Chronic sublethal exposure to silver nanoparticles disrupts thyroid hormone signaling during Xenopus laevis metamorphosis

Nanoparticles (NPs) are engineered in the nanoscale (<100 nm) to have unique physico-chemical properties from their bulk counterparts. Nanosilver particles (AgNPs) are the most prevalent NPs in consumer products due to their strong antimicrobial action. While AgNP toxicity at high concentrations has been thoroughly investigated, the sublethal effects at or below regulatory guidelines are relatively unknown. Amphibian metamorphosis is mediated by thyroid hormone (TH), and initial studies with bullfrogs (Rana catesbeiana) indicate that low concentrations of AgNPs disrupt TH-dependent responses in premetamorphic tadpole tailfin tissue. The present study examined the effects of low, non-lethal, environmentally-relevant AgNP concentrations (0.018, 0.18 or 1.8 μg/L Ag; ∼10 nm particle size) on naturally metamorphosing Xenopus laevis tadpoles in two-28 day chronic exposures beginning with either pre- or prometamorphic developmental stages. Asymmetric flow field flow fractionation with online inductively coupled plasma mass spectrometry and nanoparticle tracking analysis indicated a mixture of single AgNPs with homo-agglomerates in the exposure water with a significant portion (∼30-40%) found as dissolved Ag. Tadpoles bioaccumulated AgNPs and displayed transient alterations in snout/vent and hindlimb length with AgNP exposure. Using MAGEX microarray and quantitative real time polymerase chain reaction transcript analyses, AgNP-induced disruption of five TH-responsive targets was observed. The increased mRNA abundance of two peroxidase genes by AgNP exposure suggests the presence of reactive oxygen species even at low, environmentally-relevant concentrations. Furthermore, differential responsiveness to AgNPs was observed at each developmental stage. Therefore, low concentrations of AgNPs had developmental stage-specific endocrine disrupting effects during TH-dependent metamorphosis.