Evaluation on combinative toxicology of sodium perchlorate and sodium arsenate using zebrafish Danio rerio as a model
Both perchlorate and arsenic are environmental contaminants, and their co-occurrence has been found in contaminated water. Perchlorate is a definitive thyroid disruptor, and thus affects antioxidant defense system. Arsenate is a pro-oxidant and cause oxidative stress. Arsenic is hypothesized as a thyroid disruptor. Ultimately, both chemicals cause damage on macromolecules. Theoretically, two chemicals have an additive interaction in thyrotoxicity and damage on macromolecules. To test this hypothesis, zebrafish Danio rerio were exposed to sodium arsenate (SA) and sodium perchlorate (SP) individually or in mixture in acute, sub-chronic, and chronic tests. The 96-h LC50s of SA and SP were 272 and 1,365 mg/L, respectively, at larvae stage and 74 and 3,118 mg/L, respectively at juvenile stage. In the chronic toxicity test, we employed some endpoints to evaluate antioxidant (glutathione, GSH), thyrotoxicity (thyroid histopathology), and DNA damage (strand breaks, oxidative bases, and apoptosis). In addition, the toxicokinetics (uptake, accumulation, and depuration) of both chemicals and their mixture was examined. Fish were exposed to SP (10 and 100 mg/L), SA (1 and 10 mg/L), and the mixture—SP+SA (10+1 and 100 +10 mg/L) for up to 90 days. At day 10, 30, 60, and 90, fish were sampled and processed for endpoint assay. In the thyrotoxicity, the sensitivity of the following histopathological indicators for indicating thyroid perturbations by these two chemicals is, in descending order: epithelial cell height>percent of colloid area/follicle area>colloid area/follicular cell height >hyperplasia>angiogenesis>colloid area>follicle area. Models were applied to characterize the toxicokinetics of two chemicals. Two chemicals were taken up and depurated rapidly. Both chemicals reduced the uptake but enhanced the depuration of the other chemical from the zebrafish in mixture. Total and reduced GSH and the GSH status index were significantly altered by high concentrations of SA, SP, or their mixture. Damage to lipid and DNA was not as sensitive as expected. Two chemical displayed additive interactions in terms of some endpoints tested. In summary, this dissertation project explored the mechanism of these two chemicals and their interactions. This dissertation provides toxicological information for these two chemicals and clarifies their joint actions at different levels mechanistically.