate and they are available to the body. Multiple government organizations are working to fund and assemble toxicology information on these materials. In the interim, MIT researchers must use procedures that prevent inhalation and dermal exposures because at this time nanotoxicology information is limited.

Handling Nanoparticles

Nanomaterials of uncertain toxicity can be handled using the same precautions currently used at MIT to handle toxic materials: use of exhaust ventilation (such as fume hoods and vented enclosures) to prevent inhalation exposure during procedures that may release aerosols or fibers and use of gloves to prevent dermal exposure. The EHS Office will continue to review health and safety information about nanomaterials as it becomes available and distribute it to the MIT community.

Changes in Technology

The current nanotechnology revolution differs from past industrial processes because nanomaterials are being engineered and fabricated from the “bottom-up”, rather than occurring as a byproduct of other activities. The nanomaterials being engineered have different and unexpected properties compared to those of the parent compounds. Since their properties are different when they are small, it is expected that they will have different effects on the body and will need to be evaluated separately from the parent compounds for toxicity.

Currently, nanomaterials have a limited commercial market. Some nanomaterials are used as catalyst supports in catalytic converters; nanosized titanium dioxide particles are used as a component of sunscreens; carbon nanotubes have been used to strengthen tennis rackets; components in silicon chips are reaching the 45 to 65 nm range.

Research and industrial labs are working at the intersection of engineering and biology to extend uses to medicine as well as all areas of engineering. The impact is expected to revolutionize these areas. Government agencies in the US and Europe are beginning to fund toxicology research to understand the hazards of these materials before they become widely available.

Translocation in the Body

Once in the body, some types of nanoparticles may have the ability to translocate and be distributed to other organs, including the central nervous system. Silver, albumin, and carbon nanoparticles all showed systemic availability after inhalation exposure.

Significant amounts of 13C labeled carbon particles (22-30 nm in diameter) were found in the livers of rats after 6 hours of inhalation exposure to 80 or 180 ug/m3 (Oberdorster et al. 2002). In contrast, only very small amounts of 192Ir particles (15 nm) were found systemically. Oberdorster et al. (2004) also found that inhaled 13 C labeled carbon particles reached the olfactory bulb and also the cerebrum and cerebellum, suggesting that translocation to the brain occurred through the nasal mucosa along the olfactory nerve to the brain.

The ability of nanomaterials to move about the body may depend on their chemical reactivity, surface characteristics, and ability to bind to body proteins.

Titanium Dioxide Nanoparticles

Nanoscale titanium dioxide has shown very different properties from the micron-scale material in tests of lung toxicity. In addition, 14 to 40 nm titanium dioxide produced lung cancer in rats at doses of 10 mg/m3; micron-sized dust produced cancer only at very high doses (250 mg/m3). Based on these results the National Institute of Occupational Safety and Health (NIOSH) issued a recommended safe occupational exposure limit of 0.1 mg/m3 for nanoscale material and 1.5 mg/m3 for micron size material.

The International Agency for Research on Cancer (IARC) has also determined that titanium dioxide is a category 2B carcinogen: possibly carcinogenic to humans. Last year Wang et al (2008) showed that nanoscale titanium dioxide when inhaled could travel to the brain by way of olfactory neurons. Once in the brain, it caused oxidative stress and neuronal degeneration in several areas, including the hippocampus which is involved with short-term memory.

Nanoscale titanium dioxide joins several other types of nanomaterials (manganese oxide, nanocarbon, and some viruses) that can enter the brain directly by means of the olfactory pathway from the nose.

Skin Penetration

There is currently no consensus about the ability of nanoparticles to penetrate through the skin. Particles in the micrometer range are generally thought to be unable to penetrate through the skin. The outer skin consists of a 10 um thick, tough layer of dead keratinized cells (stratum corneum) that is difficult to pass for particles, ionic compounds, and water soluble compounds. Tinkle et al. (2003) found that 0.5 and 1 um dextran spheres penetrated “flexed” human skin in an in vitro experiment.

Particles penetrated into the epidermis and a few entered the dermis only during flexing of the skin. Particles 2 and 4 um in diameter did not penetrate. Rymen-Rasmussen et al. (2006) also found that quantum dots penetrated through pig skin and into living dermis using an in vitro pig skin bioassay which is considered a good model for human skin.

Micronized titanium dioxide (40 nm) is currently being used in sunscreens and cosmetics as sun protection. The nm particles are transparent and do not give the cosmetics the white, chalky appearance that coarser preparations did. The nm particles have been found to penetrate into the stratum corneum and more deeply into hair follicles and sweat glands than um particles though they did not reach the epidermis layer and dermis layers (Laddeman et al., 1999).

There is also a concern that nm titanium dioxide particles have higher photo-reactivity than coarser particles and may generate free radicals that can cause cell damage. Some manufacturers have addressed this issue by coating the particles to prevent free radical formation. The FDA has reviewed available information and determined that nm titanium dioxide particles are not a new ingredient but a specific grade of the original product (Luther, 2004).

The MIT EHS Office considers nanoparticles that have the potential for release into the air to be handled as particularly hazardous substance because their toxicity is, for the most part, unknown and early studies have been suggestive of toxic effects. In the future, many types of nanoparticles may turn out to be of limited toxicity but precaution must be used until we know more. The following best practices should be followed:

• Work with nanoparticles that may release particles should be conducted in enclosures, fume hood, glove boxes, and other vented enclosures.
• All work should be done with gloves (at a minimum disposable nitrile gloves)
• Currently, nanoparticles and solutions containing them are being disposed of as hazardous waste. Label all containers of nanomaterials (including waste) with the designation “nano”.
• Before work, review the Best Practices for Handling Nanomaterials in Laboratories
• Review the checklist for developing your laboratory Standard Operating Procedure for nanomaterials work
• Call the EHS Office at 617-253-0344 for exposure evaluation of experimental setups and additional information.

EHS has developed a training, Nanomaterials Health and Safety Course, which includes information on the toxicity of different types of nanomaterials and laboratory practices to prevent exposures.

If you have any questions after reviewing these materials, contact the EHS Office at environment@mit.edu or 452-3477. An EHS Officer can also visit your lab for a review of your procedures.

Nanomaterials can be handled in fume hoods, biosafety cabinets, and other exhausted enclosures. However, these hoods often have high air velocities that can be disruptive to handling dry, lightweight nanomaterials.

Laboratories in Mechanical Engineering and Center for Materials Science and Engineering have purchased a specially designed type of enclosure for handling nanopowders. This type of enclosure differs from a traditional fume hood in that the slots for exhausted air are located above the floor of the unit. Therefore air currents do not disturb the handling of light, fluffy nanopowders or nanotubes. These units were originally developed to enclose sensitive balances but can be used either to weigh nanomaterials or manipulate samples.

Contact EHS for vendors who supply these enclosures.

As nanotechnology emerges and evolves, potential environmental applications and human health and environmental implications are under consideration by the EPA and local regulators.

EPA has a number of different offices coordinating its review of this rapidly evolving technology. The EPA is currently trying a voluntary approach to testing and developing a stewardship program. There are currently no guidelines from the EPA specifically addressing the disposal of waste nanomaterials. It seems that regulation at some level is inevitable. Some political subdivisions, including the City of Cambridge, are already evaluating local regulation.

MIT is taking a cautious approach to nano waste management. It is our belief that regulation is inevitable. In order to better understand the potential volumes and characteristics of these waste streams, we are advising that all waste materials potentially contaminated with nanomaterials be identified and evaluated or collected for special waste disposal.

The following waste management guidance applies to nanomaterial-bearing waste streams consisting of:

• Pure nanomaterials (e.g., carbon nanotubes)
• Items contaminated with nanomaterials (e.g., wipes/PPE)
• Liquid suspensions containing nanomaterials
• Solid matrixes with nanomaterials that are friable or have a nanostructure loosely attached to the surface such that they can reasonably be expected to break free or leach out when in contact with air or water, or when subjected to reasonably foreseeable mechanical forces.

The guidance does not apply to nanomaterials embedded in a solid matrix that cannot reasonably be expected to break free or leach out when they contact air or water, but would apply to dusts and fines generated when cutting or milling such materials.

DO NOT put material from nanomaterial – bearing waste streams into the regular trash or down the drain. Before disposal of any waste contaminated with nanomaterial, call the EHS Office (45(617) 452-3477) for a waste determination.

Collect paper, wipes, PPE, and other items with loose contamination in a plastic bag or other sealing container stored in the laboratory hood. When the bag is full, close it, take it out of the hood and place it into a second plastic bag or other sealing container. Label the outer bag with the laboratory’s proper waste label. On the Contents section, note that it contains nano-sized particles and indicate what they are.

Currently, the disposal requirements for the base materials should be considered first when characterizing these materials. If the base material is toxic, such as silver or cadmium, or the carrier is a hazardous waste, such as a flammable solvent or acid, clearly they should carry those identifiers. Many nanoparticles may also be otherwise joined with toxic metals of chemicals. Bulk carbon is considered a flammable solid, so even carbon-based nanomaterials should be collected for determination as hazardous waste characteristics.

The EHS Office regularly seeks out new information regarding nanomaterials and will alert the MIT community about additional toxicology studies as they become available. We also request that MIT researchers alert us about studies that they learn so we can distribute them to the MIT community.

We would like to observe handling procedures in different labs so we can share good practice information within the MIT community. Many of the articles listed below can be accessed electronically through the MIT Libraries if an electronic subscription is available. Web sites are also provided where available.

Additional MIT Guidance

• Best Practices for Handling Nanomaterials in Laboratories
• Checklist for Nanomaterials Standard Operating Procedures

Web Sites

• Gradient Corp. Monthly EH&S Nano News
• National Institute for Occupational Safety and Health (NIOSH)
• National Nanotechnology Infrastructure Network (NNIN)
• National Center for Biotechnology Information (NCBI) Pub Med – Search for articles on nanoparticle toxicity
• Safe Nano (UK) – Regularly updated wensite on health and safety risks of nanotechnology with comments by toxicologists and regulators

• Borm P JA, Robbins D, Haubold S et al. The potential risks of nanomaterials: a review carried out for ECETOC. Part Fiber Toxicol 3:11-35 2006.
• Colvin VL. The potential environmental impact of engineered nanmoaterials. Nature Biotechnology 21:1166-1170 2003. [Note: Excellent and succinct overview of nanotoxicology.
• Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: An Emrging Discipline Evolving from Studies of Ultrafine Particles. Environmental Health Perspectives 113:823-839 2005.
• Health and Safety Executive (UK). Health effects of particles produced for nanotechnologies. Document EH75/6. 35 pp. December 2004. Available at: www.hse.gov.uk. [Search for EH75/6]
• Health and Safety Executive (UK). Nanoparticles: an occupational hygiene review. Research Report 274. 100 pp. 2004. Available at: www.hse.gov.uk. [Search for RR274]
• BIA. Workshop on ultrafine aerosols at workplaces. Held August 2002 in Germany. 208 pp. Available at: https://www.cdc.gov/niosh/topics/nanotech/. [Go to Nanotechnology Topic Page. Report is listed in section Non-US Governmental Resources]

[Many articles are available electronically through MIT Libraries]

• Chen HH, Yu C, Ueng TH, Chen S et al. Acute and subacute toxicity study of water soluble polyalkylsulfonated C60 in rats. Toxicol Pathol 26:143-151 1998.
• Cui D, Tian F, Ozkan CS, Wang M, Gao H. Effect of single wall carbon nanotubes on human HEK293 cells. Toxicol Lett 155:73-85 2005.
• Derfus AM, Chan WC, Bhatia SN. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 4:11-18 2004.
• Donaldson K, Aitken R, Tran L, et al. Carbon nanotubes: a review of their properties in relation to pulmonary toxicology and workplace safety. Toxicol Sci 92:5-22 2006.
• Goodman CM, McCusker CD, Yilmaz T, Rotello VM. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains. Bioconjugate Chem 15:897-900 2004.
• Helland A, Wick, P, Koehler A, Schmid K, Som, C. Reviewing the Environmental and Human Health Knowledge Base of Carbon Nanotubes. Env Hlth Perspec 115:1125-1131 2007
• Lademann J, Weigmann HJ, Rickmeyer C, Barthelmes H et al. Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular orifice. Skin Parmacol Appl Skin Physiol 12:247-256 1999.
• Lam CW, James JT, McCluskey R, Hunter RL Pulmonary toxicity of single-wall carbon nanotubes in mice 7 and 90 days after intratracheal instillation. Toxicol Sci 77:126-134 2004.
• Li Z, Hulderman T, Salmen R, Chapman R, et al. Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes. Environ Hlth Perspec 115:377-382 2007.
• Maynard AD, Baron PA, Foley M, Shvedova AA et al. Exposure to carbon nanotube material: aerosol release during the handling of unrefined single-walled carbon nanotube material. J Toxicol Environ Hlth, Part A, 67:87-107 2004.
• Monteiro-Riviere NA, Nemanich RJ, Inman AO, Wang YY et al. Multi-walled carbon nanotube interactions with human epidermal keratinocytes. Toxicol Lett 155:377-384 2005.
• Oberdorster E. Manufactured nanomaterials (fullerenes) induce oxidative stress in the brain of juvenile largemouth bass. Enn Hlth Perspec 112:1058-1062 2004.
• Oberdorster G, Ferin J, Lehnert BE. Correlation between particle size, in vivo particle persistence and lung injury. Env Hlth Perspec 102 (suppl 5):173-179 2004a.
• Oberdorster G, Sharp Z, Atudorei V, Elder A et al. Extrapulmonary translocation of ultrafine carbon particles following whole-body inhalation exposure of rats. J Toxicol Environ Hlth Part A 65:1531-1543 2002.
• Oberdorster G, Sharp Z, Atudonrei V, Elder A et al. Translocation of inhaled ultrafine particles to the brain. Inhal Toxicol 16:453-459 2004b.
• Poland CA et al. Carbon nanotubes introduced into the abdominal cabiety of mice show asbesotos-like pathogenicity in a pilot study. Nat Nanotech 3:423-428 2008.
• Rymen-Rasmussen JP, Riviere JE, Monteiro-Riviere NA. Penetration of intact skin by quantum dots with diverse physicochemical properties. Toxicol Sci 91:159-165 2006.
• Sayes CM, Fortner JD, Guo W, Lyon D et al. The differential cytotoxicity of water-soluble fullerenes. Nano Lett 4:1881-1887 2004
• Sayes CM, Liang F, Hudson JL et al. Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro. Toxicol Lett 161:135-142 2006
• Shvedova AA, Kisin ER, Mercer R, Murray AR, et al. Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice. Am J Physiol Lung Cell Mol Physiol 289:L698-L708 2005.
• Shvedova AA et al. Inhalation vs. aspiration of single-walled carbon nanotubes in C57BL/6 mice: inflammation, fibrosis, oxidative stress, and mutagenesis. Am J Physiol Lung Cell Mol Physiol 295:L552-L565 2008.
• Shiohara A, Hshino A, Hanaki K, Suzuki K, et al. On the cyto-toxicity caused by quantum dots. Microbiol Immunol 48:669-675 2004.
• Takagi A et al. Induction of mesothelioma in p53+/- mouse by intraperitoneal application of multi-wall carbon nanotube. J Toxicol Sci 33:105-116 2008.
• Tinkle SS, Antonini JM, Rich BA, Roberts JR et al. Skin as a route of exposure and sensitization in chronic beryllium disease. Env Hlth Perspec 111:1202-1208 2003.
• Wang J et al. Time dependent translocation and potential impairment on central nervous system by intranasally instilled TiO2 nanoparticles. Toxicol 254:82-90 2008
• Warheit DB, Laurence BR, Reed KL, Roach DH, et al. Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats. Toxicol Sci 77:117-125 (2004)
• Warheit DB, Webb TR, Colvin VC, et al. Pulmonary bioassay studies with nanoscale and fine-quartz particles in rats: toxicity is not dependent upon particle size but on surface characteristics. Toxicol Sci 95:270-280 2007.
• Warheit DB, Webb TR, Sayes CM et al. Pulmonary instillation studies with nanoscale TiO2 rods and dots in rats: toxicity is not dependent upon particle size and surface area. Toxicol Sci 91:227-236 2006.