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The commercialization of engineered nanomaterials (ENMs) began in the early 2000's. Since then the number of commercial products and the number of workers potentially exposed to ENMs is growing, as is the need to evaluate and manage the potential health risks. Occupational exposure limits (OELs) have been developed for some of the first generation of ENMs. These OELs have been based on risk assessments that progressed from qualitative to quantitative as nanotoxicology data became available. In this paper, that progression is characterized. It traces OEL development through the qualitative approach of general groups of ENMs based primarily on read-across with other materials to quantitative risk assessments for nanoscale particles including titanium dioxide, carbon nanotubes and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent prototypic approaches to risk assessment and OEL development for ENMs. Such substance-by-substance efforts are not practical given the insufficient data for many ENMs that are currently being used or potentially entering commerce. Consequently, categorical approaches are emerging to group and rank ENMs by hazard and potential health risk. The strengths and limitations of these approaches are described, and future derivations and research needs are discussed. Critical needs in moving forward with understanding the health effects of the numerous EMNs include more standardized and accessible quantitative data on the toxicity and physicochemical properties of ENMs., (Published by Elsevier Inc.)

The large and rapidly growing number of engineered nanomaterials (ENMs) presents a challenge to assessing the potential occupational health risks. An initial database of 25 rodent studies including 1929 animals across various experimental designs and material types was constructed to identify materials that are similar with respect to their potency in eliciting neutrophilic pulmonary inflammation, a response relevant to workers. Doses were normalized across rodent species, strain, and sex as the estimated deposited particle mass dose per gram of lung. Doses associated with specific measures of pulmonary inflammation were estimated by modeling the continuous dose-response relationships using benchmark dose modeling. Hierarchical clustering was used to identify similar materials. The 18 nanoscale and microscale particles were classified into four potency groups, which varied by factors of approximately two to 100. Benchmark particles microscale TiO 2 and crystalline silica were in the lowest and highest potency groups, respectively. Random forest methods were used to identify the important physicochemical predictors of pulmonary toxicity, and group assignments were correctly predicted for five of six new ENMs. Proof-of-concept was demonstrated for this framework. More comprehensive data are needed for further development and validation for use in deriving categorical occupational exposure limits., (Published by Elsevier Inc.)