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Two anthelmintic macrocyclic lactones-ivermectin and moxidectin-have revolutionized parasite control in cattle. These drugs are only partly metabolized by livestock, and the main route of excretion is via feces. In seasonally inundated floodplains, cattle feces come into direct contact with surface water. Important differences in pharmacokinetics and pharmacodynamics between these drugs may bear on their ecotoxicology in aquatic ecosystems. Moxidectin strongly binds to organic matter and thereby may be consumed in aquatic food webs, but there is a scarcity of data on toxicity to freshwater invertebrates. The objectives of this work were to determine the effect of moxidectin spiked in cattle dung on survival and growth of three representative aquatic invertebrates: the zooplankton Ceriodaphnia dubia, the amphipod Hyalella curvispina, and the snail Pomacea canaliculata. Moxidectin-laced dung was added in microcosms and concentrations were measured in water, sediment + dung, roots of the aquatic plant Salvinia biloba, and the aforementioned invertebrates. The influence of moxidectin on nutrient concentrations was also evaluated. Dung was spiked with moxidectin to attain concentrations of 750, 375 and 250 µg kg dung fresh weight, approximating those found in cattle dung at days 2, 3, and 5 following subcutaneous injection. Concentrations of moxidectin in dung during the first week of excretion were lethally toxic for the tested invertebrate taxa. The persistence of moxidectin in the sediment + dung and the uptake of the drug in roots of S. biloba increase its potential exposure to aquatic food webs. Moxidectin also reduced the rate of release of soluble reactive phosphorus to the water.