TI: Steven Cragg RAD Disposition Meeting 

PM: Zofia Kosim October 21, 2010 

Revised January 12, 2009 with new exposure information and a revised NCEL 

Risk Assessment for P09-417 (formerly X09-0004)

This Report Contains CBI Information 

Background Information

 

P09-417, submitted by the CNano Corporation, is comprised of multi-walled nanotubes. The 

PMN is imported and expected to be used as an Electrical conductor in conductive polymers for 

anti-static and EMI applications (70%), a mechanical strength additive for liquid epoxy resins for 

numerous composites and adhesive applications (10%), and electrical conductor in electrode 

materials for super-capacitor/battery applications (20%). 

P09-417 is comprised of multiwalled carbon nanotubes (MWCNT) with the molecular weight, 

length, and diameter ranges stated below. The PMN particles are highly agglomerated resulting 

in a size range of 95% larger than 100 micrometers based on the particle sizing method of 

Dynamic Light Scattering (DSL), which is conducted in a fluid. Consequently, at least 95% of 

the particles would not be expected to be respirable into the deep lung. Deep lung respirable 

particles are considered to have a maximum diameter of 10 micrometers thus perhaps 99% plus 

percent may not be deep lung respirable. However, there is considerable uncertainty in the DSL 

method since it is conducted in a fluid and may miss smaller particles. 

 

Physicochemical Properties (Chemistry Report)

Properties 

Molecular 

Formula: 

C Molecular Weight: 1000000.00 

%<500: %<1000: 

MP: MP Estimate: 

BP: BP Pressure (Torr): BP Estimate: >400

VP: VP Estimate: <0.000001 

Water 

Solubility: 

 Water Soluble 

Estimate: 

<0.000001 

Log P: Log P Estimate: 

Physical 

State--Neat: 

Solid Physical State--

Manuf: 

NK: Import 

Physical 

State--

Processing: 

Solid: Physical State--End 

Use: 

Solid:
Standard Review Risk Assessment for P09-417 

January 12, 2010 Page 2 of 47 

Chemical structure P09-417

Health Hazard Reports

Stated Concerns from the Structure/Activity Team (SAT) Report: 

There are possible concerns for immunotoxicity, oncogenicity and mutagenicity based on 

analogs (SAT Report) 

Absorption, Distribution, Metabolism, Excretion: 

The PMN is expected to be poorly absorbed via all routes of exposure based on analogues. 

There are concerns for lung overload for poorly soluble particulates and for lung effects based on 

submitted test data (submitted with P09-417). There are possible concerns for immunotoxicity, 

oncogenicity and mutagenicity based on analogs (SAT Report) 

General Toxicity (D. Lai): 

A number of non-genetic in vitro and in vivo toxicity studies on the PMN substance were 

submitted. P09-417 appeared to show low/no cytotoxicity and pro-inflammatory effects on 

HepG2 cells, and low/no dermal toxicity or sensitizing effects on in vitro reconstituted 

epidermis. However, in vitro assays have limited usefulness for hazard identification of 

nanoparticles due to a number of inherent issues; several studies have shown no correlations 

between in vitro and in vivo assays of some nanoparticles. 

Additional 

Chemical 

Info: 

The molecular weight is variable and depends on the size of the nanotube 

 Estimated Data: BP > 400 °C 

(High MW); VP < 0.000001 torr (High MW); WS < 0.000001 g/L (High MW). 
Standard Review Risk Assessment for P09-417 

January 12, 2010 Page 3 of 47 

A 5-day inhalation study in rats showed moderate increases in several biochemical parameters in 

the bronchoalveolar lavage fluid (BALF) analysis and mild multifocal granulomatous 

inflammation in the lungs. 

A 90-day inhalation study conducted by with P09-417 MWCNT’s revealed moderate 

granulomatous inflammation, severe alveolar histiocytosis, lipoproteinosis and minimal 

neutrophil infiltration . 

is another MWCNT analogous to P09-417 with more detailed information regarding its 

dimensions. has an average diameter of and an average length of 

. exists as simple and complex agglomerates of carbon nanotubes by weaving 

around each other and held together by van der Waals force. The carbon nanotube agglomerates 

are roughly spherical in shape and their dimensions range from about 10 to 100 μm. Some of the 

small agglomerates of (<10 μm) are respirable in humans. Furthermore, the 

agglomeration strength is not very high and they are considered loose with empty space between 

the individual carbon nanotube fibers. Once deposited in the alveolar region, simple 

agglomerates of may dissociate to individual carbon nanotubes when interacting with 

lung surfactant. Some research has suggested that carbon nanotubes may behave as asbestos 

fibers with similar consequences. Therefore, by analogy to asbestos fibers and based on data of 

some carbon nanaotubes (MWCNT and SWCNT), there is concern for pulmonary toxicity, 

fibrosis, lung cancer, and mesothelioma for these materials. Evidence in mice shows that carbon 

nanotubes can translocate from the respiratory tract to regional lymph nodes as well as penetrate 

to the pleural lining of the lung causing inflammation. In addition, there are data suggesting that 

pulmonary deposition of some nanoparticles, including carbon nanotubes, may induce 

cardiovascular toxicity when inhaled. 

Mutagenicity: 

No mutagenicity data were provided with PMN P09-417. Based upon reports on similar 

materials, P09-417 (1) may induce gene mutations in mammalian cells in culture but not in 

prokaryotes or lower eukaryotes; (2) may be a weak inducer of aneuploidy but not of structural 

chromosome aberrations in mammalian cells in culture; (3) may induce DNA effects in 

mammalian cells in culture, but not in lower eukaryotes in vivo, and; (4) may not induce cell 

transformation in mammalian cells in culture. 

 

Due to uncertainty about their ability to penetrate cells, testing of nanomaterials in genotoxicity 

assays is problematic, and negative responses would not conclusively rule out the potential 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 4 of 47 

mutagenicity hazard of nanotubule materials in humans. No testing of the PMN is recommended 

at this time. 

Immunotoxicity: 

Based on published scientific data for similar multi-walled carbon nanotubes, P09-417 as the 

potential to cause immunotoxicity. Pulmonary exposure to this PMN may lead to reduced 

alveolar macrophage phagocytosis, impaired clearance of inhaled bacteria, inflammation, 

possible systemic immunosuppression, and promotion of allergy. 

Occupational Exposure:

From the submission, the stated use of P09-417 MWCNTs is to improve electrical, thermal 

and/or mechanical properties in plastics. Other uses for analogous MWCNTs in the past have 

been for reinforcing agents for ceramics in bullet-proof vests, electrical conductors to enhance 

conductivity of electrodes for batteries, and as conductors (electrical and thermal) for use in resin 

composites. Other uses are described in the attached engineering report. 

The PMN will be imported as pure MWCNTs or mixed into “master batches” of plastic 

precursors containing from 0.5 to 20% MWCNTs. 

 It is assumed that the PMN will be used in the production of 

plastics at sites operating 250 days/year with no direct exposure of the general public. The 

number of workers is expected to range from per site. 

Health Risk Assessment

The major health concerns for the PMN are for potential pulmonary toxicity, fibrosis and cancer 

to workers exposed via the inhalation route. There are also data suggesting that pulmonary 

deposition of some nanoparticles, including carbon nanotubes, may induce cardiovascular 

toxicity when inhaled. 

Scenario # Sites # Workers Release d/ yr Inhal (mg/d) Derm (mg/d) 

Processing 1: Incorporating CNTs 

into Master Batches 

 250 0.0018 6 

Processing 2: Incorporating CNTs 

into Coatings 

 250 0.2 worst-case 6-8 

Use: Application of Coating to 

Metal or Wood 

 250 Negligible 8 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 5 of 47 

 

 

 

Human Health Testing Recommendation

The concerns for significant inhalation risks are confounded by limited understanding of both the 

health hazards and estimated exposures in this case. The need for testing is questionable because 

 Use of natural material that has not been micronized 

could be expected to provide a higher LOAEL than for unmicronized material (i.e., be toxic only 

at higher concentrations or not toxic at all). Thus, the findings in the rat study reflect artificially 

enhanced exposure not likely to be encountered in the work environment. If realistic particle 

sizes had been used in the rat study, the NCEL derived from it may have been enough higher to 

exceed estimated exposures. 

Due to the great uncertainty in assessing particle sizes of the CNT’s, better characterization of 

actual particle size distributions of respirable particles in the work environment is needed using 

instruments such as a cascade impactor. Definitive particle-size distribution information would 

indicate the need for and structure of subsequent toxicity testing on the PMN substance. 

Personal Protective Equipment and Industrial Hygiene Control Recommendations

Until such time as particle size information is better characterized, PPE and IH controls should 

include: a NIOSH-approved, full-face air-purifying particulate respirator with N, P, or R-100 

filter, or hood respirator with an assigned protection factor (APF) of at least 25; permeation 

resistant gloves; and impervious clothing. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 6 of 47 

Ecological Risk Assessment for P09-417 

Hazard Assessment: This PMN and other carbon nanotubes (CNTs) have very low water 

solubility – estimated to be less than 1 μg/L (see chemistry report). As a result, one might expect 

that the concentrations of CNTs in the water column of surface water bodies or in groundwater 

would be negligible with little or no adverse effects to aquatic species. However, reports in the 

literature indicate adverse effects to aquatic species tested in the laboratory at concentrations 

claimed to be above the expected water solubility limit. Reasons that might account for this 

apparent discrepancy include: 1) use of artificial techniques to enhance the solubility of CNTs in 

the test media (e.g., with solvents), or 2) contamination of CNTs

 used during manufacture that may leach out during solubilization and 

be the actual cause of any observed toxicity at the CNT loading rates above anticipated solubility 

limits. Beyond this, CNTs may be derivatized with chemical moieties that confer desired 

performance properties for a variety of applications. Some of these chemical moieties (e.g., 

hydroxylated derivatives, protein coats) may increase water solubility of CNTs, accounting for 

reported effects at concentrations higher than the theoretical solubility limit. With regard to 

exposure in the environment, greater than expected concentrations may be attained by CNTs in 

ambient waters due to the presence of organic particulate matter such as humic acid or other 

forms of organic materials upon which CNTs may adsorb. 

CNTs adsorbed onto in the water column or in sediments, if strongly bound, might be 

expected to show little toxicity to aquatic organisms. Or observed toxicity might be due to 

physical effects rather than direct chemical toxicity, such as particles adhering to gills thereby 

interfering with oxygen transfer, or blocking the gut of larval fish or copepods and causing 

immobilization or death from this effect. A brief review of the published literature follows. 

Using “small scale” in vitro tests with a variety of microorganisms, Blaise et al. (2008) found 

growth inhibition in Pseudokirchneriella subcapitata at a reported nominal concentration of 1 

mg/L and no effects for other organisms. Actual concentrations were not reported. 

Hyung et al. (2007) reported enhanced solubilization of MWCNTs in the presence of “natural 

organic matter” that remained stable for over 1 month at measured concentrations as high as 500 

mg/L. 

Mouchet et al (2008) studied the effects of double-walled CNTs on larvae of Xenopus laevis 

exposed for 12 days at concentrations ranging from 10 to 500 mg/L. No genotoxicity (i.e., 

erythrocyte micronuclei) were found at any concentration but frank toxicity was observed at all 

concentrations, which the authors attributed to physical blockage of the gills and/or digestive 

tract. 

Petersen et al. (2008) evaluated uptake and depuration of C14-radiolabeled single- and doublewalled CNTs on Lumbriculus variegatus finding little test substance accumulation in this 

sediment-dwelling species compared to pyrene. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 7 of 47 

Roberts et al. (2007) facilitated solubilization of SWCNTs in water by coating with the lipid, 

lysophosphatidylcholine. Daphnia were subsequently exposed to and ingested the particles. The 

lipid coating was digested leaving the uncoated particle. The authors concluded that aquatic 

organisms could alter SWCNTs. Toxicity to the daphnia occurred at 10 mg/L or higher. 

Smith et al. (2007) exposed juvenile rainbow trout to SWCNTs at concentrations of 0, 0.1, 0.25, 

or 0.5 mg/L (facilitated by the detergent-like solvent, sodium dodecyl sulfate and sonication) for 

up to 10 days under semi-static conditions monitoring a variety of endpoints including clinical 

observations, clinical chemistry, differential blood analysis, and histopathology. Effects on the 

gill and brain were found that may be related to the accumulation of SWCNTs on gills 

(inhibiting oxygen uptake) and/or to the sodium dodecylsulfate vehicle rather than a direct toxic 

effect of SWCNTs to fish. 

Templeton et al (2006) found no significant effects in full life-cycle studies with the estuarine 

meiobenthic copepod, Amphiascus tenuiremis exposed either acutely or chronically to 

chemically purified SWCNTs at sedimentary concentrations of 0, 0.58, 0.97, or 1,5, or 10 mg/L 

(presumed to be loading concentrations). 

Zhu et al. (2009) examined the acute toxicity (immobilization) of single- and multi-walled CNT 

suspensions to Daphnia magna. The 48-hr EC50s for SWCNTs was 1.3 mg/L and for 

MWCNTs was 8.7 mg/L. Reported exposure concentrations are presumed to be nominal. When 

examined microscopically, large amounts of black material were found in the guts of the 

daphnids which may have accounted for the toxicity. 

To summarize, toxicity from exposure to CNTs has been reported in multiple aquatic species at 

concentrations much higher than estimated solubility limits. Various techniques have been 

employed to increase solubilization and creation of stable suspensions. Most reported 

concentrations are nominal with high loading rates. Actual concentrations have rarely been 

reported. Thus, the actual concentrations may be much less than reported. In those studies that 

have reported significant toxicity, the reported adverse effects may have been due to: 

 2) toxic solvent vehicles; 3) physical disruption of oxygen 

transport via the gills, or; 4) intestinal blockage after ingestion of CNTs rather than direct 

toxicity from CNTs. 

Further studies need to be conducted before a concentration of concern may be derived. Such 

studies must measure actual concentrations of CNTs and must control for the effects of 

contaminants, solvents, and physical factors such as blockage of gills or intestines. 

Ecological Exposure Assessment: The average surface water concentration of these materials 

cannot be predicted reliably with the present state of knowledge (EPA/EETD). Moreover, in the 

aquatic ecotoxicity studies conducted to date, the analytical characterization of the CNT 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 8 of 47 

concentrations has been poor or not performed for most of the investigations. Rather, nominal or 

loading rate concentrations have been relied upon. For most of the studies, attendant toxicities 

have been associated with these nominal concentrations without a true understanding of actual 

concentrations. 

Ecological Risk Characterization: Consequently, the risk of such materials to aquatic organisms 

in the environment cannot be determined quantitatively by comparing predicted surface water 

concentrations with a concentration of concern. Qualitatively, risk to aquatic organisms from the 

chemical characteristics of CNTs might be expected to be low because of the extremely low 

solubility of these materials in water. No ecotoxicity testing is recommended at this time. 

References: 

Blaise, C. Gagne, F., Ferard, J.F., Eullaffroy, P., (2008). Ecotoxicity of Selected Nano-Materials 

to Aquatic Organisms. Environ. Toxicol. 23:591-598. 

Hyung, H., Fortner, J.D., Hughes, J., Kim J.H., (2007). Natural Organic Matter Stabilizes Carbon 

Nanotubes in the Aqueous Phase. Environ. Sci., Technol. 41:179-184. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 9 of 47 

Mouchet, F., Landois, P., Sarremejean, E., Bernard, G., Puech, P., Pinelli, E., Flahaut, E., 

Gauther, L., (2008). Characterisation 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 Biomodification of Lipid-Coated Carbon Nanotubes by Daphnia 

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

Smith, C.J., Shaw, B.J., Handy, R.D., (2007). Toxicity of Single Walled Carbon Nanotubes to 

Rainbow Trout, (Oncorhynchus mykiss): Respiratory Toxicity, Organ Pathologies, 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 Toxicities of Six Manufactured Nanomaterial 

Suspensions to Daphnia magna. J. Nanopart. Res. 11:67-75. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 10 of 47 

Appendices 

Structure Activity Report (SAT) (J. Kwait) Page 11 

Human Health Review (D. Lai) Page 14 

Immunotoxicity (R. Ward) Page 19 

Genotoxicity (M. Cimino) Page 22 

Chemistry Report (D. Darling) Page 26 

Engineering Report (F. Arnold) Page 29 

Exposure Report (C. Cinalli) Page 40 

Economics Report (K. Loughery) Page 43 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 11 of 47 

SAT Report 

PMN Number: P-09-0417 

SAT Date: 3/10/2009 

Print Date: 9/4/2009 

Related cases: CBI: Yes 

Health related cases: 

 Ecotox related cases: 

Concern levels:

Type of Concern: Health Eco Comments

Level of Concern: 2 1 

 Persistence Bioaccum Toxicity Comments

 3 U 

Exposure Based Review:

Health: No 

Ecotox: No 

Routes of exposure: Health: Inhalation, dermal, drinking water 

Ecotox: No releases to water 

Fate: ; 

Keywords:

 Keywords: LUNG 

IMMUNO 

UNCERT MUTA 

ONCO 

Summary of Assessment:

 Fate:

Fate Summary: 

FATE: 

Solid 

S < 0.001 mg/L at 25 EC (E) 

VP < 1.0E-6 torr at 25 EC (E) 

BP > 400 EC (E) 

H < 1.00E-8 (E) 

POTW removal (%) = U via U 

Time for complete ultimate aerobic biodeg = U 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 12 of 47 

Sorption to soils/sediments = U 

PBT Potential: P3BU 

*CEB FATE: Migration to ground water = U 

 

Health:

Health Summary: Expect poor absorption via all routes (analog). There is concern for lung 

overload for a poorly soluble particulate, and for lung effects, based on submitted test data. 

Possible concerns for immunotoxicity and oncogenicity, and uncertain concern for mutagenicity, 

based on analogs. 

 

Test Data: Submitted with the PMN: 

Rat acute (inhalation) toxicity with moderate increases in total protein and 

enzymes at all doses and increased lung weights and lung discoloration at 

higher doses; 

Rat acute oral with no toxic signs (summary only; unclear data) 

Rat 90 D inhalation toxicity with adverse lung effects; 

In vitro human skin model test showed no cytotoxicity or irritation 

Submitted with 

Rat acute oral (gavage) toxicity LD50 > 2000 mg/kg; 

Not a dermal irritant in rabbits; 

Mild eye irritant in rabbits 

 Ecotox:

Test 

Organism 

Test 

Typ

e 

Test End 

Point 

Predicted Measured Comments 

fish 96-h LC50 * 

daphnid 48-h LC50 * 

green algal 96-h EC50 * 

fish chronic value * 

daphnid _ chronic 

value 

* 

algal _ chronic 

value 

* 

Sewage 

Sludge 

3-h EC50 _ 

Sewage 

Sludge 

_ Chronic 

Value 

_ 

Ecotox Values Comments: Predictions are based on SARs for neutral organic chemicals; 

SAR chemical class = C-graphite-multi-walled carbon nanotubes; MW>1,000,000; solid; log 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 13 of 47 

Kow >> 10 (P); S = negligible; pH7; effective concentrations based on 100% active ingredients 

and nominal concentrations; DW hardness < 150.0 mg/L as CaCO3; and DW TOC <2.0 mg/L; 

Factors Values Comments 

Assessment Factor 10 

Concentration of Concern 

(ppb) 

 * 

SARs neutral organic chemicals 

SAR Class carbon allotrope 

Ecotox Factors Comments: 

 SAT Chair: J. Kwiat 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 14 of 47 

April 24, 2009 

MEMORANDUM

SUBJECT: Health Hazard Review of X-09-4 

FROM: David Lai (ECAB/RAD) 

TO: Steve Cragg (NCSAB/RAD)

THRU: Jennifer Seed (ECAB/RAD) 

 Attached is my review of the health hazard potential of the subject PMN. 

Please contact me should you have any questions regarding this review. 

 This memo. contains Confidential Business Information. 

Attachment 

cc: 

 Bob Morcock 

Health Hazard Review of X-09-4 (Re-Designated P09-417) 

 

I. CONCLUSION 

 X-09-4 contains multiwalled carbon nanotubes (MWCNT) with an

 Therefore, the PMN are mostly 

are not expected to be respirable to the lungs and permeable to 

the skin. 

A number of in vitro and in vivo toxicity studies on the PMN substance were submitted. 

X-09-4 appeared to show low/no cytotoxicity and proinflammatory effects on HepG2 cells, and 

low/no dermal toxicity or sensitizing effects on in vitro reconstituted epidermis. However, in 

vitro assays have limited usefulness for hazard identification due to a number of inherent issues; 

seversl studies have shown no correlations between in vitro and in vivo assays of some 

nanoparticles. A 5-day inhalation study in rats showed moderate increases in several 

biochemical parameters in the bronchoalveolar lavage fluid (BALF) analysis and mild multifocal 

granulomatous inflammation in the lungs. A 90-day inhalation study revealed moderate 

granulomatous inflammation, severe alveolar histiocytosis, lipoproteinosis and minimal 

neutrophil infiltration at 2.5 mg/m3

. The histopathological findings at lower concentration levels 

were similar to those observed at 2.5 mg/m3 but of less severity. The No Observed Effect 

Concentration (NOEC) was 0.1 mg/ m3

. The aerosol of X-09-4 in these inhalation studies were 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 15 of 47 

generated by brush particle generators to respirable sizes (MMAD: 0.5-2.0 μm) and may not be 

representative to the PMN substance being exposed to workers or the general populations. 

II. BASIS OF CONCLUSION 

X-09-4 contains multiwalled carbon nanotubes (MWCNT)

 the PMN are mostly 

are not expected to be respirable to the lungs and permeable to 

the skin. 

A number of in vitro and in vivo toxicity studies on the PMN substance were submitted. 

These studies were conducted following OECD guidelines for the Testing of Chemicals. 

1. In Vitro Assays

 X-09-4 

were suspended in an aqueous solution and dispersed by agitation and 

sonication. 

 In order to investigate the potential cytotoxicity of the PMN substance, the human 

hepatoma cells HepG2 were incubated with X-09-4 at concentrations of 100 μg/ml, 500 μg/ml, 

and 1 mg/ml for 24 hrs. or 48 hrs. X-09-4 did not induce LDH release, caspase-3 activation and 

secretion of IL-8 in HepG2 cells, suggesting that the PMN substance may have low/no 

cytotoxicity and pro-inflammatory effects on HepG2 cells. 

In order to determine whether X-09-4 are able to cross the cornified layer and induce 

morphological changes in epidermis, epidermis reconstituted from human keratinocytes with a 

functional stratum corneum were incubated with the PMN substance as dry powders (2.5 

mg/cm3

) directly deposited on the cornified layers for 24 hrs.or 72 hrs. No cytotoxicity, 

irritation, sensitizing effects, nor any local cell damages were observed, suggesting that X-09-4 is 

not able to cross the cornified layers of epidermis. 

 2. In Vivo Studies

A. Acute (5-day) Inhalation study. 

To determine the appropriate concentrations for a 90-day subchronic inhalation study, a 

5-day range finding study was carried out with X-09-4. Groups of 8 male Wistar rats were headnose exposed to respirable dusts of the PMN substance at 2, 8, and 32 mg/m3

 6 hr/day for 5 days. 

The aerosol of X-09-4 were generated by brush particle generators and the sizes of the generated 

aerosol (Mass Median Aerodynamic Diameter/MMAD: ) were within the respirable 

range ( ). Animals were sacrificed on study day 7 and 28. Five 

animals/group underwent bronchoalveolar lavage fluid (BALF) analysis and 3 animals/group 

were used for histopathological examination. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 16 of 47 

Examination of the BALF showed moderate increases of total proteins, total cell counts 

and enzymes in all test groups as compared to the controls. Some effects were reversible at the 

low concentration, whereas other effects, such as polymorph nuclear granulocytes activation 

were still observed, albeit less pronounced, after a 3-week recovery period. Gross necropsy 

examination showed the absolute and relative lung weights were significantly increased in 

animals exposed to 8 and 32 mg/m3. These increases were still measured in the high-dosed rats 

after a 3-week recovery period. Histopathological examination showed a concentrationdependent multifocal granulomatous inflammation accompanied by diffuse histiocytosis, 

hyperplasia/-trophy of the bronchial epithelium and granulocytic infiltration in the lungs of the 

treated rats. 

B. Subchronic (90-day) Inhalation study. 

Groups of 10 male and 10 female Wistar rats were exposed nose-only to dust aerosol of 

the PMN substance at 0, 0.1, 0.5, and 2.5 mg/m3 6 hr/day, 5 day/week for 90 days.. The MMAD 

of the aerosol generated by brush particle generators ranged between During 

necropsy, the absolute and relative lung weights were significantly increased in animals exposed 

to 0.5, and 2.5 mg/m3

. Histopathological examination showed moderate granulomatous 

inflammation, severe alveolar histiocytosis, lipoproteinosis and minimal neutrophil infiltration at 

2.5 mg/m3

. The histopathological findings at 0.5 mg/m3 were similar to those observed at 2.5 

mg/m3

 but of less severity. At 0.1 mg/m3, granulomas were also seen in one male and 4 of the 

10 female rats. Based on these findings, the No Observed Effect Concentration (NOEC) is 0.1 

mg/m3. 

 

Summary and Discussions 

X-09-4 appeared to show low/no cytotoxicity and proinflammatory effects on HepG2 

cells, and low/no dermal toxicity or sensitizing effects on in vitro reconstituted epidermis. 

However, in vitro assays have limited usefulness for hazard identification due to a number of 

inherent issues; several studies have shown no correlations between in vitro and in vivo assays of 

some nanoparticles 

In the acute and subchronic inhalation studies, findings in both BALF analysis and 

histopathological examination indicate a pulmonary carcinogenicity potential of the test 

materials. These findings are not too surprising because the test materials are long and thin 

carbon nanotubes with a high aspect ratio, and therefore, may exhibit some of their effects 

(through oxidative stress and inflammation) as asbestos fibers (Donaldson et al., 2006). A recent 

panel review has identified many similarities between high aspect ratio nanoparticles (HARN) 

and asbestos with regard to their physicochemical properties and toxicological effects and has 

concluded that there is sufficient evidence to suggest that HARN which have the same 

characteristics (diameter, length and biopersistence) as pathogenic fibers are likely to have 

similar pathology (Tran et al., 2008). Studies conducted by Lam et al. (2004) and Warheit et 

al.(2004) examining the pulmonary toxicity of SWCNT by intratracheal instillation in mice and 

rats, respectively, have both reported an epithelial granulomatous reaction to SWCNT. 

Exposures to MWCNT by pharyngeal aspiration (Wolfarth et al., 2009) or by short-term (up to 8 

days) or subchronic (90-days) inhalation (Landsiedel et al., 2009; Porter et al., 2009) have 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 17 of 47 

resulted in dose-dependent increases in pulmonary inflammation and evidence of fibrosis in rats 

and mice. Exposing the mesothelial lining of the body cavity of mice (as a surrogate for the 

mesothelial lining of the chest cavity) to long MWCNT by injection has resulted in asbestos-like, 

length-dependent, pathogenic behavior (Poland et al., 2008). Evidence that MWCNT can cause 

persistent pulmonary inflammation, can be translocated from the lung to the regional lymph node 

and can penetrate the pleura to cause pleural inflammation has indeed been shown in mice 

exposed by pharyngeal aspiration (Hubbs, et al., 2009) or by inhalation (Bonner et al., 2009). 

However, the aerosol of X-09-4 in these inhalation studies were generated by brush 

particle generators to respirable sizes (MMAD: 0.5-2.0 μm) and may not be representative to the 

PMN substance being exposed to workers or the general populations. of 

the PMN substance is expected to modify many of the physicochemical properties (e.g., surface 

properties) which are important for their toxicity/carcimnogenicity 

 have shown that preparation of a MWCNT test sample 

by can lead to generation of surface structural defects and 

chemically reactive oxidation sites in the carbon nanotube framework. Photomicrographs of the 

nanotube structures of another PMN substance before and after the 

 illustrating the disruption of the nanotubes from a solid to lacey surface has been 

shown. 

III. TEST RECOMMENDATION 

According to the submission, the agglomerated PMN particles are embedded in a 

polymeric matrix, and as such, human exposures are expected to be negligible. No further 

testing is recommended unless there is evidence that this PMN substance will be deagglomerated to respirable sizes during processing or uses. In that case, a 2-yr. inhalation 

bioassay in rats is recommended for the samples generated. 

REFERENCES

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. 

K. Donaldson, R. Aitken, L. Tran, V. Stone, R. Duffin, G. Forrest, and A. Alexander, Carbon 

nanotubes: A review of their properties in relation to pulmonary toxicology and workplace 

safety, Toxicol. Sci., 92, 5-22, 2006. 

Hubbs, A. et al., 2009. Persistent pulmonary inflammation, airway mucousmetaplasia and 

migration of multi-walled carbon nanotubes from the lung after subchronic exposure. SOT abst. 

No. 2193. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 18 of 47 

Lam, et al. 2004.Pulmonary Toxicity of Single-Walled Carbon Nanotubes in Mice 7 and 90 Days 

after Intratracheal Instillation. Toxicol. Sci. 77:126-134. 

Muller, J. et. Al., 2005. Respiratory toxicity of multi-wall carbon nanaotubes. Toxicol Apply. 

Pharmacol. 207: 221-231. 

Landsiedel et al., 2009. Carbon nanotubes tested in 5- and 90-day inhalation studies in rats. SOT 

Abst. No. 2194. 

Poland, C.A., R.Duffin, I. Kinloch, A. Maynard, W.A.H. Wallace, A. Seaton, V. Stone, S. 

Brown, W. MacNee, and K. Donaldson, Carbon nanotubes introduced into the abdominal cavity 

of mice show asbestos-like pathogenicity in a pilot study. Nature Nanotechnology 3, 423 – 428, 

2008. 

Porter et al., 2009. Pulmoanry toxicity in inhaled multi-walled carbon nanotubes. SOT Abst. No. 

2195. 

Tran, C.L. et al., 2008. An outline scoping study to determine whether high aspect ratio 

nanoparticles (HARN) should raise the same concerns as do asbestos fibres. Institute of 

Occupational Medicine, UK, Report on Project CB0406, August 13. 

Warheit D.B. et al. 2004. Comparative Pulmonary Toxicity Assessment of Single-wall Carbon 

Nanotubes in Rats. Toxicological Sciences 77:117-125. 

Wolfarth, M.G. et al., 2009. Pulmonary toxicity of multi-walled carbon nanotubes. SOT Abst. 

No. 2196. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 19 of 47 

04/27/09

MEMORANDUM 

X09-0004 has been re-designated P09-417 

SUBJECT: X09-4: Immunotoxicity Standard Review 

 

FROM: Ronald E. Ward Ph.D., Microbiologist/Immunologist 

 RAD/SSB (7403M) 

THRU: Donald Rodier, Branch Chief 

 RAD/SSB (7403M) 

 

TO: Steve Cragg Ph.D., Technical Integrator 

 NCSAB (7403M) 

 

TSCA CONFIDENTIAL BUSINESS INFORMATION 

 

Conclusion: Based on published scientific data analogs, (Multi-walled carbon 

nanotubes) would be an immunotoxicity hazard. Pulmonary exposure to this PMN may lead to 

reduced alveolar macrophage phagocytosis, impaired clearance of inhaled bacteria, 

inflammation, possible systemic immunosuppression, and promotion of allergy. 

Basis for Conclusion: X09-4 will be used as a plastics additive to improve electrical, thermal 

and/or mechanical properties (1). This PMN will be poorly absorbed into the body via all routes 

(2). Since there were no immunotoxicity data associated with this PMN, the conclusions 

reached here are based on analog published scientific data. 

 This PMN consists of nano-sized particles. There is a concern that nano-sized particles, 

having an increased surface area per unit mass, may be more toxic than larger particles. Due to 

the concerns over the risk of nanomaterials, there has been a recent increase in nanomaterialrelated safety research. In addition, several related reviews have been published. 

 According to two recent reviews (3,4), most research supports the idea that both multiwalled and single-walled carbon nanotubes have the potential to cause pulmonary toxicity. Once 

taken up by humans, carbon nanotubes may cause oxidative stress, inflammation, and cell 

damage leading to effects like granulomas, fibrosis and wall thickening. The review by Stern et 

al.(4) lists 7 published rodent pulmonary CNT toxicity studies. All but one showed evidence of 

lung toxicity. 

 Studies in the literature also support the idea that both local pulmonary immunity and 

systemic immunity can be impacted following CNT inhalation. Alveolar macrophages are 

important in both innate and adaptive immunity in the lung. These cells play a central role in the 

defense against respiratory bacteria, virus, and fungal infections. 

 In a recent publication, Shvedova and coworkers (5) showed that intratracheal instillation 

of SWCNT in mice not only elicited inflammation and lung damage, but also caused a delayed 

clearance of Listeria monocytogenes. In their experiments, C57Bl/6 mice were given SWCNT 

(0, 10 and 40 μg/mouse via pharyngeal aspirations) and 3 days later exposed to Listeria 

monocytogenes (103

 bacteria/mouse). Exposure to both SWCNT and Listeria monocytogenes 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 20 of 47 

amplified lung inflammation and collagen formation. Despite this inflammatory response, 

SWCNT pre-exposure significantly decreased the pulmonary clearance of Listeria 

monocytogenes measured 3 - 7 days after microbial infection relative to controls. Decreased 

bacterial clearance in SWCNT pre-exposed mice was associated with decreased phagocytosis of 

bacteria by macrophages and a decrease in nitric oxide production by these phagocytes. These 

results support the idea that SWCNT exposure may lead to increased susceptibility to lung 

infections in exposed populations. 

 Systemic immunotoxicity to inhaled multiwalled carbon nanotubes was the subject of a 

recent published study (6). In this study, C57BL/6 adult (10-12 weeks old) male mice were 

exposed via whole body inhalation to control air or 0.3, 1, or 5 mg/m3 respirable aggregates of 

MWCNTs (diameter=10-20 nm and length=5-15 μm) for 7 or 14 days (6 hr/day). (In a later 

publication, this material was shown to be a mixture of MWCNTs and nanofibers.) At the end of 

this period, pulmonary injury was analyzed using standard measures including histopathology, 

WBC count, and some measurements of oxidative stress and cytokine induction. In addition, the 

ability of this substance to cause systemic immunosuppression was analyzed. 

 The histopathology results of this study showed that particulate material was contained in 

alveolar macrophages, but no inflammation or tissue damage was observed. Bronchial alveolar 

lavage fluid analysis also demonstrated particle-laden macrophages, with no increase in WBC 

count. However, MWCNT/nanofiber exposure of 0.3 mg/m3 and higher concentrations caused 

systemic immunosuppression after exposure for 14, but not 7, days. The immunosuppression 

was characterized as a reduced T-cell dependent antibody response to sheep erythrocytes, as well 

as a reduced T cell proliferation induced by concanavalin A, a T cell mitogen. Animals exposed 

to 1 mg/m3 also had decreased NK cell function. These results showed that, even though the 

nanoparticle material caused no pulmonary injury or inflammation, MWCNT/nanofiber mixture 

exposure resulted in systemic immunosuppression. 

 To help elucidate a mechanism, the authors of this report found that the mRNA levels for 

the cytokine interleukin-10 (IL-10) and the enzyme NAD(P)H oxidoreductase 1 (an indicator of 

oxidative stress) were increased in the spleen, but not the lung, upon 14 day exposure. These 

authors suggest that oxidative stress and IL-10 may play roles in inducing immunosuppression. 

 In a recent publication, (7) MWCNTs have also been shown to promote allergic immune 

responses in mice. This publication showed that both MWCNT and SWCNT could act a 

adjuvants and help promote airway inflammation and a specific IgE response to ovalbumin upon 

inhalation exposure in BALB/c mice. 

 Collectively, these results support the idea that X09-4 would be a potential 

immunotoxicity hazard. Pulmonary exposure to this PMN may lead to reduced alveolar 

macrophage phagocytosis, impaired clearance of inhaled bacteria, inflammation, possible 

systemic immunosuppression, and promotion of allergy. 

References

 

3. Helland, A. et al. Reviewing the Environmental and Human Health Knowledge Base of 

Carbon Nanotubes. EHP 115 (8), 1125-1131 (2007). 

4.Stern, S, and McNeil, S. Nanotechnology Safety Concerns Revisited. Tox. Sci. 101, 4-21 

(2008). 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 21 of 47 

5. Shvedova, A. et al. Sequential Exposure to Carbon Nanotubes and Bacteria Enhances 

Pulmonary Inflammation and Infectivity. Am. J. Respir. Cell Mol. Biol., Volume 38, Number 5, 

May 2008, 579-590. 

6. Mitchell, L. A. et al. Pulmonary and Systemic Immune Response to Inhaled Multiwalled 

Carbon Nanotubes. Toxicological Sciences 100 (1), 203-214 (2007). 

7. Nygaard U.C. et al. Single-walled and Multi-walled Carbon Nanotubes Promote Allergic 

Immune Responses in Mice. Tox. Sci., 2009. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 22 of 47 

April 6, 2009 

MEMORANDUM

Since this review, X09-004 was re-designated P09-417 

SUBJECT: Mutagenicity Hazard Review of X09-4 

FROM: Michael C. Cimino, Ph.D. 

 Biologist 

 Science Support Branch 

 Risk Assessment Division (7403M) 

TO: Steven Cragg, PhD, DABT 

 Technical Integrator 

 Existing Chemicals Assessment Branch 

 

THRU: Donald Rodier 

 Branch Chief 

 Science Support Branch 

 Risk Assessment Division (7403M) 

 

THIS MEMORANDUM CONTAINS 

TSCA CONFIDENTIAL BUSINESS INFORMATION

I. CONCLUSION

 No mutagenicity data were provided with PMN X09-4. Based upon reports on similar 

materials, X09-4 (1) may induce gene mutations in mammalian cells in culture but not in 

prokaryotes or lower eukaryotes; (2) may be a weak inducer of aneuploidy but not of structural 

chromosome aberrations in mammalian cells in culture; (3) may induce DNA effects in 

mammalian cells in culture, but not in lower eukaryotes in vivo, and; (4) may not induce cell 

transformation in mammalian cells in culture. 

 

 Due to uncertainty about their ability to penetrate cells, testing of nanomaterials in 

genotoxicity assays is problematic, and negative responses would not conclusively rule out the 

potential mutagenicity hazard of nanotubule materials in humans. No testing of the PMN is 

recommended at this time. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 23 of 47 

II. STRUCTURE OF X09-4 (i.e., P09-417) AND ANALOGUES

III. BASIS FOR THE CONCLUSIONS

 No mutagenicity data were provided with the Premanufacturing Notice on PMN X09-4 

(Multi-walled carbon nanotubes; no CAS#; ; structures in Section II). 

 A document provided in the notice by “Nanocyl” states that an in vitro gene mutation 

assay in mammalian cells on multiwall carbon nanotubes (MWCNT) will be conducted. It states 

that, as part of the test, a determination is made on cellular cytotoxicity, which is characterized as 

“a pre-requisite before genotoxicity”. It is also stated that MWCNT is not cytotoxic. These 

statements imply that genotoxicity is not possible unless cytotoxicity is obtained. This is 

decidedly not the case, and not the reason cytotoxicity is determined in mutagenicity assays. 

Rather, cytotoxicity is determined in order to set dose levels. To have genotoxicity without any 

cytotoxicity is certainly possible. 

 The only basis for concern for this PMN is that it is a nanotech material. Nanotech 

analogues of the PMN have been reviewed in detail previously 

are structurally identical to 

X09-4. Both were tested and found not to be gene mutagens in Salmonella strains TA98, 

TA100, TA102, TA1535 and TA1537 and in Escherichia coli strain WP2uvrA, and not 

chromosome mutagens in mammalian CHL cells in vitro, in both cases without and with 

metabolic activation ( ). 

(Open-ended multi-walled scrolled nanotubes; synonyms: 

also was not a gene mutagen in 

Salmonella strains TA98, TA100, TA102, TA1535 and TA1537, and was not a chromosome 

mutagen in mammalian V79 cells, in both cases without and with metabolic activation 

 The data on carbon-based nanoparticles are summarized in the Table that follows (all 

data except for and SWCNT are as reported in abstracts): 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 24 of 47 

TABLE I: MUTAGENICITY DATA ON NANOTECH PRODUCTS 

 

Gene mutations Chromosome 

mutations 

Chemical DNA Other 

SAL lower 

eukaryotes 

mammalian in 

vitro 

CA 

vitro 

MN 

vitro 

 Cell 

transformation 

 neg neg 

 neg neg 

 neg neg 

SWCNT neg weak pos comet vit 

CNT pos ES vit 

neg rat BFU viv 

 neg neg SCE vit 

[5,6]FullereneC60-ih pos 

neg 

neg 

SMART 

 neg SMART neg BALBc 

carbon black pos pos L51 pos SCE vitro 

Abbreviations: 

BFU = body fluid urine 

CA = chromosome aberrations 

ES = mouse embryonic stem cells 

L51 = mouse lymphoma cells 

MN = micronucleus 

neg = negative 

pos = positive 

SAL = Salmonella

SCE = sister chromatid exchange 

SMART = somatic mutation and 

recombination test in Drosophila

vit = in vitro 

vv = in vivo 

weak = weakly positive 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 25 of 47 

 As a nanotech material, X09-4 may be a weak inducer of aneuploidy and of DNA effects in 

mammalian cells in culture. Based upon reports on similar materials, it may induce gene mutations in 

mammalian cells in culture but not in prokaryotes, lower eukaryotes, or mammals in vivo; it may not 

induce DNA effects in lower eukaryotes in vivo, nor cell transformation in mammalian cells in culture. 

 

 Due to uncertainty about their ability to penetrate cells, testing of nanomaterials in genotoxicity 

assays is problematic, and negative responses would not conclusively rule out the potential 

mutagenicity hazard of nanotubule materials in humans. No testing of the PMN is recommended at 

this time. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 26 of 47 

EETD Standard Review Report 

ICB Chemistry Section 

Case Number: X-09-4 CBI: Yes 

Chemist: Dr. Diana Darling Date: 4/06/2009

Submitter: Nanocyl Corporation (a Georgia Corporation) 

[The foundation of Nanocyl, which was established in 2002 in Belgium, stems from the research work 

of Professor Janos B. Nagy of the University of Namur and Professor Jean-Paul Pirard of the 

University of Liege.]

Chemical Name: Short tangled multi-wall carbon nanotubes 

[The submitter claims that there are two kinds of nanotubes, short tangled nanotubes and long rigid 

nanotubes. 

CAS No: NA 

 

Categorical Name: Carbon nanotube 

Trade Name:

Structure: 

 

Use: Plastic (thermoset and thermoplastic) additive to improve electrical, thermal, and/or mechanical 

properties 

 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 27 of 47 

Chemical properties affecting exposure and releases: 

Physical Form: Amorphous black powder 

Molecular Formula: Cx

Molecular Weight: > 100,000 (est) 

Vapor Pressure: < 0.0000001 torr (est) 

Water Solubility: < 0.000001 g/L (est) 

 

 

 

 

 

 

 

 

Explodability: Kst = 42 bar*m/sec (VDI). 

 Stable up to 480 °C in an oxidative atmosphere 

 

 

 

 

 

 

 

 

 

 

By-products: 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 28 of 47 

None reported 

General Nanotube information: 

Different types of nanotubes can be formed, depending on which direction the "graphite 

sheet" appears to be rolled to form the nanotube. These types of nanotubes are denoted by a 

pair of integers, n and m, and are called armchair (n=m), zigzag (n=0 or m=0), and chiral (any 

other n and m). The integers n and m represent the magnitude of vectors which add up to the 

diameter of the nanotube, and cannot be adequately described without an illustration. 

Armchair SWNTs are considered metallic, presumably because of their conductivity. 

SWNTs where n-m is divisible by 3 are semiconductors with a tiny band gap. All others are 

semiconductors, whose band gap depends on the relative values of n and m, as well as the 

nanotube diameter. 

The incorporation of 5- and 7-member rings into a nanotube can cause it to bend or kink, or 

to change at a point along its length from one type to another (i.e. one part of the nanotube 

being armchair and another part being zigzag). The sidewalls of nanotubes can be chemically 

modified, either covalently or non-covalently. The zigzag and armchair types of nanotubes 

are so named because when the nanotube is cut perpendicular to the tube axis, the pattern 

around the periphery of the tube edge resembles either a zigzag pattern or the arm and seat of 

an armchair repeated n times. 

Nanotubes are the stiffest known fiber, with a Young's modulus of 1-1.4 TPa. They have an 

expected elongation to failure of 20-30%, which combined with their stiffness, projects to a 

tensile strength above 100 GPa, by far the highest known. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 29 of 47 

STANDARD REVIEW ENGINEERING REPORT CBI: Yes 

PMN: 09-0417 

Focus Ready Draft 3/19/2009 Standard Review Report 6/22/2009 

 Revised 10/26/2009 Revised 11/04/2009

ENGINEER: Arnold \ AG 

PV (kg/yr): Import Only 

SUBMITTER: Nanocyl Corporation 

USE: Plastics additive to improve electrical, thermal, and/or 

mechanical properties; additive to coatings. 

OTHER USES:

 

 

 

 

 

MSDS: Yes Label: No 

Gen Eqpt: protecting gloves (e.g. nitrile rubber, thickness 

greater than 0.35 mm) / chemical goggles or safety glasses 

Respirator: suitable respiratory equipment with High Efficiency 

Dust Cartridge (at least a P2 filter) when directly exposed or 

handling the powder 

Health Effects: contact with eyes may cause irritation due to 

abrasive action of the dust; not expected to cause prolonged or 

significant eye irritation / skin contact: no known hazards, but 

may be mildly irritating to the skin; it is not expected to be 

absorbed through the intact skin / inhalation of the dust from 

this material may cause respiratory irritation / ingestion: no 

known hazards; not expected to be harmful if swallowed / acute 

and chronic health effects: high concentration of dusts may be 

irritating to eyes, skin, mucous membranes and respiratory tract; 

 no applicable chronic information at this moment, but none of 

the components is known to be a carcinogen or a suspected 

carcinogen 

TLV/PEL: 

Carbon nanotubes 2.5 ug/m^3 LOAEC (Low Observed Adverse Effect 

Concentration) Nanocyl recommends a LOAEC of 0.1 mg/m^3 and 

applies a safety factor of 40 to achieve an air threshold of 2.5 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 30 of 47 

ug/m^3. 

CRSS : 

Chemical Name: Multi-walled carbon nanotubes 

S-H20: 0.000001 g/L @ 

VP: 1.0E-6 torr @ 

MW: %<500 %<1000 

Physical State and Misc CRSS Info: 

Neat: Solid Mfg: NK: Import Proc/Form: NK End Use: Solid: LVE 

material entrained within polymer. The molecular weight is 

variable and depends on the size of the nanotube. It is 

expected to be much greater than 100,000 g/mole. The submitter 

claims that there are two kinds of nanotubes, short tangled 

nanotubes and long rigid nanotubes. 

 Submitted Data: Burns before 

melting; Insoluble in water; 

9

Estimated Data: BP > 400 °C (High MW); VP < 0.000001 

torr (High MW); WS < 0.000001 g/L (High MW). 

Consumer Use: No 

SAT (concerns) (03/10/2009): 

Related Cases and Related Cases and Misc SAT Info: 

 

 

Migration to groundwater: Unknown 

PBT rating: P3BT PBT: P3; B Unknown; T Unknown 

Health: 2 Dermal, Drinking Water, Inhalation 

Eco: 1 No releases to Water 

OCCUPATIONAL EXPOSURE RATING: 1-2B 

NOTES & KEY ASSUMPTIONS: 

Generated by the 06/07/2005 version of ChemSTEER. This 

submission is a LOREX case. This submission is for multi-walled 

carbon nanotubes (MWCNTs). Note that some air monitoring data 

for packaging the CNTs is provided in the attached dossier on 

page 26. This dossier also provides explanation of some risk 

management practices including engineering controls used 

(butterfly valves). See contact report. The following past 

cases were referenced for consistency:

 /// For IMPORT: Technical contact indicated up to 

20 customers for max PV (note this is an estimate). Submitter 

will offer CNTs to customers either as 100% raw CNTs or as 

incorporated into master batches. As customer choices are 

uncertain (choices have not been made yet), CEB assesses 100% of 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 31 of 47 

PV imported as raw CNTs (100% powder). Technical contact noted 

that it is possible some customers may hire another company to 

incorporate raw CNTs into master batches for them. CEB assumes 

this would not alter the total number of sites that produce 

master batches. /// For PROC (production of master batches): 

The current IRER assesses sites operating 250 days/year as 

default as actual production days/year are uncertain (see 

contact report). Consistent with past cases: 

 

 

 

 

 

 

 

 Amendment received on 

3 November 2009 indicates the usage of CNTs sold as powder will in the same 

applications as stated for other applications and in the same proportions. 

POLLUTION PREVENTION CONSIDERATIONS: 

None. 

EXPOSURE-BASED REVIEW: No 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 32 of 47 

STANDARD REVIEW ENGINEERING REPORT CBI: Yes 

PMN: 09-0417 

Processing: 

Number of Sites/ Location: 

Unknown Cus mer Sites 

Days/yr: 

Basis: 

 

 

 

 

 

 

Process Description: 

ENVIRONMENTAL RELEASES ESTIMATE SUMMARY 

IRER Note: The daily releases listed for any source below may 

coincide with daily releases from the other sources to the same 

medium. // 

 

 

Incineration or Landfill 

Output 2: 4.0E-2 kg/site-day over 250 days/yr from 

or 2.0E+2 kg/yr 

to: Incineration 

f

basis: 

 

 

Incineration 

Output 2: 4.0E-2 kg/site-day over 250 days/yr from 

or 2.0E+2 kg/yr 

to: Incineration 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 33 of 47 

from: 

basis: 

 

 

RELEASE TOTAL 

4.0E+2 kg/yr - all sites 

OCCUPATIONAL EXPOSURES ESTIMATE SUMMARY 

Tot. # of workers exposed via assessed routes: 

B

 

 

 

 

 

Dermal: 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 34 of 47 

STANDARD REVIEW ENGINEERING REPORT CBI: Yes 

PMN: 09-0417 

Processing: 

Number of Sites/ Location: 

Unknown Cus mer Sites 

Days/yr: 

Basis: 

ENVIRONMENTAL RELEASES ESTIMATE SUMMARY 

IRER Note: The daily releases listed for any source below may 

coincide with daily releases from the other sources to the same 

medium. 

Incineration or Landfill 

Output: 1.3E-3 kg/site-day over 250 days/yr from 

or 3.1E-1 kg/yr 

to: Incineration or land 

from: 

basis: 

 

 

Land or water 

Output 2: 5.3E-3 kg/site-day over 250 days/yr from 

or 1.3E+0 kg/yr 

to: Land or water 

from: 

basis: 

. 

RELEASE TOTAL 

1.6E+0 kg/yr - all sites 

OCCUPATIONAL EXPOSURES ESTIMATE SUMMARY 

Tot. # of workers exposed via assessed routes: 

Basis: 

 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 35 of 47 

Exposure to Particulate in Coating 

Output: negligible over 250 days per year 

Number of workers (all sites) with inhalation exposure: 

Basis: 

 

 

 

 

 

Dermal: 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 36 of 47 

STANDARD REVIEW ENGINEERING REPORT CBI: Yes 

PMN: 09-0417 

Use:

Number of Sites/ Location: 

Unknown Customer Sites 

Days/yr: 250 

Basis: Generic scenario for coating application in the furniture industry. 

Process Description: 

ENVIRONMENTAL RELEASES ESTIMATE SUMMARY 

IRER Note: The daily releases listed for any source below may 

coincide with daily releases from the other sources to the same 

medium. 

Incineration or Landfill 

Output: 1.3E-3 kg/site-day over 250 days/yr from 

or 1.9E+0 kg/yr 

to: Incineration or land 

from: 

basis: 

 

 

Land or water 

Output: 8.3E-4 kg/site-day over 250 days/yr from 

or 1.3E+0 kg/yr 

to: Land or water 

from: 

basis: 

 

Land or incineration 

Output: 2.4E-2 kg/site-day over 250 days/yr from 

Or 3.9E+1 kg/yr 

To: land or incineration 

From: 

B 

RELEASE TOTAL 

4.2E+1 kg/yr - all sites 

OCCUPATIONAL EXPOSURES ESTIMATE SUMMARY 

Tot. # of workers exposed via assessed routes: 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 37 of 47 

Basis: 

 

 

 

 

 

 

Dermal: 

 

 

 

 

 

 

 

 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 38 of 47 

CBI: Yes 

MEMORANDUM of CBI TELEPHONE CONVERSATION 

CALL BY: Anthony Gaglione 

Organization: ERG 

CALL TO: Michelle B. Walker 

Organization: Morris, Manning & Martin, LLP 

Date: 03/11/2009 

Time: 10:30 AM 

Phone: 

Concerning what TSCA CBI? 

LOREX: 09-0004 

 

 

 

 

 

 

 

 

CBI: Yes 

MEMORANDUM of CBI TELEPHONE CONVERSATION 

CALL BY: Anthony Gaglione 

Organization: ERG 

CALL TO: Michelle Walker, Esq 

Organization: Morris, Manning & Martin, LLP 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 39 of 47 

Date: 03/16/2009 

Time: 9:30 AM 

Phone: 

Concerning what TSCA CBI? 

LOREX: 09-0004 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 40 of 47 

NANOMATERIAL STANDARD EXPOSURE REPORT 

X-09-0004 (since Re-designated P09-417) Date 3/18/09 

Assessor: Cinalli

Production Volume: 

USE: Plastics additive to improve electrical, thermal and/or mechanical properties. 

OTHER USES: 

Chemical Name: Multi-walled carbon nanotubes 

Fate Assessment: 

Due to the novel nature of nanomaterials, it is not possible at this time to make 

assumptions about their behavior in the environment without the collection of 

physicochemical (p-chem) and fate data. The p-chem properties which seem most important 

for fate assessment are: surface reactivity, aggregation/agglomeration, physical form, particle 

size distribution, surface area solubility, dispersability, shape, adsorption tendency and 

surface charge porosity. 

These p-chem properties are novel to nanomaterials and are not estimated by our 

current collection of fate models, EPI Suite. Therefore, specific data on the actual behavior 

of the nanomaterial in waste water treatment plants (e.g., biodegradation, sorption to sludge, 

volatilization, etc.) and drinking water treatment plants (e.g., effect of chlorination, 

oxygenation, etc.) are needed to determine removal rates. Additionally, data are needed to 

assess the potential for ground water migration. Testing methods typically used for these 

parameters (e.g., ready biodegradation test, porous pot, etc.) may or may not apply. If the 

amount of the nanomaterial released is of concern, EAB recommends that the submitter 

evaluate the current OPPT guidelines for fate testing and then submit fate testing protocols 

based on their specific knowledge of the nanomaterial to the EAB’s fate experts for their 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 41 of 47 

review prior to the actual testing. It is possible that after several nanomaterials have gone 

through p-chem and fate testing, that models in EPI Suite could be validated for use, or, more 

likely, a new fate model or models could be developed to estimate the fate of a new 

nanomaterial in the environment. 

General Population and Environmental Exposure 

A qualitative evaluation of the releases estimated by CEB indicates that there is some 

potential for exposure to the general population and the environment from water, landfill 

and/or incineration releases as well as fugitive air releases. Due to the novel nature of this 

PMN chemical it is not possible to quantify the exposure from these release scenarios. 

Human inhalation, ingestion and dermal exposure may result from the water, landfill, 

incineration and fugitive releases. 

It is not possible at this time to quantify the exposure due to the uncertainty surrounding the 

environmental fate of nanomaterials in water, air, incineration and landfill, and the 

uncertainty of applying existing fate and air dispersion models that were developed based on 

chemicals that are not nanomaterials. It is recommended that the submitter work with EPA 

engineers, fate experts and exposure assessors to develop chemical-specific testing for this 

PMN chemical. 

Specific data needs from the submitter are summarized below: 

Identify all releases and their media of release. 

Questions for incineration releases: Provide information to CEB engineer on: What type of 

control technology is used for the incineration releases? What is its removal efficiency for 

the PMN substance? Are there any monitoring data available that demonstrate this 

efficiency? Provide data. Information to be provided to the EAB assessor: Are there any 

monitoring data available downwind of the incineration releases? Provide data. 

Questions for air (fugitive releases) provide information to CEB engineer on: What type of 

control technology is used for the fugitive releases? What is its removal efficiency for the 

PMN substance? Are there any monitoring data available that demonstrate this efficiency? 

Provide data. Information to be provided to the EAB assessor: Are there any monitoring 

data available downwind of the fugitive releases? Provide data. 

Questions for water releases: If the facility the PMN substance is being release from is a 

direct discharger, is the waste water discharged directly into the stream or into a on-site 

treatment plant? If it is discharged into an on-site treatment plant, what is the treatment 

method, how much of the PMN substance is removed during treatment, where is the stream 

located, and are there any monitoring data to determine the amount released? Provide data. 

If the waste water is being released into a Publicly Owned Treatment Works (POTW), how 

does the PMN substance behave during the various treatment steps typical of POTWs (e.g., 

flocculation, activated sludge, filtration, etc.)? How much of the PMN chemical is removed 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 42 of 47 

during treatment? What is the mechanism of removal (e.g., adsorption into the sludge, 

biodegradation, volatilation, etc.)? What test methodologies were used to determine the 

answer to the above questions? Also, where is the POTW located? Provide data. 

Questions for landfill releases: What type of landfill will the PMN substance be placed in? 

What is the potential for migration of the PMN substance to the ground water? What testing 

data are available to support the migration potential of the PMN substance? Provide data. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 43 of 47 

Summary Economic Analysis 

For Standard Review of PMN P-09-417 

Reviewer: Kristen Loughery 

I. BACKGROUND 

 A. Submitter: Nanocyl Corporation 

B. Chemical Name: 

C. Generic Name: MWCT, specialty synthetic graphite

D. Trade Name: Series NC 7000 

E. CAS Number: None 

F. Use(s): Additive to improve electrical, thermal, and/or 

mechanical properties of thermoplastic, thermoset, and 

coating materials. 

 

 

II. MARKET ANALYSIS 

A. Intended Uses 

The PMN states that 100% of the PMN substance will be used in production as an 

additive to improve electrical, thermal, and/or mechanical properties of thermoplastic, 

thermoset, and coating materials. 

According to the PMN, the end uses for CNTs are conductive plastics, structural 

composite materials, flat-panel displays, gas storage, electronics, radar-absorbing coating, 

technical textiles, ultra-capacitors, AFM tips, batteries, biosensors, and fibers. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 44 of 47 

The PMN substance can be used in the following industries: electronics, automotive, 

aeronautic, construction, sports, marine, foams and wires and cables. In the electronics sector, 

the PMN substance can be used in semiconductor packaging, hard disk drives, and IC test and 

burn sockets. In the automotive sector, the PMN substance can be used in fuel system line 

components, fenders, mirror housings, and door handles. In the aeronautics sector, the PMN 

substance can be used as epoxy composites and flame retardant coatings. In the construction 

sector, the PMN substance can be used as protection for construction substrates including 

metal, concrete, wood, plaster, and fiberboard. In the sports sector, the PMN substance can be 

used to make bike frames, hockey sticks, tennis rackets, golf shafts, and skis. In the marine 

sector, the PMN substance can be used to make masts for sailing vessels for improved 

mechanical durability and as antifouling paints to prevent waterborne organisms from 

adhering to the coating. The PMN substance is used in flexible and rigid foams and wires and 

cables as a flame retardant. 

B. Submitter 

The PMN was submitted by Nanocyl. Nanocyl’s current plans are to import the PMN 

substance from the Nanocyl facility in Belgium directly to sites not controlled by Nanocyl. 

There will be no manufacturing or processing of the substance in any Nanocyl-controlled 

U.S. facility. 

C. Substitutes 

 According to the submitter, the PMN substance is a substitute for carbon black and 

chopped carbon fibers. The CNTs are not directly replacing any substance. Compared to 

existing toxic marine coatings, Biocyl does not contain any solvent, biocide, or heavy metal. 

The PMN substance can be incorporated in thermoplastics as substitutes for old metallicmade auto parts. The PMN substance can also be a substitute for halogen and halogen-free 

flame retardants. 

D. Benefits of the PMN Material 

According to the PMN, the PMN substance has a lower loading needed to reach a 

given resistivity in clean room devices, therefore minimizing the contaminants in micro chips. 

The electrical conductivity can be controlled and there is no more risk of hot spots on the 

surface of sockets. The PMN substance has high electrical conductivity and mechanical 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 45 of 47 

properties, decreased weight, and improved strength, shelf life, and antistatic properties. It 

also provides flame retardant protection of applications such as tanks and exhaust parts. 

 

Telephone Log – PMN P-09-417 

DATE: July 20, 2009

EPA STAFF: Kristen Loughery 

RESPONDENT: Richard Jourdenais 202-828-8992 

The EPA staff member contacted the submitter’s technical contact to request 

information concerning the chemicals described in the PMN to complete the economic report 

for the standard review. The conversation has been paraphrased for brevity and clarity. 

Q1: Can you confirm the information in the PMN that the PMN substance is going to be 

used as an additive to improve electrical, thermal, and/or mechanical properties of 

thermoplastic, thermoset, and coating materials? Are there any other uses that the PMN 

substance could work in, even if you aren’t planning on them now? 

Can you confirm that the PMN substance will be 100% for industrial use and that there are no 

consumer or commercial uses for the substance? 

What is the percent of the PMN substance in the end formulation? 

A1: Yes, I confirm the use information. The end uses for thermoplastic materials are the 

 I can 

confirm that there are no consumer or commercial uses for the substance. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 46 of 47 

Q2: Where/who will the PMN substance be imported from? Where will it be processed (site 

controlled by Nanocyl)? Can you confirm that Nanocyl has no other manufacturing facilities 

in the United States? 

A2: Nanocyl’s current plans are to import the PMN substance from the Nanocyl facility in 

Belgium directly to sites not controlled by Nanocyl. There will be no manufacturing or 

processing of the substance in any Nanocyl-controlled U.S. facility. 

Q3: Are there any other locations in the U.S. that may manufacture the substance in the 

future? 

A3: 

Q5: Do you know of any products that the PMN substance is replacing? 

A5: Carbon black and chopped carbon fibers. The CNTs are not directly replacing anything. 

Compared to existing toxic marine coatings, BIOCYL does not contain any solvent, biocide, 

or heavy metal. 

Q6: Are there any additional benefits, besides the electrical, thermal, and mechanical 

properties improvements? 

A6: I have included all of the benefits in the PMN attachment. 
Standard Review Risk Assessment for P09-417 

 January 12, 2010 Page 47 of 47 

 

Q10: Would you like to add any other information? 

A10: No. 

The EPA staff person thanked the submitter for his cooperation.