Environmental concentrations of the antiepileptic drug carbamazepine interfere with endocrine system of Daphnia magna

Carbamazepine (CBZ) is one of the most frequently detected antiepileptic drug in aquatic environment, with concentrations up to 68 µgL -1 .  At the present study, the effects of CBZ on endocrine system of Daphnia magna weres assessed through the juvenoid and ecdysteroid actions of the compound. For that purpose, we exposed maternal daphnids and embryos to several nominal concentrations of CBZ (10 to 200 μgL -1 ; which were measured by high performance liquid chromatography (HPLC)). Fenoxycarb (FEN; 1 μgL -1 ) was used as a positive control in both bioassays, and for the assessment of anti-juvenoid activity was also added to all test solutions. The endpoints used were: number of offspring born per female; percentage of male production; molting frequency and abnormalities in the embryos development. CBZ significantly decreased the reproductive output and the number of molts of D. magna at the highest concentration tested. This compound induced the production of male offspring (12 ± 1.7%), in a non-concentration-dependent manner, actuating as a weak juvenile hormone analog. Results showed that this substance, at tested concentrations, did not antagonize the juvenoid action of FEN. Further, CBZ showed to be toxic to embryos through maternal exposure interfering with their normal gastrulation and organogenesis stages, but no producing direct embryo toxicity. Male sex of offspring was determined by CBZ during the egg maturation period and not during embryonic development, as none of the embryos directly exposed to CBZ developed into males. These findings suggest that CBZ could act as an endocrine disruptor in D. magna as it decreases the reproductive output, interferes with sex determination and development abnormality in offspring.