Biological effects of the benzotriazole ultraviolet stabilizers UV-234 and UV-320 in early-staged zebrafish (Danio rerio).

Among the benzotriazole ultraviolet stabilizers (BUVSs), UV-234 and UV-320 are frequently detected in aquatic ecosystem. Despite the fact that these chemicals are present in low ng/L levels in surface water, they show high bio-accumulation potential and pose exposure risks to aquatic organisms. However, there are limited toxicological data available in fish. In this study, zebrafish embryos were exposed to 0.01, 0.1 and 1 μM UV-234 or UV-320 for up to 6 days. Developmental toxicity as well as effects on mitochondrial bioenergetics, immune system responses, and locomotor activity in zebrafish were measured. After UV-234 treatment (0.1-1 μM), hatching time of embryos was increased compared to controls. There was also a ∼20-40% reduction in non-mitochondrial respiration and oligomycin-dependent mitochondrial respiration in embryos treated with 1 μM UV-234 for 24 and 48 h respectively; conversely basal respiration and non-mitochondrial respiration were increased ∼20-30% in embryos treated with 1 μM UV-320 at 48 h. Transcript levels of sod1 were down-regulated with BUVSs while sod2 mRNA was highly up-regulated with both UV-234 and UV-320, suggesting an oxidative damage response. Considering that mitochondrial signaling regulates innate immune pathways, we measured the expression of immune related transcripts (tlr5a, tlr5b, mmp9, il8, tnfa, cxcl-C1c, nfkb1, and ifng). Of these, only il8 and cxcl-C1c mRNA were decreased in response to 0.1 μM UV-320. To associate early molecular events with behavior, locomotor activity was assessed. UV-234 reduced larval activity in a dark photokinesis assay by ∼15%, however behavioral responses at environmentally-relevant concentrations of BUVSs were not consistent across experiments nor BUVSs. These data suggest that BUVSs can perturb mitochondrial bioenergetics, embryonic development, and locomotor activity of zebrafish, but these responses appear to be dose-, time- and BUVSs dependent, suggesting these chemicals may have unique modes of action.

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