Abstract: Boron nitride (BN) nanomaterials have been increasingly explored for potential biological applications. However, their toxicity remains poorly understood. Using Caenorhabditis elegans  as a whole-animal model for toxicity analysis of two representative types of BN nanomaterials – BN nanospheres (BNNSs) and highly water-soluble BN nanomaterial (named BN-800-2) – we found that BNNSs overall toxicity was less than soluble BN-800-2 with irregular shapes. The concentration thresholds for BNNSs and BN-800-2 were 100 µg·mL^-1 and 10 µg·mL^-1, respectively. Above this concentration, both delayed growth, decreased life span, reduced progeny, retarded locomotion behavior, and changed the expression of phenotype-related genes to various extents. BNNSs and BN-800-2 increased oxidative stress levels in C. elegans  by promoting reactive oxygen species production. Our results further showed that oxidative stress response and MAPK signaling-related genes, such as GAS1 , SOD2 , SOD3 , MEK1 , and PMK1 , might be key factors for reactive oxygen species production and toxic responses to BNNSs and BN-800-2 exposure. Together, our results suggest that when concentrations are lower than 10 µg·mL^-1, BNNSs are more biocompatible than BN-800-2 and are potentially biocompatible material.
Keywords: boron nitride nanomaterials, Caenorhabditis elegans , nanotoxicology, reactive oxygen species, toxicity