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WIREs Nanomed Nanobiotechnol
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In vitro to in vivo benchmark dose comparisons to inform risk assessment of quantum dot nanomaterials

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Engineered nanomaterials are currently under review for their potential toxicity; however, their use in consumer/commercial products has continued to outpace risk assessments. In vitro methods may be utilized as tools to improve the efficiency of risk assessment approaches. We propose a framework to compare relationships between previously published in vitro and in vivo toxicity assessments of cadmium‐selenium containing quantum dots (QDs) using benchmark dose (BMD) and dosimetric assessment methods. Although data were limited this approach was useful for identifying sensitive assays and strains. In vitro studies assessed effects of QDs in three pulmonary cell types across two mouse strains. Significant dose–response effects were modeled and a standardized method of BMD analysis was performed as a function of both exposure dose and dosimetric dose. In vivo studies assessed pulmonary effects of QD exposure across eight mouse strains. BMD analysis served as a basis for relative comparison with in vitro studies. We found consistent responses in common endpoints between in vitro and in vivo studies. Strain sensitivity was consistent between in vitro and in vivo studies, showing A/J mice more sensitive to QDs. Cell types were found to differentially take up QDs. Dosimetric adjustments identified similar sensitivity among cell types. Thus, BMD analysis can be used as an effective tool to compare the sensitivity of different strains, cell types, and assays to QDs. These methods allow for in vitro assays to be used to predict in vivo responses, improve the efficiency of in vivo studies, and allow for prioritization of nanomaterial assessments. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
BMD (circles) and BMDL (triangles) values for IL6 and CXCL1 responses following in vitro Cd QD exposure by exposure dose (a) and dosimetric dose (b). BMDs are shown for multiple cell types, two different rodent strains (vertical panels). AMs and BMDMs are similarly sensitive across all endpoints and dose metrics. MTECs were significantly less sensitive than AMs and BMDMs by exposure dose assessment (a), but equally sensitive when adjusted for dosimetry (b)
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KC (CXCL1) protein expression in BALF after oropharyngeal aspiration exposure to QDs across eight mouse strains (Scoville et al., ). A significant increase in KC expression was observed in the A/J, NOD, and NZO strains. The A/J strain showed the greatest increase in KC relative to controls while the C57BL/6J strain ranked last in sensitivity by this endpoint. A large amount of genetic variability was observed across strains in both treated and control animals
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Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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