### 1 NM: Kristan Markey 564-8716 CONTAINS TSCA CBI

TIs: Maggie Johnson 564-8924, Phil Sayre, 564-7673



### LIMITED STANDARD REVIEW: P10-0039 & 40

SUMMARY: Human Health Hazard and Risk: No data were submitted with this case; risk is

estimated based on analogous case ; concerns for lung effects based on 90-D rat inhalation

study on which had a LOAEC of 0.1 mg/m3. Possible concerns for immunotoxicity,

oncogenicity and mutagenicity based on analogs. NCEL of 0.0037 mg/m3 is based on LOAEC. RAD

assumes that all material to which workers are exposed is respirable ( ≤ 10μm). MOEs indicate a

potential for risk exists from occupational inhalation exposures during both Manufacturing and Use.

NOTE: Worker exposure data submitted by the company is currently under review. The current risk

management options and testing in this risk assessment are sufficiently protective of health and

the environment.

Recommendations include Tiered Testing as follows:

(1) Particle Size Distribution Testing reflective of workplace exposures to specifically provide the

fraction of the size distribution in the respirable range for humans and using a method acceptable to

EETD.

(2) Subchronic Inhalation Toxicity Test Following receipt and analysis of these data, subchronic

inhalation toxicity testing on the PMN substance may be required. The specific test is OPPTS

870.3465: 90-day inhalation toxicity test, by nos e-only exposure with a post-exposure observation

period of up to 3 months, bronchoalveolar lavage fluid (BALF) analysis, aggregation/agglomeration

state, shape, size/size particle distribution and surface properties of materials as-administered,

aggregation/agglomeration state, shape, size/size particle distribution and surface properties of

materials of the delivered materials after administration, determination of cardiovascular toxicity, heart

histopathology, and data on pulmonary deposition.

(3) PPE & IH Controls Until such testing is completed and PPE & IH Controls specifically a NIOSHapproved, 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.

Aquatic Toxicity & Risk : Minimal releases to water are possible during Mfg of

nanotube sheets. Data from the literature indicate that effects on aquatic species can occur at

concentrations as low as 100 ppb. exposed juvenile rainbow trout to CNTs at

concentrations of 0, 0.1, 0.25, or 0.5 mg/L (f acilitated 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

CNTs on gills (inhibiting oxygen uptake) and/or to the sodium dodecylsulfate vehicle rather than a

direct toxic effect of CNTs to fish.

Surface water concentrations cannot be predicted by traditional methods;

Since the EETD assumption of is made without justification, the ecotoxicity value

above cannot be compared to the surface water concentrations and a subsequent ecological risk

assessment cannot be completed.

### 2 I. BACKGROUND

Structure:

Identity : Multi-walled carbon nanotubes (MWNT),

Submitter: Nanocomp Technologies Inc.

P/Chem Properties: MW = 1,000,000; High BP Solid; WS = Insoluble; Non volatile;

MW is variable and depends on the size of the nanotube. It is estimated to be

>1,000,000 g/mole.

NOTE: To be conservative RAD at this time is assuming all materials are respirable

and ≤ 10 μm. However, area monitoring data are under review in EETD at the time this risk assessment

was written and the EETD analysis will likely not conclude for at least several weeks. Since this

analysis, per EETD correspondence, will not likely change (or could perhaps lower) the estimated

exposures to workers, the current risk assessment conclusions and risk management

recommendations should be protective of human health and the environment.

Fate Ratings (per EETD, see Focus Report): Removal in WWT/POTW = 0-90% via sorption

SAT (11/13/2009) Ratings: HH = 1, Eco = 1

### 3 Health Concerns FOCUS Report 11/23/2009 (attached): Absorption is nil all routes (pchem);

No significant health concerns.

Exposure Routes of Concern (Engineering Reports attached): Engineering estimates indicate

occupation exposure is possible via inhalation of particulates. Exposure values are provided below.

Consumer exposure is not expected.

Toxicity Data Provided : None provided with submission. Hazards will be estimated by analogy to a

previous

II. HEALTH ASSESSMENT

Information below is summarized from Risk Assessment for RAD Dispo by Steve Cragg

attached).

Absorption, Distribution, Metabolism, Excretion: PMN is poorly absorbed via all routes; concerns for

lung overload for poorly soluble particulates and for lung effects based on submitted test data

(submitted with . There are possible concerns for immunotoxicity, oncogenicity and

mutagenicity based on analogs (SAT Report for ).

General Toxicity: A 90-day inhalation study conducted by MWCNT’s revealed

moderate granulomatous inflammation, severe alveol ar 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 Lowest Observed Adverse Effect

Concentration (LOAEC) from th is study was 0.1 mg/m3.

Mutagenicity: Concern exists for mutagenicity based on reports on analogous materials, however no

testing of the PMN is recommended at this time.

Immunotoxicity: Published scientific data for similar MWCNT indicate potential to cause

immunotoxicity. Pulmonary exposure to this PMN may lead to lung effects including: reduced alveolar

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

immunosuppression, and promotion of allergy.

Occupational Inhalation Exposure Values: Assumptions are that 100% of the material is respirable

( ≤ 10 microns), estimated toxicity is occurring from both nano-particle containing elemental carbon

and organic carbon and workers are exposed to dust. T =

typical & WC = Worst Case.

### 4 Development of a New Chemical Exposure Limit (NCEL) A NCEL of 0.0037 mg/m3 for inhalation

exposure was derived based on by dividing the LOAEC of 0.1 mg/m 3 

### from

that study by uncertainty factors (see Table 1). This rationale is described in a memo from Steven

Cragg to Phil Sayre, dated 2009-10-19 (attached).

Table 1. Calculation of a New Chemical Ex posure Limit (NCEL) for Non-Cancer Effects

Using LOAEC from Inhalation Study (UF = Uncertainty Factor)

LOAEC UF using

subchronic

not

chronic

study UF

extrapolating

rat to

humans UF

extrapolating

LOAEL to

NOAEL UF

uncertainty

to protect

most

sensitive

worker UF

Uncertainty

in data

base Permissible

Daily Dose

mg/m3 unitless unitless uni tless unitless unitless mg/m3

0.1 ÷

by 1 ÷

by 1 ÷

by 3 ÷

by 3 ÷

by 3 = 0.0037

Table 2. Occupational Inhalation Exposure and Risk MOE Calculations

Using LOAEC from

Dose Air Vol Exp conc NCEL

mg/day m3/day mg/m3 mg/m3 MOE

P10-0039

Typical 0.73 ÷by 10 = 0.073 ÷by 0.0037 = 20

Worst Case 2.5 ÷by 10 = 0.250 ÷by 0.0037 = 68

Typical 0.095 ÷by 10 = 0.010 ÷by 0.0037 = 3

Worst Case 3.20 ÷by 10 = 0.320 ÷by 0.0037 = 86

P10-0040

Typical 0.037 ÷by 10 = 0.004 ÷by 0.0037 = 1

Worst Case 0.12 ÷by 10 = 0.012 ÷by 0.0037 = 3

Typical 0.0067 ÷by 10 = 0.001 ÷by 0.0037 = 0.2

Worst Case 0.023 ÷by 10 = 0.002 ÷by 0.0037 = 1



### MOEs indicate a potential for risk does exist from occupational inhalation exposures during

both Manufacturing and Use.

RECOMMENDATIONS

Tiered testing is recommended:

(1) Particle size distribution of respirable particles Due to the great uncertainty in assessing particle

sizes of the PMN better characterization of actual particle size distributions, including the fraction of the

distribution that represents respirable particles in the work environment, are 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.

### 5 (2.) 90-day inhalation toxicity test (OPPTS 870-3465) by nose-only exposure with a post-exposure

observation period of up to 3 months, bronchoalveolar lavage fluid (BALF) analysis,

aggregation/agglomeration state, shape, size/size particle distribution and surface properties of

materials as-administered, aggregation/agglomeration state, shape, size/size particle distribution and

surface properties of materials of the delivered materials after administration, determination of

cardiovascular toxicity, heart histopathology, and data on pulmonary deposition.

(3). Personal Protective Equipment and Industrial Hygiene Control Recommendations Until such

time as particle size information is better charac terized, PPE and IH controls should include: a NIOSHapproved, 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.

III. AQUATIC TOXICITY AND RISK

Minimal releases to water are possible during Mfg of nanotube . Data from the

literature indicate that effects on aquatic species can occur at concentrations as low as 100 ppb. Smith

et al. (2007) exposed juvenile rainbow trout to CNTs 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 CNTs on gills (inhibiting oxygen uptake) and/or to the sodium

dodecylsulfate vehicle rather than a direct toxic effect of CNTs to fish.

Surface water concentrations cannot be predicted by traditional methods; EETD assumed

ince the EETD

assumption of is made without justification, the ecotoxicity value above cannot be

compared to the surface water concentrations and a subsequent ecological risk assessment cannot be

completed.

REFERENCES CITED

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.

ATTACHMENTS Pages

Chemistry Reports 7

Engineering Reports (Focus ready draft) 11

Exposure Reports (pages with 7Q10 predictions only) 23

FOCUS Reports 11/23/2009 27

Risk Assessment for RAD Dispo by Steve Cragg 39

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