Occupational Exposure to Carbon Nanotubes and Nanofibers

5 CNT Risk Assessment and RecommendedExposure Limit5.1 Risk Assessment andRecommended ExposureLimit (REL)NIOSH bases its recommended exposure limits(RELs) on quantitative risk assessments when possible.Quantitative risk assessment provides estimatesof the severity and likelihood of an adverseresponse associated with exposure to a hazardoussubstance. The hazard and quantitative risk assessments(Section 4 and Appendix A) provide thehealth basis for developing a recommended exposurelimit (REL) for CNT and CNF. Establishinghealth-based exposure limits is the first considerationby NIOSH in setting a REL. The analyticalfeasibility of measuring worker exposures to airborneCNT and CNF is also taken into account inthe establishment of the REL (Section 6.1).In general, quantitative risk assessment involvesthe following steps: first a data set is selected thatbest depicts a dose-response relationship, in thiscase, the relationship between exposure to CNTand pulmonary effects in animals. Then, a criticaldose in the animal lungs is calculated. A frequentlyused indicator of critical dose is the benchmarkdose (BMD) which is defined as the dose correspondingto a small increase in response (e.g. 10%)over the background level of response [Crump1984]. Next, the dose in humans, that is equivalentto the critical dose in the animals, is estimated. Thisrequires adjusting for species differences betweenanimals and humans. It is assumed in the absenceof specific data that an equivalent dose in animalsand humans will result in the same risk of disease,based on the assumption that the same mechanismof action is operating in both animals and humans.After the critical average dose in human lungsNIOSH CIB 65 • Carbon Nanotubes and Nanofibersis estimated from the animal data, an equivalentworkplace concentration over a full working lifetimeis derived. This is accomplished by usingmathematical and physiological models to estimatethe fraction of the dose that reaches various partsof the respiratory tract and is deposited and cleared[Kuempel et al. 2006; Schulte et al. 2010; NIOSH2011a]. Variability in human dose and response,including sensitive subpopulations, and uncertaintyin the extrapolating animal data to humans aretypically addressed with uncertainty factors in theabsence of specific data.NIOSH determined that the best data to use for aquantitative risk assessment and as the basis for aREL were the nonmalignant pulmonary data fromshort-term and subchonic animal studies. In thesestudies, lung exposures to CNT (i.e., various typesof MWCNT and SWCNT, purified and unpurified,dispersed or agglomerated, and with different metalcontent) were observed to cause early-stage adverselung effects including, pulmonary inflammation,granuloma, alveolar septal thickening, and pulmonaryfibrosis (Section 3 and Appendix A). NIOSHconsiders these animal lung effects to be relevantto workers because similar lung effects have alsobeen observed in workers with occupational lungdisease associated with exposure to various types ofinhaled particles and fibers [Rom and Markowitz2006; Hubbs et al. 2011]. Human-equivalent riskestimates were derived from animal dose-responsedata (in rats and mice). Human-equivalent exposuresover a 45-year working lifetime were estimatedto be associated with either a specified risk level(e.g., 10%) of early-stage lung effects or with a noobserved adverse effect level based on the animalstudies. In the absence of validated lung dosimetrymodels for CNT, lung doses were estimated using37