Environmental Science and Pollution Research

, Volume 26, Issue 1, pp 600–616 | Cite as

Sub-lethal effects induced by a mixture of different pharmaceutical drugs in predicted environmentally relevant concentrations on Lithobates catesbeianus (Shaw, 1802) (Anura, ranidae) tadpoles

  • Diogo Ferreira do Amaral
  • Mateus Flores Montalvão
  • Bruna de Oliveira Mendes
  • Amanda Pereira da Costa Araújo
  • Aline Sueli de Lima Rodrigues
  • Guilherme MalafaiaEmail author
Research Article


The increasing consumption of medications by humans has negative effects such as the increased disposal of these compounds in the environment. Little is known about how the disposal of a “drug mix” (DM) in aquatic ecosystems can affect their biota. Thus, we evaluated whether the exposure of Lithobates casteibeianus tadpoles to a DM composed of different medication classes (antibiotic, anti-inflammatory, antidepressant, anxiolytic, analgesic, and antacid drugs)—at environmentally relevant concentrations—may change their oral morphology, trigger behavioral disorders, and have mutagenic effects on erythrocyte cells. Based on our data, animals exposed to the DM showed changes in mandibular sheath pigmentation, dentition, and swimming activity, as well as atypical behavior in the social aggregation test [with co-specific and interspecific (Physalaemus cuvieri) individuals] and antipredatory defensive response deficit (chemical stimulus from Odonata larvae), after 15 exposure days. The mutagenic analysis revealed higher frequency of nuclear abnormalities in the erythrocytes of tadpoles exposed to the DM (e.g., multilobulated, blebbed, kidney-shaped, notched nucleus, binuclear, and micronucleated erythrocytes). Given the chemical complexity of the DM, we assumed that several organic functions may have been affected, either by the isolated, synergistic, antagonistic, or additive action of DM compounds. Finally, our study confirms the toxicological potential of DM in L. catesbeianus tadpoles, with emphasis to impacts that can affect the fitness of individuals and their natural populations. Thus, we suggest that more attention should be given to the disposal of medications in the environment and reinforce the need of improving water and sewage treatment systems.


Medicinal waste Amphibians Aquatic ecosystems Toxicity biomarkers Environmental toxicology 



The authors are grateful to the Brazilian National Council for Research (CNPq) (Brazilian research agency) (Proc. No 467801/2014-2) and Instituto Federal Goiano for the financial support (Proc. No Processo 23219.000626/2018-11). Moreover, the authors are grateful to the CNPq for supporting scholarship to the student who developed this study.


This study was funded by the Brazilian National Council for Research (CNPq) (Brazilian research agency) (Proc. No 467801/2014-2) and by Instituto Federal Goiano – Campus Urutaí (GO, Brazil) (Proc. No 23219.000753/2017-11).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All the procedures were approved by The Ethics Committee on Animal Use of Goiano Federal Institute (Comissão de Ética no Uso de Animais do Instituto Federal Goiano), GO, Brazil (protocol No. 7257130418). Meticulous efforts were made to assure that animals suffered the least possible and to reduce external sources of stress, pain, and discomfort. The current study did not exceed the number of animals necessary to produce trustworthy scientific data. This article does not contain any study with human participants.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Diogo Ferreira do Amaral
    • 1
  • Mateus Flores Montalvão
    • 1
  • Bruna de Oliveira Mendes
    • 1
  • Amanda Pereira da Costa Araújo
    • 1
  • Aline Sueli de Lima Rodrigues
    • 1
    • 2
  • Guilherme Malafaia
    • 1
    • 2
    • 3
    Email author
  1. 1.Post-Graduation Program in Conservation of Cerrado Natural Resources – Biological Research LaboratoryGoiano Federal Institute—Urutaí CampusUrutaíBrazil
  2. 2.Biologigal Sciences Department, Post-Graduation Program in Conservation of Cerrado Natural ResourcesGoiano Federal Institute—Urutaí CampusUrutaíBrazil
  3. 3.Laboratório de Pesquisas BiológicasInstituto Federal Goiano—Campus UrutaíUrutaíBrazil

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