Multivariate Modeling of Engineered Nanomaterial Features Associated With Developmental Toxicity

NanoImpact. 2019 Apr;16:10.1016/j.impact.2019.100185. doi: 10.1016/j.impact.2019.100185. Epub 2019 Nov 1.


Despite the increasing prevalence of engineered nanomaterials (ENMs) in consumer products, their toxicity profiles remain to be elucidated. ENM physicochemical characteristics (PCC) are known to influence ENM behavior, however the mechanisms of these effects have not been quantified. Further confounding the question of how the PCC influence behavior is the inclusion of structural and molecular descriptors in modeling schema that minimize the effects of PCC on the toxicological endpoints. In this work, we analyze ENM physico-chemical measurements that have not previously been studied within a developmental toxicity framework using an embryonic zebrafish model. In testing a panel of diverse ENMs to build a consensus model, we found nonlinear relationships between any singular PCC and bioactivity. By using a machine learning (ML) method to characterize the information content of combinatorial PCC sets, we found that concentration, surface area, shape, and polydispersity can accurately capture the developmental toxicity profile of ENMs with consideration to whole-organism effects.

Keywords: Developmental toxicity; Engineered nanomaterials; Feature analysis; Predictive modeling; zebrafish.