Bioaccumulation of abacavir and efavirenz in Rhinella arenarum tadpoles after exposure to environmentally relevant concentrations.

Antiretrovirals are pharmaceuticals used in the treatment of the human immunodeficiency virus; they are contaminants of emerging concern that have received considerable attention in recent decades due to their potential negative environmental effects. Data on the bioaccumulation and possible environmental risks posed by these drugs to aquatic organisms are very scarce. Therefore, the aim of this study was to evaluate the bioaccumulation of abacavir and efavirenz in Rhinella arenarum tadpoles subjected to acute static toxicity tests (96 h) at environmentally relevant concentrations. The analytical procedure consisted of the development and optimization of a method involving ultra-high performance liquid chromatography with tandem mass spectrometry detection. The instrumental conditions, optimized by design of experiments using the response surface methodology, yielded limits of detection of 0.3 µg L-1 for abacavir and 0.9 µg L-1 for efavirenz; and limits of quantification of 1.9 µg L-1 for abacavir and 5.6 µg L-1 for efavirenz. Subsequently, the bioaccumulation of the pharmaceutical drugs in tadpoles was evaluated at three exposure concentrations. Efavirenz displayed the highest bioaccumulation levels. This study shows the bioaccumulation potential of abacavir and efavirenz in amphibian tadpoles at exposure concentrations similar to those already detected in the environment, indicating an ecological risk for R. arenarum and probably other aquatic organisms exposed to these drugs in water bodies.

Bioaccumulation and glutathione S-transferase activity on Rhinella arenarum tadpoles after short-term exposure to antiretrovirals.

The aim of the present study was to investigate the bioaccumulation and toxicological effects of four antiretrovirals (lamivudine, stavudine, zidovudine and nevirapine) on Rhinella arenarum tadpoles, after short-term (48 h) exposure to these drugs at sublethal concentrations. The analytical procedure involved a simple extraction method followed by ultra-high performance liquid chromatography with diode array detection and chemometric analysis for data processing. Under the conditions studied, the analytes investigated, particularly nevirapine, showed possible bioaccumulation in tadpoles. Besides, an increase in the bioaccumulation was observed when increasing the exposure concentration. In addition, the enzymatic biomarkers measured to evaluate the toxicological effects showed that acethylcholinesterase activity was similar to that of the control group, while glutathione S-transferase activity was increased, indicating potential oxidative stress damage. Our results also allowed demonstrating the usefulness of chemometric algorithms to quantitate analytes in complex matrices, such as those absorbed by tadpoles in aquatic ecosystems. The results also evidenced the short-term antiretroviral bioaccumulation in tadpoles and the alteration of antioxidant systems, highlighting the need of environmental studies to elucidate the ecotoxicological risk of antiretrovirals in humans and wildlife.