Occupational Exposure to Carbon Nanotubes and Nanofibers

ContentsA.1 Introduction .......................................................... 93A.2 Methods .............................................................. 94A.2.1 Rodent Dose-Response Data ....................................... 95A.2.1.1 Data selection ............................................ 95A.2.1.2 Dose rate evaluation ....................................... 96A.2.1.3 Lung responses evaluated .................................. 96A.2.1.4 Summary of dose-response data ............................ 97A.2.2 Estimated Lung Dose in Animals ................................... 98A.2.3 Animal Dose-Response Modeling and BMD Estimation ................... 101A.2.3.1 Dichotomous Response Data ............................... 101A.2.3.2 Continuous response data .................................. 101A.2.3.3 BMD model fitting ........................................ 102A.2.3.4 Human-equivalent dose and working lifetime exposure ........ 103A.3 Results ............................................................... 108A.3.1 Benchmark Dose and Working Lifetime Exposure Estimates ........... 108A.3.2 Comparison of Short-Term and Subchronic Dose-Response Data ....... 113A.3.3 Estimated Excess Risks of Working Lifetime Exposuresto Low-Mass Concentrations of MWCNT ........................... 113A.4 Discussion ............................................................ 116A.4.1 The Use of Short-Term Data to Predict Longer-Term Response .............. 117A.4.2 Physical-Chemical Properties and Metal Content ..................... 118A.4.3 Lung Dose Estimation ............................................ 120A.4.4 Critical Effect Level Estimates ..................................... 121A.4.5 Animal Dose-Response Data Quality ............................... 122A.5 Conclusions ........................................................... 122A.6 Sensitivity Analyses .................................................... 122A.6.1 Lung Dose Estimation ............................................ 122A.6.1.1 Lung dosimetry model-based deposition fractionand dose estimates ........................................ 123A.6.1.2 Cobalt tracer vs. dosimetry model estimates ofMWCNT lung dose ....................................... 124A.6.1.3 Pulmonary Ventilation Rate ............................... 126A.6.2 Critical Effect Level Selection . ..................................... 127A.6.3 Alternative OEL Estimation Methods . .............................. 129A.6.3.1 Illustration of human-equivalent concentration estimation ..... 129A.6.3.2 Evaluation of dosimetric adjustment Factors ................. 130A.6.3.3 Selection of uncertainty factors and OEL derivation ........... 133A.6.4 Summary of Sensitivity Analyses Findings .......................... 134NIOSH CIB 65 • Carbon Nanotubes and Nanofibers93