Silver exposure in developing zebrafish (Danio rerio): Persistent effects on larval behavior and survival

The increased use of silver nanoparticles in consumer and medical products has led to elevated human and environmental exposures. Silver nanoparticles act as antibacterial/antifungal agents by releasing Ag+ and recent studies show that Ag+ impairs neural cell replication and differentiation in culture, suggesting that in vivo exposures could compromise neurodevelopment. To determine whether Ag+ impairs development in vivo, we examined the effects of exposure on survival, morphological, and behavioral parameters in zebrafish embryos and larvae. We exposed zebrafish from 0 to 5 days post-fertilization to concentrations of Ag+ ranging from 10 nM to 100 µM in order to assess effects on survival and early embryonic development. We then tested whether concentrations below the threshold for dysmorphology altered larval behavior and subsequent survival. Ag+ concentrations ≥ 3 µM significantly reduced embryonic survival, whereas 1 µM delayed hatching with no effect on survival. Reducing the concentration to as low as 0.1 µM delayed the inflation of the swim bladder without causing gross dysmorphology or affecting hatching. At this concentration, swimming activity was impaired, an effect that persisted past the point where swim bladder inflation became normal; in contrast, general motor function was unaffected. The early behavioral impairment was then predictive of subsequent decreases in survival. Ag+ is a developmental toxicant at concentrations only slightly above allowable levels. At low concentrations, Ag+ acts as a neurobehavioral toxicant even in the absence of dysmorphology.