In this Current Intelligence Bulletin, NIOSH continues its long-standing history of using the best available scientific information to assess potential hazards and risks and to provide guidance for protecting workers. Since it is early in the development of these materials and their applications, there is limited information on which to make protective recommendations. To date, NIOSH is not aware of any reports of adverse health effects in workers using or producing CNT or CNF. However, there are studies of animals exposed to CNT and CNF that are informative in predicting potential human health effects consistent with ways in which scientists traditionally have used such data in recommending risk management strategies. NIOSH systematically reviewed 54 laboratory animal studies, many of which indicated that CNT/CNF could cause adverse pulmonary effects including inflammation (44/54), granulomas (27/54), and pulmonary fibrosis (25/54) (Tables 3-1 through 3-8). NIOSH considers these animal study findings to be relevant to human health risks because similar lung effects have been observed in workers exposed to respirable particulates of other materials in dusty jobs [Rom and Markowitz 2006; Hubbs et al. 2011]. There are well established correlations between results of animal studies and adverse effects in workers exposed to particulates and other air contaminants [NIOSH 2002, 2006, 2011a, b]. Moreover, in animal studies where CNTs were compared with other known fibrogenic materials (e.g., silica, asbestos, ultrafine carbon black), the CNTs were of similar or greater potency [Lam et al. 2004; Muller et al. 2005; Shvedova et al. 2005; Murray et al. 2012], and the effects, including fibrosis, developed soon after exposure and persisted [Shvedova et al. 2005, 2008; Porter et al. 2010; Mercer et al. 2011]. These are significant findings that warrant protective action. NIOSH conducted a quantitative assessment of risk using the animal studies with sufficient dose-response data, which included two subchronic (90-day) inhalation studies [Ma-Hock et al. 2009; Pauluhn 2010a] and five additional studies [Lam et al. 2004; Muller et al. 2005; Shvedova et al. 2005,2008; Mercer et al. 2011] conducted by other routes or durations. The estimated risk of developing early-stage (slight or mild) lung effects over a working lifetime if exposed to CNT at the analytical limit of quantification (NIOSH Method 5040) of 1 microg/m3 (8-hr time-weighted average [TWA] as respirable elemental carbon) is approximately 0.5% to 16% (upper confidence limit estimates) (Table A-8). In addition, the working lifetime equivalent estimates of the animal no observed adverse effect level (NOAEL) of CNT or CNF were also near 1 microg/m3 (8-hr TWA) (Sections A.6.3.3 and A.7.6). Therefore, NIOSH recommends that exposures to CNT and CNF be kept below the recommended exposure limit (REL) of 1 microg/m3 of respirable elemental carbon as an 8-hr TWA. Because there may be other sources of elemental carbon in the workplace that could interfere in the determination of CNT and CNF exposures, other analytical techniques such as transmission electron microscopy are described that could assist in characterizing exposures. Studies have shown that airborne background (environmental and in non-process areas in the workplace) concentrations to elemental carbon are typically less than 1 microg/m3 and that an elevated exposure to elemental carbon in the workplace is a reasonable indicator of CNT or CNF exposure [Evans et al. 2010; Birch 2011a, b; Dahm et al. 2011]. Studies have also shown in some manufacturing operations that exposures can be controlled below the REL when engineering controls are used [Dahm et al. 2011]. However, NIOSH has not assessed the extent to which exposures can be controlled during the life cycle of CNT/CNF product use, but since airborne CNT/CNF behave as classical aerosols, the control of worker exposures appears feasible with standard exposure control techniques (e.g., source enclosure, local-exhaust ventilation) [NIOSH 2009a]. Previously in a 2010 draft of this CIB for public comment, NIOSH indicated that the risks could occur with exposures less than 1 microg/m3 but that the analytic limit of quantification was 7 microg/m3. Based on subsequent improvements in sampling and analytic methods, NIOSH is now recommending an exposure limit at the current analytical limit of quantification of 1 microg/m3. More research is needed to fully characterize the health risks of CNT/CNF. Long-term animal studies and epidemiologic studies in workers would be especially informative. However, the toxicity seen in the short-term animal studies indicates that protective action is warranted. The recommended exposure limit is in units of mass/unit volume of air, which is how the exposures in the animal studies were quantified and it is the exposure metric that generally is used in the practice of industrial hygiene. In the future, as more data are obtained, a recommended exposure limit might be based on a different exposure metric better correlated with toxicological effects, such as CNT/CNF number concentration [Schulte et al. 2012]. There are many uncertainties in assessing risks to workers exposed to CNT/CNF. These uncertainties, as described and evaluated in this document, do not lessen the concern or diminish the recommendations. Other investigators and organizations have been concerned about the same effects and have recommended occupational exposure limits (OELs) for CNT within the range of 1-50 microg/m3 [Nanocyl 2009; Aschberger et al. 2010; Pauluhn 2010b; Nakanishi (ed) 2011a,b]. The relative consistency in these proposed OELs demonstrates the need to manage CNT/CNF as a new and more active form of carbon. To put this in perspective, since there is no Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for CNT/CNF, the PEL for graphite (5,000 microg/m3) or carbon black (3,500 microg/m3) [NIOSH 2007] might inappropriately be applied as a guide to control worker exposures to CNT/CNF. Based on the information presented in this document, the PELs for graphite or carbon black would not protect workers exposed to CNT/CNF. The analysis conducted by NIOSH was focused on the types of CNT and CNF included in published research studies. Pulmonary responses were qualitatively similar across the various types of CNT and CNF, purified or unpurified with various metal content, and different dimensions [Lam et al. 2004; Shvedova et al. 2005, 2008; Muller et al. 2005; Ma-Hock et al. 2009; Pauluhn 2010a; Porter et al. 2010; Mercer et al. 2011; Murray et al. 2012; DeLorme et al. 2012]. The fibrotic lung effects in the animal studies developed early (within a few weeks) after exposure to CNT or CNF, at relatively low-mass lung doses, and persisted or progressed during the post-exposure follow-up (approximately 1-6 months) [Shvedova et al. 2005, 2008; Mercer et al. 2008; Porter et al. 2010; Pauluhn 2010a; Murray et al. 2012]. However, the studied CNT and CNF only represent a fraction of the types of CNT and CNF that are, or will be, in commerce and it is anticipated that materials with different physical and chemical parameters could have different toxicities. At this time, however, given the findings in the published literature, NIOSH recommends that exposures to all CNT and CNF be controlled to less than 1 microg/m3 of respirable elemental carbon as an 8-hr TWA, and that the risk management guidance described in this document be followed. Until results from research can fully explain the physical-chemical properties of CNT and CNF that define their inhalation toxicity, all types of CNT and CNF should be considered a respiratory hazard and exposure should be controlled below the REL. In addition to controlling exposures below the REL, it is prudent for employers to institute medical surveillance and screening programs for workers who are exposed to CNT and CNF for the purpose of possibly detecting early signs of adverse pulmonary effects including fibrosis. Such an assessment can provide a secondary level of prevention should there be inadequacies in controlling workplace exposures. In 2009, NIOSH concluded that there was insufficient evidence to recommend specific medical tests for workers exposed to the broad category of engineered nanoparticles but when relevant toxicological information became available, specific medical screening recommendations would be forthcoming [NIOSH 2009b]. As described in this document, the toxicologic evidence on CNT/CNF has advanced to make specific recommendations for the medical surveillance and screening of exposed workers. That is, the strong evidence for pulmonary fibrosis from animal studies and the fact that this effect can be detected by medical tests is the basis for NIOSH specific medical screening recommendations. NIOSH also recommends other risk management practices in addition to controlling exposure and medical surveillance. These include education and training of workers and the use of personal protective equipment (e.g., respirators, clothing, and gloves). In summary, the findings and recommendations in this Current Intelligence Bulletin are intended to minimize the potential health risks associated with occupational exposure to CNT and CNF by recommending a working lifetime exposure limit (1 microg/m3, 8-hr TWA, 45 years), a sampling and analytical method to detect CNT and CNF, medical surveillance and screening and other guidelines. The expanding use of CNT/CNF products in commerce and research warrants these protective actions.