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The synthesis and application of nanoparticles can lead to occupational exposure. Thus, this poses potential negative health outcomes associated with exposure to emitted nanoparticles. This is a result of the characteristics of nanoparticles, namely their high surface area, small size, and ability to penetrate the deeper regions of the respiratory system. This study focused on measuring the concentrations of silver nanoparticles and gold nanoparticles emitted during their synthesis, and the application of gold nanoparticles on carbon black electrodes. Utilising experimental design within a controlled laboratory environment, the study employed an OECD 3-tiered approach to collect data, formulate exposure scenarios, monitor emissions, and model total lung particle deposition. A partectorTEM sampler coupled with 3-mm lacy carbon-coated 300 mesh copper grids measured alveolar lung-deposited surface area concentration near the receptor’s breathing zone, considering particle size distribution for particle deposition efficiency. Since the partectorTEM does not provide information on the particle size distribution and breathing zone concentration, a NanoScan SMPS, Optical Particle Sizer Spectrometer, and P-Trak Ultrafine Particle Counter were used. The Multiple-Path Particle Dosimetry (MPPD) model was utilised to predict lung particle deposition and potential retention as well as clearance of nanoparticles based on exposure scenarios and breathing zone concentrations. The lung-deposited surface area concentration of gold nanoparticles was highest at 78.6 µm2/cm3, followed by silver nanoparticles at 40.3 µm2/cm3, and the lowest at 34 µm2/cm3 with the application of gold nanoparticles to carbon black electrodes. For silver nanoparticles, the particle mass concentration was 0.36 µg/m3 and 3.99 µg/m3 for the NanoScan SMPS and Optical Particle Sizer, respectively, and was below the occupational exposure limit set at 0.19 µg/m3. The proposed provisional Nano Reference Value for gold nanoparticles is 20,000 particles/cm3. For the synthesis of gold nanoparticles, the particle number concentrations recorded by the NanoScan SMPS and Optical Particle Sizer, respectively, were 7.56E+3 particles/cm3 and 3.74E+4 particles/cm3. For the application of gold nanoparticles, the particle number concentration was 6.35E+2 particles/cm3 and 4.78E+2 particles/cm3. Based on the OPS, emissions from the synthesis of gold nanoparticles exceeded the proposed nano reference value, whereas the application of the gold nanoparticles remained within the set limits. While the P-Trak results showed that the synthesis of gold nanoparticles was below the proposed nano reference value (1.39E+4 particles/cm3), the application of gold nanoparticles was above the proposed nano reference value (2.33E+4 particles/cm3). This suggests that the type of real-time instrumentation, as well as instrument sensitivity, yielded different results. It is noted that most nanoparticles were predicted to penetrate the alveoli region and may not be effectively cleared by the respiratory system, raising concerns regarding their potential translocation and bioaccumulation in the human body.