## Summary of EPA’s Current Assessments of Health and

Environmental Effects of Carbon Nanotubes

U.S. Environmental Protection Agency

May 2010

Docket Identification Number

EPA-HQ-OPPT-2008-0252Summary of EPA’s Current Assessments of Health and Environmental

Effects of Carbon Nanotubes

Human Health Effects Su mmary for Carbon Nanotubes:

Absorption is expected to be poor via all routes for the carbon nanotubes based on test data for

chemicals with similar molecular structures and chemicals with similar physical/chemical properties. Data on other analogous substances indicate the potent ial for generation of increased amounts of respirable or absorbable particles dur ing processing and use of nanoscale materials.

Much more evaluation is needed to determine the toxicity of nanoscale mate rials for all routes of exposure. There are concerns for lung effect s, based on the EPA Respirable, Poorly Soluble

Particulates chemical cate gory. See www.epa.gov/oppt/newch ems/pubs/cat02.htm#Respirable. Based on test data for analogous chemicals includ ing other carbon nanotubes, there are concerns for pulmonary toxicity, fibrosis, carcinogenicit y, mutagenicity, and immunotoxicity of the PMN substance, There are also data suggesti ng that pulmonary deposition of some nanoscale materials, including carbon nano[tubes] in the agglomerated form, may induce cardiovascular toxicity when these nanoscale materials are inha led. The major health concerns are for potential pulmonary toxicity, fibrosis and cancer to wo rkers exposed via inhalation. Based on the uncertainty of the characterizati on and exposure of nanoscale materi als in general, there may be additional potential for translocation across the dermis and effects on target organs.

Bonner, J.C. et al., (2009). Inhaled multi -walled carbon nanotubes stimulate a pleural inflammatory response in the lung of mice. SOT Abst. NO. 2205.

Holker V, et al., (2005). Cardiova scular responses in unrestrained WKY rats to inhaled ultrafine carbon particles. Inhal. Toxicol. 17:29-42.

Hubbs, A. et al., (2009). Persistent pulmonary inflammation, airway mucousmetaplasia and migration of multi-walled carbon nanotubes from th e lung after subchronic exposure. SOT abst.

No. 2193.

Jia, G. et al., (2005). Cytotoxicity of carbon nanomaterials: Single-wall nanotube, multi-wall nanotube, and fullerene. Environ. Sci. & Technol. 39(5):1378-1383.

K. Donaldson, R. Aitken, L. Tran, V. Stone, R. Duffin, G. Forrest, a nd A. Alexander, (2006). Carbon nanotubes: A review of their propertie s in relation to pulmonary toxicology and workplace safety, Toxicol. Sci.

, 92 , 5-22.

Lam, et al., (2004). Pulmonary Toxicity of Single-Walled Carbon Nanotubes in Mice 7 and 90 Days after Intratracheal Instil lation. Toxicol. Sci. 77:126-134.

Landsiedel et al., (2009). Carbon na notubes tested in 5- and 90-day inhalation studies in rats.

SOT Abst. No. 2194.

Muller, J. et al., (2005). Respir atory toxicity of multi-wall carbon nanotubes. Toxicol Apply.

Pharmacol. 207: 221-231.

Muller, J. et al., (2008). Structur al defects play a major role in the acute lung toxicity of mutiwalled carbon nanotubes: Toxicological aspects. Chem. Res. Toxicol. 21:1698-1750.- 3 -

Nemmar A. et al., (2003). Size e ffect of intratracheally inst illed particles on pulmonary

inflammation and vascular thrombosis. Toxicol. Appl. Pharmacol. 186:38-45.

Nurkiewicz, et al., (2008). Nanoparticle inhala tion augments particle-dependent systemic microvascular dysfunction. Particle and Fibre Toxicology 5,1. Available from: http://www.particleandfibretoxicology.com/content/5/1/1.

Poland, C.A., R.Duffin, I. Kinloch, A. Maynard , W.A.H. Wallace, A. Seaton, V. Stone, S. Brown, W. MacNee, and K. Dona ldson, (2008). Carbon nanotubes intr oduced into the abdominal cavity of mice show asbestos-like pat hogenicity in a pilot study. Nature Nanotechnology 3 , 423 –

428.

Porter et al., (2009). Pulmonary toxicity in inhaled multi-walled carbon nanotubes. SOT Abst.

No. 2195.

Sayes, C.M. et al., (2005). Functionalizati on density dependence of single-walled carbon nanotubes cytotoxicity in v itro. Toxicol. Lett. 162:135-142.

Schladweier, et al., (2009). Single-walled carbon nanotubes indu ced pulmonary and vascular response following intratracheal instillation. SOT Abst. No. 2203.

Shvedova A.A., et al., (2005). Unusual Inflamma tory and Fibrogenic Pulmonary Responses to Single Walled Carbon Nanotubes in Mice. Am. J. Physiol. Lung Cell Mol. Physiol.: 10.1152-

1184.

Warheit D.B. et al., (2004). Comparative Pulm onary Toxicity Assessment of Single-wall Carbon Nanotubes in Rats. Toxicological Sciences 77:117-125.

Wolfarth, M.G. et al., (2009). Pulmonary toxici ty of multi-walled carbon nanotubes. SOT Abst.

No. 2196.- 4 -

Environmental Effects Su mmary for Carbon Nanotubes:

Toxicity from carbon nanotubes exposure has been reported in many aquatic species at concentrations much higher than any estimated solubility limits. Ev en though CNTs are not appreciably water soluble as manufactured, aque ous suspensions can be easily made through reaction with strong acids, ozone, or dispersing ag ents. Recent laboratory research shows that carbon nanotubes combine with dissolved organic matter to form stable aqueous suspensions.

No studies on carbon nanotubes are available in which a broad range of production methods, sources, purification, functionalizat ion, etc. were investigated. EPA expects that some fraction of the carbon nanotubes, if released into the envi ronment, will eventually become suspended in water. Sublethal effects have been noted for sing le-walled carbon nanotubes in fish at levels as low as 100 ppb. Noted effects included respiratory stress, ventilation rate, gill mucus secretion, gill damage, and aggressive behaviors. Liver cell injuries were also readily apparent at these exposure levels and suggest the possibility of liv er tumor formation over longer exposure periods. This response is also notable because effects were seen in cells closest to blood vessels, suggesting transport of respired or ingested single walled carbon nanotubes via the blood stream. Some effects in the gut lumen were also observed at these exposure levels. Further studies need

to be conducted before EPA can determine a c oncentration of concern. Such studies must

measure actual concentrations of carbon nanotubes and control fo r the effects of contaminants, solvents, and physical factors such as blockage of gills or intestines. Before such testing is conducted, advanced fate testing may also be n eeded to determine the environmental behavior.

Baun, A., Hartmann, N.B., Grieger, K. Kusk, K.O., (2008). Ecotoxicity of Engineered Nanoparticles to Aquatic Invert ebrates: A Brief Review and Recommendations for Future Toxicity Testing. Ec otoxicology. 17:387-395.

Blaise, C. Gagne, F., Ferard, J.F., Eullaffroy, P ., (2008). Ecotoxicity of Selected Nano-Materials to Aquatic Organisms. Environ. Toxicol. 23:591-598.

Cheng, J., Flahaut, E., Cheng, S.H., (2007). Effect of Carbon Nanotubes on Developing Zebrafish ( Danio rerio ) Embryos. Environ. Toxicol. Chem. 26:708-716.

Farre, M., Gajda-Schrantz, K., Kantiani, L., Ba rcelo, D., (2009). Ecotoxicity and Analysis of Nanomaterials in the Aquatic Environm ent. Anal. Bioanal. Chem. 393:81-85.

Handy, R.D., Owen, R., Valsami-Jones, E., (2008 ). The Ecotoxicology of Nanoparticles and Nanomaterials: Current Status, Knowledge Gaps, Challenges, and Future Needs. Ecotoxicology.

17:315-325.

Hyung, H., Fortner, J.D., Hughes, J., Kim J.H., ( 2007). Natural Organic Matt er Stabilizes Carbon Nanotubes in the Aqueous Phase. Environ. Sci., Technol. 41:179-184.

Klaine, S.J., Alvarez, P.J.J., Batley, G.E., Fe rnandes, T.F., Handy, R.D., Lyon, D.Y., Mahendra, S., McLaughlin, M.J., Lead, J.R., (2008). Nanomat erials in the Environment: Behavior, Fate, Bioavailability, and Effects. E nviron. Technol. Chem. 27(9):1825-1851.- 5 -

Maynard, A.D., Baron,P.A., Foley, M., Shvedova , A.A., Kisin, E.R., Castranova, V. (2004). Exposure to Carbon Nanobube Material: Aerosol release During the Handling of Unrefined Single-Walled Carbon Nanotube Ma terial. Journal of Toxicol ogy and Environmental Health, Part A. 67(1):87-107.

Mouchet, F., Landois, P., Sarremejean, E., Bern ard, G., Puech, P., Pinelli, E., Flahaut, E., Gauther, L., (2008). Characteris ation and in vivo ecotoxicity evaluation of double-wall carbon nanotubes in larvae of the amphibian Xenopus laevis . Aquatic Toxicol. 87:127-137.

Petersen, E.J., Huang, Q., Weber, W.J., (2008) . Ecological Uptake and Depuration of Carbon Nanotubes by Lumbriculus variegatus . Environ. Health Perspec. 116(4):496-500.

Roberts, A.P., Mount, A.S., Seda, B., Souther, J., Qiao, R., Lin, S., Pu Chun Ke, Rao, A.M., Klaine, S.J., (2007). In vivo Biomodificat ion of Lipid-Coated Carbon Nanotubes by Daphnia

magna . Environ. Sci. Technol. 41:3025-3029.

Smith, C.J., Shaw, B.J., Handy, R.D., (2007). To xicity of Single Walled Carbon Nanotubes to Rainbow Trout, (Oncorhynchus mykiss): Respirat ory Toxicity, Organ Pa thologies, and other Physiological Effects. Aquatic Toxicol. 82:84-109.

Templeton, R.C., Ferguson, P.W., Washburn, K.M ., Scrivens, W.A., Chandler, G.T., (2006). Life-Cycle Effects of Single- Walled Carbon Nanotubes (SWNTs) on an Estuarine Meiobenthic Copepod. Environ. Sci. Technol. 40:7387-7393.

Zhu, X., Zhu, L., Chen, Y., (2009). Acute Toxi cities of Six Manufactured Nanomaterial Suspensions to Daphnia magna . J. Nanopart. Res. 11:67-75.