Occupational health surveillance can be used to track illness or change in a biological function over time, identify and characterize trends, and define the magnitude and scope of exposure and response. Surveillance can also inform attempts to identify causal associations between exposure and health outcomes for the development of prevention strategies. Integral parts of occupational health surveillance are hazard identifications and surveillance and medical screening. Medical screening focuses on the early diagnosis and treatment of exposed individuals. Identifying and characterizing the exposure and health data over time can lead to implementation of strategies for prevention (substitution, engineering or administrative controls, training). Figure 1 identifies the role of biomarkers of exposure and biomarkers of effect in understanding the progression from exposure to health response. The surveillance paradigm presented in Figure 2 integrates the use of biomarkers of exposure and biomarkers of effect with hazard, exposure, and medical surveillance; these tools are used to confirm worker protection and enable early identification and mitigation of potential adverse health outcomes resulting from exposure. A surveillance program that integrates biomarkers of exposure and effect should consider various physical characteristics of ENMs and biological activities associated with nanomaterial exposures. These elements include the physicochemical characterization of the nanomaterial, models of particle transport and translocation, cellular uptake, and biological response pathways. When publishing Current Intelligence Bulletin 60, “Interim Guidance for Medical Screening and Hazard Surveillance for Workers Potentially Exposed to Engineered Nanoparticles,” NIOSH noted that insufficient scientific and medical evidence existed to recommend specific medical screening for the broad categories of materials that are considered ENMs. Instead, NIOSH recommended providing the same screening and surveillance, if any, that would be recommended for the “bulk” or “parent” material. NIOSH also discussed the need for continued and toxicological research to identify candidate biomarkers that could be used in medical screening. Importantly, the testing (assays) for these biomarkers as part of a surveillance program should have the requisite sensitivity, specificity, and positive predictive values for viability. Current Intelligence Bulletin 63, “Occupational Exposure to Titanium Dioxide,” reviewed various mechanisms of toxicity related to exposure to fine or ultra-fine titanium dioxide. In that review, NIOSH referred to the previously mentioned “Interim Guidance for Medical Screening” in lieu of specific medical screening or surveillance of biomarkers for titanium dioxide. Although NIOSH noted that pulmonary inflammation was an exposure-related health effect that may act as a precursor for tumor initiation, it was concluded that pulmonary inflammation in itself could not be used as a specific biomarker for lung cancer. Current Intelligence Bulletin 65, “Occupational Exposure to Carbon Nanotubes and Nanofibers,” reviewed various mechanisms of toxicity related to these nanoparticles. NIOSH recommended establishing a baseline medical and occupational history and performing spirometry and chest X-ray as an initial step for medical surveillance, and investigating abnormal findings according to the recommendations of a qualified medical professional. No specific biomarkers were recommended, although one approach to setting a Recommended Exposure Limit considered (among other factors) the role of nanoparticle-specific surface area in pulmonary inflammation measured as percent neutrophils in bronchoalveolar fluid. OSHA has included the consideration of biomarkers in several substance-specific health standards. For example, the OSHA standard for occupational exposure to lead requires employers to make available biological monitoring in the form of blood sampling and analysis for lead and zinc protoporphyrin levels to covered employees. Additional OSHA standards that include requirements for medical screening and surveillance can be found on the OSHA . As production and use of ENMs increase, occupational health surveillance, potentially incorporating the use of nanobiomonitoring, will remain critically important in safeguarding human health. Innovative studies using well-characterized ENMs and state-of the-art techniques with consideration for appropriate routes of exposure in appropriate human cell systems are required to critically evaluate the biological effects of nanomaterials on human health. Such studies are likely to identify novel organ/cell type-specific biomarkers. Discovery of novel biomarkers specific for ENM exposure will not only assist in monitoring human exposure to ENMs but will also aid in predicting the short- and long-term adverse biological effects on human health. Application of the components of occupational health surveillance, including hazard and medical surveillance, is critically important in helping to define the magnitude and scope of occupational health risks among those exposed to ENMs. Biomarkers of exposure and effect are important components of nanobiomonitoring and surveillance efforts that are intended to provide for early detection of adverse health effects potentially associated with nanomaterial exposures. The development and application of nanobiomonitoring will potentially allow for the development of early intervention strategies to limit or mitigate exposures. However, given the heterogenicity of nanomaterials’ physical and chemical properties, a major challenge will be to identify and validate biomarkers of exposure and effect that apply to all nanomaterials, routes of exposure, and health endpoints. Ethical considerations and issues surrounding informed consent, confidentiality, and potential stigma and discrimination based on surveillance results should also be considered.

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