Developmental Toxicology of Metal Mixtures in Drosophila: Unique Properties of Potency and Interactions of Mercury Isoforms

Mercury ranks third on the U.S. Agency of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead. We have undertaken uncovering the mechanisms underlying the developmental toxicity of methylmercury (MeHg), inorganic mercury (HgCl2), lead acetate (Pb), and sodium arsenite (As). To probe these differences, we used the Drosophila model, taking advantage of three developmental transitions—pupariation, metamorphosis, and eclosion—to differentiate potentially unique windows of toxicity. We elaborated dose response profiles for each individual metal administered in food and accounted for internal body burden, also extending analyses to evaluate combinatorial metal mixture effects. We observed all four metals producing larval lethality and delayed pupariation, with MeHg being most potent. Compared to other metals, MeHg’s potency is caused by a higher body burden with respect to dose. MeHg uniquely caused dose-dependent failure in eclosion that was unexpectedly rescued by titrating in HgCl2. Our results highlight a unique developmental window and toxicokinetic properties where MeHg acts with specificity relative to HgCl2, Pb, and As. These findings will serve to refine future studies aimed at revealing tissue morphogenesis events and cell signaling pathways, potentially conserved in higher organisms, that selectively mediate MeHg toxicity and its antagonism by HgCl2.

Risk assessment of eight metals and their mixtures to aquatic biota in sediments with diffusive gradients in thin films (DGT): a case study in Pearl River intertidal zone

Background The ecotoxicological risk posed by metals and their mixtures in sediments depends on their bioavailability. Many methods for evaluating the bioavailability of metals in sediments/soils are time-consuming and expensive, and frequently result in equivocal outcomes. The diffusive gradients in thin films (DGT) technique is a good measure of bioavailability for metals that can avoid the above drawbacks. Therefore, more effective approaches to this method should be developed that focus on metal bioavailability. No studies have been conducted using DGT to assess metal mixtures to aquatic biota in sediments. This study is therefore the first attempt to assess sediment toxicity of metals and their mixtures to aquatic biota based on the DGT technique. The intertidal zone of the Pearl River Estuary is selected as a case study. Results The bioavailable (DGT-labile) concentrations of metals range as follows (μg/L): Cd, 0.34–3.62; Pb, 1.35–1.92; Ni, 0.67–92.83; Cu, 0.74–10.30; Zn, 28.60–296.94; Co, 0.03–58.85; Fe, 7.23–4539.36; and Mn, 19.40–6626.83. The risk quotient (RQ), which is the ratio between the measured metal concentrations in the environment (MEC) and the predicted no-effect concentration (PNEC), is conducted to evaluate the single metal risk. The RQ based on summing up the MEC/PNEC ratios (RQMEC/PNEC) and the RQ based on sum of toxic units (RQSTU) are used to assess risk of metal mixture. TheRQ values of Cd, Pb, Ni, Cu, Zn, Fe, and Mn significantly exceed 1, indicating that the adverse effects of the metals are not negligible. Regarding the toxicity of metal mixtures, the values of RQMEC/PNEC and RQSTU are both between 62.45 and 743.48, revealing that the possible risk has already occurred in the study area. Conclusions The two methods of RQMEC/PNEC and RQSTU based on DGT-labile metal concentrations are effective and suitable to estimate the toxicity of metal mixtures in sediments.